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Sample records for delayed drug release

  1. Polymer micelles for delayed release of therapeutics from drug-releasing surfaces with nanotubular structures.

    Science.gov (United States)

    Sinn Aw, Moom; Addai-Mensah, Jonas; Losic, Dusan

    2012-08-01

    A new approach to engineer a local drug delivery system with delayed release using nanostructured surface with nanotube arrays is presented. TNT arrays electrochemically generated on a titanium surface are used as a model substrate. Polymer micelles as drug carriers encapsulated with drug are loaded at the bottom of the TNT structure and their delayed release is obtained by loading blank micelles (without drug) on the top. The delayed and time-controlled drug release is successfully demonstrated by controlling the ratio of blank and drug loaded-micelles. The concept is verified using four different polymer micelles (regular and inverted) loaded with water-insoluble (indomethacin) and water-soluble drugs (gentamicin).

  2. Novel mesalamine-loaded beads in tablets for delayed release of drug to the colon.

    Science.gov (United States)

    Nguyen, Chien; Christensen, J Mark; Ayres, James W

    2012-01-01

    Novel 'beads-in-a-tablet' formulations (total weight ∼740-780 mg) have been prepared that meet USP 31 requirements for Delayed Release of mesalamine. Several methods are presented that overcome breakage of beads during tablet compaction were explored. Bead formulations comprise a combination of extrusion and spheronization to produce a relatively high drug load (80%), followed by coating (25%) with a colonic-targeted drug release polymer (polymethacrylates, Eudragit(®) S100), overcoated (3%) with hydroxypropyl methylcellulose (Opadry(®)) to improve bead binding and compactability, and using 20% coat of lactose/sodium starch glycolate (Explotab(®)) as binder/disintegrant/cushioning agent, thus allowing a sufficiently thick coating to be uniform and without being broken during tablet compaction. Then, the aforementioned beads were compressed into tablets at 1500 pounds of pressure containing 400 mg of mesalamine, and finally coating the compressed tablets with Surelease(®) (ethylcellulose):Opadry(®) = 1:0.5 ranging from 1.5-2.5% weight gain; the resulting tablets met USP 31 dissolution requirements for delayed release tablets.

  3. Liver targeting and the delayed drug release of the nanoparticles of adriamycin polybutylcyanoacrylate in mice

    Institute of Scientific and Technical Information of China (English)

    SHEN Liang-fang; ZHANG Yang-de; SHEN Hai-ju; ZENG Shan; WANG Xin; WANG Cheng; LE Yuan; SHEN Hong

    2006-01-01

    Background Liver targeting drug delivery systems can improve the curative effects and relieve the cytotoxicityof the chemotherapy drugs in the treatment of liver diseases. Nanoparticles carrying therapeutic drugs arecurrently under hot investigation with great clinical significance. This study was aimed to investigate thedifferent tissue distribution of the adriamycin polybutylcyanoacrylate nanoparticle (ADM-PBCA-NP) in the micebody after an injection via lateral tail vein, and to study the liver targeting effects of ADM-PBCA-NP in differentdiameters on normal mice liver.Methods One hundred and eighty Kunming mice were randomly divided into 6 groups with 30 mice in eachgroup (5 treatment groups of ADM-PBCA-NP in the different diameter ranges, non-conjugated free adriamycininjection was employed as the control group). A single dose of either conjugated or free adriamycin equaled2 mg/kg of body weight was delivered via the tail vein. Five mice in each trail were sacrificed at 5, 15, 30minutes, 1, 5 and 12 hours postinjection, respectively. The adriamycin concentrations in the respectivelycollected liver, kidney, spleen, heart, lung and plasma were demonstrated using a high performance liquidchromatography with fluorescence detector.Results Compared with the control group, adriamycin was hardly detected in the heart muscle of the treatmentgroups (P<0.05). The nanoparticle-conjugated adriamycin was cleaned up quickly from the kidney tissue. Theadriamycin concentrations of the mice liver and spleen in the experimental groups were significantly higher thanthat in the control group, except for the group with the nanoparticles diameters of (22.3±6.2) nm (P<0.05). TheADM-PBCA-NP in (101.0±20.3) nm diameter had the highest liver distribution, and the second highestadriamycin distribution in liver was the group of (143.0±23.5) nm diameter (P<0.05). Moreover, adriamycinwas released slowly in the liver during the detection period in the experimental groups. ADM

  4. Blends of hydrophobic and swelling agents in the swelling layer in the preparation of delayed-release pellets of a hydrophilic drug with low MW: Physicochemical characterizations and in-vivo evaluations

    Directory of Open Access Journals (Sweden)

    Chang You

    2014-08-01

    Full Text Available In this study, a hydrophobic material, ethylcellulose, which was used as its aqueous suspension Surelease®, was combined with a swelling agent as the swelling layer to prepare delayed-release pellets for Danshensu, which is a hydrophilic drug with low MW. A rupturable, delayed-release pellet consists of a drug core, a swelling layer containing a swelling agent (cross-linked sodium carboxymethyl cellulose with a hydrophobic agent (Surelease®, and a controlled layer composed by an insoluble, water-permeable polymeric coating (aqueous ethylcellulose dispersions was developed in a fluidised bed. Results showed that blending Surelease® into the swelling layer could effectively extend the release of Danshensu from the pellets, which may be attributed to the slowed swelling rate by reduction of water penetration and improvement of mechanical integrity of the swelling layer. Drug in the delayed pellets showed sustained release in beagle dogs after oral administration with comparable in-vivo exposure to the uncoated drug pellets. In conclusion, blends of hydrophobic and swelling agents in the swelling layer in double-membrane pellets could achieve a delayed drug-release profile in vitro, as well as delayed and sustained absorption in vivo for highly soluble, low-MW drug. The present study highlighted the potential use of a delayed-release system for other hydrophilic, low-MW drugs to meet the formulation requirements for chronopharmacological diseases.

  5. Intracellular drug release nanosystems

    Directory of Open Access Journals (Sweden)

    Fenghua Meng

    2012-10-01

    Full Text Available In order to elicit therapeutic effects, many drugs including small molecule anticancer drugs, proteins, siRNA, and DNA have to be delivered and released into the specific cellular compartments typically the cytoplasm or nucleus of target cells. Intracellular environment-responsive nanosystems that exhibit good extracellular stability while rapidly releasing drugs inside cancer cells have been actively pursued for effective cancer therapy. Here, we highlight novel designs of smart nanosystems that release drugs in response to an intracellular biological signal of cancer cells such as acidic pH in endo/lysosomal compartments, enzymes in lysosomes, and redox potential in cytoplasm and the cell nucleus.

  6. Influence of operational variables in multi-particulate delayed release systems for colon-targeted drug delivery of celecoxib using extrusion spheronization

    Directory of Open Access Journals (Sweden)

    Sinha V

    2010-01-01

    Full Text Available The present research was aimed to formulate and evaluate pH and time-dependent multiparticulate systems for colon-targeted drug delivery of celecoxib (CXB with maximum drug absorption, reduced peak plasma fluctuations, and minimum potential side effects. Multiple unit delayed release systems of the drug in MCC (Avicel® PH-102 grade were prepared using polymethacrylate polymers (Eudragit® L-100 and RSPO as a granulating binder by the extrusion-spheronization technique and characterized for their shape, size, size distribution, friability, density, and moisture content. In vitro release studies were performed in 0.1N HCl, for first 2 h then further performed in phosphate buffer (pH 6.8 for 24 h. The resulting pellets were prepared by extrusion spheronization using different grades of polymethacrylate polymers as a granulating binder, showing a substantial decrease in drug release in initial 5 h (16.28-16.7% and releasing most of the drug in 12-24 h. The geometric and arithmetic mean diameter ranged from (490 to 780 ΅m and (636 to 734 μm, respectively. The minimum to maximum range for circularity, elongation and rectangle were found to be (0.847±0.009 to 0.965±0.078, (1.036±0.057 to 1.185±0.023, and (0.724±0.041 to 0.791±0.047 respectively showing the proper shape and size of the pellets. The content of CXB in the prepared pellets was observed between 98.70 and 99.47% justifying the uniform drug distribution. The in vitro dissolution studies showed that the retardant effect in initial 5 h and most of the drug release in 24 h depended on the ratio and concentration of different grades of methacrylate polymers used in the formulation. CXB-loaded MUPS prepared by the extrusion-spheronization technique using polymethacrylate polymers showed immense potential for colon-specific drug delivery of the drug.

  7. Delayed-release lansoprazole plus naproxen.

    Science.gov (United States)

    Curran, Monique P; Wellington, Keri

    2004-01-01

    A combination package containing delayed-release capsules of the proton pump inhibitor lansoprazole (15 mg once daily) and tablets of the NSAID naproxen (375 or 500 mg twice daily) has been approved for reducing the risk of NSAID-associated gastric ulcers in NSAID-requiring patients with a documented history of gastric ulcer. In a large, 12-week trial in NSAID (including naproxen)-requiring patients with a documented history of gastric ulcer, significantly more recipients of delayed-release lansoprazole 15 mg once daily than placebo recipients were free from gastric ulcer (p ulcer were 80% with lansoprazole 15 mg and 51% with placebo. In a subgroup analysis of recipients of naproxen (89% received 750-1000 mg/day), the percentage of patients free from gastric ulcer after 12 weeks of treatment was significantly higher with delayed-release lansoprazole 15 mg than with placebo (89% vs 33%; p ulcer, the incidence of treatment-related adverse events in recipients of delayed-release lansoprazole 15 mg once daily was low (7%), and similar to that in recipients of placebo (10%).

  8. Formulation, Development and Evaluation of delayed release capsules of Duloxetine Hydrochloride made of different Enteric Polymers

    Directory of Open Access Journals (Sweden)

    Pallavi Yerramsetty

    2012-03-01

    Full Text Available Delayed release systems have acquired a centre stage in the arena of pharmaceutical research and development. The present study involves formulation and evaluation of Duloxetine Hydrochloride delayed release capsules. Duloxetine Hydrochloride is an acid labile drug. It degrades in the acidic environment of the stomach thus leading to therapeutic inefficacy. Therefore it is necessary to bypass the acidic pH of the stomach which can be achieved by formulating delayed release dosage form by using different enteric polymers. Protection of drug from acidic environment is done by coating the drug with enteric polymers by using suspension layering technique in Fluidized bed processor (FBP with different enteric polymers like HPMCAS (Hydroxy Propyl Methyl Cellulose Acetate Succinate, Acryl EZE and HPMCP (Hydroxy propyl methyl cellulose phthalate.The formulation (E12 of delayed release capsules of Duloxetine Hydrochloride containing HPMCP (HP-55: HP- 50 as enteric polymer can be taken as optimized

  9. Microwave Activation of Drug Release

    DEFF Research Database (Denmark)

    Jónasson, Sævar Þór

    Due to current limitations in control of pharmaceutical drug release in the body along with increasing medicine use, methods of externally-controlled drug release are of high interest. In this thesis, the use of microwaves is proposed as a technique with the purpose of externally activating...... setup, called the microwave activation system has been developed and tested on a body phantom that emulates the human torso. The system presented in this thesis, operates unobtrusively, i.e. without physically interfering with the target (patient). The torso phantom is a simple dual-layered cylindrical...... the phantom is of interest for disclosing essential information about the limitations of the concept, the phantom and the system. For these purposes, a twofold operation of the microwave activation system was performed, which are reciprocal of each other. In the first operation phase, named mapping...

  10. Glutathione-triggered drug release from nanostructures.

    Science.gov (United States)

    Latorre, Alfonso; Somoza, Álvaro

    2014-01-01

    The delivery of drugs can be improved with the use of different carriers, such as those based on nanoparticles. The nanostructures loaded with the therapeutic molecules should be able to reach the target cells and, what is more, release the drugs efficiently. Ideally, the drugs should be delivered only in the target cells, and not along their way to the cells. For these reasons several approaches have been developed to control the release of the drugs at the desired sites. In this review article we have summarized the reports that describe the use of glutathione to trigger the release of the therapeutic molecules from different nanostructures.

  11. Understanding Drug Release Data through Thermodynamic Analysis

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    Marjorie Caroline Liberato Cavalcanti Freire

    2017-06-01

    Full Text Available Understanding the factors that can modify the drug release profile of a drug from a Drug-Delivery-System (DDS is a mandatory step to determine the effectiveness of new therapies. The aim of this study was to assess the Amphotericin-B (AmB kinetic release profiles from polymeric systems with different compositions and geometries and to correlate these profiles with the thermodynamic parameters through mathematical modeling. Film casting and electrospinning techniques were used to compare behavior of films and fibers, respectively. Release profiles from the DDSs were performed, and the mathematical modeling of the data was carried out. Activation energy, enthalpy, entropy and Gibbs free energy of the drug release process were determined. AmB release profiles showed that the relationship to overcome the enthalpic barrier was PVA-fiber > PVA-film > PLA-fiber > PLA-film. Drug release kinetics from the fibers and the films were better fitted on the Peppas–Sahlin and Higuchi models, respectively. The thermodynamic parameters corroborate these findings, revealing that the AmB release from the evaluated systems was an endothermic and non-spontaneous process. Thermodynamic parameters can be used to explain the drug kinetic release profiles. Such an approach is of utmost importance for DDS containing insoluble compounds, such as AmB, which is associated with an erratic bioavailability.

  12. Ronidazole pharmacokinetics in cats following delivery of a delayed-release guar gum formulation.

    Science.gov (United States)

    Papich, M G; Levine, D N; Gookin, J L; Davidson, G S; Stagner, W C; Hayes, R B

    2013-08-01

    Ronidazole (RDZ) is the only known effective treatment for feline diarrhea caused by Tritrichomonas foetus. This study aimed to develop guar gum-coated colon-targeted tablets of RDZ and to determine the pharmacokinetics of this delayed-release formulation in cats. Guar gum-coated tablets were administered orally once to five healthy cats (mean dose 32.3 mg/kg). The tablets were then administered once daily for 5 days to four cats (mean dose 34.5 mg/kg), and absorption studies repeated on day 5. Plasma was collected and analyzed for RDZ concentration, and pharmacokinetic noncompartmental and deconvolution analysis were performed on the data. There was negligible RDZ release until after 6 h, and a delayed peak plasma concentration (mean Cmax 28.9 μg/mL) at approximately 14.5 h, which coincides with colonic arrival in cats. Maximum input rate (mg/kg per hour) occurred between 6 and 16 h. This delayed release of ronidazole from guar gum-coated tablets indicates that release of RDZ may be delayed to deliver the medication to a targeted area of the intestine. Repeated dosing with guar gum tablets to steady-state did not inhibit drug bioavailability or alter the pharmacokinetics. Such targeted RDZ drug delivery may provide improved efficacy and reduce adverse effects in cats.

  13. Drug release mechanisms of compressed lipid implants.

    Science.gov (United States)

    Kreye, F; Siepmann, F; Siepmann, J

    2011-02-14

    The aim of this study was to elucidate the mass transport mechanisms controlling drug release from compressed lipid implants. The latter steadily gain in importance as parenteral controlled release dosage forms, especially for acid-labile drugs. A variety of lipid powders were blended with theophylline and propranolol hydrochloride as sparingly and freely water-soluble model drugs. Cylindrical implants were prepared by direct compression and thoroughly characterized before and after exposure to phosphate buffer pH 7.4. Based on the experimental results, an appropriate mathematical theory was identified in order to quantitatively describe the resulting drug release patterns. Importantly, broad release spectra and release periods ranging from 1 d to several weeks could easily be achieved by varying the type of lipid, irrespective of the type of drug. Interestingly, diffusion with constant diffusivities was found to be the dominant mass transport mechanism, if the amount of water within the implant was sufficient to dissolve all of the drug. In these cases an analytical solution of Fick's second law could successfully describe the experimentally measured theophylline and propranolol hydrochloride release profiles, even if varying formulation and processing parameters, e.g. the type of lipid, initial drug loading, drug particles size as well as compression force and time. However, based on the available data it was not possible to distinguish between drug diffusion control and water diffusion control. The obtained new knowledge can nevertheless significantly help facilitating the optimization of this type of advanced drug delivery systems, in particular if long release periods are targeted, which require time consuming experimental trials.

  14. SYNTHESIS AND DRUG RELEASE OF CROSSLINKING POLYPHOSPHATES

    Institute of Scientific and Technical Information of China (English)

    LuoYi; ZhuoRenxi; 等

    1995-01-01

    A new class of crosslinking polyphosphates were synthesized and characterized by IR 1HNMR,31PNMR spectroscopy as well as elemental analysis.In vitro degradation of the polyphosphates obtained and the release of antineoplastic drug Methotrexate(MTX) and contraceptive Levonorgestrel(LNG) by using these polymers as matrix were studied.Zero order release rate was observed in the case of LNG release.

  15. Hybrid nanostructured drug carrier with tunable and controlled drug release

    Energy Technology Data Exchange (ETDEWEB)

    Depan, D.; Misra, R.D.K., E-mail: dmisra@louisiana.edu

    2012-08-01

    We describe here a transformative approach to synthesize a hybrid nanostructured drug carrier that exhibits the characteristics of controlled drug release. The synthesis of the nanohybrid architecture involved two steps. The first step involved direct crystallization of biocompatible copolymer along the long axis of the carbon nanotubes (CNTs), followed by the second step of attachment of drug molecule to the polymer via hydrogen bonding. The extraordinary inorganic-organic hybrid architecture exhibited high drug loading ability and is physically stable even under extreme conditions of acidic media and ultrasonic irradiation. The temperature and pH sensitive characteristics of the hybrid drug carrier and high drug loading ability merit its consideration as a promising carrier and utilization of the fundamental aspects used for synthesis of other promising drug carriers. The higher drug release response during the application of ultrasonic frequency is ascribed to a cavitation-type process in which the acoustic bubbles nucleate and collapse releasing the drug. Furthermore, the study underscores the potential of uniquely combining CNTs and biopolymers for drug delivery. - Graphical abstract: Block-copolymer crystallized on carbon nanotubes (CNTs). Nanohybrid drug carrier synthesized by attaching doxorubicin (DOX) to polymer crystallized CNTs. Crystallized polymer on CNTs provide mechanical stability. Triggered release of DOX. Highlights: Black-Right-Pointing-Pointer The novel synthesis of a hybrid nanostructured drug carrier is described. Black-Right-Pointing-Pointer The drug carrier exhibits high drug loading ability and is physically stable. Black-Right-Pointing-Pointer The high drug release is ascribed to a cavitation-type process.

  16. Electrospinning nanofibers for controlled drug release

    Science.gov (United States)

    Banik, Indrani

    Electrospinning is the most widely studied technique for the synthesis of nanofibers. Electrospinning is considered as one of the technologies that can produce nanosized drugs incorporated in polymeric nanofibers. In vitro and in vivo studies have demonstrated that the release rates of drugs from these nanofiber formulations are enhanced compared to those from original drug substance. This technology has the potential for enhancing the oral delivery of poorly soluble drugs. The electrospun mats were made using Polycaprolactone/PCL, Poly(DL-lactide)/PDL 05 and Poly(DL-lactide-co-glycolide)/PLGA. The drugs incorporated in the electrospun fibers were 5-Fluorouracil and Rapamycin. The evidence of the drugs being embedded in the polymers was obtained by scanning electron microscopy (SEM), Raman and infrared spectroscopy. The release of 5-Fluorouracil and Rapamycin were followed by UV-VIS spectroscopy.

  17. Solid lipid nanoparticles (SLN) for controlled drug delivery--drug release and release mechanism.

    Science.gov (United States)

    zur Mühlen, A; Schwarz, C; Mehnert, W

    1998-03-01

    Solid lipid nanoparticles (SLN) are particulate systems for parenteral drug administration with mean particle diameters ranging from 50 up to 1000 nm. The model drugs tetracaine, etomidate and prednisolone were incorporated (1, 5 and 10%) to study the drug load, effect of drug incorporation on the structure of the lipid matrix and the release profiles and mechanism. SLN were produced by high pressure homogenization of aqueous surfactant solutions containing the drug-loaded lipids in the melted or in the solid state (500/1500 bar, 3/10 cycles). In case of tetracaine and etomidate, high drug loadings up to 10% could be achieved when using Compritol 888 ATO and Dynasan 112 as matrix material. The melting behavior of the drug loaded particles revealed that little or no interactions between drug and lipid occurred. A burst drug release (100% release < 1 min) was observed with tetracaine and etomidate SLN, which was attributed to the large surface area of the nanoparticles and drug enrichment in the outer shell of the particles. In contrast, prednisolone loaded SLN showed a distinctly prolonged release over a monitored period of 5 weeks. Depending on the chemical nature of the lipid matrix, 83.8 and 37.1% drug were released (cholesterol and compritol, respectively). These results demonstrate the principle suitability of SLN as a prolonged release formulation for lipophilic drugs.

  18. CMS releases data on drug spending

    OpenAIRE

    Robbins RA

    2016-01-01

    No abstract available. Article truncated at 150 words. Yesterday (11/14/16) the Centers for Medicare and Medicaid Services (CMS) released data on spending for drugs under Medicare and Medicaid (1,2). Medicare paid $137.4 billion on drugs covered by its prescription drug benefit in 2015. About $8.7 billion of that spending occurred on drugs that had "large" price hikes, defined as a more than 25 percent increase between 2014 and 2015. In 2015, Medicaid paid $57.3 billion about $5.1 billion of ...

  19. CMS releases data on drug spending

    OpenAIRE

    2016-01-01

    No abstract available. Article truncated at 150 words. Yesterday (11/14/16) the Centers for Medicare and Medicaid Services (CMS) released data on spending for drugs under Medicare and Medicaid (1,2). Medicare paid $137.4 billion on drugs covered by its prescription drug benefit in 2015. About $8.7 billion of that spending occurred on drugs that had "large" price hikes, defined as a more than 25 percent increase between 2014 and 2015. In 2015, Medicaid paid $57.3 billion about $5.1 billion of ...

  20. CMS releases data on drug spending

    Directory of Open Access Journals (Sweden)

    Robbins RA

    2016-11-01

    Full Text Available No abstract available. Article truncated at 150 words. Yesterday (11/14/16 the Centers for Medicare and Medicaid Services (CMS released data on spending for drugs under Medicare and Medicaid (1,2. Medicare paid $137.4 billion on drugs covered by its prescription drug benefit in 2015. About $8.7 billion of that spending occurred on drugs that had "large" price hikes, defined as a more than 25 percent increase between 2014 and 2015. In 2015, Medicaid paid $57.3 billion about $5.1 billion of which was spent on drugs that had large price increases. The Medicare spending database highlights 11 drugs that doubled in price. The Medicaid database identified 20 drugs that more than doubled in price with 9 of these being old, generic drugs. Medicare drugs were led by Glumetza, a Type 2 diabetes drug which saw its price soar 380 percent and hydroxychloroquine sulfate, a generic malaria drug, which went up 370 percent. Medicaid drugs were led by Ativan, an anti-anxiety ...

  1. Review of the new delayed-release oral tablet and intravenous dosage forms of posaconazole.

    Science.gov (United States)

    Guarascio, Anthony J; Slain, Douglas

    2015-02-01

    The triazole antifungal posaconazole was first approved as an oral suspension formulation. Despite pharmacokinetic target attainment and clinical efficacy in premarketing trials, postmarketing analyses indicated unpredictable bioavailability resulting in subtherapeutic concentrations and reports of breakthrough fungal infections. The newly approved posaconazole delayed-release tablet and intravenous formulations display more consistent bioavailability in the presence of concomitant disease states, medications, and dietary considerations that classically alter drug concentrations of the oral suspension. Both the delayed-release tablet and intravenous formulation display a similar adverse-effect profile to the oral suspension. The posaconazole delayed-release oral tablet is not significantly affected by gastric acid suppression therapy, and the intravenous dosage form provides an option for patients who are intubated or unable to tolerate oral medications. Pharmacoeconomic considerations, particularly with intravenous posaconazole, will likely play a role in dosage form selection and frequency of use. Due to sustained, higher drug concentrations, the new posaconazole formulations hold promise for greater efficacy in antifungal prophylaxis and bring opportunity for further study in the treatment of invasive mycoses.

  2. Effect of Drug Loading Method on Drug Content and Drug Release from Calcium Pectinate Gel Beads

    OpenAIRE

    2010-01-01

    Drug-loaded calcium pectinate gel (CaPG) beads were prepared by either mixing, absorption, or swelling method. The effects of drug loading method as well as the drug loading factors (i.e., drug concentration, soaking time in drug solution, type of solvent) on drug content and drug release were investigated. The amount of drug uptake (i.e., drug content) into CaPG beads increased as the initial drug concentration increased and varied depending on the loading method. The in vitro release studie...

  3. Delays in clinical development of neurological drugs in Japan.

    Science.gov (United States)

    Ikeda, Masayuki

    2017-06-28

    The delays in the approval and development of neurological drugs between Japan and other countries have been a major issue for patients with neurological diseases. The objective of this study was to analyze factors contributing to the delay in the launching of neurological drugs in Japan. We analyzed data from Japan and the US for the approval of 42 neurological drugs, all of which were approved earlier in the US than in Japan, and examined the potential factors that may cause the delay of their launch. Introductions of the 42 drugs in Japan occurred at a median of 87 months after introductions in the US. The mean review time of new drug applications for the 20 drugs introduced in Japan in January 2011 or later (15 months) was significantly shorter than that for the other 22 drugs introduced in Japan in December 2010 or earlier (24 months). The lag in the Japan's review time behind the US could not explain the approval delays. In the 31 of the 42 drugs, the application data package included overseas data. The mean review time of these 31 drugs (17 months) was significantly shorter than that of the other 11 drugs without overseas data (26 months). The mean approval lag behind the US of the 31 drugs (78 months) was also significantly shorter than that of the other 11 drugs (134 months). These results show that several important reforms in the Japanese drug development and approval system (e.g., inclusion of global clinical trial data) have reduced the delays in the clinical development of neurological drugs.

  4. POLYURETHANE COMPOSITES AS DRUG CARRIERS:: RELEASE PATTERNS

    Directory of Open Access Journals (Sweden)

    M. V. Grigoreva

    2013-10-01

    Full Text Available Biodegradable polyurethanes attract interest of those developing composite materials for biomedical applications. One of their features is their ability to serve as carriers, or matrixes, for medicines and other bioactive compounds to produce a therapeutic effect in body through targeted and/or prolonged delivery of these compounds in the process of their controlled release from matrix. The review presents polyurethane composites as matrices for a number of drugs. The relation between structure of the composites and their degradability both in vitro and in vivo and the dependence of drug release kinetics on physicochemical properties of polyurethane matrix are highlighted. The release of drugs (cefazolin, naltrexone and piroxicam from the composites based on cross-linked polyurethanes (synthesized from laprols, Mw between 1,500 and 2,000 Da and toluylene diisocyanate demonstrated more or less the same pattern (about 10 days in vitro and three to five days in vivo. In contrast, the composites with dioxydine based on a linear polyurethanes (synthesized from oligotetramethilene glycol, Mw 1,000 Da, diphenylmethane-4,4’-diisocyanate and 1,4-butanediol retained their antimicrobial activity at least 30 days. They also showed a significantly higher breaking strength as compared to that of the composites based on cross-linked polyurethanes.

  5. Development and validation of dissolution testings in acidic media for rabeprazole sodium delayed-release capsules.

    Science.gov (United States)

    Tan, Yinhe; Si, Xiaoqing; Zhong, Lulu; Feng, Xin; Yang, Xinmin; Huang, Min; Wu, Chuanbin

    2016-10-01

    Rabeprazole sodium (RAB) dissolved in acidic media is accompanied by its degradation in the course of dissolution testing. To develop and establish the accumulative release profiles of ACIPHEX(®) Sprinkle (RAB) delayed-release capsules (ACIPHEX(®) Sprinkle) in acidic media using USP apparatus 2 (paddle apparatus) as a dissolution tester, the issues of determination of accumulative release amount of RAB in these acidic media and interference of hydroxypropylmethyl cellulose phthalate were solved by adding appropriate hydrochloric acid (HCl) into dissolution samples coupled with centrifugation so as to remove the interference and form a solution of degradation products of RAB, which is of a considerably stable ultraviolet (UV) absorbance at the wavelength of 298 nm within 2.0 h. Therefore, the accumulative release amount of RAB in dissolution samples at each sample time points could be determined by UV-spectrophotometry, and the accumulative release profiles of ACIPHEX(®) Sprinkle in the media of pH 1.0, pH 6.0, and pH 6.8 could be established. The method was validated per as the ICH Q2 (R1) guidelines and demonstrated to be adequate for quality control of ACIPHEX(®) Sprinkle and the accumulative release profiles can be used as a tool to guide the formulation development and quality control of a generic drug for ACIPHEX(®) Sprinkle.

  6. Bioequivalence of two lansoprazole delayed release capsules 30 mg in healthy male volunteers under fasting, fed and fasting-applesauce conditions: a partial replicate crossover study design to estimate the pharmacokinetics of highly variable drugs.

    Science.gov (United States)

    Thota, S; Khan, S M; Tippabhotla, S K; Battula, R; Gadiko, C; Vobalaboina, V

    2013-11-01

    An open-label, 2-treatment, 3-sequence, 3-period, single-dose, partial replicate crossover studies under fasting (n=48), fed (n=60) and fasting-applesauce (n=48) (sprinkled on one table spoonful of applesauce) modalities were conducted in healthy adult male volunteers to evaluate bioequivalence between 2 formulations of lansoprazole delayed release capsules 30 mg. In all the 3 studies, as per randomization, either test or reference formulations were administered in a crossover manner with a required washout period of at least 7 days. Blood samples were collected adequately (0-24 h) to determine lansoprazole plasma concentrations using a validated LC-MS/MS analytical method. To characterize the pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞, Tmax, Kel and T1/2) of lansoprazole, non-compartmental analysis and ANOVA was applied on ln-transformed values. The bioequivalence was tested based on within-subject variability of the reference formulation. In fasting and fed studies (within-subject variability>30%) bioequivalence was evaluated with scaled average bioequivalence, hence for the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞, the 95% upper confidence bound for (μT-μR)2-θσ2 WR was ≤0, and the point estimates (test-to-reference ratio) were within the regulatory acceptance limit 80.00-125.00%. In fasting-applesauce study (within-subject variability<30%) bioequivalence was evaluated with average bioequivalence, the 90% CI of ln-transformed data of Cmax, AUC0-t and AUC0-∞ were within the regulatory acceptance limit 80.00-125.00%. Based on these aforesaid statistical inferences, it was concluded that the test formulation is bioequivalent to reference formulation.

  7. Prevention of invasive fungal infections in immunocompromised patients: the role of delayed-release posaconazole

    Directory of Open Access Journals (Sweden)

    Soysal A

    2015-09-01

    Full Text Available Ahmet SoysalDivision of Pediatric Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Marmara University, Istanbul, TurkeyAbstract: Posaconazole is a triazole antifungal agent that has broad-spectrum activity against many yeasts and filamentous fungi, including Candida species, Cryptococcus neoformans, Aspergillus species, and Zygomycetes. This drug has been approved for the prevention of invasive fungal infections in patients with neutropenia and for the treatment of invasive fungal infections in hematopoietic stem cell transplant recipients with graft-versus-host disease. Studies on the clinical efficacy, safety, tolerability, and cost-effectiveness of posaconazole therapy were performed using the oral suspension form of the drug. Pharmacokinetic studies have found that the oral suspension form of posaconazole has problemeatic bioavailability: its absorption is affected by concomitant medication and food. This article discusses the pharmacokinetic properties of the newly developed posaconazole delayed-release tablet formulation and reviews the efficacy, safety, and cost-effectiveness of both the oral suspension and the new tablet formulation. In conclusion, the posaconazole tablet formulation has better systemic bioavailability, thereby enabling once-daily administration and better absorption in the presence of concomitant medication and food. However, well-designed clinical studies are needed to evaluate the use of the tablet formulation in real-life settings.Keywords: posaconazole delayed-release tablet, prophylaxis, invasive fungal infections

  8. Agglomerates containing pantoprazole microparticles: modulating the drug release.

    Science.gov (United States)

    Raffin, Renata P; Colombo, Paolo; Sonvico, Fabio; Rossi, Alessandra; Jornada, Denise S; Pohlmann, Adriana R; Guterres, Silvia S

    2009-01-01

    Pantoprazole-loaded microparticles were prepared using a blend of Eudragit S100 and Methocel F4M. The accelerated stability was carried out during 6 months at 40 degrees C and 75% relative humidity. In order to improve technological characteristics of the pantoprazole-loaded microparticles, soft agglomerates were prepared viewing an oral delayed release and gastro-resistant solid dosage form. The agglomeration was performed by mixing the pantoprazole microparticles with spray-dried mannitol/lecithin powders. The effects of factors such as the amount of lecithin in the spray-dried mannitol/lecithin powders and the ratio between pantoprazole microparticles and spray-dried mannitol/lecithin powders were evaluated. The pantoprazole-loaded microparticles present no significant degradation in 6 months. The agglomerates presented spherical shape, with smooth surface and very small quantity of non-agglomerated particles. The agglomerates presented different yields (35.5-79.0%), drug loading (58-101%), and mechanical properties (tensile strength varied from 44 to 69 mN mm(-2)), when the spray-dried mannitol/lecithin powders with different lecithin amounts were used. The biopharmaceutical characteristics of pantoprazole microparticles, i.e., their delayed-release properties, were not affected by the agglomeration process. The gastro-resistance of the agglomerates was affected by the amount of spray-dried mannitol/lecithin powders. The ratio of lecithin in the spray-dried mannitol/lecithin powders was the key factor in the agglomerate formation and in the drug release profiles. The agglomerates presenting better mechanical and biopharmaceutical characteristics were prepared with 1:2 (w/w) ratio of pantoprazole-loaded microparticles and mannitol/lecithin (80:20) powder.

  9. 3D Printing of Medicines: Engineering Novel Oral Devices with Unique Design and Drug Release Characteristics.

    Science.gov (United States)

    Goyanes, Alvaro; Wang, Jie; Buanz, Asma; Martínez-Pacheco, Ramón; Telford, Richard; Gaisford, Simon; Basit, Abdul W

    2015-11-02

    Three dimensional printing (3D printing) was used to fabricate novel oral drug delivery devices with specialized design configurations. Each device was loaded with multiple actives, with the intent of applying this process to the production of personalized medicines tailored at the point of dispensing or use. A filament extruder was used to obtain drug-loaded--paracetamol (acetaminophen) or caffeine--filaments of poly(vinyl alcohol) with characteristics suitable for use in fused-deposition modeling 3D printing. A multinozzle 3D printer enabled fabrication of capsule-shaped solid devices containing the drug with different internal structures. The design configurations included a multilayer device, with each layer containing drug, whose identity was different to the drug in the adjacent layers, and a two-compartment device comprising a caplet embedded within a larger caplet (DuoCaplet), with each compartment containing a different drug. Raman spectroscopy was used to collect 2-dimensional hyper spectral arrays across the entire surface of the devices. Processing of the arrays using direct classical least-squares component matching to produce false color representations of distribution of the drugs was used. This clearly showed a definitive separation between the drug layers of paracetamol and caffeine. Drug release tests in biorelevant bicarbonate media showed unique drug release profiles dependent on the macrostructure of the devices. In the case of the multilayer devices, release of both paracetamol and caffeine was simultaneous and independent of drug solubility. With the DuoCaplet design, it was possible to engineer either rapid drug release or delayed release by selecting the site of incorporation of the drug in the device; the lag-time for release from the internal compartment was dependent on the characteristics of the external layer. The study confirms the potential of 3D printing to fabricate multiple-drug containing devices with specialized design

  10. 21 CFR 343.90 - Dissolution and drug release testing.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Dissolution and drug release testing. 343.90...-COUNTER HUMAN USE Testing Procedures § 343.90 Dissolution and drug release testing. (a) [Reserved] (b) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in...

  11. Cerebral Rhizomucor Infection Treated by Posaconazole Delayed-Release Tablets in an Allogeneic Stem Cell Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Diego O. Andrey

    2017-02-01

    Full Text Available Mucormycosis (zygomycosis is an emerging fungal disease in allogeneic hematopoietic stem cell transplant (allo-HSCT recipients. A 30-year-old woman diagnosed with acute myelomonocytic leukemia and needing allo-HSCT presented pulmonary and cerebral infection due to Rhizomucor pusillus. This fungal infection was treated with surgical treatment and posaconazole delayed-release tablets. This strategy allowed reaching high drug levels that could not be obtained with the posaconazole solution.

  12. Determining drug release rates of hydrophobic compounds from nanocarriers.

    Science.gov (United States)

    D'Addio, Suzanne M; Bukari, Abdallah A; Dawoud, Mohammed; Bunjes, Heike; Rinaldi, Carlos; Prud'homme, Robert K

    2016-07-28

    Obtaining meaningful drug release profiles for drug formulations is essential prior to in vivo testing and for ensuring consistent quality. The release kinetics of hydrophobic drugs from nanocarriers (NCs) are not well understood because the standard protocols for maintaining sink conditions and sampling are not valid owing to mass transfer and solubility limitations. In this work, a new in vitroassay protocol based on 'lipid sinks' and magnetic separation produces release conditions that mimic the concentrations of lipid membranes and lipoproteins in vivo, facilitates separation, and thus allows determination of intrinsic release rates of drugs from NCs. The assay protocol is validated by (i) determining the magnetic separation efficiency, (ii) demonstrating that sink condition requirements are met, and (iii) accounting for drug by completing a mass balance. NCs of itraconazole and cyclosporine A (CsA) were prepared and the drug release profiles were determined. This release protocol has been used to compare the drug release from a polymer stabilized NC of CsA to a solid drug NP of CsA alone. These data have led to the finding that stabilizing block copolymer layers have a retarding effect on drug release from NCs, reducing the rate of CsA release fourfold compared with the nanoparticle without a polymer coating.This article is part of the themed issue 'Soft interfacial materials: from fundamentals to formulation'.

  13. Comparison of sequential drug release in vitro and in vivo.

    Science.gov (United States)

    Sundararaj, Sharath C; Al-Sabbagh, Mohanad; Rabek, Cheryl L; Dziubla, Thomas D; Thomas, Mark V; Puleo, David A

    2016-10-01

    Development of drug-delivery devices typically involves characterizing in vitro release performance with the inherent assumption that this will closely approximate in vivo performance. Yet, as delivery devices become more complex, for instance with a sequential drug release pattern, it is important to confirm that in vivo properties correlate with the expected "programming" achieved in vitro. In this work, a systematic comparison between in vitro and in vivo biomaterial erosion and sequential release was performed for a multilayered association polymer system comprising cellulose acetate phthalate and Pluronic F-127. After assessing the materials during incubation in phosphate-buffered saline, devices were implanted supracalvarially in rats. Devices with two different doses and with different erosion rates were harvested at increasing times post-implantation, and the in vivo thickness loss, mass loss, and the drug release profiles were compared with their in vitro counterparts. The sequential release of four different drugs observed in vitro was successfully translated to in vivo conditions. Results suggest, however, that the total erosion time of the devices was longer and that release rates of the four drugs were different, with drugs initially released more quickly and then more slowly in vivo. Many comparative studies of in vitro and in vivo drug release from biodegradable polymers involved a single drug, whereas this research demonstrated that sequential release of four drugs can be maintained following implantation. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1302-1310, 2016.

  14. Drug release characteristics of dosage forms:a review

    Institute of Scientific and Technical Information of China (English)

    Satinder Kakar; Ramandeep Singh; Alok Semwal

    2014-01-01

    Area of drug delivery is vast, and various advances have been made in the medical field. Besides the versatility in the dosage forms, various orders for the drug release are known, which includes zero order, first order, Higuchi model, Hixon Crowell model and Korsmeyer Peppas model. In vitro dissolution is recognized as an important element in the development of drug. The nature of the drug such as its shape, crystallinity, particle size and solubility reflects the kinetics of the drug. Various models are used to study the dissolution profiles of the new drug substances. Qualitative and quantitative changes in the drug alters the drug release and performance that is action of drug in the body, which is in vivo performance. Various model dependent methods and model independent methods have been taken into consideration for studying the drug release kinetics.

  15. Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections

    Directory of Open Access Journals (Sweden)

    Wiederhold NP

    2015-12-01

    Full Text Available Nathan P Wiederhold Departments of Pathology and Medicine/Infectious Diseases, University of Texas Health Science Center at San Antonio, South Texas Reference Laboratories, San Antonio, TX, USA Abstract: Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various pathogenic fungi, including yeast and moulds. Clinical studies have demonstrated that this agent is efficacious as prophylaxis against invasive fungal infections in patients at high risk, and may also be useful as salvage therapy against invasive aspergillosis and mucormycosis. However, the bioavailability of posaconazole following administration by oral suspension, which was the only formulation clinically available for many years, is highly variable and negatively influenced by several factors. Because of this, many patients had subtherapeutic or undetectable posaconazole levels when the oral suspension was used. To overcome this limitation, a delayed-release tablet was developed and is now available for clinical use. Hot-melt extrusion technology is used to combine a pH-sensitive polymer with posaconazole to produce a formulation that releases the drug in the elevated pH of the intestine where absorption occurs rather than in the low-pH environment of the stomach. This results in enhanced bioavailability and increased posaconazole exposure. Studies in healthy volunteers have demonstrated significantly higher and more consistent exposures with the tablet formulation compared to the oral suspension. In addition, pharmacokinetic parameters following administration of the tablets were not significantly affected by medications that raise gastric pH or increase gastric motility, and the tablets could also be administered without regard to food. Similar results have also been found in patients at high risk for invasive fungal infections who have received posaconazole tablets. The tablet formulation also appears to be well tolerated to date, although data

  16. Fast Drug Release Using Rotational Motion of Magnetic Gel Beads

    Directory of Open Access Journals (Sweden)

    Jun-Ichi Takimoto

    2008-03-01

    Full Text Available Accelerated drug release has been achieved by means of the fast rotation of magnetic gel beads. The magnetic gel bead consists of sodium alginate crosslinked by calcium chlorides, which contains barium ferrite of ferrimagnetic particles, and ketoprofen as a drug. The bead underwent rotational motion in response to rotational magnetic fields. In the case of bead without rotation, the amount of drug release into a phosphate buffer solution obeyed non-Fickian diffusion. The spontaneous drug release reached a saturation value of 0.90 mg at 25 minutes, which corresponds to 92% of the perfect release. The drug release was accelerated with increasing the rotation speed. The shortest time achieving the perfect release was approximately 3 minutes, which corresponds to 1/8 of the case without rotation. Simultaneous with the fast release, the bead collapsed probably due to the strong water flow surrounding the bead. The beads with high elasticity were hard to collapse and the fast release was not observed. Hence, the fast release of ketoprofen is triggered by the collapse of beads. Photographs of the collapse of beads, time profiles of the drug release, and a pulsatile release modulated by magnetic fields were presented.

  17. Sustain-release of various drugs from leucaena leucocephala polysaccharide.

    Science.gov (United States)

    Jeevanandham, S; Sekar, M; Dhachinamoorthi, D; Muthukumaran, M; Sriram, N; Joysaruby, J

    2010-01-01

    This study examines the sustained release behavior of both water-soluble (acetaminophen, caffeine, theophylline and salicylic acid) and water-insoluble (indomethacin) drugs from Leucaena leucocephala seed Gum isolated from Leucaena leucocephala kernel powder. It further investigates the effect of incorporation of diluents like microcrystalline cellulose and lactose on release of caffeine and partial cross-linking of the gum (polysaccharide) on release of acetaminophen. Applying exponential equation, the mechanism of release of soluble drugs was found to be anomalous. The insoluble drug showed near case II or zero-order release mechanism. The rate of release was in the decreasing order of caffeine, acetaminophen, theophylline, salicylic acid and indomethacin. An increase in release kinetics of drug was observed on blending with diluents. However, the rate of release varied with type and amount of blend in the matrix. The mechanism of release due to effect of diluents was found to be anomalous. The rate of release of drug decreased on partial cross-linking and the mechanism of release was found to be super case II.

  18. Impairment of the in vitro drug release behaviour of oral modified release preparations in the presence of alcohol.

    Science.gov (United States)

    Fadda, Hala M; Mohamed, Mohamed A M; Basit, Abdul W

    2008-08-06

    Recently, there has been concern by regulatory authorities of the risk of alcohol-induced dose dumping of oral modified release (MR) formulations. The aim of this work was to use in vitro dissolution methodology to investigate the vulnerability of MR products to alcohol under different physiological conditions of the upper gastrointestinal tract. A variety of dissolution scenarios with ethanol concentrations in the range of 5-40% v/v were explored. Mesalazine (5-aminosalicylic acid) was selected as the model drug and the release behaviour of three commercially available MR, monolithic and multi-particulate preparations with pH-dependent or independent release mechanisms was evaluated (Salofalk, Asacol and Pentasa). Each product was found to have a distinctive release profile and behaved differently in the scenarios screened. In the case of Pentasa, complete dose dumping occurred on exposure to 40% ethanol in acid for 2h. Asacol, however, displayed a contrarian trend with drug release being substantially delayed in small intestinal media after pre-exposure to acid/ethanol for the same duration. Salofalk underwent accelerated drug release in the presence of ethanol in the dissolution media, with unexpected trends observed between the different scenarios. For the three preparations explored, there appears to be a complex interplay between the various formulation variables and ethanol in the dissolution media. The unpredictable release profiles under the different conditions makes it necessary to screen several in vitro scenarios of ethanol exposure for each preparation before a decision is reached on its susceptibility to drug release impairment on consumption with ethanol.

  19. Molecularly imprinted nanotubes for enantioselective drug delivery and controlled release.

    Science.gov (United States)

    Yin, Junfa; Cui, Yue; Yang, Gengliang; Wang, Hailin

    2010-11-07

    Molecularly imprinted nanotubes for enantioselective drug delivery and controlled release are fabricated by the combination of template synthesis and ATRP grafting. The release of R-propranolol from the imprinted nanotubes in rats is restricted while the release of pharmacologically active S-enantiomer is greatly promoted.

  20. A REVIEW ON ADVANCES OF SUSTAINED RELEASE DRUG DELIVERY SYSTEM

    Directory of Open Access Journals (Sweden)

    Sujit Bose

    2013-06-01

    Full Text Available Sustained release matrix tablets facilitate prolonged and continuous drug release and improve the bioavailability of drugs while avoiding unwanted side effects. Ofloxacin is a broad spectrum antibacterial agent used for treating wide range of gram positive and gram negative infections. The goal in designing sustained or controlled delivery systems is to reduce frequency of dosing or to increase the effectiveness of the drug by localization at the site of action, reducing the dose required, providing uniform drug delivery. Sustained release drug administration means not only prolongation of duration of drug delivery, but the term also implies the predictability and reproducibility of drug release kinetics. The controlled release of drug substances and their effective transport to sites of action can be exploited to maximize the beneficial clinical response and to minimize the incidence of unbeneficial adverse reactions and side effects. Oral ingestion has long been the most convenient and commonly employed route of drug delivery. Indeed, for sustained release systems, oral route of administration has received most of the attention with respect to research on physiological and drug constraints as well as design and testing of products.

  1. Assembly of bio-nanoparticles for double controlled drug release.

    Directory of Open Access Journals (Sweden)

    Wei Huang

    Full Text Available A critical limiting factor of chemotherapy is the unacceptably high toxicity. The use of nanoparticle based drug carriers has significantly reduced the side effects and facilitated the delivery of drugs. Source of the remaining side effect includes (1 the broad final in vivo distribution of the administrated nanoparticles, and (2 strong basal drug release from nanoparticles before they could reach the tumor. Despite the advances in pH-triggered release, undesirable basal drug release has been a constant challenge under in vivo conditions. In this study, functionalized single walled carbon nanohorn supported immunoliposomes were assembled for paclitaxel delivery. The immunoliposomes were formulated with polyethylene glycol, thermal stable and pH sensitive phospholipids. Each nanohorn was found to be encapsulated within one immunoliposome. Results showed a highly pH dependent release of paclitaxel in the presence of serum at body temperature with minimal basal release under physiological conditions. Upon acidification, paclitaxel was released at a steady rate over 30 days with a cumulative release of 90% of the loaded drug. The drug release results proved our hypothesized double controlled release mechanism from the nanoparticles. Other results showed the nanoparticles have doubled loading capacity compared to that of traditional liposomes and higher affinity to breast cancer cells overexpressing Her2 receptors. Internalized nanoparticles were found in lysosomes.

  2. Chitosan-genipin microspheres for the controlled release of drugs: clarithromycin, tramadol and heparin.

    Science.gov (United States)

    Harris, Ruth; Lecumberri, Elena; Heras, Angeles

    2010-05-26

    The aim of this study was to first evaluate whether the chitosan hydrochloride-genipin crosslinking reaction is influenced by factors such as time, and polymer/genipin concentration, and second, to develop crosslinked drug loaded microspheres to improve the control over drug release. Once the crosslinking process was characterized as a function of the factors mentioned above, drug loaded hydrochloride chitosan microspheres with different degrees of crosslinking were obtained. Microspheres were characterized in terms of size, morphology, drug content, surface charge and capacity to control in vitro drug release. Clarithromycin, tramadol hydrochloride, and low molecular weight heparin (LMWH) were used as model drugs. The obtained particles were spherical, positively charged, with a diameter of 1-10 microm. X-Ray diffraction showed that there was an interaction of genipin and each drug with chitosan in the microspheres. In relation to the release profiles, a higher degree of crosslinking led to more control of drug release in the case of clarithromycin and tramadol. For these drugs, optimal release profiles were obtained for microspheres crosslinked with 1 mM genipin at 50 °C for 5 h and with 5 mM genipin at 50 °C for 5 h, respectively. In LMWH microspheres, the best release profile corresponded to 0.5 mM genipin, 50 °C, 5 h. In conclusion, genipin showed to be eligible as a chemical-crosslinking agent delaying the outflow of drugs from the microspheres. However, more studies in vitro and in vivo must be carried out to determine adequate crosslinking conditions for different drugs.

  3. Chitosan-Genipin Microspheres for the Controlled Release of Drugs: Clarithromycin, Tramadol and Heparin

    Directory of Open Access Journals (Sweden)

    Ruth Harris

    2010-05-01

    Full Text Available The aim of this study was to first evaluate whether the chitosan hydrochloride-genipin crosslinking reaction is influenced by factors such as time, and polymer/genipin concentration, and second, to develop crosslinked drug loaded microspheres to improve the control over drug release. Once the crosslinking process was characterized as a function of the factors mentioned above, drug loaded hydrochloride chitosan microspheres with different degrees of crosslinking were obtained. Microspheres were characterized in terms of size, morphology, drug content, surface charge and capacity to control in vitro drug release. Clarithromycin, tramadol hydrochloride, and low molecular weight heparin (LMWH were used as model drugs. The obtained particles were spherical, positively charged, with a diameter of 1–10 μm. X-Ray diffraction showed that there was an interaction of genipin and each drug with chitosan in the microspheres. In relation to the release profiles, a higher degree of crosslinking led to more control of drug release in the case of clarithromycin and tramadol. For these drugs, optimal release profiles were obtained for microspheres crosslinked with 1 mM genipin at 50 ºC for 5 h and with 5 mM genipin at 50 ºC for 5 h, respectively. In LMWH microspheres, the best release profile corresponded to 0.5 mM genipin, 50 ºC, 5 h. In conclusion, genipin showed to be eligible as a chemical-crosslinking agent delaying the outflow of drugs from the microspheres. However, more studies in vitro and in vivo must be carried out to determine adequate crosslinking conditions for different drugs.

  4. Delayed ulnar neuropathy at the wrist following open carpal tunnel release.

    Science.gov (United States)

    Pingree, Matthew J; Bosch, E Peter; Liu, Patrick; Smith, Benn E

    2005-03-01

    Open carpal tunnel release is a common and successful treatment of median neuropathy at the wrist (carpal tunnel syndrome). We report a case of delayed ulnar neuropathy at the wrist with onset 2 months after open carpal tunnel release. Clinical findings, electrophysiological studies, magnetic resonance imaging, and surgical exploration demonstrated ulnar nerve compression at Guyon's canal resulting from translocation of the carpal tunnel contents. To our knowledge, this is an unreported complication of open carpal tunnel release that merits wide appreciation.

  5. Fabrication of drug eluting implants: study of drug release mechanism from titanium dioxide nanotubes

    Science.gov (United States)

    Hamlekhan, Azhang; Sinha-Ray, Suman; Takoudis, Christos; Mathew, Mathew T.; Sukotjo, Cortino; Yarin, Alexander L.; Shokuhfar, Tolou

    2015-06-01

    Formation of titanium dioxide nanotubes (TNTs) on a titanium surface holds great potential for promoting desirable cellular response. However, prolongation of drug release from these nano-reservoirs remains to be a challenge. In our previous work TNTs were successfully loaded with a drug. In this study the effect of TNTs dimensions on prolongation of drug release is quantified aiming at the introduction of a simple novel technique which overcomes complications of previously introduced methods. Different groups of TNTs with different lengths and diameters are fabricated. Samples are loaded with a model drug and rate of drug release over time is monitored. The relation of the drug release rate to the TNT dimensions (diameter, length, aspect ratio and volume) is established. The results show that an increase in any of these parameters increases the duration of the release process. However, the strongest parameter affecting the drug release is the aspect ratio. In fact, TNTs with higher aspect ratios release drug slower. It is revealed that drug release from TNT is a diffusion-limited process. Assuming that diffusion of drug in (Phosphate-Buffered Saline) PBS follows one-dimensional Fick’s law, the theoretical predictions for drug release profile is compatible with our experimental data for release from a single TNT.

  6. Microporous material from kanemite for drug inclusion and release.

    Science.gov (United States)

    Ambrogi, V; Chiappini, I; Fardella, G; Grandolini, G; Marmottini, F; Perioli, L

    2001-01-01

    A microporous material obtained from kanemite, a layered polysilicate, was studied in order to investigate its feasibility of including drugs and then releasing them. Diphenydramine hydrochloride was chosen as a model drug. The preparation of the microporous material and its loading with the drug are described. As kanemite is able to intercalate anions between its layers, the intercalation compound of diphenydramine and kanemite was also prepared. Both the drug-loaded microporous material and the intercalation compound were submitted to dissolution tests at pH 7.5. The drug release profiles from these two different materials and from a physical mixture were compared.

  7. Prevention of invasive fungal infections in immunocompromised patients: the role of delayed-release posaconazole.

    Science.gov (United States)

    Soysal, Ahmet

    2015-01-01

    Posaconazole is a triazole antifungal agent that has broad-spectrum activity against many yeasts and filamentous fungi, including Candida species, Cryptococcus neoformans, Aspergillus species, and Zygomycetes. This drug has been approved for the prevention of invasive fungal infections in patients with neutropenia and for the treatment of invasive fungal infections in hematopoietic stem cell transplant recipients with graft-versus-host disease. Studies on the clinical efficacy, safety, tolerability, and cost-effectiveness of posaconazole therapy were performed using the oral suspension form of the drug. Pharmacokinetic studies have found that the oral suspension form of posaconazole has problemeatic bioavailability: its absorption is affected by concomitant medication and food. This article discusses the pharmacokinetic properties of the newly developed posaconazole delayed-release tablet formulation and reviews the efficacy, safety, and cost-effectiveness of both the oral suspension and the new tablet formulation. In conclusion, the posaconazole tablet formulation has better systemic bioavailability, thereby enabling once-daily administration and better absorption in the presence of concomitant medication and food. However, well-designed clinical studies are needed to evaluate the use of the tablet formulation in real-life settings.

  8. The use of solid lipid nanoparticles for sustained drug release.

    Science.gov (United States)

    Attama, Anthony A; Umeyor, Chukwuebuka E

    2015-01-01

    Novel solid lipid drug delivery systems such as solid lipid nanoparticles (SLN) have attracted wide and increasing attention in recent years. It has been sought as an interesting alternative drug delivery carrier system for bioactives for a variety of delivery routes. They show major advantages such as sustained release, improved bioavailability, improved drug incorporation and very wide application. This paper presents a discussion on the production protocols of SLN, lyophilization of SLN and delivery of SLN across the blood-brain barrier. Special attention was also paid to entrapment and release of drugs from SLN and strategies to enhance drug entrapment in SLN for sustained release. Analytical methods for the characterization of SLN were also discussed. Various routes of administration of SLN were presented as well as a consideration of the ethical issues and future prospects in the production and use of SLN for sustained release of bioactives.

  9. Design, Development and Characterization of Extended Release Multiunit Particulate System of Anti-Inflammatory Drug

    Directory of Open Access Journals (Sweden)

    Dhiren Daslaniya

    2009-07-01

    Full Text Available Multi unit particulate system has long been employed to improve the bioavailability of drugs. Mesalamine pellets were prepared by Coating drug solution on sugar sphere followed by various functional coating. The influence of rate controlling membrane made up of Eudragit RSPO and Eudragit RLPO in combination with delay release polymer coating with Eudragit L100 in different proportions on drug release kinetics was studied. Pellets were for the various parameter like Physical characteristics, assay and in-vitro dissolution profile. The study confirmed that mesalamine can be delivered by multi unit particulate system into lower part of intestine. Optimized formulations were evaluated for In-vitro release profile. The optimized formula was stable at accelerated storage condition 40°C / 75 % RH. Prepared Pellets can be used in the treatment of the ulcerative colitis.

  10. Effect of diluents on tablet integrity and controlled drug release.

    Science.gov (United States)

    Zhang, Y E; Schwartz, J B

    2000-07-01

    The objective of this study was to evaluate the effect of diluents and wax level on tablet integrity during heat treatment and dissolution for sustained-release formulations and the resultant effect on drug release. Dibasic calcium phosphate dihydrate (DCPD), microcrystalline cellulose (MCC), and lactose were evaluated for their effect on tablet integrity during drug dissolution and heat treatment in wax matrix formulations. A newly developed direct compression diluent, dibasic calcium phosphate anhydrous (DCPA), was also evaluated. Compritol 888 ATO was used as the wax matrix material, with phenylpropanolamine hydrochloride (PPA) as a model drug. Tablets were made by direct compression and then subjected to heat treatment at 80 degrees C for 30 min. The results showed that MCC, lactose, and DCPA could maintain tablets intact during heat treatment above the melting point of wax (70 degrees C-75 degrees C). However, DCPD tablets showed wax egress during the treatment. MCC tablets swelled and cracked during drug dissolution and resulted in quick release. DCPD and lactose tablets remained intact during dissolution and gave slower release than MCC tablets. DCPA tablets without heat treatment disintegrated very quickly and showed immediate release. In contrast, heat-treated DCPA tablets remained intact through the 24-hr dissolution test and only released about 80% PPA at 6 hr. In the investigation of wax level, DCPD was used as the diluent. The drug release rate decreased as the wax content increased from 15% to 81.25%. The dissolution data were best described by the Higuchi square-root-of-time model. Diluents showed various effects during heat treatment and drug dissolution. The integrity of the tablets was related to the drug release rate. Heat treatment retarded drug release if there was no wax egress.

  11. A New Drug Release Method in Early Development of Transdermal Drug Delivery Systems

    OpenAIRE

    Bing Cai; Karin Söderkvist; Håkan Engqvist; Susanne Bredenberg

    2012-01-01

    In vitro drug release tests are a widely used tool to measure the variance between transdermal product performances and required by many authorities. However, the result cannot provide a good estimation of the in vivo drug release.  In the present work, a new method for measuring drug release from patches has been explored and compared with the conventional USP apparatus 2 and 5 methods. Durogesic patches, here used as a model patch, were placed on synthetic skin simulator and three moisture ...

  12. Clinical utility of risedronate in postmenopausal osteoporosis: patient considerations with delayed-release formulation

    Directory of Open Access Journals (Sweden)

    Boyanov M

    2012-04-01

    Full Text Available Plamen Kinov1, Mihail Boyanov21Department of Orthopedics and Traumatology, University Hospital Queen Giovanna – ISUL, 2Department of Internal Medicine, Clinic of Endocrinology, University Hospital Alexandrovska, Medical University of Sofia, Sofia, BulgariaAbstract: Bisphosphonates are the most widely prescribed treatment for postmenopausal osteoporosis, secondary osteoporosis, and male osteoporosis. Notwithstanding their high effectiveness and favorable safety profile, the adherence to bisphosphonate treatment remains low. Different treatment strategies aim to improve the clinical effectiveness of bisphosphonate therapy. This review paper assesses the clinical utility of oral intermittent risedronate in the treatment of postmenopausal osteoporosis. The new delayed-release risedronate formulation is a safer and easy to use alternative to other risedronate therapy. Oral risedronate, a potent nitrogen-containing bisphosphonate, has been extensively studied using daily regimens. A new intermittent (weekly dosing regimen confirmed its clinical effectiveness in relation to vertebral and nonvertebral fracture prevention. The absence of significant differences in the incidence of adverse effects confirmed the favorable tolerability of the weekly dosage. In efforts to improve patient adherence to treatment, an innovative, delayed-release formulation of risedronate, which ensures adequate bioavailability of the active compound when taken with food, was introduced. The once-weekly delayed-release formulation of risedronate proved to be noninferior to the daily dosage of risedronate in terms of bone mineral density and markers of bone turnover. In addition, the incidence of new morphometric vertebral fractures was comparable in both treatment regimens. The new delayed-release formulation of risedronate showed a favorable safety profile. Delayed-release risedronate is a promising, new, effective, and convenient alternative to current bisphosphonate

  13. Review article: similarities and differences among delayed-release proton-pump inhibitor formulations.

    Science.gov (United States)

    Horn, J R; Howden, C W

    2005-12-01

    Proton-pump inhibitors are acid-labile, and require an enteric coating to protect them from degradation in the stomach when given orally. However, this leads to delayed absorption and onset of action of the proton-pump inhibitor. This article aims to review the similarities and differences between the various formulations of delayed release proton-pump inhibitors. Delayed-release omeprazole and delayed-release lansoprazole have been suspended in sodium bicarbonate for tube administration; however, for omeprazole, absorption is further impaired and antisecretory effects are disappointing. Although such formulations may be more convenient for clinical use in certain patient groups, absorption of the proton-pump inhibitor is still influenced by residual enteric coating. There are few differences among the currently available delayed-release proton-pump inhibitors with respect to their pharmacodynamic effects during chronic administration. There are minor formulation-based pharmacokinetic differences among these agents, primarily reflected in their bioavailability following the first few doses. Differences in bioavailability may explain slight differences in the rate of onset of maximal antisecretory effect. However, minor pharmacodynamic and pharmacokinetic differences are not associated with meaningful differences in clinical outcomes.

  14. Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study

    Science.gov (United States)

    Bohrey, Sarvesh; Chourasiya, Vibha; Pandey, Archna

    2016-03-01

    Nanoparticles formulated from biodegradable polymers like poly(lactic-co-glycolic acid) (PLGA) are being extensively investigated as drug delivery systems due to their two important properties such as biocompatibility and controlled drug release characteristics. The aim of this work to formulated diazepam loaded PLGA nanoparticles by using emulsion solvent evaporation technique. Polyvinyl alcohol (PVA) is used as stabilizing agent. Diazepam is a benzodiazepine derivative drug, and widely used as an anticonvulsant in the treatment of various types of epilepsy, insomnia and anxiety. This work investigates the effects of some preparation variables on the size and shape of nanoparticles prepared by emulsion solvent evaporation method. These nanoparticles were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM). Zeta potential study was also performed to understand the surface charge of nanoparticles. The drug release from drug loaded nanoparticles was studied by dialysis bag method and the in vitro drug release data was also studied by various kinetic models. The results show that sonication time, polymer content, surfactant concentration, ratio of organic to aqueous phase volume, and the amount of drug have an important effect on the size of nanoparticles. Hopefully we produced spherical shape Diazepam loaded PLGA nanoparticles with a size range under 250 nm with zeta potential -23.3 mV. The in vitro drug release analysis shows sustained release of drug from nanoparticles and follow Korsmeyer-Peppas model.

  15. Hydrophobic Drug-Loaded PEGylated Magnetic Liposomes for Drug-Controlled Release

    Science.gov (United States)

    Hardiansyah, Andri; Yang, Ming-Chien; Liu, Ting-Yu; Kuo, Chih-Yu; Huang, Li-Ying; Chan, Tzu-Yi

    2017-05-01

    Less targeted and limited solubility of hydrophobic-based drug are one of the serious obstacles in drug delivery system. Thus, new strategies to enhance the solubility of hydrophobic drug and controlled release behaviors would be developed. Herein, curcumin, a model of hydrophobic drug, has been loaded into PEGylated magnetic liposomes as a drug carrier platform for drug controlled release system. Inductive magnetic heating (hyperthermia)-stimulated drug release, in vitro cellular cytotoxicity assay of curcumin-loaded PEGylated magnetic liposomes and cellular internalization-induced by magnetic guidance would be investigated. The resultant of drug carriers could disperse homogeneously in aqueous solution, showing a superparamagnetic characteristic and could inductive magnetic heating with external high-frequency magnetic field (HFMF). In vitro curcumin release studies confirmed that the drug carriers exhibited no significant release at 37 °C, whereas exhibited rapid releasing at 45 °C. However, it would display enormous (three times higher) curcumin releasing under the HFMF exposure, compared with that without HFMF exposure at 45 °C. In vitro cytotoxicity test shows that curcumin-loaded PEGylated magnetic liposomes could efficiently kill MCF-7 cells in parallel with increasing curcumin concentration. Fluorescence microscopy observed that these drug carriers could internalize efficiently into the cellular compartment of MCF-7 cells. Thus, it would be anticipated that the novel hydrophobic drug-loaded PEGylated magnetic liposomes in combination with inductive magnetic heating are promising to apply in the combination of chemotherapy and thermotherapy for cancer therapy.

  16. Biodegradable hollow fibres for the controlled release of drugs

    NARCIS (Netherlands)

    Schakenraad, J.M.; Oosterbaan, J.A.; Nieuwenhuis, P.; Molenaar, I.; Olijslager, J.; Potman, W.; Eenink, M.J.D.; Feijen, Jan

    1988-01-01

    Biodegradable hollow fibres of poly-l-lactic acid (PLLA) filled with a suspension of the contraceptive hormone levonorgestrel in castor oil were implanted subcutaneously in rats to study the rate of drug release, rate of biodegradation and tissue reaction caused by the implant. The in vivo drug

  17. Biodegradable hollow fibres for the controlled release of drugs

    NARCIS (Netherlands)

    Schakenraad, J.M.; Oosterbaan, J.A.; Nieuwenhuis, P.; Molenaar, I.; Olijslager, J.; Potman, W.; Eenink, M.J.D.; Feijen, J.

    1988-01-01

    Biodegradable hollow fibres of poly-l-lactic acid (PLLA) filled with a suspension of the contraceptive hormone levonorgestrel in castor oil were implanted subcutaneously in rats to study the rate of drug release, rate of biodegradation and tissue reaction caused by the implant. The in vivo drug rele

  18. Desensitization in delayed drug hypersensitivity reactions -- an EAACI position paper of the Drug Allergy Interest Group.

    Science.gov (United States)

    Scherer, K; Brockow, K; Aberer, W; Gooi, J H C; Demoly, P; Romano, A; Schnyder, B; Whitaker, P; Cernadas, J S R; Bircher, A J

    2013-07-01

    Drug hypersensitivity may deprive patients of drug therapy, and occasionally no effective alternative treatment is available. Successful desensitization has been well documented in delayed drug hypersensitivity reactions. In certain situations, such as sulfonamide hypersensitivity in HIV-positive patients or hypersensitivity to antibiotics in patients with cystic fibrosis, published success rates reach 80%, and this procedure appears helpful for the patient management. A state of clinical tolerance may be achieved by the administration of increasing doses of the previously offending drug. However, in most cases, a pre-existent sensitization has not been proven by positive skin tests. Successful re-administration may have occurred in nonsensitized patients. A better understanding of the underlying mechanisms of desensitization is needed. Currently, desensitization in delayed hypersensitivity reactions is restricted to mild, uncomplicated exanthems and fixed drug eruptions. The published success rates vary depending on clinical manifestations, drugs, and applied protocols. Slower protocols tend to be more effective than rush protocols; however, underreporting of unsuccessful procedures is very probable. The decision to desensitize a patient must always be made on an individual basis, balancing risks and benefits. This paper reviews the literature and presents the expert experience of the Drug Hypersensitivity Interest Group of the European Academy of Allergy and Clinical Immunology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Pharmacokinetics and safety of posaconazole delayed-release tablets for invasive fungal infections.

    Science.gov (United States)

    Wiederhold, Nathan P

    2016-01-01

    Posaconazole is a broad-spectrum triazole antifungal agent with potent activity against various pathogenic fungi, including yeast and moulds. Clinical studies have demonstrated that this agent is efficacious as prophylaxis against invasive fungal infections in patients at high risk, and may also be useful as salvage therapy against invasive aspergillosis and mucormycosis. However, the bioavailability of posaconazole following administration by oral suspension, which was the only formulation clinically available for many years, is highly variable and negatively influenced by several factors. Because of this, many patients had subtherapeutic or undetectable posaconazole levels when the oral suspension was used. To overcome this limitation, a delayed-release tablet was developed and is now available for clinical use. Hot-melt extrusion technology is used to combine a pH-sensitive polymer with posaconazole to produce a formulation that releases the drug in the elevated pH of the intestine where absorption occurs rather than in the low-pH environment of the stomach. This results in enhanced bioavailability and increased posaconazole exposure. Studies in healthy volunteers have demonstrated significantly higher and more consistent exposures with the tablet formulation compared to the oral suspension. In addition, pharmacokinetic parameters following administration of the tablets were not significantly affected by medications that raise gastric pH or increase gastric motility, and the tablets could also be administered without regard to food. Similar results have also been found in patients at high risk for invasive fungal infections who have received posaconazole tablets. The tablet formulation also appears to be well tolerated to date, although data regarding clinical efficacy are needed.

  20. Oral suspensions of morphine hydrochloride for controlled release: rheological properties and drug release.

    Science.gov (United States)

    Morales, M E; López, G; Gallardo, V; Ruiz, M A

    2011-04-04

    Recent developments in pharmaceutical technology have facilitated the design and production of modified release formulas for drugs whose physical, chemical or biological properties impede release and thus might compromise their efficacy or safety. One such drug is morphine, whose short half-life requires repeated doses at short intervals. The use of biocompatible polymers such as ethylcellulose has made it possible to develop microencapsulated formulations which facilitate liquid, sustained-release pharmaceutical formulas for oral administration. We developed a stable final formulation of morphine with an acceptable release profile by comparing the rheological properties and stability of formulations with different thickeners (xanthan gum, Carbopol, and carboxymethylcellulose with microcrystalline cellulose) at different concentrations from 0.25% to 1.0%. Release assays in a Franz-type cell were done to determine the most suitable release profile for the formulation.

  1. A Biochemical Logic Approach to Biomarker-Activated Drug Release

    CERN Document Server

    Bocharova, V; MacVittie, K; Arugula, M A; Guz, N V; Dokukin, M E; Halamek, J; Sokolov, I; Privman, V; Katz, E; 10.1039/C2JM32966B

    2013-01-01

    The present study aims at integrating drug-releasing materials with signal-processing biocomputing systems. Enzymes alanine transaminase (ALT) and aspartate transaminase (AST)---biomarkers for liver injury---were logically processed by a biocatalytic cascade realizing Boolean AND gate. Citrate produced in the system was used to trigger a drug-mimicking release from alginate microspheres. In order to differentiate low vs. high concentration signals, the microspheres were coated with a protective shell composed of layer-by-layer adsorbed poly(L-lysine) and alginate. The alginate core of the microspheres was prepared from (Fe3+)-cross-linked alginate loaded with rhodamine 6G dye mimicking a drug. Dye release from the core occurred only when both biomarkers, ALT and AST, appeared at their high pathophysiological concentrations jointly indicative of liver injury. The signal-triggered response was studied at the level of a single microsphere, yielding information on the dye release kinetics.

  2. Drug release kinetics from carboxymethylcellulose-bacterial cellulose composite films.

    Science.gov (United States)

    Juncu, Gheorghe; Stoica-Guzun, Anicuta; Stroescu, Marta; Isopencu, Gabriela; Jinga, Sorin Ion

    2016-08-30

    Composite films of sodium carboxymethyl cellulose and bacterial cellulose (NaCMC-BC) cross-linked with citric acid (CA) were prepared by solution casting method. Ibuprofen sodium salt (IbuNa) has been used to study the mechanism of drug release from composite films. Surface morphology was investigated by scanning electron microscopy (SEM) and proved that the BC content influences the aspect of the films. Fourier transformed infrared spectroscopy (FTIR) revealed specific peaks in IR spectra of composite films which sustain that NaCMC was cross-linked with CA. Starting from swelling observations, the release kinetic of IbuNa was described using a model which neglects the volume expansion due to polymer swelling and which considers non-linear diffusion coefficients for drug and solvent. The IbuNa release is also influenced by BC content, the drug release rate was decreasing with the increase of BC content.

  3. Drug release from porous silicon for stable neural interface

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Tao, E-mail: taosun@hotmail.com.hk [Institute of Microelectronics, Agency for Science, Technology and Research (A-STAR) (Singapore); Tsang, Wei Mong [Institute of Microelectronics, Agency for Science, Technology and Research (A-STAR) (Singapore); Park, Woo-Tae [Institute of Microelectronics, Agency for Science, Technology and Research (A-STAR) (Singapore); Department of Mechanical and Automotive Engineering, Seoul National University of Science and Technology, Seoul (Korea, Republic of)

    2014-02-15

    70 μm-thick porous Si (PSi) layer with the pore size of 11.1 ± 7.6 nm was formed on an 8-in. Si wafer via an anodization process for the microfabrication of a microelectrode to record neural signals. To reduce host tissue responses to the microelectrode and achieve a stable neural interface, water-soluble dexamethesone (Dex) was loaded into the PSi via incubation with the drug solution overnight. After the drug loading process, the pore size of PSi reduced to 4.7 ± 2.6 nm on the basis of scanning electron microscopic (SEM) images, while its wettability was remarkably enhanced. Fluorescence images demonstrated that Dex was loaded into the porous structure of the PSi. Degradation rate of the PSi was investigated by incubation in distilled water for 21 days. Moreover, the drug release profile of the Dex-loaded PSi was a combination of an initial burst release and subsequent sustained release. To evaluate cellular responses to the drug release from the PSi, primary astrocytes were seeded on the surface of samples. After 2 days of culture, the Dex-loaded PSi could not only moderately prevent astrocyte adhesion in comparison with Si, but also more effectively suppress the activation of primary astrocytes than unloaded PSi due to the drug release. Therefore, it might be an effective method to reduce host tissue responses and stabilize the quality of the recorded neural signal by means of loading drugs into the PSi component of the microelectrode.

  4. Drug release from slabs and the effects of surface roughness.

    Science.gov (United States)

    Kalosakas, George; Martini, Dimitra

    2015-12-30

    We discuss diffusion-controlled drug release from slabs or thin films. Analytical and numerical results are presented for slabs with flat surfaces, having a uniform thickness. Then, considering slabs with rough surfaces, the influence of a non-uniform slab thickness on release kinetics is numerically investigated. The numerical release profiles are obtained using Monte Carlo simulations. Release kinetics is quantified through the stretched exponential (or Weibull) function and the resulting dependence of the two parameters of this function on the thickness of the slab, for flat surfaces, and the amplitude of surface fluctuations (or the degree of thickness variability) in case of roughness. We find that a higher surface roughness leads to a faster drug release. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Modified release drug delivery in veterinary medicine.

    Science.gov (United States)

    Rathbone, Michael J; Martinez, Marilyn N

    2002-08-01

    To successfully research and develop an animal pharmaceutical dosage form, a diverse array of issues covering basic medicine, pharmacology and technology must be addressed. Societal concerns regarding animal and public health, as well as the rapidly changing farming and economic environments, provide additional challenges that require integration into an already complex web of issues. Here, we examine the drive towards reducing the frequency of administration to animals and the closing of gaps between the human and veterinary drug product development.

  6. Low temperature direct 3D printed bioceramics and biocomposites as drug release matrices.

    Science.gov (United States)

    Gbureck, Uwe; Vorndran, Elke; Müller, Frank A; Barralet, Jake E

    2007-09-26

    The aim of this study was to investigate the adsorption and desorption kinetics of antibiotics to microporous bioceramics fabricated by a novel low temperature 3D powder direct printing process. The adsorption of vancomycin, ofloxacin and tetracycline onto hydroxyapatite, brushite and monetite showed a linear correlation with the drug concentration in the immersion solution, whereas a non-linear relationship was found between the immersion time and the amount of adsorbed drug. Differences in the total amount of adsorbed drugs were correlated to the specific surface areas of the matrices, which varied between 2.4-13.1 m(2)/g. Normalised drug loadings were found to be in the range of 1.5-1.8 mg/m(2) for vancomycin and ofloxacin, whereas higher loads of up to 5-7 mg/m(2) were obtained for tetracycline. Vancomycin and ofloxacin were rapidly released into PBS buffer within 1-2 days, while tetracycline showed a much slower release rate of approximately 25% after 5 days of immersion. Additional polymer impregnation of the drug loaded matrix with PLA/PGA polymer solutions enabled the release kinetics to be delayed such that sustained release was achieved in polymer ceramic biocomposites.

  7. Differential acetylcholine release in the prefrontal cortex and hippocampus during pavlovian trace and delay conditioning.

    Science.gov (United States)

    Flesher, M Melissa; Butt, Allen E; Kinney-Hurd, Brandee L

    2011-09-01

    Pavlovian trace conditioning critically depends on the medial prefrontal cortex (mPFC) and hippocampus (HPC), whereas delay conditioning does not depend on these brain structures. Given that the cholinergic basal forebrain system modulates activity in both the mPFC and HPC, it was reasoned that the level of acetylcholine (ACh) release in these regions would show distinct profiles during testing in trace and delay conditioning paradigms. To test this assumption, microdialysis probes were implanted unilaterally into the mPFC and HPC of rats that were pre-trained in appetitive trace and delay conditioning paradigms using different conditional stimuli in the two tasks. On the day of microdialysis testing, dialysate samples were collected during a quiet baseline interval before trials were initiated, and again during performance in separate blocks of trace and delay conditioning trials in each animal. ACh levels were quantified using high-performance liquid chromatography and electrochemical detection techniques. Consistent with our hypothesis, results showed that ACh release in the mPFC was greater during trace conditioning than during delay conditioning. The level of ACh released during trace conditioning in the HPC was also greater than the levels observed during delay conditioning. While ACh efflux in both the mPFC and HPC selectively increased during trace conditioning, ACh levels in the mPFC during trace conditioning testing showed the greatest increases observed. These results demonstrate a dissociation in cholinergic activation of the mPFC and HPC during performance in trace but not delay appetitive conditioning, where this cholinergic activity may contribute to attentional mechanisms, adaptive response timing, or memory consolidation necessary for successful trace conditioning.

  8. Drug release kinetics from a drug-eluting stent with asymmetrical coat

    DEFF Research Database (Denmark)

    Zhang, Haijun; Li, Xiaodong; Deng, Wei

    2017-01-01

    The aim of this study was to investigate the drug release profiles of biodegradable polymer sirolimus- or paclitaxel-eluting stents with asymmetrical coating (BPSES-A or BPPES-A) both in vitro and in vivo. In vitro, the drug release profile was characterized by measuring the drug concentration...... by HPLC over a time-course. In vivo, a porcine aorta stenting model was employed. The results showed that the drug release rates of BPSES-A and BPPES-A were slower, more stable and less burst releasing than those of conventionally coated stents (BPSES-C and BPPES-C respectively), both in vitro and in vivo...... demonstrated the effectiveness of both sirolimus and paclitaxel as stent coating agents, and revealed the favorable drug release kinetics and pharmacokinetics of asymmetrical coated stents compared with conventional coated stents....

  9. pH-triggered drug release from biodegradable microwells for oral drug delivery

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Nagstrup, Johan; Gordon, Sarah;

    2015-01-01

    Microwells fabricated from poly-L-lactic acid (PLLA) were evaluated for their application as an oral drug delivery system using the amorphous sodium salt of furosemide (ASSF) as a model drug. Hot embossing of PLLA resulted in fabrication of microwells with an inner diameter of 240 μm and a height...... of microwell cavities with an Eudragit® layer prevented drug release in biorelevant gastric medium. An immediate release of the ASSF from coated microwells was observed in the intestinal medium. This pH-triggered release behavior demonstrates the future potential of PLLA microwells as a site-specific oral drug...

  10. Infuence of Microstructure in Drug Release Behavior of Silica Nanocapsules

    Science.gov (United States)

    Zoltan, Tamara

    2013-01-01

    Meso- and nanoporous structures are adequate matrices for controlled drug delivery systems, due to their large surface areas and to their bioactive and biocompatibility properties. Mesoporous materials of type SBA-15, synthesized under different pH conditions, and zeolite beta were studied in order to compare the different intrinsic morphological characteristics as pore size, pore connectivity, and pore geometry on the drug loading and release process. These materials were characterized by X-ray diffraction, nitrogen adsorption, scanning and transmission electron microscopy, and calorimetric measurements. Ibuprofen (IBU) was chosen as a model drug for the formulation of controlled-release dosage forms; it was impregnated into these two types of materials by a soaking procedure during different periods. Drug loading and release studies were followed by UV-Vis spectrophotometry. All nano- and mesostructured materials showed a similar loading behavior. It was found that the pore size and Al content strongly influenced the release process. These results suggest that the framework structure and architecture affect the drug adsorption and release properties of these materials. Both materials offer a good potential for a controlled delivery system of ibuprofen. PMID:23986870

  11. Infuence of Microstructure in Drug Release Behavior of Silica Nanocapsules

    Directory of Open Access Journals (Sweden)

    Gema Gonzalez

    2013-01-01

    Full Text Available Meso- and nanoporous structures are adequate matrices for controlled drug delivery systems, due to their large surface areas and to their bioactive and biocompatibility properties. Mesoporous materials of type SBA-15, synthesized under different pH conditions, and zeolite beta were studied in order to compare the different intrinsic morphological characteristics as pore size, pore connectivity, and pore geometry on the drug loading and release process. These materials were characterized by X-ray diffraction, nitrogen adsorption, scanning and transmission electron microscopy, and calorimetric measurements. Ibuprofen (IBU was chosen as a model drug for the formulation of controlled-release dosage forms; it was impregnated into these two types of materials by a soaking procedure during different periods. Drug loading and release studies were followed by UV-Vis spectrophotometry. All nano- and mesostructured materials showed a similar loading behavior. It was found that the pore size and Al content strongly influenced the release process. These results suggest that the framework structure and architecture affect the drug adsorption and release properties of these materials. Both materials offer a good potential for a controlled delivery system of ibuprofen.

  12. Fabricating a Shell-Core Delayed Release Tablet Using Dual FDM 3D Printing for Patient-Centred Therapy.

    Science.gov (United States)

    Okwuosa, Tochukwu C; Pereira, Beatriz C; Arafat, Basel; Cieszynska, Milena; Isreb, Abdullah; Alhnan, Mohamed A

    2017-02-01

    Individualizing gastric-resistant tablets is associated with major challenges for clinical staff in hospitals and healthcare centres. This work aims to fabricate gastric-resistant 3D printed tablets using dual FDM 3D printing. The gastric-resistant tablets were engineered by employing a range of shell-core designs using polyvinylpyrrolidone (PVP) and methacrylic acid co-polymer for core and shell structures respectively. Filaments for both core and shell were compounded using a twin-screw hot-melt extruder (HME). CAD software was utilized to design a capsule-shaped core with a complementary shell of increasing thicknesses (0.17, 0.35, 0.52, 0.70 or 0.87 mm). The physical form of the drug and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. A shell thickness ≥0.52 mm was deemed necessary in order to achieve sufficient core protection in the acid medium. The technology proved viable for incorporating different drug candidates; theophylline, budesonide and diclofenac sodium. XRPD indicated the presence of theophylline crystals whilst budesonide and diclofenac sodium remained amorphous in the PVP matrix of the filaments and 3D printed tablets. Fabricated tablets demonstrated gastric resistant properties and a pH responsive drug release pattern in both phosphate and bicarbonate buffers. Despite its relatively limited resolution, FDM 3D printing proved to be a suitable platform for a single-process fabrication of delayed release tablets. This work reveals the potential of dual FDM 3D printing as a unique platform for personalising delayed release tablets to suit an individual patient's needs.

  13. Continuous drug release by sea anemone Nematostella vectensis stinging microcapsules.

    Science.gov (United States)

    Tal, Yossi; Ayalon, Ari; Sharaev, Agnesa; Kazir, Zoya; Brekhman, Vera; Lotan, Tamar

    2014-01-27

    Transdermal delivery is an attractive option for drug delivery. Nevertheless, the skin is a tough barrier and only a limited number of drugs can be delivered through it. The most difficult to deliver are hydrophilic drugs. The stinging mechanism of the cnidarians is a sophisticated injection system consisting of microcapsular nematocysts, which utilize built-in high osmotic pressures to inject a submicron tubule that penetrates and delivers their contents to the prey. Here we show, for the first time, that the nematocysts of the starlet sea anemone Nematostella vectensis can be isolated and incorporated into a topical formulation for continuous drug delivery. We demonstrate quantitative delivery of nicotinamide and lidocaine hydrochloride as a function of microcapsular dose or drug exposure. We also show how the released submicron tubules can be exploited as a skin penetration enhancer prior to and independently of drug application. The microcapsules are non-irritant and may offer an attractive alternative for hydrophilic transdermal drug delivery.

  14. Continuous Drug Release by Sea Anemone Nematostella vectensis Stinging Microcapsules

    Science.gov (United States)

    Tal, Yossi; Ayalon, Ari; Sharaev, Agnesa; Kazir, Zoya; Brekhman, Vera; Lotan, Tamar

    2014-01-01

    Transdermal delivery is an attractive option for drug delivery. Nevertheless, the skin is a tough barrier and only a limited number of drugs can be delivered through it. The most difficult to deliver are hydrophilic drugs. The stinging mechanism of the cnidarians is a sophisticated injection system consisting of microcapsular nematocysts, which utilize built-in high osmotic pressures to inject a submicron tubule that penetrates and delivers their contents to the prey. Here we show, for the first time, that the nematocysts of the starlet sea anemone Nematostella vectensis can be isolated and incorporated into a topical formulation for continuous drug delivery. We demonstrate quantitative delivery of nicotinamide and lidocaine hydrochloride as a function of microcapsular dose or drug exposure. We also show how the released submicron tubules can be exploited as a skin penetration enhancer prior to and independently of drug application. The microcapsules are non-irritant and may offer an attractive alternative for hydrophilic transdermal drug delivery. PMID:24473172

  15. Predicting the Drug Release Kinetics of Matrix Tablets

    CERN Document Server

    Baeumer, Boris; Hinow, Peter; Rades, Thomas; Radunskaya, Ami; Tucker, Ian

    2008-01-01

    In this paper we develop two mathematical models to predict the release kinetics of a water soluble drug from a polymer/excipient matrix tablet. The first of our models consists of a random walk on a weighted graph, where the vertices of the graph represent particles of drug, excipient and polymer, respectively. The graph itself is the contact graph of a multidisperse random sphere packing. The second model describes the dissolution and the subsequent diffusion of the active drug out of a porous matrix using a system of partial differential equations. The predictions of both models show good qualitative agreement with experimental release curves. The models will provide tools for designing better controlled release devices.

  16. Preparation and Drug-release Behavior of β-TCP Ceramics Drug Carrier in vitro

    Institute of Scientific and Technical Information of China (English)

    ZHANG Qihuan; YAN Xin; YAN Yuhua; DAI Honglian; JIANG Xin; LI Shipu

    2012-01-01

    β-TCP ceramics drug carrier was first prepared and characterized.SEM showed that β-TCP carrier was in porous amorphous structure with diameters around 10 μm.The physical properties including apparent porosity,volume-weight,tensile strength and the permeability were measured and the results indicated those properties fit the clinical usage of β-TCP drug carrier.Furthermore,drug release experiment in vitro showed that the carrier could prolong drug release in simulated body fluid which provides basis for the clinical use of β-TCP ceramics as drug carrier.

  17. Strategies that delay or prevent the timely availability of affordable generic drugs in the United States.

    Science.gov (United States)

    Jones, Gregory H; Carrier, Michael A; Silver, Richard T; Kantarjian, Hagop

    2016-03-17

    High cancer drug prices are influenced by the availability of generic cancer drugs in a timely manner. Several strategies have been used to delay the availability of affordable generic drugs into the United States and world markets. These include reverse payment or pay-for-delay patent settlements, authorized generics, product hopping, lobbying against cross-border drug importation, buying out the competition, and others. In this forum, we detail these strategies and how they can be prevented.

  18. The Time Delay Between Drug Intake and Bronchospasm for Nonsteroidal Antiinflammatory Drugs Sensitive Patients

    Science.gov (United States)

    2010-01-01

    A study was performed to assess the time between drug intake and drug induced hypersensitivity reaction for patients sensitive to nonsteroidal antiinflammatory drugs (NSAID) in clinical patient history and after oral provocation tests. Drug hypersensitivity ENDA questionnaires were filled for the patients with suspected sensitivity to NSAID. Oral provocation tests were performed with suspected NSAID according to the ENDA/EAACI recommendations. There were 76 patients with history of hypersensitivity reactions after use of NSAID enrolled in the study. Recorded were 154 hypersensitivity reactions to NSAID in the clinical history. In the clinical history median time of immediate reactions (76 cases, 81%) between drug intake and bronchospasm was 20 minutes [15-30 minutes]. Median time of nonimmediate reactions (18 cases, 19%) was 120 minutes [120-390 minutes]. There were 50 oral provocation tests performed, 14 of them (28%) were positive. Median time between drug intake and immediate reactions (8; 57% of cases) was 22.5 minutes [20-30 minutes] and median time of nonimmediate reactions (6; 43% of cases) was 167.5 minutes [125-206.25 minutes]. Time delay between drug intake and bronchospasm in the clinical history and after oral provocation test was not statistically different. PMID:23282984

  19. [Drug release system controlled by near infrared light].

    Science.gov (United States)

    Niidome, Takuro

    2013-01-01

    Gold nanorods have absorption bands in the near-infrared region; in this spectral range, light penetrates deeply into tissues. The absorbed light energy is converted into heat by gold nanorods. This is the so-called photothermal effect. Gold nanorods are therefore expected to act not only as thermal converters for photothermal therapy, but also as controllers for drug-release systems responding to irradiation with near-infrared light. To achieve a controlled-release system that could be triggered by light irradiation, the gold nanorods were modified with double-stranded DNA (dsDNA). When the dsDNA-modified gold nanorods were irradiated with near-infrared light, single-stranded DNA (ssDNA) was released from the gold nanorods because of the photothermal effect. The release of ssDNA was also observed in tumors grown on mice after near-infrared light irradiation. We also proposed a different controlled-release system responding to near-infrared light. Gold nanorods were modified with polyethylene glycol (PEG) through Diels-Alder cycloadducts. When the gold nanorods were irradiated with near-infrared light, the PEG chains were released from the gold nanorods because of the retro Diels-Alder reaction induced by the photothermal effect. Such controlled-release systems triggered by near-infrared light irradiation will be expanded for gold nanorod drug delivery system applications.

  20. Improved nanoparticles preparation and drug release for liver targeted delivery

    Directory of Open Access Journals (Sweden)

    Qiao Weili

    2009-05-01

    Full Text Available "nTargeted delivery of drugs and proteins to liver can be achieved via asialoglycoprotein receptor, which can recognize and combine the galactose- and N-acetygalatosamine-terminated glycoproteins. Glycosyl is usually conjugated with drugs directly to fabricate prodrugs or with nanoparticles encapsulated drugs via forming covalent bonds, while the covalent bonds may lead to some shortages for drug release. Therefore, we have a hypothesis that we can prepare nanoparticles for efficient targeting by glycosylation using galactosylated poly (L-glutamic acid (Gal-PLGA as a carrier to entrap the model drugs in nanoparticles core physically rather than forming covalent drug conjugation. The means of incorporation of drug in nanoparticles may improve drug release to maintain its activity, raise its therapeutic index and diminish the adverse effect. Based on previous researches, it is achievable to obtain nanoparticles that we hypothesize to prepare. Due to their nanometer-size and galactosyl, the nanoparticles may be a potential delivery system for passive and active targeting to liver parenchymal cells for therapy of hepatitis and liver cancer.

  1. Organically modified titania nanoparticles for sustained drug release applications.

    Science.gov (United States)

    Sethi, Komal; Roy, Indrajit

    2015-10-15

    In this paper, we report the synthesis, characterization of drug-doped organically modified titania nanoparticles, and their applications in sustained drug release. The drug-doped nanoparticles were synthesized in the hydrophobic core of oil-in-water microemulsion medium. Structural aspects obtained through TEM and FESEM depicted that organically modified titania nanoparticles are monodispersed with spherical morphology, with an average size of around 200 nm. Their polymorphic forms and porosity were determined using powder XRD and BET, respectively, which showed that they are present in the anatase form, with a surface area of 136.5 m(2)/g and pore-diameter of 5.23 nm. After synthesis and basic structural characterizations, optical properties were studied for both fluorophore and drug encapsulated nanoparticles. The results showed that though the optical properties of the fluorophore are partially diminished upon nanoencapsulation, it became more stable against chemical quenching. The nanoparticles showed pH-dependent drug release pattern. In vitro studies showed that the nanoparticles were efficiently uptaken by cells. Cell viability assay results showed that though the placebo nanoparticles are non-cytotoxic, the drug-doped nanoparticles show drug-induced toxicity. Therefore, such porous nanoparticles can be used in non-toxic drug delivery applications.

  2. Prodigiosin release from an implantable biomedical device: kinetics of localized cancer drug release

    Energy Technology Data Exchange (ETDEWEB)

    Danyuo, Y.; Obayemi, J.D.; Dozie-Nwachukwu, S. [Department of Materials Science and Engineering, African University of Science and Technology (AUST), Abuja, Federal Capital Territory (Nigeria); Ani, C.J. [Department of Theoretical Physics, African University of Science and Technology (AUST), Abuja, Federal Capital Territory (Nigeria); Odusanya, O.S. [Biotechnology and Genetic Engineering Advanced Laboratory, Sheda Science and Technology Complex (SHESTCO), Abuja, Federal Capital Territory (Nigeria); Oni, Y. [Department of Chemistry, Bronx Community College, New York, NY (United States); Anuku, N. [Department of Chemistry, Bronx Community College, New York, NY (United States); Princeton Institute for the Science and Technology of Materials (PRISM), 70 Prospect Street, Princeton, NJ 08544 (United States); Malatesta, K. [Department of Chemistry, Bronx Community College, New York, NY (United States); Soboyejo, W.O., E-mail: soboyejo@princeton.edu [Department of Materials Science and Engineering, African University of Science and Technology (AUST), Abuja, Federal Capital Territory (Nigeria); Princeton Institute for the Science and Technology of Materials (PRISM), 70 Prospect Street, Princeton, NJ 08544 (United States); Department of Mechanical and Aerospace Engineering 1 Olden Street, Princeton, NJ 08544 (United States)

    2014-09-01

    This paper presents an implantable encapsulated structure that can deliver localized heating (hyperthermia) and controlled concentrations of prodigiosin (a cancer drug) synthesized by bacteria (Serratia marcesce (subsp. marcescens)). Prototypical Poly-di-methyl-siloxane (PDMS) packages, containing well-controlled micro-channels and drug storage compartments, were fabricated along with a drug-storing polymer produced by free radical polymerization of Poly(N-isopropylacrylamide)(PNIPA) co-monomers of Acrylamide (AM) and Butyl-methacrylate (BMA). The mechanisms of drug diffusion of PNIPA-base gels were elucidated. Scanning Electron Microscopy (SEM) was also used to study the heterogeneous porous structure of the PNIPA-based gels. The release exponents, n, of the gels were found to between 0.5 and 0.7. This is in the range expected for Fickian (n = 0.5). Deviation from Fickian diffusion was also observed (n > 0.5) diffusion. The gel diffusion coefficients were shown to vary between 2.1 × 10{sup −12} m{sup 2}/s and 4.8 × 10{sup −6} m{sup 2}/s. The implications of the results are then discussed for the localized treatment of cancer via hyperthermia and the controlled delivery of prodigiosin from encapsulated PNIPA-based devices. - Highlights: • Fabricated thermo-sensitive hydrogels for localized drug release from an implantable biomedical device. • Determined the cancer drug diffusion mechanisms of PNIPA-co-AM copolymer hydrogel. • Encapsulated PNIPA-based hydrogels in PDMS capsules for controlled drug delivery. • Established the kinetics of drug release from gels and channels in an implantable biomedical device. • Demonstrated the potential for the controlled release of prodigiosin (PG) as an anticancer drug.

  3. Transient early neurotrophin release and delayed inflammatory cytokine release by microglia in response to PAR-2 stimulation.

    Science.gov (United States)

    Chen, Chen-Wen; Chen, Qian-Bo; Ouyang, Qing; Sun, Ji-Hu; Liu, Fang-Ting; Song, Dian-Wen; Yuan, Hong-Bin

    2012-06-25

    Activated microglia exerts both beneficial and deleterious effects on neurons, but the signaling mechanism controlling these distinct responses remain unclear. We demonstrated that treatment of microglial cultures with the PAR-2 agonist, 2-Furoyl-LIGRLO-NH2, evoked early transient release of BDNF, while sustained PAR-2 stimulation evoked the delayed release of inflammatory cytokines (IL-1 β and TNF-α) and nitric oxide. Culture medium harvested during the early phase (at 1 h) of microglial activation induced by 2-Furoyl-LIGRLO-NH2 (microglial conditioned medium, MCM) had no deleterious effects on cultured neurons, while MCM harvested during the late phase (at 72 h) promoted DNA fragmentation and apoptosis as indicated by TUNEL and annexin/PI staining. Blockade of PAR-1 during the early phase of PAR-2 stimulation enhanced BDNF release (by 11%, small but significant) while a PAR-1 agonist added during the late phase (24 h after 2-Furoyl-LIGRLO-NH2 addition) suppressed the release of cytokines and NO. The neuroprotective and neurotoxic effects of activated microglial exhibit distinct temporal profiles that are regulated by PAR-1 and PAR-2 stimulation. It may be possible to facilitate neuronal recovery and repair by appropriately timed stimulation and inhibition of microglial PAR-1 and PAR-2 receptors.

  4. Sequential-release of anticancer drugs microcapsulated with ethylcellulose

    Institute of Scientific and Technical Information of China (English)

    顾耕华; 黄剑奇; 何虹

    2002-01-01

    Objective To approach the sequential release of antitumor drugs and promote the effect of chemotherapy.Methods Adriamycin (ADM) and carboplatin (CBP) were respectively microcapsulated with ethylcellulose by organic phase separation. The morphology and sizes of the microcapsules were observed and measured with light microscope and scanning electromicroscope. The contents and the release rates of ADM and CBP in microcapsules were measured with fluorescence spectrophotometer and high-efficiency phantom chromatic (HPC) spectrum respectively. The antitumor sensitivity test in vitro was devised with MTT assay.Results The microcapsules of ADM and CBP were spherical in shape with diameters of 196?4 μm and 214?8 μm respectively. The contents of one-layer and two-layer CBP and ADM microcapsules were 51.4%, 35.7% and 39.8% respectively, with the release rates in vitro of 62.4%/day, 54.8%/day and 48.2% /8h. The results of drug sensitivity test in vitro demonstrated that the current preparation has never affected the stability and antitumor activity of CBP and ADM.Conclusion Microcapsules with different drugs and different thickness of material have different release rate. Combined arterial chemoembolization with different microcapsules could approach the sequential release and promote the effect of chemotherapy.

  5. Superior Serum Concentrations with Posaconazole Delayed-Release Tablets Compared to Suspension Formulation in Hematological Malignancies

    OpenAIRE

    2015-01-01

    Posaconazole (PCZ), approved for prophylaxis against invasive fungal disease in high-risk patients, is commercially available orally as a suspension formulation (PCZ-susp) and as a delayed-release tablet (PCZ-tab). We evaluated the serum steady-state concentrations (Css) of PCZ stratified by the administered formulation for antifungal prophylaxis in patients with myeloid malignancies (n = 150). The primary outcome was the attainment rate of the target Css of ≥700 ng/ml. Secondary outcomes inc...

  6. Drug release from hydrazone-containing peptide amphiphiles

    Energy Technology Data Exchange (ETDEWEB)

    Matson, John B.; Stupp, Samuel I. (NWU)

    2012-03-15

    Hydrolytically-labile hydrazones in peptide amphiphiles were studied as degradable tethers for release of the drug nabumetone from nanofiber gels. On-resin addition of the novel compound tri-Boc-hydrazido adipic acid to a lysine E-amine allowed for precise placement of a hydrazide in a peptide sequence.

  7. Prediction of drug release from HPMC matrices: effect of physicochemical properties of drug and polymer concentration.

    Science.gov (United States)

    Fu, X C; Wang, G P; Liang, W Q; Chow, M S S

    2004-03-05

    A working equation to predict drug release from hydroxypropyl methylcellulose (HPMC) matrices was derived using a training set of HPMC matrices having different HPMC concentration (w/w, 16.5-55%) and different drugs (solubilities of 1.126-125.5 g/100 ml in water and molecular volumes of 0.1569-0.4996 nm(3)). The equation was log(M(t)/M( infinity ))=-0.6747+1.027 log t -0.1759 (log C(s)) log t +0.4027 (log V) log t -1.041C(H) +0.3213 (log C(s)) C(H) -0.4101 (log V) C(H) -0.3521 (log V) log C(s) (n=263, r=0.9831), where M(t) is the amount of drug released at time t, M( infinity ) the amount of drug released over a very long time, which corresponds in principle to the initial loading, t the release time (h), C(s) the drug solubility in water (g/100 ml), V the volume of drug molecule (nm(3)), and C(H) is HPMC concentration (w/w). The benefit of the novel model is to predict M(t)/M( infinity ) values of a drug from formulation and its physicochemical properties, so applicable to the HPMC matrices of different polymer levels and different drugs including soluble drugs and slightly soluble drugs.

  8. Graphene as a photothermal switch for controlled drug release

    Science.gov (United States)

    Matteini, Paolo; Tatini, Francesca; Cavigli, Lucia; Ottaviano, Stefania; Ghini, Giacomo; Pini, Roberto

    2014-06-01

    Graphene has recently emerged as a novel material in the biomedical field owing to its optical properties, biocompatibility, large specific surface area and low cost. In this paper, we provide the first demonstration of the possibility of using light to remotely trigger the release of drugs from graphene in a highly controlled manner. Different drugs including chemotherapeutics and proteins are firmly adsorbed onto reduced graphene oxide (rGO) nanosheets dispersed in a biopolymer film and then released by individual millisecond-long light pulses generated by a near infrared (NIR) laser. Here graphene plays the dual role of a versatile substrate for temporary storage of drugs and an effective transducer of NIR-light into heat. Drug release appears to be narrowly confined within the size of the laser spot under noninvasive conditions and can be precisely dosed depending on the number of pulses. The approach proposed paves the way for tailor-made pharmacological treatments of chronic diseases, including cancer, anaemia and diabetes.Graphene has recently emerged as a novel material in the biomedical field owing to its optical properties, biocompatibility, large specific surface area and low cost. In this paper, we provide the first demonstration of the possibility of using light to remotely trigger the release of drugs from graphene in a highly controlled manner. Different drugs including chemotherapeutics and proteins are firmly adsorbed onto reduced graphene oxide (rGO) nanosheets dispersed in a biopolymer film and then released by individual millisecond-long light pulses generated by a near infrared (NIR) laser. Here graphene plays the dual role of a versatile substrate for temporary storage of drugs and an effective transducer of NIR-light into heat. Drug release appears to be narrowly confined within the size of the laser spot under noninvasive conditions and can be precisely dosed depending on the number of pulses. The approach proposed paves the way for tailor

  9. Simultaneous drug release at different rates from biodegradable polyurethane foams.

    Science.gov (United States)

    Sivak, Wesley N; Zhang, Jianying; Petoud, Stephané; Beckman, Eric J

    2009-09-01

    In this study, we present an approach for the simultaneous release of multiple drug compounds at different rates from single-phase polyurethane foams constructed from lysine diisocyanate (LDI) and glycerol. The anti-cancer compounds DB-67 and doxorubicin were covalently incorporated into polyurethane foams, whereby drug release can then occur in concert with material degradation. To begin, the reactions of DB-67 and doxorubicin with LDI in the presence of a tertiary amine catalyst were monitored with infrared spectroscopy; each compound formed urethane linkages with LDI. Fluorescent spectra of DB-67 and doxorubicin were then recorded in phosphate-buffered saline, pH 7.4 (PBS), to ensure that each anti-cancer compound could be quantitatively detected alone and in combination. Doxorubicin and DB-67 were then incorporated into a series of degradable LDI-glycerol polyurethane foams alone and in combination with one another. The sol content, average porosity and drug distribution throughout each foam sample was measured and found to be similar amongst all foam samples. The stability of DB-67 and doxorubicin's fluorescent signal was then assessed over a 2-week period at 70 degrees C. Release rates of the compounds from the foams were assessed over a 10-week period at 4, 22, 37 and 70 degrees C by way of fluorescence spectroscopy. Release was found to be temperature-dependent, with rates related to the chemical structure of the incorporated drug. This study demonstrates that differential release of covalently bound drugs is possible from simple single-phase, degradable polyurethane foams.

  10. Modified drug release using atmospheric pressure plasma deposited siloxane coatings

    Science.gov (United States)

    Dowling, D. P.; Maher, S.; Law, V. J.; Ardhaoui, M.; Stallard, C.; Keenan, A.

    2016-09-01

    This pilot study evaluates the potential of atmospheric plasma polymerised coatings to modify the rate of drug release from polymeric substrates. The antibiotic rifampicin was deposited in a prototype multi-layer drug delivery system, consisting of a nebulized layer of active drug between a base layer of TEOS deposited on a plastic substrate (polystyrene) and an overlying layer of plasma polymerised PDMS. The polymerised TEOS and PDMS layers were deposited using a helium atmospheric plasma jet system. Elution of rifampicin was measured using UV-VIS spectroscopy, in addition to a antimicrobial well diffusion assay with an established indicator organism. The multi-layered plasma deposited coatings significantly extended the duration of release of the rifampicin from 24 h for the uncoated polymer to 144 h for the coated polymer.

  11. Drug incorporation and release of water soluble drugs from novel functionalized poly(glycerol adipate) nanoparticles.

    Science.gov (United States)

    Puri, Sanyogita; Kallinteri, Paraskevi; Higgins, Sean; Hutcheon, Gillian A; Garnett, Martin C

    2008-01-04

    We have previously demonstrated the ability of poly(glycerol adipate) backbone (PGA) and PGA polymer backbone substituted with varying amounts of pendant C(18) chain length acyl groups to yield Dexamethasone phosphate DXMP loaded nanoparticles. The aim of this study was to obtain a deeper understanding of the underlying principles responsible for good drug incorporation and controlled release of drugs from poly (glycerol adipate) (PGA) nanoparticles. We compared the incorporation of the water soluble drugs DXMP and Cytosine arabinoside (CYT-ARA) in both unmodified and substituted PGA polymers. We investigated the effect of change in acyl group chain length and the degree of substitution on the physicochemical properties, drug loading and release of DXMP and CYT-ARA. Nanoparticles were prepared by the interfacial deposition technique and the simultaneous emulsification method. Amongst the nanoparticles prepared using acylated polymers with varying chain lengths (C(2) to C(10)) for DXMP incorporation, polymers with acyl group chain lengths containing 8 carbon atoms (C(8)) showed maximum drug incorporation. Amongst the C(8) series, polymers with 100% acylation provided both good drug incorporation and a controlled release for DXMP while for CYT-ARA it was the unsubstituted polymer backbone that had maximum drug loading and slower release. A number of inter-related factors are responsible for producing particles with particular size, zeta potential, drug loading and release characteristics. Drug loading and release from nanoparticles are primarily influenced by the nature of interactions between the drug and polymers which in turn depend upon the type of drug used and the physical chemistry of the polymer.

  12. pH-triggered drug release from biodegradable microwells for oral drug delivery

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Nagstrup, Johan; Gordon, Sarah

    2015-01-01

    of 100 μm. The microwells were filled with ASSF using a modified screen printing technique, followed by coating of the microwell cavities with a gastroresistant lid of Eudragit® L100. The release behavior of ASSF from the coated microwells was investigated using a μ-Diss profiler and a UV imaging system......, and under conditions simulating the changing environment of the gastrointestinal tract. Biorelevant gastric medium (pH 1.6) was employed, after which a change to biorelevant intestinal release medium (pH 6.5) was carried out. Both μ-Diss profiler and UV imaging release experiments showed that sealing...... of microwell cavities with an Eudragit® layer prevented drug release in biorelevant gastric medium. An immediate release of the ASSF from coated microwells was observed in the intestinal medium. This pH-triggered release behavior demonstrates the future potential of PLLA microwells as a site-specific oral drug...

  13. Electrically controlled drug release from nanostructured polypyrrole coated on titanium

    Science.gov (United States)

    Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J.

    2011-02-01

    Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s - 1. Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

  14. Electrically controlled drug release from nanostructured polypyrrole coated on titanium

    Energy Technology Data Exchange (ETDEWEB)

    Sirivisoot, Sirinrath; Pareta, Rajesh; Webster, Thomas J, E-mail: Thomas_Webster@Brown.edu [School of Engineering, Brown University, Providence, RI 02912 (United States)

    2011-02-25

    Previous studies have demonstrated that multi-walled carbon nanotubes grown out of anodized nanotubular titanium (MWNT-Ti) can be used as a sensing electrode for various biomedical applications; such sensors detected the redox reactions of certain molecules, specifically proteins deposited by osteoblasts during extracellular matrix bone formation. Since it is known that polypyrrole (PPy) can release drugs upon electrical stimulation, in this study antibiotics (penicillin/streptomycin, P/S) or an anti-inflammatory drug (dexamethasone, Dex), termed PPy[P/S] or PPy[Dex], respectively, were electrodeposited in PPy on titanium. The objective of the present study was to determine if such drugs can be released from PPy on demand and (by applying a voltage) control cellular behavior important for orthopedic applications. Results showed that PPy films possessed nanometer-scale roughness as analyzed by atomic force microscopy. X-ray photoelectron spectroscopy confirmed the presence of P/S and Dex encapsulated within the PPy films. Results from cyclic voltammetry showed that 80% of the drugs were released on demand when sweep voltages were applied for five cycles at a scan rate of 0.1 V s{sup -1}. Furthermore, osteoblast (bone-forming cells) and fibroblast (fibrous tissue-forming cells) adhesion were determined on the PPy films. Results showed that PPy[Dex] enhanced osteoblast adhesion after 4 h of culture compared to plain Ti. PPy-Ti (with or without anionic drug doping) inhibited fibroblast adhesion compared to plain Ti. These in vitro results confirmed that electrodeposited PPy[P/S] and PPy[Dex] can release drugs on demand to potentially fight bacterial infection, reduce inflammation, promote bone growth or reduce fibroblast functions, further implicating the use of such materials as implant sensors.

  15. Encapsulation of methotrexate loaded magnetic microcapsules for magnetic drug targeting and controlled drug release

    Energy Technology Data Exchange (ETDEWEB)

    Chakkarapani, Prabu [Department of Pharmaceutical Technology & Centre for Excellence in Nanobio Translational Research, Anna University, Bharathidasan Institute of Technology Campus, Tiruchirappalli 620024, Tamil Nadu (India); Subbiah, Latha, E-mail: lathasuba2010@gmail.com [Department of Pharmaceutical Technology & Centre for Excellence in Nanobio Translational Research, Anna University, Bharathidasan Institute of Technology Campus, Tiruchirappalli 620024, Tamil Nadu (India); Palanisamy, Selvamani; Bibiana, Arputha [Department of Pharmaceutical Technology & Centre for Excellence in Nanobio Translational Research, Anna University, Bharathidasan Institute of Technology Campus, Tiruchirappalli 620024, Tamil Nadu (India); Ahrentorp, Fredrik; Jonasson, Christian; Johansson, Christer [Acreo Swedish ICT AB, Arvid Hedvalls backe 4, SE-411 33 Göteborg (Sweden)

    2015-04-15

    We report on the development and evaluation of methotrexate magnetic microcapsules (MMC) for targeted rheumatoid arthritis therapy. Methotrexate was loaded into CaCO{sub 3}-PSS (poly (sodium 4-styrenesulfonate)) doped microparticles that were coated successively with poly (allylamine hydrochloride) and poly (sodium 4-styrenesulfonate) by layer-by-layer technique. Ferrofluid was incorporated between the polyelectrolyte layers. CaCO{sub 3}-PSS core was etched by incubation with EDTA yielding spherical MMC. The MMC were evaluated for various physicochemical, pharmaceutical parameters and magnetic properties. Surface morphology, crystallinity, particle size, zeta potential, encapsulation efficiency, loading capacity, drug release pattern, release kinetics and AC susceptibility studies revealed spherical particles of ~3 µm size were obtained with a net zeta potential of +24.5 mV, 56% encapsulation and 18.6% drug loading capacity, 96% of cumulative drug release obeyed Hixson-Crowell model release kinetics. Drug excipient interaction, surface area, thermal and storage stability studies for the prepared MMC was also evaluated. The developed MMC offer a promising mode of targeted and sustained release drug delivery for rheumatoid arthritis therapy. - Highlights: • Development of methotrexate magnetic microcapsules (MMC) by layer-by-layer method. • Characterization of physicochemical, pharmaceutical and magnetic properties of MMC. • Multiple layers of alternative polyelectrolytes prolongs methotrexate release time. • MMC is capable for targeted and sustained release rheumatoid arthritis therapy.

  16. In vitro drug release profiles of pH-sensitive hydroxyethylacryl chitosan/sodium alginate hydrogels using paracetamol as a soluble model drug.

    Science.gov (United States)

    Treenate, Pitchaya; Monvisade, Pathavuth

    2017-06-01

    The aim of this study is to investigate in vitro drug release profiles of pH-sensitive hydrogels composed of hydroxyethylacryl chitosan (HC) and sodium alginate (SA). The hydrogels were crosslinked by dipping method using different ionic crosslinkers (e.g., Ca(2+), Zn(2+) and Cu(2+)). The crosslinking reaction was confirmed by FT-IR. Swelling behavior and stability of the hydrogels in simulated digestive media were investigated. The result indicated that the combination between HC and SA could delay the degradation time of the hydrogels. Calcium crosslinking system showed higher stability than that of zinc or copper crosslinking system. In vitro drug release profiles were studied using paracetamol as a soluble model drug. The amount of paracetamol release in simulated gastric fluid (SGF) was relatively low (<20%). In simulated intestinal fluid (SIF), the burst release of paracetamol was depressed with increasing HC content and/or applying crosslinker. The HC75SA25 formulation demonstrated the linearity of drug release profile. Additionally, the amount of drug release from the 0.5M calcium HC50SA50 hydrogel in SIF was lower than 20%. The comprehensive results of this study suggested their potential in the application of site-specific oral drug delivery in intestine and colon. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Contact lenses as drug controlled release systems: a narrative review

    Directory of Open Access Journals (Sweden)

    Helena Prior Filipe

    2016-06-01

    Full Text Available ABSTRACT Topically applied therapy is the most common way to treat ocular diseases, however given the anatomical and physiological constraints of the eye, frequent dosing is required with possible repercussions in terms of patient compliance. Beyond refractive error correction, contact lenses (CLs have, in the last few decades emerged as a potential ophthalmic drug controlled release system (DCRS. Extensive research is underway to understand how to best modify CLs to increase residence time and bioavailability of drugs within therapeutic levels on the ocular surface.These devices may simultaneously correct ametropia and have a role in managing ophthalmic disorders that can hinder CL wear such as dry eye, glaucoma, ocular allergy and cornea infection and injury. In this narrative review the authors explain how the ocular surface structures determine drug diffusion in the eye and summarize the strategies to enhance drug residence time and bioavailability. They synthesize findings and clinical applications of drug soaked CLs as DCRS combined with delivery diffusion barriers, incorporation of functional monomers, ion related controlled release, molecular imprinting, nanoparticles and layering. The authors draw conclusions about the impact of these novel ophthalmic agents delivery systems in improving drug transport in the target tissue and patient compliance, in reducing systemic absorption and undesired side effects, and discuss future perspectives.

  18. Evaluation of Pharmaceutical Quality of Mesalamine Delayed Release Tablets Using a New High Sensitivity Reversed-Phase UPLC Method for its Genotoxic/Aniline Impurity

    Directory of Open Access Journals (Sweden)

    Rakshit Kanubhai Trivedi

    2011-01-01

    Full Text Available A reversed phase ultra performance liquid chromatography (UPLC method was developed and validated for the quantification of aniline in mesalamine delayed-release tablets. The optimization of the experimental condition was carried out considering some important requirements like, detection limit, short run time and reproducibility. In the present study, isocratic reversed-phase UPLC method was developed for determination and separation of aniline from the drug product. The drug and impurity are well separated by using a reversed phase (Reprosil Gold C18-XBD column and mobile phase comprising of buffer pH 6.0 and acetonitrile in the ratio of 90:10 v/v. Other UPLC parameters which were optimised are flow rate, 0.5 mL/min; detection wavelength, 200 nm; column oven temperature, 50 °C and injection volume 7 µL. Stability indicating capability was also established by forced degradation experiments. The method was validated as per ICH guideline. LOQ (limit of quantification concentration (18 ng/mL was found precise with RSD of less than 2%. In essence, the present study provides an improved low detection limit and lower run time for evaluation of pharmaceutical quality of mesalamine delayed-release formulation. Moreover, the developed method was also successfully applied for quantification of aniline in mesalamine delayed-release formulation. The same method can also be used for determination of aniline from drug substances.

  19. Mesoporous hydroxyapatite: Preparation, drug adsorption, and release properties

    Energy Technology Data Exchange (ETDEWEB)

    Gu, Lina; He, Xiaomei; Wu, Zhenyu, E-mail: zhenyuwuhn@sina.com

    2014-11-14

    Mesoporous hydroxyapatite (HA) was synthesized through gas–liquid chemical precipitation method at ambient temperature without any template. Structure, morphology and pore size distribution of HA were analyzed via X-ray powder diffraction, scanning electron microscopy, transmission electron microscopy, high-resolution electron microscopy and N{sub 2} adsorption/desorption. The chemotherapeutic agent doxorubicin (DOX) was used to investigate the drug adsorption and release behavior of HA. The kinetics of DOX adsorption on HA followed the pseudo-second-order rate expression. Adsorption isotherms at various temperatures were obtained, and the equilibrium data fitted the Langmuir model. The values of thermodynamic parameters (Gibbs free energy, entropy, and enthalpy changes) demonstrated that the adsorption process was spontaneous and endothermic. In vitro pH-responsive (pH = 7.4, 5.8) controlled release was investigated. DOX-loaded HA showed a slow, long-term, and steady release rate. The release rate at pH5.8 was larger than that at pH7.4. Consequently, the as-prepared mesoporous HA has potential applications in controlled drug delivery systems. - Highlights: • Mesoporous HA was synthesized by a simple precipitation method without any template. • The kinetics of adsorption followed the pseudo-second-order rate expression. • Thermodynamics investigation showed that adsorption was spontaneous and endothermic. • DOX-loaded HA showed a long-term, steady, and pH-controlled release rate.

  20. Tailored sequential drug release from bilayered calcium sulfate composites

    Energy Technology Data Exchange (ETDEWEB)

    Orellana, Bryan R.; Puleo, David A., E-mail: puleo@uky.edu

    2014-10-01

    The current standard for treating infected bony defects, such as those caused by periodontal disease, requires multiple time-consuming steps and often multiple procedures to fight the infection and recover lost tissue. Releasing an antibiotic followed by an osteogenic agent from a synthetic bone graft substitute could allow for a streamlined treatment, reducing the need for multiple surgeries and thereby shortening recovery time. Tailorable bilayered calcium sulfate (CS) bone graft substitutes were developed with the ability to sequentially release multiple therapeutic agents. Bilayered composite samples having a shell and core geometry were fabricated with varying amounts (1 or 10 wt.%) of metronidazole-loaded poly(lactic-co-glycolic acid) (PLGA) particles embedded in the shell and simvastatin directly loaded into either the shell, core, or both. Microcomputed tomography showed the overall layered geometry as well as the uniform distribution of PLGA within the shells. Dissolution studies demonstrated that the amount of PLGA particles (i.e., 1 vs. 10 wt.%) had a small but significant effect on the erosion rate (3% vs. 3.4%/d). Mechanical testing determined that introducing a layered geometry had a significant effect on the compressive strength, with an average reduction of 35%, but properties were comparable to those of mandibular trabecular bone. Sustained release of simvastatin directly loaded into CS demonstrated that changing the shell to core volume ratio dictates the duration of drug release from each layer. When loaded together in the shell or in separate layers, sequential release of metronidazole and simvastatin was achieved. By introducing a tunable, layered geometry capable of releasing multiple drugs, CS-based bone graft substitutes could be tailored in order to help streamline the multiple steps needed to regenerate tissue in infected defects. - Highlights: • Bilayered CS composites were fabricated as potential bone graft substitutes. • The shell

  1. Hydrogel based drug carriers for controlled release of hydrophobic drugs and proteins

    NARCIS (Netherlands)

    Ke Peng,

    2011-01-01

    The aim of this study is to prepare in situ forming hydrogels based on biocompatible polymers for the controlled release of hydrophobic drug and proteins. In order to load hydrophobic drug to the hydrophilic hydrogel matrix, beta-cyclodextrin and human serum albumin was introduced to the hydrogel ne

  2. Electrically actuatable smart nanoporous membrane for pulsatile drug release.

    Science.gov (United States)

    Jeon, Gumhye; Yang, Seung Yun; Byun, Jinseok; Kim, Jin Kon

    2011-03-09

    We report on the fabrication of electrically responsive nanoporous membrane based on polypyrrole doped with dodecylbenzenesulfonate anion (PPy/DBS) that was electropolymerized on the upper part of anodized aluminum oxide membrane. The membrane has regular pore size and very high pore density. Utilizing a large volume change of PPy/DBS depending on electrochemical state, the pore size was acutated electrically. The actuation of the pores was experimentally confirmed by in situ atomic force microscopy and in situ flux measurement. We also demonstrated successfully pulsatile (or on-demand) drug release by using fluorescently labeled protein as a model drug. Because of a fast switching time (less than 10 s) and high flux of the drugs, this membrane could be used for emergency therapy of angina pectoris and migraine, which requires acute and on-demand drug delivery, and hormone-related disease and metabolic syndrome.

  3. A concise review on smart polymers for controlled drug release.

    Science.gov (United States)

    Aghabegi Moghanjoughi, Arezou; Khoshnevis, Dorna; Zarrabi, Ali

    2016-06-01

    Design and synthesis of efficient drug delivery systems are of critical importance in health care management. Innovations in materials chemistry especially in polymer field allows introduction of advanced drug delivery systems since polymers could provide controlled release of drugs in predetermined doses over long periods, cyclic and tunable dosages. To this end, researchers have taken advantages of smart polymers since they can undergo large reversible, chemical, or physical fluctuations as responses to small changes in environmental conditions, for instance, in pH, temperature, light, and phase transition. The present review aims to highlight various kinds of smart polymers, which are used in controlled drug delivery systems as well as mechanisms of action and their applications.

  4. Mathematical modelling of the release of drug from porous, nonswelling transdermal drug-delivery devices.

    Science.gov (United States)

    Lee, A J; King, J R; Hibberd, S

    1998-06-01

    A general model is presented for the release of drug from porous nonswelling, transdermal drug-delivery devices and it is shown to reduce to previously proposed models in suitable limits. The processes which govern the release of drug are considered to be diffusion of dissolved drug and dissolution of dispersed drug, both in the body of the device and in the device pores, and transfer of drug between the two domains. In the classical limit of large dissolution rates, the problem reduces to one of the moving-boundary type, and solution of this problem in the case where the initial drug loading is much greater than the drug solubility in the device yields expressions for the flux of drug to a perfect sink (modelling in vitro conditions). It is shown that behaviour greatly differing from the classical first-order drug delivery (alpha t 1/2) may be exhibited, depending upon the parameter regime. In some situations the dissolution rates may not be so large and solutions of the general model are derived in the case where the dispersed drug is considered to be undepleted and the diffusivity in the solvent-filled pores is much larger than in the body of the delivery device. Numerical studies are undertaken, and the coupling of delivery device and skin-diffusion models (in order to model the complete transdermal drug-delivery process) is also considered.

  5. Design and development of ankle-foot prosthesis with delayed release of plantarflexion

    Directory of Open Access Journals (Sweden)

    Michael Mitchell, MSc

    2013-05-01

    Full Text Available A computer-controlled mechanism that fits a standard ankle-foot prosthesis was designed to capture the absorbed energy in the ankle and delay its release until specific times in the gait cycle. This mechanism used a direct current motor to take up and hold the compression of a carbon-fiber ankle joint. Based on the timing of the contact forces between the foot and the ground, a microprocessor released the spring at preset times later in the gait cycle. This mechanism was added to a Talux prosthetic foot and was employed by a user of a conventional energy-storage ankle-foot prosthesis. His gait was recorded using a motion analysis system. Five settings: 0, 55, 65, 75, and 85 ms delay were tested on separate days, and the standard kinematic and kinetic gait data were recorded. The user reported some settings were more comfortable than others. When these preferences were tested with a randomized double-blind trial, the preferences were not consistent. A second user showed a preference for the 55 ms delay. The modifications to the device resulted in changes to the gait of the subjects, including increased cadence and kinematics of the unaffected joints and a longer, slower push from the ankle, which was noticed by both of the subjects.

  6. Design and development of ankle-foot prosthesis with delayed release of plantarflexion.

    Science.gov (United States)

    Mitchell, Michael; Craig, Katelynn; Kyberd, Peter; Biden, Edmund; Bush, Greg

    2013-01-01

    A computer-controlled mechanism that fits a standard ankle-foot prosthesis was designed to capture the absorbed energy in the ankle and delay its release until specific times in the gait cycle. This mechanism used a direct current motor to take up and hold the compression of a carbon-fiber ankle joint. Based on the timing of the contact forces between the foot and the ground, a microprocessor released the spring at preset times later in the gait cycle. This mechanism was added to a Talux prosthetic foot and was employed by a user of a conventional energy-storage ankle-foot prosthesis. His gait was recorded using a motion analysis system. Five settings: 0, 55, 65, 75, and 85 ms delay were tested on separate days, and the standard kinematic and kinetic gait data were recorded. The user reported some settings were more comfortable than others. When these preferences were tested with a randomized double-blind trial, the preferences were not consistent. A second user showed a preference for the 55 ms delay. The modifications to the device resulted in changes to the gait of the subjects, including increased cadence and kinematics of the unaffected joints and a longer, slower push from the ankle, which was noticed by both of the subjects.

  7. Preparation of acetylsalicylic acid-acylated chitosan as a novel polymeric drug for drug controlled release.

    Science.gov (United States)

    Liu, Changkun; Wu, Yiguang; Zhao, Liyan; Huang, Xinzheng

    2015-01-01

    The acetylsalicylic acid-acylated chitosan (ASACTS) with high degree of substitution (DS) was successfully synthesized, and characterized with FTIR, (1)H NMR and elemental analysis methods. The optimum synthesis conditions were obtained which gave the highest DS (about 60%) for ASACTS. Its drug release experiments were carried out in simulated gastric and intestine fluids. The results show that the drugs in the form of acetylsalicylic acid (ASA) and salicylic acid (SA) were released in a controlled manner from ASACTS only in simulated gastric fluid. The release profile can be best fitted with logistic and Weibull model. The research results reveal that ASACTS can be a potential polymeric drug for the controlled release of ASA and SA in the targeted gastric environment.

  8. Evaluation of the drug solubility and rush ageing on drug release performance of various model drugs from the modified release polyethylene oxide matrix tablets.

    Science.gov (United States)

    Shojaee, Saeed; Nokhodchi, Ali; Maniruzzaman, Mohammed

    2017-02-01

    Hydrophilic matrix systems are currently some of the most widely used drug delivery systems for controlled-release oral dosage forms. Amongst a variety of polymers, polyethylene oxide (PEO) is considered an important material used in pharmaceutical formulations. As PEO is sensitive to thermal oxidation, it is susceptible to free radical oxidative attack. The aim of this study was to investigate the stability of PEO based formulations containing different model drugs with different water solubility, namely propranolol HCl, theophylline and zonisamide. Both polyox matrices 750 and 303 grade were used as model carriers for the manufacture of tablets stored at 40 °C. The results of the present study suggest that the drug release from the matrix was affected by the length of storage conditions, solubility of drugs and the molecular weight of the polymers. Generally, increased drug release rates were prevalent in soluble drug formulations (propranolol) when stored at the elevated temperature (40 °C). In contrast, it was not observed with semi soluble (theophylline) and poorly soluble (zonisamide) drugs especially when formulated with PEO 303 polymer. This indicates that the main parameters controlling the drug release from fresh polyox matrices are the solubility of the drug in the dissolution medium and the molecular weight of the polymer. DSC traces indicated that that there was a big difference in the enthalpy and melting points of fresh and aged PEO samples containing propranolol, whereas the melting point of the aged polyox samples containing theophylline and zonisamide was unaffected. Graphical abstract ᅟ.

  9. Interfacial Fast Release Layer in Monodisperse Poly (lactic-co-glycolic acid) Microspheres Accelerates the Drug Release.

    Science.gov (United States)

    Wu, Jun; Zhao, Xiaoli; Yeung, Kelvin W K; To, Michael K T

    2016-01-01

    Understanding microstructural evolutions of drug delivery devices during drug release process is essential for revealing the drug release mechanisms and controlling the drug release profiles. In this study, monodisperse poly (lactic-co-glycolic acid) microspheres in different diameters were fabricated by microfluidics in order to find out the relationships between the microstructural evolutions and the drug release profiles. It was found that poly (lactic-co-glycolic acid) microspheres underwent significant size expansion which took place from the periphery to the center, resulting in the formation of interfacial fast release layers. At the same time, inner pores were created and the diffusion rate was increased so that the early stage drug release was accelerated. Due to the different expansion rates, small poly (lactic-co-glycolic acid) microspheres tendered to follow homogeneous drug release while large poly (lactic-co-glycolic acid) microspheres tendered to follow heterogeneous drug release. This study suggests that the size expansion and the occurrence of interfacial fast release layer were important mechanisms for early stage drug release of poly (lactic-co-glycolic acid) microspheres.

  10. Controlled drug release on amine functionalized spherical MCM-41

    Science.gov (United States)

    Szegedi, Agnes; Popova, Margarita; Goshev, Ivan; Klébert, Szilvia; Mihály, Judit

    2012-10-01

    MCM-41 silica with spherical morphology and small particle sizes (100 nm) was synthesized and modified by post-synthesis method with different amounts of 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, was carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N2 physisorption, elemental analysis, thermal analysis and FT-IR spectroscopy. A new method was developed for the quantitative determination of amino groups in surface modified mesoporous materials by the ninhydrin reaction. Good correlation was found between the amino content of the MCM-41 materials determined by the ninhydrin method and their ibuprofen adsorption capacity. Amino modification resulted in high degree of ibuprofen loading and slow release rate in comparison to the parent non-modified MCM-41.

  11. Continuous Drug Release by Sea Anemone Nematostella vectensis Stinging Microcapsules

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    Yossi Tal

    2014-01-01

    Full Text Available Transdermal delivery is an attractive option for drug delivery. Nevertheless, the skin is a tough barrier and only a limited number of drugs can be delivered through it. The most difficult to deliver are hydrophilic drugs. The stinging mechanism of the cnidarians is a sophisticated injection system consisting of microcapsular nematocysts, which utilize built-in high osmotic pressures to inject a submicron tubule that penetrates and delivers their contents to the prey. Here we show, for the first time, that the nematocysts of the starlet sea anemone Nematostella vectensis can be isolated and incorporated into a topical formulation for continuous drug delivery. We demonstrate quantitative delivery of nicotinamide and lidocaine hydrochloride as a function of microcapsular dose or drug exposure. We also show how the released submicron tubules can be exploited as a skin penetration enhancer prior to and independently of drug application. The microcapsules are non-irritant and may offer an attractive alternative for hydrophilic transdermal drug delivery.

  12. Drug release characterization and preparation of Ca-Alginate microparticle drug carrier using membrane emulsification method

    Energy Technology Data Exchange (ETDEWEB)

    You, Jin Oh; Park, Seong Bae; Park, Ham Yong; Haam, Seung Joo; Kim, Jung Hyun; Kim, Woo Sik [Dept. of Chemical Engineering, Yonsei University, Seoul (Korea)

    1999-10-01

    Conventional alginate bead has been limited to be used as a drug carrier because of its large size. To overcome the disadvantages of conventional large-size alginate drug beads, Ca-alginate microparticles were prepared using membrane emulsification method controlled with the sodium alginate concentration and the pressure of reactor. The optimal monodispersed microparticles were obtained with the concentration of 2 wt % alginate solution and the pressure of 0.4*10{sup 5} Pa. The mean size of our prepared microparticles was about 4 {gamma}m. As the drug solutions, lidocaine{center_dot}HCI(cationic), sodium salicylate(anionic) and 4-acetamidophenol(nonionic) were selected. These three different drugs were loaded in the drug carrier of prepared alginate microparticles. Drug releases were performed in the sodium phosphate buffers of pH 2 and pH 7 and ionic strength of 0.2. The release behavior with the variation of drug charge shoed that of the cationic drug release was retarded more than anionic one due to the ionic interaction between carboxyl group of alginates and positive charge of cationic drug. >From the comparison experiments of the buffers of pH 2 and pH 7, the release was much retarded at pH 2 buffer due to the ionic repulsive force or ionic attractive force between the carboxyl group and the hydroxy or sodium ion in the buffer. Conclusively, the usage of small-size pH sensitive microparticle as a drug carrier has a high potential for the application of drug delivery systems. 19 refs., 9 figs.

  13. Development of controlled drug release systems based on thiolated polymers.

    Science.gov (United States)

    Bernkop-Schnürch, A; Scholler, S; Biebel, R G

    2000-05-03

    The purpose of the present study was to generate mucoadhesive matrix-tablets based on thiolated polymers. Mediated by a carbodiimide, L-cysteine was thereby covalently linked to polycarbophil (PCP) and sodium carboxymethylcellulose (CMC). The resulting thiolated polymers displayed 100+/-8 and 1280+/-84 micromol thiol groups per gram, respectively (means+/-S.D.; n=6-8). In aqueous solutions these modified polymers were capable of forming inter- and/or intramolecular disulfide bonds. The velocity of this process augmented with increase of the polymer- and decrease of the proton-concentration. The oxidation proceeded more rapidly within thiolated PCP than within thiolated CMC. Due to the formation of disulfide bonds within thiol-containing polymers, the stability of matrix-tablets based on such polymers could be strongly improved. Whereas tablets based on the corresponding unmodified polymer disintegrated within 2 h, the swollen carrier matrix of thiolated CMC and PCP remained stable for 6.2 h (mean, n=4) and more than 48 h, respectively. Release studies of the model drug rifampicin demonstrated that a controlled release can be provided by thiolated polymer tablets. The combination of high stability, controlled drug release and mucoadhesive properties renders matrix-tablets based on thiolated polymers useful as novel drug delivery systems.

  14. Nanoporous anodic titanium dioxide layers as potential drug delivery systems: Drug release kinetics and mechanism.

    Science.gov (United States)

    Jarosz, Magdalena; Pawlik, Anna; Szuwarzyński, Michał; Jaskuła, Marian; Sulka, Grzegorz D

    2016-07-01

    Nanoporous anodic titanium dioxide (ATO) layers on Ti foil were prepared via a three step anodization process in an electrolyte based on an ethylene glycol solution with fluoride ions. Some of the ATO samples were heat-treated in order to achieve two different crystallographic structures - anatase (400°C) and a mixture of anatase and rutile (600°C). The structural and morphological characterizations of ATO layers were performed using a field emission scanning electron microscope (SEM). The hydrophilicity of ATO layers was determined with contact angle measurements using distilled water. Ibuprofen and gentamicin were loaded effectively inside the ATO nanopores. Afterwards, an in vitro drug release was conducted for 24h under a static and dynamic flow conditions in a phosphate buffer solution at 37°C. The drug concentrations were determined using UV-Vis spectrophotometry. The absorbance of ibuprofen was measured directly at 222nm, whether gentamicin was determined as a complex with silver nanoparticles (Ag NPs) at 394nm. Both compounds exhibited long term release profiles, despite the ATO structure. A new release model, based on the desorption of the drug from the ATO top surface followed by the desorption and diffusion of the drug from the nanopores, was derived. The proposed release model was fitted to the experimental drug release profiles, and kinetic parameters were calculated.

  15. pH-dependent anticancer drug release from silk nanoparticles.

    Science.gov (United States)

    Seib, F Philipp; Jones, Gregory T; Rnjak-Kovacina, Jelena; Lin, Yinan; Kaplan, David L

    2013-12-01

    Silk has traditionally been used as a suture material because of its excellent mechanical properties and biocompatibility. These properties have led to the development of different silk-based material formats for tissue engineering and regenerative medicine. Although there have been a small number of studies about the use of silk particles for drug delivery, none of these studies have assessed the potential of silk to act as a stimulus-responsive anticancer nanomedicine. This report demonstrates that an acetone precipitation of silk allows the formation of uniform silk nanoparticles (98 nm diameter, polydispersity index 0.109), with an overall negative surface charge (-33.6 ± 5.8 mV), in a single step. Silk nanoparticles are readily loaded with doxorubicin (40 ng doxorubicin/μg silk) and show pH-dependent release (pH 4.5≫ 6.0 > 7.4). In vitro studies with human breast cancer cell lines demonstrates that the silk nanoparticles are not cytotoxic (IC50 > 120 μg mL(-1) ) and that doxorubicin-loaded silk nanoparticles are able to overcome drug resistance mechanisms. Live cell fluorescence microscopy studies show endocytic uptake and lysosomal accumulation of silk nanoparticles. In summary, the pH-dependent drug release and lysosomal accumulation of silk nanoparticles demonstrate the ability of drug-loaded silk nanoparticles to serve as a lysosomotropic anticancer nanomedicine.

  16. Tunable drug loading and release from polypeptide multilayer nanofilms

    Directory of Open Access Journals (Sweden)

    Bingbing Jiang

    2009-03-01

    Full Text Available Bingbing Jiang1, Bingyun Li1,2,31Biomaterials, Bioengineering and Nanotechnology Laboratory, Department of Orthopaedics, School of Medicine, West Virginia University, Morgantown, WV, USA; 2WVNano Initiative, WV, USA; 3Department of Chemical Engineering, College of Engineering and Mineral Resources, West Virginia University, Morgantown, WV, USA Abstract: Polypeptide multilayer nanofilms were prepared using electrostatic layer-by-layer self-assembly nanotechnology. Small charged drug molecules (eg, cefazolin, gentamicin, and methylene blue were loaded in polypeptide multilayer nanofilms. Their loading and release were found to be pH-dependent and could also be controlled by changing the number of film layers and drug incubation time, and applying heat-treatment after film formation. Antibiotic-loaded polypeptide multilayer nanofilms showed controllable antibacterial properties against Staphylococcus aureus. The developed biodegradable polypeptide multilayer nanofilms are capable of loading both positively- and negatively-charged drug molecules and promise to serve as drug delivery systems on biomedical devices for preventing biomedical device-associated infection, which is a significant clinical complication for both civilian and military patients.Keywords: polypeptide, self-assembly, polyelectrolyte multilayer, nanofilm, charged molecule, tunable release

  17. Equilibrium and release properties of hyaluronic acid-drug complexes.

    Science.gov (United States)

    Battistini, Franco David; Olivera, María Eugenia; Manzo, Rubén Hilario

    2013-07-16

    With the aim to provide more rational basis about the potentiality of hyaluronic acid (or hyaluronan) as drug carrier a set of ionic complexes of its acid form (HA) and its sodium salt (NaHA) with three model drugs (D) (atenolol, propranolol and lidocaine) were prepared. Besides NaHA subjected to hyalurodinase depolimerization (NaHA(d)) was also used. Transparent dispersions were obtained. They exhibited negative electrokinetic potential and a high degree of counterionic condensation with affinity constants (log Kcc) in the range of 5.8-6.1 for propranolol complexes (pK(a) 9.45) and 4.0-4.6 for lidocaine ones (pK(a) 7.92). Delivery rates of D from the complexes were measured in a Franz-type bicompartimental device. Loaded D were slowly released from the three types of complexes, even when a neutral salt was added to the dispersion placed in the donor compartment, revealing the high affinity between the protonated drugs and the ionisable groups of the polymer. Complex dispersions based on HA or on NaHA(d) exhibited lower viscosity than those of NaHA but their complexing ability remained unaltered. The results reported on equilibrium and release properties of Hyaluronan-model D complexes contribute to expand the use of HA and NaHA as drug carriers for different routes of administration.

  18. Design, synthesis, characterization and drug release kinetics of PAMAM dendrimer based drug formulations

    Science.gov (United States)

    Kurtoglu, Yunus Emre

    The drug release characteristics of G4-polyamidoamine (PAMAM) dendrimer-ibuprofen conjugates with ester, amide, and peptide linkers were investigated, in addition to a linear PEG-ibuprofen conjugate to understand the effect of architecture and linker on drug release. Ibuprofen was directly conjugated to NH2 -terminated dendrimer by an amide bond and OH-terminated dendrimer by an ester bond. A tetra-peptide linked dendrimer conjugate and a linear mPEG-ibuprofen conjugate were also studied for comparison to direct linked dendrimer conjugates. It is demonstrated that the 3-D nanoscale architecture of PAMAM dendrimer-drug conjugates, along with linking chemistry govern the drug release mechanisms as well as kinetics. Understanding these structural effects on their drug release characteristics is crucial for design of dendrimer conjugates with high efficacy such as poly(amidoamine) dendrimer-N-Acetylcysteine conjugates with disulfide linkages. N-Acetylcysteine (NAC) is an anti-inflammatory agent with significant potential for clinical use in the treatment of neuroinflammation, stroke and cerebral palsy. A poly(amidoamine) dendrimer-NAC conjugate that contains a disulfide linkage was synthesized and evaluated for its release kinetics in the presence of glutathione (GSH), Cysteine (Cys), and bovine serum albumin (BSA) at both physiological and lysosomal pH. FITC-labeled conjugates showed that they enter cells rapidly and localize in the cytoplasm of lipopolysaccharide (LPS)-activated microglial cells. The efficacy of the dendrimer-NAC conjugate was measured in activated microglial cells using reactive oxygen species (ROS) assays. The conjugates showed an order of magnitude increase in anti-oxidant activity compared to free drug. When combined with intrinsic and ligand-based targeting with dendrimers, these types of GSH sensitive nanodevices can lead to improved drug release profiles and in vivo efficacy.

  19. NAIL AS A PROMISING DRUG DELIVERY SYSTEM FOR CONTROLLED RELEASE

    Directory of Open Access Journals (Sweden)

    G. Sai Krishna*, P. Prem Kumar, K. Bala Murugan

    2013-03-01

    Full Text Available ABSTRACT: The effectiveness of topical therapies is limited by minimal drug permeability through the nail plate. Nail permeability is however quite low and limits topical therapy to early/mild disease states such as onychomycosis (fungal infections of the nail. Current research on nail permeation that focuses on altering the nail plate barrier by means of chemical treatments, penetration enhancers as well as physical and mechanical methods is reviewed also the recent research into ungual drug delivery is reviewed, a new method of nail sampling is examined. Topical therapy is worth pursuing however, as local action is required in many nail disorders. Drug transport into the nail plate can be assisted by filing the nail plate before topical application of drug formulations as well as by the use of chemical enhancers. Finally limitations of current ungual drug permeability studies are briefly discussed and the factors, which affect drug uptake and permeation through the nail plate such as solute molecular size, hydrophilicity/hydrophobicity, charge, and the nature of the vehicle, are then discussed, and drug-containing nail lacquers which, like cosmetic varnish, are brushed onto the nail plates to form a film, and from which drug is released and penetrates into the nail are reviewed. The nail plate behaves like a concentrated hydrogel to permeating molecules and diffusion of molecules through the nail plate has been compared to the diffusion of non-electrolytes through polymer gels. Thus, for optimal ungual permeation and uptake, drug molecules must be of small size and be uncharged.

  20. Water boiling inside carbon nanotubes: toward efficient drug release.

    Science.gov (United States)

    Chaban, Vitaly V; Prezhdo, Oleg V

    2011-07-26

    We show using molecular dynamics simulation that spatial confinement of water inside carbon nanotubes (CNTs) substantially increases its boiling temperature and that a small temperature growth above the boiling point dramatically raises the inside pressure. Capillary theory successfully predicts the boiling point elevation down to 2 nm, below which large deviations between the theory and atomistic simulation take place. Water behaves qualitatively different inside narrow CNTs, exhibiting transition into an unusual phase, where pressure is gas-like and grows linearly with temperature, while the diffusion constant is temperature-independent. Precise control over boiling by CNT diameter, together with the rapid growth of inside pressure above the boiling point, suggests a novel drug delivery protocol. Polar drug molecules are packaged inside CNTs; the latter are delivered into living tissues and heated by laser. Solvent boiling facilitates drug release.

  1. Pharmacokinetics of diltiazem hydrochloride delay-onset sustained-release pellet capsules in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Xi-Qing Yan

    2013-03-01

    Full Text Available The pharmacokinetics (PK of ordinary tablets and sustained release capsules of diltiazem hydrochloride in human clinical trials had been studied. The PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules, a new dosage form, has not been reported, although it is very important to clinical use. In this paper, we investigated the PK of diltiazem hydrochloride delay-onset sustained-release pellet capsules and the food influence in Chinese healthy volunteers. The PK parameters indicated that the diltiazem hydrochloride delay-onset sustained-release pellet capsules appeared marked characteristics of delayed and controlled release. An opened-label, randomized and parallel clinical trial was conducted in 36 Chinese healthy volunteers with single oral dose (90 mg, 180 mg or 270 mg and a multiple oral dose (90 mg d-1×6 d administration. The effect of food on the PK of one single oral dose (360 mg was investigated in 24 healthy Chinese volunteers. Plasma diltiazem concentration was determined by reversed-phase high-performance liquid chromatography (RP-HPLC and the main pharmacokinetic parameters were analyzed by PKSolver (Ver 2.0. All clinical studies were conducted in the Clinical Pharmacological Center (No. JDX1999064 of Xiangya Hospital Affiliated Central South University, China. The PK parameters suggested that the new formulation had marked characteristics of delayed and controlled release of diltiazem, and food intake did not alter significantly diltiazem pharmacokinetic parameters.Embora a farmacocinética (PK do cloridrato de diltiazem nas formas de comprimidos de liberação imediata e cápsulas de liberação modificada em ensaios clínicos já tenha sido relatada, a pesquisa da PK do cloridrato de diltiazem na forma de cápsulas com peletes de liberação retardada e sustentada ainda é muito importante. Neste trabalho, propusemos avaliar a farmacocinética do cloridrato de diltiazem administrado através desta nova forma

  2. Compression-Coated Tablet for Colon Targeting: Impact of Coating and Core Materials on Drug Release.

    Science.gov (United States)

    Maity, Siddhartha; Sa, Biswanath

    2016-04-01

    This work was envisaged to develop compression-coated tablets using a blend of Ca(+2) ion cross-linked carboxymethyl xanthan gum (CMXG) and sodium alginate (SAL) for delayed release of immediate pulse release tablets of prednisolone (PDL) in the colon without the need of colonic bacterial intervention for degradation of the polysaccharide coat. The core tablets containing PDL and other compatible excipients were prepared by direct compression method and subsequently compression coated with different ratios of CMXG and SAL. Long T lag, the time required to restrict the drug release below 10%, and short T rap, the time required for immediate release following the T lag, were considered as suitable release parameters for evaluation of colon targeting of PDL tablets. Among the various compression coats, a blend of CMXG and SAL in a ratio of 1.5:3.5 provided T lag of 5.12 ± 0.09 h and T rap of 6.50 ± 0.05 h. The increase in microcrystalline cellulose (MCC) and crospovidone (CP) in the core tablets did not change T lag significantly although decreased the T rap marginally. Inclusion of an osmogen in the core tablets decreased the T lag to 4.05 ± 0.08 h and T rap to 3.56 ± 0.06 h. The increase in coat weight to 225 mg provided a reasonably long T lag (6.06 ± 0.09 h) and short T rap (4.36 ± 0.20 h). Drug release from most of the formulations followed the Hixson-Crowell equation and sigmoidal pattern as confirmed by the Weibull equation. In conclusion, tablets, compression coated with CMXG and SAL in a ratio of 1.5:3.5 and having 225-mg coat weight, were apparently found suitable for colon targeting.

  3. Externally controlled triggered-release of drug from PLGA micro and nanoparticles.

    Directory of Open Access Journals (Sweden)

    Xin Hua

    Full Text Available Biofilm infections are extremely hard to eradicate and controlled, triggered and controlled drug release properties may prolong drug release time. In this study, the ability to externally control drug release from micro and nanoparticles was investigated. We prepared micro/nanoparticles containing ciprofloxacin (CIP and magnetic nanoparticles encapsulated in poly (lactic-co-glycolic acid PLGA. Both micro/nanoparticles were observed to have narrow size distributions. We investigated and compared their passive and externally triggered drug release properties based on their different encapsulation structures for the nano and micro systems. In passive release studies, CIP demonstrated a fast rate of release in first 2 days which then slowed and sustained release for approximately 4 weeks. Significantly, magnetic nanoparticles containing systems all showed ability to have triggered drug release when exposed to an external oscillating magnetic field (OMF. An experiment where the OMF was turned on and off also confirmed the ability to control the drug release in a pulsatile manner. The magnetically triggered release resulted in a 2-fold drug release increase compared with normal passive release. To confirm drug integrity following release, the antibacterial activity of released drug was evaluated in Pseudomonas aeruginosa biofilms in vitro. CIP maintained its antimicrobial activity after encapsulation and triggered release.

  4. Polylactide conjugates of camptothecin with different drug release abilities.

    Science.gov (United States)

    Oledzka, Ewa; Horeglad, Paweł; Gruszczyńska, Zuzanna; Plichta, Andrzej; Nałęcz-Jawecki, Grzegorz; Sobczak, Marcin

    2014-11-25

    Camptothecin-polylactide conjugates (CMPT-PLA) were synthesized by covalent incorporation of CMPT into PLA of different microstructure, i.e., atactic PLA and atactic-block-isotactically enriched PLA (Pm = 0.79) via urethane bonds. The kinetic release of CPMT from CMPT-PLA conjugates, tested in vitro under different conditions, is possible in both cases and notably, strongly dependent on PLA microstructure. It shows that release properties of drug-PLA conjugates can be tailored by controlled design of the PLA microstructure, and allow in the case of CMPT-PLA conjugates for the development of highly controlled biodegradable CMPT systems-important delivery systems for anti-cancer agents.

  5. Polylactide Conjugates of Camptothecin with Different Drug Release Abilities

    Directory of Open Access Journals (Sweden)

    Ewa Oledzka

    2014-11-01

    Full Text Available Camptothecin-polylactide conjugates (CMPT-PLA were synthesized by covalent incorporation of CMPT into PLA of different microstructure, i.e., atactic PLA and atactic-block-isotactically enriched PLA (Pm = 0.79 via urethane bonds. The kinetic release of CPMT from CMPT-PLA conjugates, tested in vitro under different conditions, is possible in both cases and notably, strongly dependent on PLA microstructure. It shows that release properties of drug-PLA conjugates can be tailored by controlled design of the PLA microstructure, and allow in the case of CMPT-PLA conjugates for the development of highly controlled biodegradable CMPT systems—important delivery systems for anti-cancer agents.

  6. A Fibrous Localized Drug Delivery Platform with NIR-Triggered and Optically Monitored Drug Release.

    Science.gov (United States)

    Liu, Heng; Fu, Yike; Li, Yangyang; Ren, Zhaohui; Li, Xiang; Han, Gaorong; Mao, Chuanbin

    2016-09-06

    Implantable localized drug delivery systems (LDDSs) with intelligent functionalities have emerged as a powerful chemotherapeutic platform in curing cancer. Developing LDDSs with rationally controlled drug release and real-time monitoring functionalities holds promise for personalized therapeutic protocols but suffers daunting challenges. To overcome such challenges, a series of porous Yb(3+)/Er(3+) codoped CaTiO3 (CTO:Yb,Er) nanofibers, with specifically designed surface functionalization, were synthesized for doxorubicin (DOX) delivery. The content of DOX released could be optically monitored by increase in the intensity ratio of green to red emission (I550/I660) of upconversion photoluminescent nanofibers under 980 nm near-infrared (NIR) excitation owing to the fluorescence resonance energy transfer (FRET) effect between DOX molecules and the nanofibers. More importantly, the 808 nm NIR irradiation enabled markedly accelerated DOX release, confirming representative NIR-triggered drug release properties. In consequence, such CTO:Yb,Er nanofibers presented significantly enhanced in vitro anticancer efficacy under NIR irradiation. This study has thus inspired another promising fibrous LDDS platform with NIR-triggered and optics-monitored DOX releasing for personalized tumor chemotherapy.

  7. Cyclodextrin-gated mesoporous silica nanoparticles as drug carriers for red light-induced drug release

    Science.gov (United States)

    Chai, Shiqiang; Guo, Yu; Zhang, Zhenyu; Chai, Zhen; Ma, Yurong; Qi, Limin

    2017-04-01

    Long wavelength light-responsive drug delivery systems based on mesoporous silica nanoparticles (MSNs) have attracted much attention in the last few years. In this paper, a red light (660 nm)-responsive drug delivery system based on low-cost cyclodextrin (CD)-gated MSNs containing a photodynamic therapy (PDT) photosensitizer (Chlorin e6, Ce6) was developed for the first time. The drug release experiment in water demonstrated that with the irradiation of red light, Ce6 can be excited to generate singlet oxygen, which can further cleave the singlet oxygen sensitive linker to trigger the departure of CD and the release of cargo. Further in vitro release experiments confirmed that cargo can be released from MSNs with the irradiation of red light and spread into the entire cell. The relative low power density (0.5 W cm‑2) of excitation light together with the short irradiation time (one–three min) result in a low light dose (30–90 J cm‑2) for the drug delivery, contributing to their potential clinical applications.

  8. Drug release from hydrogel: a new understanding of transport phenomena.

    Science.gov (United States)

    Perale, G; Rossi, F; Santoro, M; Marchetti, P; Mele, A; Castiglione, F; Raffa, E; Masi, M

    2011-06-01

    In tissue engineering, i.e., in combined advanced technologies to replace damaged or missing parts of living tissues, emerging strategies strongly point toward the use of hydrogels also for their ability of being vehicles for local controlled drug delivery. The investigation of drug release mechanisms in such matrices thus plays a key role in the design of smart system but literature is still very controversial on theoretical interpretations and understanding of available data. In this framework we used the new HRMAS-NMR DOSY technique to study the diffusive motions of sodium fluorescein, a drug mimetic small chromophoric molecule, loaded in a promising hydrogel developed for tissue engineering. While fluorescein behavior in water was as expected, also showing aggregation from mid concentrations, data collected within hydrogel samples surprisingly showed no aggregation and diffusion coefficients were always higher with respect to aqueous solution. Furthermore, the promotion of diffusion increased along with fluorescein concentration. The proportion of this effect was directly linked to hydrogel mesh size, thus carrying intrinsic novelty, but also complexity, and suggesting that not only strictly hydrodynamic effects should be considered but also electrostatic interactions between polymer chains and drug molecules might be key players in avoiding fluorescein aggregation and also affecting diffusivity.

  9. Kinetics of drug release from ointments: Role of transient-boundary layer.

    Science.gov (United States)

    Xu, Xiaoming; Al-Ghabeish, Manar; Krishnaiah, Yellela S R; Rahman, Ziyaur; Khan, Mansoor A

    2015-10-15

    In the current work, an in vitro release testing method suitable for ointment formulations was developed using acyclovir as a model drug. Release studies were carried out using enhancer cells on acyclovir ointments prepared with oleaginous, absorption, and water-soluble bases. Kinetics and mechanism of drug release was found to be highly dependent on the type of ointment bases. In oleaginous bases, drug release followed a unique logarithmic-time dependent profile; in both absorption and water-soluble bases, drug release exhibited linearity with respect to square root of time (Higuchi model) albeit differences in the overall release profile. To help understand the underlying cause of logarithmic-time dependency of drug release, a novel transient-boundary hypothesis was proposed, verified, and compared to Higuchi theory. Furthermore, impact of drug solubility (under various pH conditions) and temperature on drug release were assessed. Additionally, conditions under which deviations from logarithmic-time drug release kinetics occur were determined using in situ UV fiber-optics. Overall, the results suggest that for oleaginous ointments containing dispersed drug particles, kinetics and mechanism of drug release is controlled by expansion of transient boundary layer, and drug release increases linearly with respect to logarithmic time.

  10. Influence of Drug Properties and Formulation on In Vitro Drug Release and Biowaiver Regulation of Oral Extended Release Dosage Forms.

    Science.gov (United States)

    Lin, Zhongqiang; Zhou, Deliang; Hoag, Stephen; Qiu, Yihong

    2016-03-01

    Bioequivalence (BE) studies are often required to ensure therapeutic equivalence for major product and manufacturing changes. Waiver of a BE study (biowaiver) is highly desired for such changes. Current regulatory guidelines allow for biowaiver of proportionally similar lower strengths of an extended release (ER) product provided it exhibits similar dissolution to the higher strength in multimedia. The objective of this study is to demonstrate that (1) proportionally similar strengths of ER tablets exhibiting similar in vitro dissolution profiles do not always assure BE and (2) different strengths that do not meet the criteria for dissolution profile similarity may still be bioequivalent. Four marketed ER tablets were used as model drug products. Higher and lower (half) strength tablets were prepared or obtained from commercial source. In vitro drug release was compared using multi-pH media (pH 1.2, 4.5, 6.8) per regulatory guidance. In vivo performance was assessed based on the available in vivo BE data or established in vitro-in vivo relationships. This study demonstrated that the relationship between in vitro dissolution and in vivo performance is complex and dependent on the characteristics of specific drug molecules, product design, and in vitro test conditions. As a result, proportionally similar strengths of ER dosage forms that meet biowaiver requirements per current regulatory guidelines cannot ensure bioequivalence in all cases. Thus, without an established relationship between in vitro and in vivo performance, granting biowaiver based on passing in vitro tests may result in the approval of certain bioinequivalent products, presenting risks to patients. To justify any biowaiver using in vitro test, it is essential to understand the effects of drug properties, formulation design, product characteristics, test method, and its in vivo relevance. Therefore, biowaiver requirements of different strengths of ER dosage forms specified in the current regulatory

  11. Evaluation of Drug Release From Coated Pellets Based on Isomalt, Sugar, and Microcrystalline Cellulose Inert Cores

    OpenAIRE

    2010-01-01

    The objective of the present study was to investigate the effect of the pellet core materials isomalt, sugar, and microcrystalline cellulose on the in vitro drug release kinetics of coated sustained-release pellets as well as to evaluate the influence of different ratios of polymethacrylate copolymers exhibiting different permeability characteristics on the drug release rate. For characterization of the drug release process of pellets, the effect of osmolality was studied using glucose as an ...

  12. Chitosan nanoparticles as a modified diclofenac drug release system

    Science.gov (United States)

    Duarte Junior, Anivaldo Pereira; Tavares, Eraldo José Madureira; Alves, Taís Vanessa Gabbay; de Moura, Márcia Regina; da Costa, Carlos Emmerson Ferreira; Silva Júnior, José Otávio Carréra; Ribeiro Costa, Roseane Maria

    2017-08-01

    This study evaluated a modified nanostructured release system employing diclofenac as a drug model. Biodegradable chitosan nanoparticles were prepared with chitosan concentrations between 0.5 and 0.8% ( w/ v) by template polymerization method using methacrylic acid in aqueous solution. Chitosan-poly(methacrylic acid) (CS-PMAA) nanoparticles showed uniform size around 50-100 nm, homogeneous morphology, and spherical shape. Raw material and chitosan nanoparticles were characterized by thermal analysis, Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM), confirming the interaction between chitosan and methacrylic acid during nanoparticles preparation. Diclofenac sorption on the chitosan nanoparticles surface was achieved by incubation in water/ethanol (1:1) drug solution in concentrations of 0.5 and 0.8 mg/mL. The diclofenac amount sorbed per gram of CS-PMAA nanoparticles, when in a 0.5 mg/mL sodium diclofenac solution, was as follows: 12.93, 15, 20.87, and 29.63 mg/g for CS-PMAA nanoparticles 0.5, 0.6, 0.7, and 0.8% ( w/ v), respectively. When a 0.8 mg/mL sodium diclofenac solution was used, higher sorption efficiencies were obtained: For CS-PMAA nanoparticles with chitosan concentrations of 0.5, 0.6, 0.7, and 0.8% ( w/ v), the sorption efficiencies were 33.39, 49.58, 55.23, and 67.2 mg/g, respectively. Diclofenac sorption kinetics followed a second-order kinetics. Drug release from nanoparticles occurred in a period of up to 48 h and obeyed Korsmeyer-Peppas model, which was characterized mainly by Fickian diffusion transport. [Figure not available: see fulltext.

  13. Mechanoresponsive materials for drug delivery: Harnessing forces for controlled release.

    Science.gov (United States)

    Wang, Julia; Kaplan, Jonah A; Colson, Yolonda L; Grinstaff, Mark W

    2017-01-01

    Mechanically-activated delivery systems harness existing physiological and/or externally-applied forces to provide spatiotemporal control over the release of active agents. Current strategies to deliver therapeutic proteins and drugs use three types of mechanical stimuli: compression, tension, and shear. Based on the intended application, each stimulus requires specific material selection, in terms of substrate composition and size (e.g., macrostructured materials and nanomaterials), for optimal in vitro and in vivo performance. For example, compressive systems typically utilize hydrogels or elastomeric substrates that respond to and withstand cyclic compressive loading, whereas, tension-responsive systems use composites to compartmentalize payloads. Finally, shear-activated systems are based on nanoassemblies or microaggregates that respond to physiological or externally-applied shear stresses. In order to provide a comprehensive assessment of current research on mechanoresponsive drug delivery, the mechanical stimuli intrinsically present in the human body are first discussed, along with the mechanical forces typically applied during medical device interventions, followed by in-depth descriptions of compression, tension, and shear-mediated drug delivery devices. We conclude by summarizing the progress of current research aimed at integrating mechanoresponsive elements within these devices, identifying additional clinical opportunities for mechanically-activated systems, and discussing future prospects.

  14. Establishing Structure Property Relationship in Drug Partitioning into and Release from Niosomes: Physical Chemistry Insights with Anti-Inflammatory Drugs.

    Science.gov (United States)

    Dasgupta, Moumita; Kishore, Nand

    2017-08-31

    Understanding physical chemistry underlying interactions of drugs with delivery formulations is extremely important in devising effective drug delivery systems. The partitioning and release kinetics of diclofenac sodium and naproxen from Brij 30 and Triton X-100 niosomal formulations have been addressed based on structural characterization, partitioning energetics and release kinetics, thus establishing relationship between structures and observed properties. Both the drugs partition in nonpolar regions of TX-100 niosomes via stacking of aromatic rings. The combined effects of interactions of the drugs with polar head groups and the rigidity of the niosome vesicles determine entry and partitioning of drugs into niosomes. The observed slower rate of release of the drugs from the drug encapsulated niosomes of TX-100 than those of Brij 30, suggest stable complexation of drugs in the nonpolar interior of the former. No release of drugs from the niosomes was observed till 24 h even upon varying pH conditions without SDS. However SDS in drug loaded niosomes led to release of drugs in as early as 6 h. The sustained pattern of in vitro release kinetics of the drugs thus observed from our niosomal preparations suggest these vesicular systems to be promising for pharamaceutical applications as potential drug delivery vehicles.

  15. Lack of a pharmacokinetic drug-drug interaction with venlafaxine extended-release/indinavir and desvenlafaxine extended-release/indinavir.

    Science.gov (United States)

    Jann, Michael W; Spratlin, Vicky; Momary, Kathryn; Zhang, Hailing; Turner, David; Penzak, Scott R; Wright, Alan; VanDenBerg, Chad

    2012-05-01

    To assess the effects of venlafaxine extended-release (XR) capsules and desvenlafaxine extended-release (XR) tablets upon indinavir pharmacokinetic properties when co-administrated to healthy volunteers. This was an open-label, two-period, fixed-dose study conducted at the clinical research unit located on a university campus. Twenty-four healthy volunteers enrolled in the study (mean age 28.3 ± 8.0 years). Each subject received a single dose of indinavir 800 mg on day 1. Subsequently, subjects were then randomly assigned to either the venlafaxine XR group (N = 12) or the desvenlafaxine XR group (N = 12). Starting on day 2, venlafaxine XR was dosed at 37.5 mg/day for 4 days and increased to 75 mg/day for 6 days. Desvenlafaxine XR was dosed at 50 mg/day for 10 days. On day 12, indivanvir 800 mg was co-administered to both the venlafaxine XR and the desvenlafaxine XR groups. The pharmacokinetics of indinavir were determined both before and at the end of antidepressant dosing. Plasma indinavir, venlafaxine, and desvenlafaxine concentrations were assayed by high-performance liquid chromatography with ultra-violet (UV) detection. Indinavir pharmacokinetic parameters were calculated by noncompartmental analysis using validated computer software. Venlafaxine XR and desvenlafaxine XR did not produce any significant changes in indinavir disposition. Both antidepressants were well tolerated by the subjects with only minor adverse side effects. No pharmacokinetic drug-drug interaction was demonstrated between venlafaxine XR and indinavir or between desvenlafaxine XR and indinvair. The lack of interaction could be due to the venlafaxine and desvenlafaxine extended-release formulation.

  16. MOVING BOUNDARY PROBLEM FOR DIFFUSION RELEASE OF DRUG FROM A CYLINDER POLYMERIC MATRIX

    Institute of Scientific and Technical Information of China (English)

    谭文长; 吴望一; 严宗毅; 温功碧

    2001-01-01

    An approximate analytical solution of moving boundary problem for diffusion release of drug from a cylinder polymeric matrix was obtained by use of refined integral method. The release kinetics has been analyzed for non-erodible matrices with perfect sink condition. The formulas of the moving boundary and the fractional drug release were given.The moving boundary and the fractional drug release have been calculated at various drug loading levels, and the calculated results were in good agreement with those of experiments.The comparison of the moving boundary in spherical, cylinder, planar matrices has been completed. An approximate formula for estimating the available release time was presented.These results are useful for the clinic experiments. This investigation provides a new theoretical tool for studying the diffusion release of drug from a cylinder polymeric matrix and designing the controlled released drug.

  17. In silico study on the effects of matrix structure in controlled drug release

    Science.gov (United States)

    Villalobos, Rafael; Cordero, Salomón; Maria Vidales, Ana; Domínguez, Armando

    2006-07-01

    Purpose: To study the effects of drug concentration and spatial distribution of the medicament, in porous solid dosage forms, on the kinetics and total yield of drug release. Methods: Cubic networks are used as models of drug release systems. They were constructed by means of the dual site-bond model framework, which allows a substrate to have adequate geometrical and topological distribution of its pore elements. Drug particles can move inside the networks by following a random walk model with excluded volume interactions between the particles. The drug release time evolution for different drug concentration and different initial drug spatial distribution has been monitored. Results: The numerical results show that in all the studied cases, drug release presents an anomalous behavior, and the consequences of the matrix structural properties, i.e., drug spatial distribution and drug concentration, on the drug release profile have been quantified. Conclusions: The Weibull function provides a simple connection between the model parameters and the microstructure of the drug release device. A critical modeling of drug release from matrix-type delivery systems is important in order to understand the transport mechanisms that are implicated, and to predict the effect of the device design parameters on the release rate.

  18. Release kinetics of coated, donut-shaped tablets for water soluble drugs.

    Science.gov (United States)

    Kim, C J

    1999-02-01

    Coated, donut-shaped tablets (CDST) were designed to achieve parabolic and linear drug release profiles. When rapidly erodible polymers (HPMC E3, HPC, PEG8000, PEOs (Mw=100000 and 200000)) were used, the release profiles of diltiazem HCl from the tablets becomes parabolic whereas zero-order release was achieved by using slowly erodible polymers (HPMC E5, HPMC E15, PEO (Mw=300000)). Drug release from the rapidly erodible polymers was governed by the pure erosion of the polymer while both polymer erosion and drug diffusion controlled drug release from the slowly erodible polymers. As drug loading was increased from 10% to 39% w/w, the drug release rate from CDST based on HPMC E3 became faster and parabolic whereas that from CDST based on HPMC E5 was linear. The slowly erodible polymer (HPMC E5) provided parabolic release profiles when drug loading was greater than 49% w/w. In this case, drug release mechanisms likely shifted from a combination of polymer erosion and drug diffusion to pure polymer erosion due to the enhancement of polymer erosion by faster influx of water. As drug solubility decreased from 61.6% w/v (diltiazem HCl), 1.0% w/v (theophylline), to 0.5% w/v (nicardipine HCl), the drug release rate from CDST based on HPMC E3 decreased due to polymer erosion mechanism but there was little difference in release rate from CDST based on HPMC E5 due to the greater contribution of drug diffusion to drug release kinetics along with polymer erosion. As expected, the drug release rate of diltiazem HCl from HPMC E3 and E5 was significantly influenced by stirring rate and hole size.

  19. INVESTIGATION OF DRUG RELEASE FROM BIODEGRADABLE PLG MICROSPHERES: EXPERIMENT AND THEORY

    Energy Technology Data Exchange (ETDEWEB)

    ANDREWS, MALCOLM J. [Los Alamos National Laboratory; BERCHANE, NADER S. [Los Alamos National Laboratory; CARSON, KENNETH H. [Los Alamos National Laboratory; RICE-FICHT, ALLISON C. [Los Alamos National Laboratory

    2007-01-30

    Piroxicam containing PLG microspheres having different size distributions were fabricated, and in vitro release kinetics were determined for each preparation. Based on the experimental results, a suitable mathematical theory has been developed that incorporates the effect of microsphere size distribution and polymer degradation on drug release. We show from in vitro release experiments that microsphere size has a significant effect on drug release rate. The initial release rate decreased with an increase in microsphere size. In addition, the release profile changed from first order to concave-upward (sigmoidal) as the system size was increased. The mathematical model gave a good fit to the experimental release data.

  20. Losartan potassium loaded sustained release matrix tablets: Influence of various hydrophilic and hydrophobic polymers on drug release behaviour

    Directory of Open Access Journals (Sweden)

    D D Vohra

    2012-01-01

    Full Text Available Losartan potassium is an angiotensin II receptor antagonist readily absorbed from the GIT, following oral administration. It has low bioavailability as it undergoes extensive first pass metabolism and low elimination half-life. The present study was aimed at studying sustained release behaviour of the drug using hydrophilic and hydrophobic polymers and to optimise using a 32 full factorial design. Eudragit and HPMC were used to evaluate the effect of hydrophilic and hydrophobic polymers on the release pattern of the drug. A full factorial was implemented at 20, 30 and 40% concentration of hydrophilic polymer and 2.5, 5 and 7.5% of hydrophobic polymer correlating with the release behaviour. Process variables were investigated and the results showed excellent adaptability in releasing drug over prolonged periods. Based on the results, it was found suitable to formulate a dosage form using optimum concentration of hydrophobic polymer along with hydrophilic polymer to vary the release behaviour for over 12 hours.

  1. Controlled drug release from hydrogels for contact lenses: Drug partitioning and diffusion.

    Science.gov (United States)

    Pimenta, A F R; Ascenso, J; Fernandes, J C S; Colaço, R; Serro, A P; Saramago, B

    2016-12-30

    Optimization of drug delivery from drug loaded contact lenses assumes understanding the drug transport mechanisms through hydrogels which relies on the knowledge of drug partition and diffusion coefficients. We chose, as model systems, two materials used in contact lens, a poly-hydroxyethylmethacrylate (pHEMA) based hydrogel and a silicone based hydrogel, and three drugs with different sizes and charges: chlorhexidine, levofloxacin and diclofenac. Equilibrium partition coefficients were determined at different ionic strength and pH, using water (pH 5.6) and PBS (pH 7.4). The measured partition coefficients were related with the polymer volume fraction in the hydrogel, through the introduction of an enhancement factor following the approach developed by the group of C. J. Radke (Kotsmar et al., 2012; Liu et al., 2013). This factor may be decomposed in the product of three other factors EHS, Eel and Ead which account for, respectively, hard-sphere size exclusion, electrostatic interactions, and specific solute adsorption. While EHS and Eel are close to 1, Ead>1 in all cases suggesting strong specific interactions between the drugs and the hydrogels. Adsorption was maximal for chlorhexidine on the silicone based hydrogel, in water, due to strong hydrogen bonding. The effective diffusion coefficients, De, were determined from the drug release profiles. Estimations of diffusion coefficients of the non-adsorbed solutes D=De×Ead allowed comparison with theories for solute diffusion in the absence of specific interaction with the polymeric membrane.

  2. Drug-sensing hydrogels for the inducible release of biopharmaceuticals

    Science.gov (United States)

    Ehrbar, Martin; Schoenmakers, Ronald; Christen, Erik H.; Fussenegger, Martin; Weber, Wilfried

    2008-10-01

    Drug-dependent dissociation or association of cellular receptors represents a potent pharmacologic mode of action for regulating cell fate and function. Transferring the knowledge of pharmacologically triggered protein-protein interactions to materials science will enable novel design concepts for stimuli-sensing smart hydrogels. Here, we show the design and validation of an antibiotic-sensing hydrogel for the trigger-inducible release of human vascular endothelial growth factor. Genetically engineered bacterial gyrase subunit B (GyrB) (ref. 4) coupled to polyacrylamide was dimerized by the addition of the aminocoumarin antibiotic coumermycin, resulting in hydrogel formation. Addition of increasing concentrations of clinically validated novobiocin (Albamycin) dissociated the GyrB subunits, thereby resulting in dissociation of the hydrogel and dose- and time-dependent liberation of the entrapped protein pharmaceutical VEGF121 for triggering proliferation of human umbilical vein endothelial cells. Pharmacologically controlled hydrogels have the potential to fulfil the promises of stimuli-sensing materials as smart devices for spatiotemporally controlled delivery of drugs within the patient.

  3. The Controlled-releasing Drug Implant based on the Three Dimensional Printing Technology:Fabrication and Properties of Drug Releasing in vivo

    Institute of Scientific and Technical Information of China (English)

    WU Weigang; ZHENG Qixin; GUO Xiaodong; HUANG Weidong

    2009-01-01

    Three dimensional(3D)printing technology was utilized to fabricate a new type of drug implant with complicated architectures,employing levofloxacin(LVFX)and rifampicine(RFP) as model drugs.The prepared drug implant prototype consists of a double-layer structure,of which the upper region is a reservoir system containing RFP and the lower region is a matrix one containing LVFX.The release test in vivo revealed that LVFX was released in the early stage;no RFP was de-tected until 8th day;both of them continuously released more than 6 weeks.Therefore,3D printing technology provides a precise and feasible method to fabricate a controlled-releasing drug implant with complicated architectures and this drug implant may present a new strategy for the prophylaxis and treatment of bone diseases such as combined bone infections and bone tuberculosis in the near future.

  4. Comparator pH study to evaluate the single-dose pharmacodynamics of dual delayed-release dexlansoprazole 60 mg and delayed-release esomeprazole 40 mg

    Directory of Open Access Journals (Sweden)

    Kukulka M

    2011-09-01

    Full Text Available Michael Kukulka1, Corey Eisenberg2, Sai Nudurupati31Clinical Pharmacology, 2Clinical Science, 3Statistics, Takeda Global Research & Development Center Inc, Deerfield, IL, USABackground: This paper describes a Phase 1, single-center, randomized, open-label, two-period crossover study which compared the pharmacodynamic effects of single doses of dexlansoprazole modified-release 60 mg and esomeprazole 40 mg on 24-hour intragastric pH in healthy adult subjects.Methods: Forty-four subjects aged 20–54 years were randomized in a 1:1 ratio to two sequence groups defining the order in which they received dexlansoprazole and esomeprazole in periods 1 and 2. Primary pharmacodynamic end points over 24 hours postdose were percentage of time with intragastric pH > 4 and mean pH, and secondary pharmacodynamic end points were percentage of time intragastric pH > 4, and mean pH at 0–12 hours, and at >12–24 hours postdose. Each drug was given after an overnight fast and one hour before breakfast. Continuous pH recording began immediately before dosing through to 24 hours postdose.Results: At 0–24 hours postdose, the mean percentage of time with pH > 4 for dexlansoprazole and esomeprazole was 58% and 48%, respectively; the difference was statistically significant (P = 0.003. The average of mean pH values at 0–24 hours postdose for dexlansoprazole and esomeprazole were 4.3 and 3.7, respectively; the difference was statistically significant (P < 0.001. At >12–24 hours postdose, mean percentage of time with pH > 4 and average of mean pH were greater for dexlansoprazole (60% and 4.5, respectively compared with esomeprazole (42% and 3.5, respectively; the difference was statistically significant (P < 0.001 for both intervals. At 0–12 hours postdose, the difference in dexlansoprazole and esomeprazole values for the pharmacodynamic end points was not statistically significant.Conclusion: For the entire 24-hour postdose period, predominantly resulting from

  5. Tailored beads made of dissolved cellulose - Investigation of their drug release properties

    DEFF Research Database (Denmark)

    Yildir, Emrah; Kolakovic, Ruzica; Genina, Natalja;

    2013-01-01

    In the frame of this work, we have investigated drug entrapping and release abilities of new type of porous cellulose beads (CBs) as a spherical matrix system for drug delivery. For that purpose, CBs prepared with three different methods were used as drug carriers and three compounds, anhydrous...... efficacy. Also, the drug release rates were controlled by solubility of model drugs (diffusion controlled release). In conclusion, CBs from dissolved cellulose show promise in achieving controlled drug delivery. © 2013 Elsevier B.V. All rights reserved....

  6. Studies on pectins as potential hydrogel matrices for controlled-release drug delivery.

    Science.gov (United States)

    Sungthongjeen, S; Pitaksuteepong, T; Somsiri, A; Sriamornsak, P

    1999-12-01

    Polymeric hydrogels are widely used as controlled-release matrix tablets. In the present study, we investigated high-methoxy pectins for their potential value in controlled-release matrix formulations. The effects of compression force, ratio of drug to pectin, and type of pectin on drug release from matrix tablets were also investigated. The results of the in vitro release studies show that the drug release from compressed matrix tablets prepared from pectin can be modified by changing the amount and the type of pectin in the matrix tablets. However, compression force did not significantly affect the drug release. The mechanisms controlling release rate were discussed with respect to drug diffusion through the polymer matrices, but may be more complex.

  7. Magnetothermal release of payload from iron oxide/silica drug delivery agents

    Science.gov (United States)

    Luong, T. T.; Knoppe, S.; Bloemen, M.; Brullot, W.; Strobbe, R.; Locquet, J.-P.; Verbiest, T.

    2016-10-01

    The release of covalently bound Rhodamine B from iron oxide/mesoporous silica core/shell nanoparticles under magnetically induced heating was studied. The system acts as a model to study drug delivery and payload release under magnetothermal heating.

  8. Effect of carboxymethylation on rheological and drug release characteristics of locust bean gum matrix tablets.

    Science.gov (United States)

    Chakravorty, Amrita; Barman, Gouranga; Mukherjee, Sudipta; Sa, Biswanath

    2016-06-25

    This study was undertaken to investigate correlation between the carboxymethylation-induced rheological changes and drug release characteristics of locust bean gum (LBG) matrix tablets. LBG was derivatized to carboxymethyl LBG (CMLBG) and characterized by (13)C NMR, FTIR and elemental analyses. Rheological studies revealed that LBG, in contact with water, produced a strong elastic gel which swelled less due to lower penetration of water resulting in slower drug release. On the other hand, CMLBG formed a viscous polymer solution through which higher influx of water resulted in rapid swelling of the matrix and faster drug release. Although the release from a particular matrix was dependent on drugs' solubilities, CMLBG matrix tablet produced faster release of all the drugs than LBG matrix tablets. In conclusion, rheological study appeared to be an useful tool to predict release of drugs from polysaccharide matrix tablets.

  9. Management of gastroesophageal reflux disease and erosive esophagitis in pediatric patients: Focus on delayed-release esomeprazole

    Directory of Open Access Journals (Sweden)

    Elizabet V Guimarães

    2010-10-01

    Full Text Available Elizabet V Guimarães, Paula VP Guerra, Francisco J PennaDepartment of Pediatrics, Medical School, Universidade Federal de Minas Gerais, Belo Horizonte, BrazilObjective: To review the literature on the treatment of gastroesophageal reflux disease (GERD with emphasis on proton pump inhibitors (PPIs, particularly on delayed-release esomeprazole, and to identify properties and adverse effects of PPIs observed in the treatment of GERD in children and adolescents.Sources: Electronic search of PubMed/Medline and Cochrane Collaboration databases, and of abstracts on DDW, NASPGHAN, and ESPGHAN. We focused on controlled and randomized studies published since 2000 and identified reviews that presented a consensual position, and directives published within the last 10 years.Main results: PPIs are considered better antisecretory agents than H2-receptor antagonists. Although all PPIs are similar, they are not identical in their pharmacologic properties. For example, the acid-suppressive effect of esomeprazole, the S-isomer of omeprazole, persists for more than 16 hours after administration of the morning dose. Therefore, it can control acidity after night meals better than a single dose of omeprazole. Moreover, the onset of the suppressive effect of esomeprazole is faster. It achieves acid inhibition faster than other PPIs.Conclusion: Currently, the mainstream treatment for GERD in children is a PPI. Although PPIs are safe drugs, effective in healing erosive esophagitis, and in relieving symptoms, studies with esomeprazole have shown that this drug has as powerful an ability to inhibit acid secretion as omeprazole. It also seems that some pharmacologic properties of esomeprazole are actually better for the treatment of GERD.Keywords: gastroesophageal reflux, therapy, child, adolescent.

  10. Synthetic Zeolites as Controlled-Release Delivery Systems for Anti-Inflammatory Drugs.

    Science.gov (United States)

    Khodaverdi, Elham; Soleimani, Hossein Ali; Mohammadpour, Fatemeh; Hadizadeh, Farzin

    2016-06-01

    Scientists have always been trying to use artificial zeolites to make modified-release drug delivery systems in the gastrointestinal tract. An ideal carrier should have the capability to release the drug in the intestine, which is the main area of absorption. Zeolites are mineral aluminosilicate compounds with regular structure and huge porosity, which are available in natural and artificial forms. In this study, soaking, filtration and solvent evaporation methods were used to load the drugs after activation of the zeolites. Weight measurement, spectroscopy FTIR, thermogravimetry and scanning electronic microscope were used to determine drug loading on the systems. Finally, consideration of drug release was made in a simulated gastric fluid and a simulated intestinal fluid for all matrixes (zeolites containing drugs) and drugs without zeolites. Diclofenac sodium (D) and piroxicam (P) were used as the drug models, and zeolites X and Y as the carriers. Drug loading percentage showed that over 90% of drugs were loaded on zeolites. Dissolution tests in stomach pH environment showed that the control samples (drug without zeolite) released considerable amount of drugs (about 90%) within first 15 min when it was about 10-20% for the matrixes. These results are favorable as NSAIDs irritate the stomach wall and it is ideal not to release much drugs in the stomach. Furthermore, release rate of drugs from matrixes has shown slower rate in comparison with control samples in intestine pH environment.

  11. Cationic vesicles based on biocompatible diacyl glycerol-arginine surfactants: physicochemical properties, antimicrobial activity, encapsulation efficiency and drug release.

    Science.gov (United States)

    Tavano, L; Pinazo, A; Abo-Riya, M; Infante, M R; Manresa, M A; Muzzalupo, R; Pérez, L

    2014-08-01

    Physicochemical characteristics of cationic vesicular systems prepared from biocompatible diacyl glycerol-arginine surfactants are investigated. These systems form stable cationic vesicles by themselves and the average diameter of the vesicles decreases as the alkyl chain length of the surfactant increases. The addition of DPPC also modifies the physicochemical properties of these vesicles. Among the drugs these cationic formulations can encapsulate, we have considered Ciprofloxacin and 5-Fluorouracil (5-FU). We show that the percentage of encapsulated drug depends on both the physicochemical properties of the carrier and the type of drug. The capacity of these systems to carry different molecules was evaluated performing in vitro drug release studies. Finally, the antimicrobial activity of empty and Ciprofloxacin-loaded vesicles against Gram-positive and Gram-negative bacteria has been determined. Three bacteria were tested: Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. The in vitro drug release from all formulations was effectively delayed. Empty cationic vesicles showed antimicrobial activity and Ciprofloxacin-loaded vesicles showed similar or higher antimicrobial activity than the free drug solution. These results suggest that our formulations represent a great innovation in the pharmaceutical field, due to their dual pharmacological function: one related to the nature of the vehiculated drug and the other related to the innate antibacterial properties of the surfactant-based carriers.

  12. Physicochemical characterization of liposomes after ultrasound exposure - mechanisms of drug release

    DEFF Research Database (Denmark)

    Evjen, Tove J; Hupfeld, Stefan; Barnert, Sabine

    2013-01-01

    Ultrasound is investigated as a novel drug delivery tool within cancer therapy. Non-thermal ultrasound treatment of solid tumours post i.v.-injection of drug-carrying liposomes may induce local drug release from the carrier followed by enhanced intracellular drug uptake. Recently, ultrasound......-mediated drug release of liposomes (sonosensitivity) was shown to strongly depend on liposome membrane composition. In the current study the ultrasound-mediated drug release mechanism of liposomes was investigated. The results showed that differences in ultrasound drug release kinetics obtained for different...... liposomal compositions were caused by distinctive release mechanisms of the carriers. Two types of liposomes composed of 1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine (DOPE) and hydrogenated soy L-α-phosphatidylcholine (HSPC) as main lipids, respectively, were recently shown to vary in sonosensitivity...

  13. Controlled release of an anti-cancer drug from DNA structured nano-films

    Science.gov (United States)

    Cho, Younghyun; Lee, Jong Bum; Hong, Jinkee

    2014-02-01

    We demonstrate the generation of systemically releasable anti-cancer drugs from multilayer nanofilms. Nanofilms designed to drug release profiles in programmable fashion are promising new and alternative way for drug delivery. For the nanofilm structure, we synthesized various unique 3-dimensional anti cancer drug incorporated DNA origami structures (hairpin, Y, and X shaped) and assembled with peptide via layer-by-layer (LbL) deposition method. The key to the successful application of these nanofilms requires a novel approach of the influence of DNA architecture for the drug release from functional nano-sized surface. Herein, we have taken first steps in building and controlling the drug incorporated DNA origami based multilayered nanostructure. Our finding highlights the novel and unique drug release character of LbL systems in serum condition taken full advantages of DNA origami structure. This multilayer thin film dramatically affects not only the release profiles but also the structure stability in protein rich serum condition.

  14. Neutrophilia and an Anti-Inflammatory Drug as Markers of Inflammation in Delayed Muscle Soreness.

    Science.gov (United States)

    Smith, Lucille L.; And Others

    This study reexamined the concept that delayed muscle soreness (DMS) is a form of inflammatory pain. This was accomplished by having 32 male volunteers perform exercise known to induce DMS and then assess the total and differential white blood cell changes. In addition, an anti-inflammatory drug, idomethacin, was administered to determine whether…

  15. Drug-loaded electrospun mats of poly(vinyl alcohol) fibres and their release characteristics of four model drugs

    Science.gov (United States)

    Taepaiboon, Pattama; Rungsardthong, Uracha; Supaphol, Pitt

    2006-05-01

    Mats of PVA nanofibres were successfully prepared by the electrospinning process and were developed as carriers of drugs for a transdermal drug delivery system. Four types of non-steroidal anti-inflammatory drug with varying water solubility property, i.e. sodium salicylate (freely soluble in water), diclofenac sodium (sparingly soluble in water), naproxen (NAP), and indomethacin (IND) (both insoluble in water), were selected as model drugs. The morphological appearance of the drug-loaded electrospun PVA mats depended on the nature of the model drugs. The 1H-nuclear magnetic resonance results confirmed that the electrospinning process did not affect the chemical integrity of the drugs. Thermal properties of the drug-loaded electrospun PVA mats were analysed by differential scanning calorimetry and thermogravimetric analysis. The molecular weight of the model drugs played a major role on both the rate and the total amount of drugs released from the as-prepared drug-loaded electrospun PVA mats, with the rate and the total amount of the drugs released decreasing with increasing molecular weight of the drugs. Lastly, the drug-loaded electrospun PVA mats exhibited much better release characteristics of the model drugs than drug-loaded as-cast films.

  16. Utilization of posaconazole oral suspension or delayed-released tablet salvage treatment for invasive fungal infection.

    Science.gov (United States)

    Kim, Jong Hun; Benefield, Russell J; Ditolla, Kali

    2016-11-01

    Posaconazole may be useful for salvage treatment (ST) for invasive fungal infections (IFIs). The aim of this study was to evaluate the efficacy of posaconazole ST with either posaconazole oral suspension (SUS) or delayed-released tablet (TAB) in patients with IFI. A retrospective review of patients who received posaconazole ST for IFI at the University of Utah Health Sciences Center between December 2007 and March 2014 was conducted. A total of 14 episodes of posaconazole ST for proven (9 episodes) and probable (5 episodes) IFI were identified in 14 patients. The median age was 54 years and the majority of patients (64.3%) had underlying haematological diseases. Posaconazole SUS and TAB were used in 11 episodes and 3 episodes respectively. The duration of posaconazole ST ranged from 28 to 370 days with a median of 65 days. Posaconazole ST with TAB achieved favourable serum posaconazole trough concentrations (median 1.4 μg mL(-1) ) compared to posaconazole SUS (median 1.0 μg mL(-1) ). The overall clinical success rate with posaconazole ST was 71.4% (10 of 14 episodes). One patient died of progression of IFI. Adverse events were noted in two patients. Posaconazole SUS or TAB may be used effectively for IFI ST.

  17. Temporal control of drug release from biodegradable polymer: multicomponent diclofenac sodium releasing PLGA 80/20 rod.

    Science.gov (United States)

    Nikkola, Lila; Viitanen, Petrus; Ashammakhi, Nureddin

    2009-05-01

    In our previous studies we have reported on the development of diclofenac sodium (DS) releasing rods. However, their drug release profiles were unsatisfactory. To enhance the drug release properties of the implant, we have developed a system whereby various elements can be combined into one implant. Melt extruded, self-reinforced (SR), and sterilized (S) DS-containing SR-PLGA 80/20 billets were combined to produce multicomponent implants with various compositions. These components were basically heat pressed together to form multicomponent rods. Drug release from single component and multicomponent rods was defined using a UV-Vis spectrophotometer. DS was released from individual components within 82-111 days and from multicomponent rods within 50-70 days. Thermal properties were analyzed using differential scanning calorimetry (DSC). The melting temperature (T(m)) of multicomponent implants was about 157 degrees C, change in heat fusion (DeltaH) was 13.3 J/g, and the glass transition temperature (T(g)) was 55.4 degrees C. Mechanical strength was measured for 2 weeks and it decreased from 55 to 15 MPa. In conclusion, by compression molding three components with different release rates it is possible to control the temporal release from multicomponent rods. Released DS concentrations were within range for 49-74 days depending on the fractions of individual components used.

  18. Understanding release kinetics of biopolymer drug delivery microcapsules for biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Desai, Salil, E-mail: sdesai@ncat.ed [Department of Industrial and Systems Engineering, North Carolina A and T State University, NC 27411 (United States); Center for Advanced Materials and Smart Structures, North Carolina A and T State University, Greensboro, NC 27411 (United States); Wake Forest University Institute for Regenerative Medicine, Winston-Salem, NC 27157 (United States); Perkins, Jessica [Department of Industrial and Systems Engineering, North Carolina A and T State University, NC 27411 (United States); Center for Advanced Materials and Smart Structures, North Carolina A and T State University, Greensboro, NC 27411 (United States); Harrison, Benjamin S. [Wake Forest University Institute for Regenerative Medicine, Winston-Salem, NC 27157 (United States); Sankar, Jag [Center for Advanced Materials and Smart Structures, North Carolina A and T State University, Greensboro, NC 27411 (United States)

    2010-04-15

    Drug delivery and dosage concentrations are considered as major focal points in conventional as well as battlefield emergency medicine. The concept of localizing drug delivery via microcapsules is an evolving field to confine the adverse side effects of high concentration drug doses. This paper focuses on understanding release kinetics through biopolymer microcapsules for time-dependent drug release. Calcium alginate microcapsules were manufactured using a direct-write inkjet technique. Rhodamine 6G was used as the release agent to observe the release kinetics from calcium alginate beads in distilled water. A design of experiments was constructed to compare the effect of the microcapsule diameter and different concentrations of calcium chloride (M) and sodium alginate (%, w/v) solutions on the release kinetics profiles of the microcapsules. This research gives insight to identify favorable sizes of microcapsules and concentrations of sodium alginate and calcium chloride solutions for controlled release behavior of drug delivery microcapsules.

  19. Effect of drug physicochemical properties on drug release and their relationship with drug skin permeation behaviors in hydroxyl pressure sensitive adhesive.

    Science.gov (United States)

    Liu, Chao; Quan, Peng; Fang, Liang

    2016-10-10

    The aim of this study was to investigate the influence of drug physicochemical properties on drug release behaviors and their relationship with skin permeation behaviors, which provided transdermal enhancement strategies for the design of transdermal drug delivery system. Six model drugs with different physicochemical properties were selected and hydroxyl pressure sensitive adhesive (PSA) was synthesized. Horizontal diffusion cell was used to evaluate drug release and skin permeation behaviors. The relationship between physicochemical properties and release behaviors was conducted with regression analysis. Release behavior of 0.25% drug loading was linear related with polar surface area, which represented the hydrogen bond. Release behavior of 2.0% drug loading was dependent on the polarizability and log P, which represented dipole-dipole interaction and lipophilicity, respectively. According to the results of Fourier transform infrared spectroscopy, it was inferred that hydrogen bond was limited in controlling release of drug due to the limited quantity of bonding site, thus dipole-dipole interaction and log P became dominate control factors. Combining the drug release study and drug skin permeation study, it was concluded that drugs with different physicochemical properties should be applied with different transdermal enhancement strategies, which was useful for the design of transdermal drug delivery system. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. A mathematical model to predict the release of water-soluble drugs from HPMC matrices.

    Science.gov (United States)

    Fu, X C; Wang, G P; Fu, C Y; Liang, W Q

    2004-09-01

    A mathematical model to predict the fraction of water-soluble drug released as a function of release time (t, h), HPMC concentration (CH, w/w), and volume of drug molecule (V, nm3) was derived with ranitidine hydrochloride, diltiazem hydrochloride, and ribavirin as model drugs. The model is log (M(t)/M(infinity)) = 0.5 log t-0.3322CH-0.2222V-0.2988 (n = 140, r = 0.9848), where M(t) is the amount of drug released at time t, M(infinity) is the amount of drug released over a very long time, which corresponds in principle to the initial loading, n is the number of samples, and r is the correlation coefficient. The model was validated using isoniazid and satisfactory results were obtained. The model can be used to predict the release fraction of various soluble drugs from HPMC matrices having different polymer levels.

  1. Enzyme-triggered nanomedicine: Drug release strategies in cancer therapy (Invited Review)

    DEFF Research Database (Denmark)

    Andresen, Thomas Lars; Thompson, David H.; Kaasgaard, Thomas

    2010-01-01

    of drugs to obtain a slow drug leakage from the formulations after accumulation in the cancerous site. However, this strategy is only applicable to a relatively small range of drugs and cannot be applied to biologicals. Many advanced drug release strategies have therefore been investigated. Such strategies...... field, but the concepts and conclusions are equally important for polymer-based systems....

  2. Simultaneous monitoring of the drug release and antitumor effect of a novel drug delivery system-MWCNTs/DOX/TC.

    Science.gov (United States)

    Dong, Xia; Sun, Zhiting; Wang, Xiaoxiao; Zhu, Dunwan; Liu, Lanxia; Leng, Xigang

    2017-11-01

    Monitoring drug release and therapeutic efficacy is crucial for developing drug delivery systems. Our preliminary study demonstrated that, as compared with pristine multiwalled carbon nanotubes (MWCNTs), transactivator of transcription (TAT)-chitosan functionalized MWCNTs (MWCNTs-TC) were a more promising candidate for drug delivery in cancer therapy. In the present study, a MWCNTs/TC-based drug delivery system was developed for an anticancer drug, doxorubicin (DOX). The drug loading and in vitro release profiles, cellular uptake and cytotoxicity were assessed. More importantly, the in vivo drug release and antitumor effect of MWCNTs/DOX/TC were evaluated by noninvasive fluorescence and bioluminescence imaging. It was demonstrated that MWCNTs/DOX/TC can be efficiently taken up by BEL-7402 hepatoma cells. The release of DOX from MWCNTs/DOX/TC was faster under lower pH condition, which was beneficial for intrcellular drug release. The in vivo release process of DOX and antitumor effect in animal model were monitored simultaneously by noninvasive fluorescence and luminescence imaging, which demonstrated the application potential of MWCNTs/DOX/TC for cancer therapy.

  3. Modulating pH-independent release from coated pellets: effect of coating composition on solubilization processes and drug release.

    Science.gov (United States)

    Ensslin, Simon; Moll, Klaus Peter; Metz, Hendrik; Otz, Markus; Mäder, Karsten

    2009-05-01

    The aim of the study was to clarify the influences of three coating parameters on the drug release from chlorpheniramine maleate (CPM) pellets, coated with blends of poly(vinyl acetate) (PVAc) and poly(vinyl alcohol)-poly(ethylene glycol) (PVA-PEG) graft copolymer. A central composite design was implemented to investigate the effect of the polymer blend ratio, the film coat thickness and the plasticizer concentration on the drug release. The solubilization inside the pellets was monitored by EPR spectroscopy. The blending ratio of both the polymers and the film thickness were found to have a major influence on the drug release and the solubilization speed, in contrast to the plasticizer concentration. A pH-independent release profile was adjustable via modulating the polymer blend ratio and the coating thickness. A mathematical model was developed, providing a good predictability of the release profile, based on the film coat composition. This model offers the possibility to achieve a defined drug-release profile by selective adaptation of the film coat composition, in view of process times, feasibility or polymer costs.

  4. Investigation and Optimization of the Effect of Polymers on Drug Release of Norfloxacin from Floating Tablets.

    Science.gov (United States)

    Gadade, Dipak D; Sarda, Kalpana; Shahi, Sadhana R

    2016-01-01

    Norfloxacin is fluoroquinolone anti-infective used in the treatment of urinary tract infections, prostatitis, gonorrhea and genital tract infections. It has plasma half life of 3 to 4 h requiring multiple dosing in the treatment. Releaseretarding polymers can be used to modulate the drug release of norfloxacin. The objective of this study was to investigate the effect of release-retarding polymers on the drug release of norfloxacin from floating tablets. Norfloxacin was procured as a gift sample from Concept Pharma Ltd. Aurangabad (India) and HPMC K100M was procured as a gift sample from Colorcon Asia Pvt. Ltd., Goa (India). The tablets were prepared by direct compression method and various pharmaceutical parameters were evaluated. It was observed that all tablet formulations F1-F9 retained the drug release up to 12 h with good floating property but only Batch-F4 complies with the USP dissolution limits with a minimum floating lag time. The drug release kinetics were evaluated by the model-dependent (curve fitting) method using PCP Disso v3 software shows Batch-F4 shows to best fit with Peppas model for which R2 value was 0.9921 and the release exponent value was 0.6892. The drug release kinetics study indicates that the floating tablets release the drug by diffusion followed by erosion mechanism. Obtained in-vitro drug release data was analyzed by design expert software for drug release at first hour and at 12th h values and found that release the selected independent variables like HPMC K100M and sodium alginate concentration has a significant effect on drug release.

  5. Superior Serum Concentrations with Posaconazole Delayed-Release Tablets Compared to Suspension Formulation in Hematological Malignancies.

    Science.gov (United States)

    Cumpston, Aaron; Caddell, Ryan; Shillingburg, Alexandra; Lu, Xiaoxiao; Wen, Sijin; Hamadani, Mehdi; Craig, Michael; Kanate, Abraham S

    2015-08-01

    Posaconazole (PCZ), approved for prophylaxis against invasive fungal disease in high-risk patients, is commercially available orally as a suspension formulation (PCZ-susp) and as a delayed-release tablet (PCZ-tab). We evaluated the serum steady-state concentrations (Css) of PCZ stratified by the administered formulation for antifungal prophylaxis in patients with myeloid malignancies (n = 150). The primary outcome was the attainment rate of the target Css of ≥700 ng/ml. Secondary outcomes included toxicity assessment (hepatotoxicity and corrected QT [QTc] interval prolongation) and breakthrough fungal infections. Patients who received the PCZ-susp (n = 118) or PCZ-tab (n = 32) and had PCZ Css assessment after at least 7 days of therapy were eligible. The median Css in the PCZ-susp group was 390 ng/ml (range, 51 to 1,870 ng/ml; mean, 436 ng/ml) compared to 1,740 ng/ml (range, 662 to 3,350 ng/ml; mean, 1,781 ng/ml) in the PCZ-tab group (P < 0.0001). The percentages of patients achieving the target goal of ≥700 ng/ml were 17% versus 97%, respectively (P < 0.0001). Hepatotoxicity (grade 2 or higher) occurred in 1 patient in each group. QTc interval measurements were available for 32 patients in the PCZ-susp group and for 12 patients in the PCZ-tab group, and prolonged intervals of grade 2 or higher were noted in 9% (n = 3) and 17% (n = 2), respectively (P = 0.6). Breakthrough fungal infections in the PCZ-susp and PCZ-tab groups were 7% (n = 8) and 3% (n = 1), respectively (P = 0.68). We conclude that the use of PCZ-tab was associated with higher Css and with the probability of achieving therapeutic goals without worsening of adverse effects.

  6. Drug Release Properties of a Series of Adenine-Based Metal-Organic Frameworks.

    Science.gov (United States)

    Oh, Hyojae; Li, Tao; An, Jihyun

    2015-11-16

    The drug uptake and release properties of a series of biomolecule-based metal-organic frameworks (bMOF-1, bMOF-4, bMOF-100, and bMOF-102) have been studied. The bMOFs were loaded with the small molecule etilefrine hydrochloride and release profiles were collected in both Nanopure water and simulated body fluid (SBF). Each bMOF exhibited an initial burst of drug release at the initial stages of the experiment followed by a gradual release of the remaining drug molecules over time. bMOF-1 released 50% of the drug after 15 days and complete release at 80 days in SBF. bMOF-4 released 50% of the drug within two days and complete release at 49 days in SBF. bMOF-100 and bMOF-102 released 50% of the drug after 4 h and complete release at 69 and 54 days in SBF, respectively.

  7. Changes in the drug release pattern of fresh and set simvastatin-loaded brushite cement.

    Science.gov (United States)

    Mestres, Gemma; Kugiejko, Karol; Pastorino, David; Unosson, Johanna; Öhman, Caroline; Karlsson Ott, Marjam; Ginebra, Maria-Pau; Persson, Cecilia

    2016-01-01

    Calcium phosphate cements are synthetic bone graft substitutes able to set at physiological conditions. They can be applied by minimally invasive surgery and can also be used as drug delivery systems. Consequently, the drug release pattern from the cement paste (fresh cement) is of high clinical interest. However, previous studies have commonly evaluated the drug release using pre-set cements only. Therefore, the aim of this work was to determine if the time elapsed from cement preparation until immersion in the solution (3 min for fresh cements, and 1h and 15 h for pre-set cements) had an influence on its physical properties, and correlating these to the drug release profile. Simvastatin was selected as a model drug, while brushite cement was used as drug carrier. This study quantified how the setting of a material reduces the accessibility of the release media to the material, thus preventing drug release. A shift in the drug release pattern was observed, from a burst-release for fresh cements to a sustained release for pre-set cements.

  8. Design of cationic microspheres based on aminated gelatin for controlled release of peptide and protein drugs.

    Science.gov (United States)

    Morimoto, Kazuhiro; Chono, Sumio; Kosai, Tadashi; Seki, Toshinobu; Tabata, Yasuhiko

    2008-02-01

    Two different types of cationized microspheres based on a native cationic gelatin (NGMS) and aminated gelatin with ethylendiamine (CGMS) were investigated for the controlled release of three model acidic peptide/protein drugs with different molecular weights (MWs) and isoelectric points (IEPs). Recombinant human (rh)-insulin (MW: 5.8 kDa, IEP: 5.3), bovine milk lactoalbumin, BMLA (MW: 14 kDa, IEP: 4.3), and bovine serum albumin (BSA MW: 67 kDa, IEP: 4.9) were used as model acidic peptide/protein drugs. The in vitro release profiles of these acidic peptide/protein drugs from NGMS and CGMS were compared and different periods of cross-linking were obtained. The slower release of these acidic peptide/protein drugs from CGMS compared with those from NGMS with cross-linking for 48 hr. was caused by the suppression of burst release during the initial phase. The degree of suppression of burst release of the three peptide/protein drugs during the initial phase by CGMS was in the following order: (rh)-insulin > BMLA > BSA. The release of insulin with a lower molecular weight from CGMS was particularly suppressed compared with the other two drugs with higher molecular weights in the initial phase. The control of the release rate of acidic peptide/protein drugs from gelatin microsphere can be achieved by amination of gelatin. Therefore, CGMS is useful for the controlled release of acidic peptide/ protein drugs.

  9. Modulating drug release from gastric-floating microcapsules through spray-coating layers.

    Directory of Open Access Journals (Sweden)

    Wei Li Lee

    Full Text Available Floating dosage forms with prolonged gastric residence time have garnered much interest in the field of oral delivery. However, studies had shown that slow and incomplete release of hydrophobic drugs during gastric residence period would reduce drug absorption and cause drug wastage. Herein, a spray-coated floating microcapsule system was developed to encapsulate fenofibrate and piroxicam, as model hydrophobic drugs, into the coating layers with the aim of enhancing and tuning drug release rates. Incorporating fenofibrate into rubbery poly(caprolactone (PCL coating layer resulted in a complete and sustained release for up to 8 h, with outermost non-drug-holding PCL coating layer serving as a rate-controlling membrane. To realize a multidrug-loaded system, both hydrophilic metformin HCl and hydrophobic fenofibrate were simultaneously incorporated into these spray-coated microcapsules, with metformin HCl and fenofibrate localized within the hollow cavity of the capsule and coating layer, respectively. Both drugs were observed to be completely released from these coated microcapsules in a sustained manner. Through specific tailoring of coating polymers and their configurations, piroxicam loaded in both the outer polyethylene glycol and inner PCL coating layers was released in a double-profile manner (i.e. an immediate burst release as the loading dose, followed by a sustained release as the maintenance dose. The fabricated microcapsules exhibited excellent buoyancy in simulated gastric fluid, and provided controlled and sustained release, thus revealing its potential as a rate-controlled oral drug delivery system.

  10. Investigation of Drug Release from PEO Tablet Matrices in the Presence of Vitamin E as Antioxidant.

    Science.gov (United States)

    Shojaee, Saeed; Nokhodchi, Ali; Cumming, Iain; Alhalaweh, Amjad; Kaialy, Waseem

    2015-01-01

    The objective of this study was to investigate the influence of drug type on the release of drug from PEO matrix tablets accompanied with the impact of vitamin E succinate as antioxidant. The result showed that the presence of vitamin E promoted a stable release rate of soluble drug propranolol HCl from aged PEO matrix tablets, which was similar to fresh sample, regardless of molecular weight (MW) of PEO. However, the influence of the presence of vitamin E on the release rate of partially soluble drug, theophylline, was dependent on the MW of PEO; i.e., fast and unstable drug release was obtained in the case of low MW PEO 750 whereas stable drug release was obtained in the case of high MW PEO 303. The release of low water-soluble drug zonisamide was stable regardless of both the presence of vitamin E and the MW of PEO. The presence of vitamin E slightly slowed the release of zonisamide from aged PEO 303 matrices but not PEO 750 matrices. Therefore, in order to achieve a suitable controlled release profile from PEO matrices, not only the presence of vitamin E but also the solubility of the drug and the MW of polyox should be considered.

  11. Modulating drug release from gastric-floating microcapsules through spray-coating layers.

    Science.gov (United States)

    Lee, Wei Li; Tan, Jun Wei Melvin; Tan, Chaoyang Nicholas; Loo, Say Chye Joachim

    2014-01-01

    Floating dosage forms with prolonged gastric residence time have garnered much interest in the field of oral delivery. However, studies had shown that slow and incomplete release of hydrophobic drugs during gastric residence period would reduce drug absorption and cause drug wastage. Herein, a spray-coated floating microcapsule system was developed to encapsulate fenofibrate and piroxicam, as model hydrophobic drugs, into the coating layers with the aim of enhancing and tuning drug release rates. Incorporating fenofibrate into rubbery poly(caprolactone) (PCL) coating layer resulted in a complete and sustained release for up to 8 h, with outermost non-drug-holding PCL coating layer serving as a rate-controlling membrane. To realize a multidrug-loaded system, both hydrophilic metformin HCl and hydrophobic fenofibrate were simultaneously incorporated into these spray-coated microcapsules, with metformin HCl and fenofibrate localized within the hollow cavity of the capsule and coating layer, respectively. Both drugs were observed to be completely released from these coated microcapsules in a sustained manner. Through specific tailoring of coating polymers and their configurations, piroxicam loaded in both the outer polyethylene glycol and inner PCL coating layers was released in a double-profile manner (i.e. an immediate burst release as the loading dose, followed by a sustained release as the maintenance dose). The fabricated microcapsules exhibited excellent buoyancy in simulated gastric fluid, and provided controlled and sustained release, thus revealing its potential as a rate-controlled oral drug delivery system.

  12. [Preparation and drug releasing property of curcumin nanoparticles].

    Science.gov (United States)

    Liu, Zhan-jun; Han, Gang; Yu, Jiu-gao; Dai, Hong-guang

    2009-02-01

    To prepare curcumin nanoparticles and evaluate the in vitro release of curcumin. The chitosan-graft-vinyl acetate copolymers were synthesized by free radical polymerization. Curcumin nanoparticles were synthesized by ultrasonic irradiation. The encapsulation efficiency of the nanoparticles and the in vitro release of curcumin were studied. The nanoparticles were discrete and uniform spheres, covered with positive charges. The encapsulation efficiency of nanoparticles was up to 91.6%. The in vitro release profile showed the slower release rate of curcumin. The methods is simple. The nanoparticles possess good physical performance and sustained release character in vitro.

  13. Grafting amino drugs to poly(styrene-alt-maleic anhydride) as a potential method for drug release

    Energy Technology Data Exchange (ETDEWEB)

    Khazaei, Ardeshir; Saednia, Shahnaz; Saien, Javad; Abbasi, Fatemeh, E-mail: Khazaei_1326@yahoo.com, E-mail: ssaednia@gmail.com [Faculty of Chemistry, Bu-Ali Sina University, Hamedan (Iran, Islamic Republic of); Kazem-Rostami, Masoud [Young Researchers Club and Elite, Takestan Branch, Islamic Azad University, Takestan (Iran, Islamic Republic of); Sadeghpour, Mahdieh [Department of Chemistry, Takestan Branch, Islamic Azad University, Takestan (Iran, Islamic Republic of); Borazjani, Maryam Kiani [Faculty of Science, Department of Chemistry, Bushehr Payame Noor University (PNU), Bushehr (Iran, Islamic Republic of)

    2013-07-15

    Drug delivery systems based on polymer-drug conjugates give an improved treatment with lower toxicity or side effects and be used for the treatment of different diseases. Conjugates of biodegradable poly(styrene-alt-maleic anhydride) (PSMA), with a therapeutic agents such as amantadine hydrochloride, amlodipine, gabapentin, zonisamide and mesalamine, were afforded by the formation of the amide bonds of the amino drugs that reacted with the PSMA anhydride groups. The amounts of covalently conjugated drugs were determined by a {sup 1}H NMR spectroscopic method, and the in vitro release rate in buffer solution (pH 1.3) was studied at body temperature 37 Degree-Sign C. In kinetic studies, different dissolution models were examined to obtain drug release data and the collected data were well-fitted to the Korsmeyer-Peppas equation, revealing a dominant Fickian diffusion mechanism for drug release under the in vitro conditions. (author)

  14. 1,25-Dihydroxyvitamin D3-glycoside of herbal origin exhibits delayed release pharmacokinetics when compared to its synthetic counterpart.

    Science.gov (United States)

    Bachmann, Heinrich; Offord-Cavin, Elizabeth; Phothirath, Phoukham; Horcajada, Marie-Noelle; Romeis, Peter; Mathis, Georg A

    2013-07-01

    Vitamin D requires two metabolic steps to become biologically active. In a first step 25-hydroxyvitamin D3 is formed, which acts as storage form. After a tightly controlled step in kidney the active metabolite 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is formed. Because kidney is the relevant metabolic organ for this conversion, 1,25(OH)2D3 needs to be supplemented in patients with kidney malfunction or kidney failure. Synthetic 1,25(OH)2D3 (calcitriol) has been available as a drug for decades. Due to its high potency and its kinetic profile (fast absorption and rapid elimination) its therapeutic windows has proven to be relatively narrow. A natural form of the active metabolite was identified in a few plants, such as Solanum glaucophyllum (SG) and suggested as alternative for animal and human health. An extract of a SG variety bred for high and uniform level of glycosylated 1,25(OH)2D3 was chemically characterized. Among the typical pharmaceutically inactive plant components (carbohydrates 54.3%, protein 24.9%, minerals 17.1% and water 4.1%) high levels of 1,25(OH)2D3 and a unique flavonoid content was found (1.11mg total quercetin/g extract) consisting exclusively of the quercetin glycosides hyperoside, isoquercetin, rutin and apinosylrutin. The molecular distribution of glycosyl moieties in 1,25(OH)2D3 extracted from SG as determined by gel permeation chromatography was found to be 1-10 hexose units per aglycone. 1,25(OH)2D3-1-β-glucopyranoside was identified in the SG extract, while a di- and triglycoside have been identified in SG by other groups. The pharmacokinetic properties of synthetic 1,25(OH)2D3 and glycosylated 1,25(OH)2D3 extracted from SG were compared in male rats. When compared to synthetic 1,25(OH)2D3, SG-derived 1,25(OH)2D3 exhibited delayed absorption and elimination characteristics, resulting in delayed Tmax (6-12h vs. 1h) and increased T½ (approximately 30h vs. 23h). This putative modified release pattern may be attributed to the glycosylation

  15. Preparation and drug release mechanism of CTS-TAX-NP-MSCs drug delivery system.

    Science.gov (United States)

    Dai, Tian; Yang, Enyun; Sun, Yongjun; Zhang, Linan; Zhang, Li; Shen, Ning; Li, Shuo; Liu, Lei; Xie, Yinghua; Wu, Shaomei; Gao, Zibin

    2013-11-01

    Targeting delivery of anticancer agents is a promising field in anticancer therapy. Inherent tumor-tropic and migratory properties of mesenchymal stem cells (MSCs) make them potential vehicles for targeting drug delivery systems for tumors. Although, MSCs have been successfully studied and discussed as a vehicle for cancer gene therapy, they have not yet been studied adequately as a potential vehicle for traditional chemical anticancer drugs. In this study, we have engineered MSCs as a potential targeting delivery vehicle for paclitaxel (TAX)-loaded nanoparticles (NPs). The size, surface charge, starving time of MSCs, incubating time and concentration of NPs could influence the efficiency of NPs uptake. In vitro release of TAX from CTS (chitosan)-TAX-NP-MSCs and the expression of P-glycoprotein demonstrated that release of TAX from MSCs might involve both passive diffusion and active transport. In vitro migration assays indicated that MSCs at passage number 3 have the highest migrating ability. Although, the migration ability of CTS-TAX-NP-MSCs could be inhibited by uptake of CTS-TAX-NPs, this ability could recover 6 days after the internalization.

  16. Quinoline based polymeric drug for biological applications: synthesis, characterization, antimicrobial, and drug releasing studies.

    Science.gov (United States)

    Uma, P; Suresh, J; Selvaraj, Revathy; Karthik, S; Arun, A

    2015-01-01

    Novel acrylate monomer of quinoline-based chalcone 1-(4-(7-chloroquinolin-4-ylamino)phenyl) acrylate (CPA) was synthesized using (4-(2-chloroquinolin-5-ylamino)phenyl)-3-(4-hydroxyphenyl)prop-2-en-1-one (CPE) and acryloyl chloride. CPA is characterized by different techniques like IR, (1)H NMR and UV-visible spectrometry techniques. Poly(CPA), poly(CPA-co-AA) and poly(CPA-co-HEA) are prepared by solution polymerization technique using CPA, acrylic acid (AA) and hydroxyethylacrylate (HEA), respectively. The antimicrobial activities of the compounds are tested using four different micro-organisms. In vitro cumulative drug release studies are done using UV visible spectroscopic technique. The molecular weights of these polymers are found to be around 5000 g/mol. The synthesized polymers showed two stages of thermal decomposition temperature centred around 220 and 350 °C, respectively. The antimicrobial activity of the polymer sample is found to be very high and especially for gram-negative bacteria with a minimum value of 3.91 μg/mL. The in vitro drug-releasing rate is dependent on the comonomer, pH and temperature of the medium.

  17. Comparative release studies of two cationic model drugs from different cellulose nanocrystal derivatives.

    Science.gov (United States)

    Akhlaghi, Seyedeh Parinaz; Tiong, Daryl; Berry, Richard M; Tam, Kam Chiu

    2014-09-01

    Native cellulose nanocrystal (CNC), oxidized CNC (CNC-OX) and chitosan oligosaccharide grafted CNC (CNC-CSOS) were evaluated as potential drug delivery carriers for two model drug compounds, procaine hydrochloride (PrHy) and imipramine hydrochloride (IMI). The loading of PrHy and IMI was performed at pH 8 and 7, respectively. IMI displayed higher binding to CNC derivatives than PrHy. Drug selective membranes were prepared for each model drug and a drug selective electrode system was used to measure the drug concentration in the filtrate and release medium. Isothermal Titration Calorimetry (ITC) was used to elucidate the types of interactions between model drugs and CNC and its derivatives. The complexation between model drugs and CNC derivatives was confirmed by zeta potential and transmittance measurements. The binding and release of these drugs correlated with the nature and types of interactions that exist between the CNC and drug molecules.

  18. Preparation and in vitro evaluation of sustained release drug delivery system for verapamil HCL

    Directory of Open Access Journals (Sweden)

    Bhalekar M

    2007-01-01

    Full Text Available Verapamil HCl is a calcium channel blocker administered on thrice a day dosage regimen. In the present study resinates of verapamil HCl were formulated using Indion resins. Drug loading process was optimized with respect to drug:resin ratio, pH of loading solution, and particle size of resin. Resinates were characterized using XRPD. In vitro drug release rates from resinate was not adequately sustained. Hence resinates were incorporated in pellets using extrusion spheronization to achieve desired release pattern. Optimum drug loading was seen at pH of 3.5 in drug resin ratio of 1:1 and was seen to increase with temperature. XRPD studies revealed verapamil to be present in amorphous form in resinates. Drug release from resinates was complete in four hours. Resinates were pelletized using hydroxypropylmethylcellulose. Resinate of Indion 254 with 5% hydroxypropylmethylcellulose fulfilled USP criteria for extended release verapamil preparation.

  19. Drug release from non-aqueous suspensions. II. The release of methylxanthines from paraffin suspensions

    NARCIS (Netherlands)

    Blaey, C.J. de; Fokkens, J.G.

    1984-01-01

    The release of 3 methylxanthines, i.e. caffeine, theobromine and theophylline, from suspensions in liquid paraffin to an aqueous phase was determined in an in vitro apparatus. The release rates were determined as a function of the pH of the aqueous phase. It was proved that the release process was n

  20. Retrospective Comparison of Posaconazole Levels in Patients Taking the Delayed-Release Tablet versus the Oral Suspension.

    Science.gov (United States)

    Durani, Urshila; Tosh, Pritish K; Barreto, Jason N; Estes, Lynn L; Jannetto, Paul J; Tande, Aaron J

    2015-08-01

    While posaconazole prophylaxis decreases the risk of invasive fungal infection compared to fluconazole, low bioavailability of the oral-suspension formulation limits its efficacy. A new delayed-release tablet formulation demonstrated an improved pharmacokinetic profile in healthy volunteers. However, serum levels for the two formulations have not been compared in clinical practice. This study compared achievement of therapeutic posaconazole levels in patients taking the delayed-release tablet to those taking the oral suspension. This retrospective cohort study included 93 patients initiated on posaconazole between 2012 and 2014 and had at least one serum posaconazole level measured. The primary measure was the proportion of patients achieving an initial therapeutic level (>700 ng/ml). An initial therapeutic posaconazole level was seen in 29 of 32 (91%) patients receiving tablets and 37 of 61 (61%) patients receiving suspension (P = 0.003). Among patients with a steady-state level measured 5 to 14 days after initiation, a therapeutic level was observed in 18 of 20 (90%) patients receiving tablets and 25 of 43 (58%) patients receiving suspension (P = 0.01). In these patients, the median posaconazole level of the tablet cohort (1655 ng/ml) was twice that of the suspension cohort (798 ng/ml) (P = 0.004). In this cohort study, the improved bioavailability of delayed-release posaconazole tablets translates into a significantly higher proportion of patients achieving therapeutic serum levels than in the cohort receiving the oral suspension. The results of this study strongly support the use of delayed-release tablets over suspension in patients at risk for invasive fungal infection.

  1. PCL films incorporated with paclitaxel/5-fluorouracil: Effects of formulation and spacial architecture on drug release.

    Science.gov (United States)

    Rong, Hao-Jun; Chen, Wei-Luan; Guo, Sheng-Rong; Lei, Lei; Shen, Yuan-Yuan

    2012-05-10

    The bi/tri-layered poly(ɛ-caprolactone) (PCL)-based films co-loaded with 5-fluorouracil (5-FU) and paclitaxel (PTX) are presented for biodegradable film-based stent application. A gradient elution HPLC analytical method was used for simultaneous quantification of 5-FU and PTX. Scanning electron microscopy (SEM) was performed to observe the microscopic architecture and morphologies, and X-ray diffraction (XRD) was employed for analyzing the physical state of the components in the single layer film. Horizontal cells diffusion test results indicated that the multi-layered structure endowed the film with drug release in unidirectional pattern. The in vitro release results showed that drug release was dependent on the drug loading, the ratio of 5-FU/PTX, the composition of surface layer, as well as the addition of hydrophilic PEG. The cytotoxicity results indicated that the PCL-based films co-loaded with 5-FU and PTX could effectively inhibit the proliferation of Eca-109 cells. The in vivo drug release results showed that the in vivo drug release was highly correlative with the in vitro drug releases. This study provided PCL-based films co-loaded with 5-FU and PTX with great potential for anti-tumor stent application, due to their unidirectional and rate-tunable drug release characteristics and dual drug loading capacity.

  2. A new proposal for drug conditioning with implications for drug addiction: the Pavlovian two-step from delay to trace conditioning.

    Science.gov (United States)

    Carey, Robert J; Carrera, Marinette Pinheiro; Damianopoulos, Ernest N

    2014-12-15

    Pavlovian conditioning of drug effects is generally acknowledged to be a critical factor in the development and persistence of drug addiction. In drug conditioning the focus has essentially been on one type of Pavlovian conditioning, namely, delay conditioning in which the CS and drug UCS overlap and are temporally contiguous. Another type of Pavlovian conditioning is trace-conditioning in which the CS terminates before the onset of the UCS. While trace conditioning has been extensively studied in conditioning studies using a punctual CS and a non-drug UCS, trace conditioning has not been considered as having a role in drug conditioning. In several recent reports we have conducted experiments in which we first established a contextual drug CS using a delay conditioning protocol and subsequently used this same CS in a trace drug conditioning protocol with the same or different drug treatment and showed that the CS could be strongly modified by trace conditioning. These observations take on importance in that it has been well established that delay and trace conditioning are mediated by different CNS systems. Delay conditioning is mediated by cerebellar mechanisms, conforming to the general idea of Pavlovian conditioning as a reflexive type of learning whereas trace conditioning involves the hippocampus and frontal cortex brain structures more commonly associated with voluntary behavior. In this proposal we suggest that the emergence of potent drug associations that motivate drug-seeking behavior and addiction are initiated by delay conditioning and subsequently amplified and linked to higher brain functions by trace conditioning.

  3. Coatings from blends of Eudragit® RL and L55: a novel approach in pH-controlled drug release.

    Science.gov (United States)

    Wulff, R; Leopold, C S

    2014-12-10

    The aim of the present study was to investigate the drug release from theophylline pellets coated with blends of quaternary polymethacrylate and methacrylic acid-ethyl acrylate copolymers. Pellets were coated with blends of Eudragit(®) RL PO (RL) and Eudragit(®) L 100-55 (L55) in either organic solution or aqueous dispersion at various copolymer ratios. Generally, the coatings were less permeable for theophylline in phosphate buffer pH 6.8 than they were in hydrochloric acid pH 1.2. Further dissolution experiments revealed that the differences in drug release are caused by the different pH values. A design of experiments for historical data was performed on drug release data of pellets with different coating levels and blend ratios of RL and L55. Drug release in hydrochloric acid was predominantly affected by the coating level, whereas for drug release in phosphate buffer pH 6.8 the blend ratio was the determining factor. As expected, dissolution experiments at different pH values showed that drug release depends on the ratio of dissociated L55 to RL because ionization is a requirement for the functional groups to interact. With the dissolution test for delayed-release solid dosage forms (Ph. Eur.) it was demonstrated that the unique release behavior in neutral media is preserved after the exposition to hydrochloric acid. These findings indicate that the combination of RL and L55 in coatings prepared from solutions is a promising approach for controlled drug release.

  4. Chitosan-polycarbophil complexes in swellable matrix systems for controlled drug release.

    Science.gov (United States)

    Lu, Z; Chen, W; Hamman, J H

    2007-10-01

    A prerequisite for progress in the design of novel drug delivery systems is the development of excipients that are capable of fulfilling multifunctional roles such as controlling the release of the drug according to the therapeutic needs. Although several polymers have been utilised in the development of specialised drug delivery systems, their scope in dosage form design can be enlarged through combining different polymers. When a polymer is cross-linked or complexed with an oppositely charged polyelectrolyte, a three-dimensional network is formed in which the drug can be incorporated to control its release. The swelling properties and release kinetics of two model drugs with different water solubilities (i.e. diltiazem and ibuprofen) from monolithic matrix tablets consisting of an interpolyelectrolyte complex between chitosan and polycarbophil are reported. Matrix tablets consisting of this polymeric complex without drug or excipients exhibited extremely high swelling properties that are completely reversible upon drying. The drug release from matrix systems with different formulations depended on the concentration of the chitosan-polycarbophil interpolyelectrolyte complex and approached zero order release kinetics for both model drugs. The chitosan-polycarbophil interpolyelectrolyte complex has demonstrated a high potential as an excipient for the production of swellable matrix systems with controlled drug release properties.

  5. Triggered Drug Release from Superhydrophobic Meshes using High-Intensity Focused Ultrasound

    OpenAIRE

    Yohe, Stefan T.; Kopechek, Jonathan A.; Porter, Tyrone M; Colson, Yolonda L.; Grinstaff, Mark W.

    2013-01-01

    Application of high-intensity focused ultrasound to drug-loaded superhydrophobic meshes affords triggered drug release by displacing an entrapped air layer. The air layer within the superhydrophobic meshes is characterized using direct visualization and B-mode imaging. Drug-loaded superhydrophobic meshes are cytotoxic in an in vitro assay after ultrasound treatment.

  6. The effects of cyclodextrins on drug release from fatty suppository bases : II. In vivo observations

    NARCIS (Netherlands)

    Frijlink, H.W.; Eissens, Anko; Schoonen, Adelbert; Lerk, C.F.

    The effects of cyclodextrin complexation on the absorption of drugs from fatty suppositories was evaluated in human volunteers. Three model drugs: diazepam, ibuprofen and prednisolone were used. When diazepam was complexed with γ-cyclcodextrin the drug release from the fatty suppositories was

  7. One-dimensional drug release from finite Menger sponges: In silico simulation

    Energy Technology Data Exchange (ETDEWEB)

    Villalobos, Rafael [Division de Estudios de Posgrado (Tecnologia Farmaceutica), Facultad de Estudios Superiores Cuautitlan, Universidad Nacional Autonoma de Mexico, Av. Primero de Mayo S/N, Cuautitlan Izcalli 54740, Estado de Mexico (Mexico)], E-mail: yeccanv@yahoo.com; Dominguez, Armando [UAM-Iztapalapa, Depto. de Quimica, Av. San Rafael Atlixco 186, Col. Vicentina, 09340 Mexico City (Mexico); Ganem, Adriana [Division de Estudios de Posgrado (Tecnologia Farmaceutica), Facultad de Estudios Superiores Cuautitlan, Universidad Nacional Autonoma de Mexico, Av. Primero de Mayo S/N, Cuautitlan Izcalli 54740, Estado de Mexico (Mexico); Vidales, Ana Maria [Laboratorio de Ciencia de Superficies y Medios Porosos, Departamento de Fisica, CONICET, Universidad Nacional de San Luis, 5700 San Luis (Argentina); Cordero, Salomon [UAM-Iztapalapa, Depto. de Quimica, Av. San Rafael Atlixco 186, Col. Vicentina, 09340 Mexico City (Mexico)

    2009-12-15

    The purpose of this work was to evaluate the consequences of the spatial distribution of components in pharmaceutical matrices type Menger sponge on the drug release kinetic from this kind of platforms by means of Monte Carlo computer simulation. First, six kinds of Menger sponges (porous fractal structures) with the same fractal dimension, d{sub f}=2.727, but with different random walk dimension, d{sub w} element of [2.149,3.183], were constructed as models of drug release device. Later, Monte Carlo simulation was used to describe drug release from these structures as a diffusion-controlled process. The obtained results show that drug release from Menger sponges is characterized by an anomalous behavior: there are important effects of the microstructure anisotropy, and porous structures with the same fractal dimension but with different topology produce different release profiles. Moreover, the drug release kinetic from heteromorphic structures depends on the axis used to transport the material to the external medium. Finally, it was shown that the number of releasing sites on the matrix surface has a significant impact on drug release behavior and it can be described quantitatively by the Weibull function.

  8. Liquid crystalline systems for transdermal delivery of celecoxib: in vitro drug release and skin permeation studies.

    Science.gov (United States)

    Estracanholli, Eder André; Praça, Fabíola Silva Garcia; Cintra, Ana Beatriz; Pierre, Maria Bernadete Riemma; Lara, Marilisa Guimarães

    2014-12-01

    Liquid crystalline systems of monoolein/water could be a promising approach for the delivery of celecoxib (CXB) to the skin because these systems can sustain drug release, improve drug penetration into the skin layers and minimize side effects. This study evaluated the potential of these systems for the delivery of CXB into the skin based on in vitro drug release and skin permeation studies. The amount of CXB that permeated into and/or was retained in the skin was assayed using an HPLC method. Polarizing light microscopy studies showed that liquid crystalline systems of monoolein/water were formed in the presence of CXB, without any changes in the mesophases. The liquid crystalline systems decreased drug release when compared to control solution. Drug release was independent of the initial water content of the systems and CXB was released from cubic phase systems, irrespective of the initial water content. The systems released the CXB following zero-order release kinetics. In vitro drug permeation studies showed that cubic phase systems allowed drug permeation and retention in the skin layers. Cubic phase systems of monoolein/water may be promising vehicles for the delivery of CXB in/through the skin because it improved CXB skin permeation compared with the control solution.

  9. Effects of process variables on micromeritic properties and drug release of non-degradable microparticles

    Directory of Open Access Journals (Sweden)

    Mitra Jelvehgari

    2011-06-01

    Full Text Available Introduction: The purpose of this investigation was to evaluate microencapsulated controlled release preparation of theophylline using Eudragit RS 100 as the retardant material with high entrapment efficiency. Methods: Microspheres were prepared by the emulsion-solvent evaporation method. A mixed solvent system consisting of methanol and acetone and light liquid paraffin as oily phase were chosen. Sucrose stearate was used as the surfactant to stabilize the emulsification process. The prepared microspheres were characterized by drug loading, Fourier-transform infrared spectroscopy (FTIR, differential scanning colorimetry (DSC and scanning electron microscopy (SEM. The in vitro release studies were performed at pH 1.2 and 7.4 aqueous medium. Results: Increasing the concentration of emulsifier, sucrose fatty acid ester F-70, decreased the particle size which contributed to increased drug release rate. The drug loading microparticle Eudragit RS100 (1:6 showed 60-75% of entrapment and mean particle size 205.93-352.76 µm. The results showed that, an increase in the ratio of polymer: drug (F5, 6: 1 resulted in a reduction in the release rate of the drug which may be attributed to the hydrophobic nature of the polymer. Conclusion: The release of theophylline is influenced by the drug to polymer ratio and particle size. Drug release is controlled by diffusion and the best-fit release kinetic is Higuchi model.

  10. Delayed release dexlansoprazole in the treatment of GERD and erosive esophagitis

    Directory of Open Access Journals (Sweden)

    Eric T Wittbrodt

    2009-11-01

    Full Text Available Eric T Wittbrodt1, Charles Baum2, David A Peura31Takeda Pharmaceuticals North America, Inc., 2Takeda Pharmaceuticals International, Inc., Deerfield, IL, USA; 3University of Virginia, School of Medicine, Charlottesville, VA, USAAbstract: Although proton pump inhibitors (PPI have a record of remarkable effectiveness and safety in the management of gastroesophageal reflux disease (GERD, several treatment challenges with PPI have emerged. Dexlansoprazole MR is the (R-enantiomer of lansoprazole contained in a formulation that produces two distinct releases of drug and significantly extends the duration of active plasma concentrations and % time pH > 4 beyond that of conventional singlerelease PPI. Dexlansoprazole MR can be administered without regard to meals or the timing of meals in most patients. Dexlansoprazole MR 60 mg demonstrated similar efficacy for healing of erosive esophagitis at 8 weeks compared with lansoprazole 30 mg, and dexlansoprazole MR 30 mg was superior to placebo for maintenance of healed erosive esophagitis at 6 months with 99% of nights and 96% of days heartburn-free over 6 months in patients taking dexlansoprazole MR 30 mg. Superior relief of heartburn occurred in patients taking dexlansoprazole MR 30 mg (55% heartburn-free 24-hour periods vs placebo (14% for symptomatic nonerosive GERD. The safety profile of dexlansoprazole MR is similar to that of lansoprazole. The extended pharmacodynamic effects, added convenience, and efficacy and safety of dexlansoprazole MR offer a novel approach to gastric pH control in patients with acid-related disorders.Keywords: dexlansoprazole MR, gastroesophageal reflux disease, GERD, erosive esophagitis, TAK-390MR

  11. Delayed drug interactions in psychiatry: armodafinil and risperidone as a potential case in point.

    Science.gov (United States)

    Andrade, Chittaranjan

    2015-12-01

    Modafinil or armodafinil (ar/mod) augmentation of antipsychotic medication in schizophrenia patients may be considered with a view to reduce negative symptoms associated with the illness or excessive daytime drowsiness due to any cause. The available data suggest that there is no role for ar/mod in reducing negative symptom burden. A recent pharmacokinetic (PK) study suggested that armodafinil (250 mg/d) reduces key PK parameters of risperidone by about 50%, and key PK parameters of 9-hydroxyrisperidone (paliperidone) by about 20%-30%, probably through induction of CYP3A4. Ar/mod augmentation is therefore best avoided in patients receiving risperidone or paliperidone (and most other atypical antipsychotic drugs, as well, because most atypical antipsychotics are metabolized by enzymes that ar/mod induce). If the ar/mod-antipsychotic drug combination is necessary, for whatever reason, then the dose of the atypical antipsychotic drug may need to be appropriately raised. If this is not done, relapse may occur; because the relapse may postdate the introduction of ar/mod by many months, the causal role of a metabolic drug interaction may not be suspected, and physicians may attribute the relapse to the natural course of the illness. Physicians need to be aware that any agent that induces the metabolism of psychotropic drugs that are used in maintenance therapy may, through lowered psychotropic drug levels, result in a delayed drug interaction that is characterized by illness relapse.

  12. A novel fluoride anion modified gelatin nanogel system for ultrasound-triggered drug release.

    Science.gov (United States)

    Wu, Daocheng; Wan, Mingxi

    2008-01-01

    Controlled drug release, especially tumor-targeted drug release, remains a great challenge. Here, we prepare a novel fluoride anion-modified gelatin nanogel system and investigate its characteristics of ultrasound-triggered drug release. Adriamycin gelatin nanogel modified with fluoride anion (ADM-GNMF) was prepared by a modified co-precipitation method with fluoride anion and sodium sulfate. The loading and encapsulation efficiency of the anti-neoplastic agent adriamycin (ADM) were measured by high performance liquid chromatography (HPLC). The size and shape of ADM-GNMF were determined by electron microscopy and photo-correlation spectroscopy. The size distribution and drug release efficiency of ADM-GNMF, before and after sonication, were measured by two designed measuring devices that consisted of either a submicron particle size analyzer and an ultrasound generator as well as an ultrasound generator, automatic sampler, and HPLC. The ADM-GNMF was stable in solution with an average diameter of 46+/-12 nm; the encapsulation and loading efficiency of adriamycin were 87.2% and 6.38%, respectively. The ultrasound-triggered drug release and size change were most efficient at a frequency of 20 kHz, power density of 0.4w/cm2, and a 1~2 min duration. Under this ultrasound-triggered condition, 51.5% of drug in ADM-GNMF was released within 1~2 min, while the size of ADM-GNMF changed from 46 +/- 12 nm to 1212 +/- 35 nm within 1~2 min of sonication and restored to its previous size in 2~3 min after the ultrasound stopped. In contrast, 8.2% of drug in ADM-GNMF was released within 2~3 min without sonication, and only negligible size changes were found. The ADM-GNMF system efficiently released the encompassed drug in response to ultrasound, offering a novel and promising controlled drug release system for targeted therapy for cancer or other diseases.

  13. Swelling and drug release behavior of metformin HCl-loaded tamarind seed polysaccharide-alginate beads.

    Science.gov (United States)

    Nayak, Amit Kumar; Pal, Dilipkumar; Santra, Kousik

    2016-01-01

    The paper describes the preparation, characterization, in vitro swelling and in vitro drug release of metformin HCl-loaded tamarind seed polysaccharide (TSP)-alginate beads were prepared by ionotropic-gelation technique and using CaCl2 as cross-linker. The prepared beads exhibited 32.73 ± 1.41% of drug loading (%), 94.86 ± 3.92% of drug encapsulation efficiency (%), and 1.24 ± 0.07 mm of average bead size. The bead surface morphology was analyzed by SEM. The drug-polymer interaction in the bead matrix was analyzed by FTIR analyses. These metformin HCl-loaded ionotropically gelled TSP-alginate beads demonstrated sustained in vitro drug release profile over 10h. These in vitro drug release exhibited pH-dependent drug release behavior. The in vitro drug release from these metformin HCl-loaded beads followed controlled-release (zero-order) pattern with super case-II transport mechanism. The swelling and degradation of these metformin HCl-loaded polymeric beads were found to be influenced by the pH of test mediums.

  14. Hooked on Cryogels: A Carbamate Linker Based Depot for Slow Drug Release.

    Science.gov (United States)

    Aydin, Duygu; Arslan, Mehmet; Sanyal, Amitav; Sanyal, Rana

    2017-05-17

    Poly(ethylene glycol) (PEG) based bulk hydrogels and cryogels containing activated carbonate groups as amine reactive handles to facilitate drug conjugations through carbamate linkages were fabricated and evaluated as slow releasing drug reservoirs. As an initial approach, photopolymerization of N-hydroxysuccinimide (NHS)-activated carbonate functional group containing monomer and PEG-methacrylate in the presence of a cross-linker was utilized to obtain bulk hydrogels with high gel conversions. The resultant hydrogels possessed moderate water uptake (170-340%) which was dependent on the monomer ratios. These hydrogels were functionalized with an anticancer drug, namely, doxorubicin. Surprisingly, while negligible drug release was observed from the bulk hydrogels under normal pH, only about 6% drug release was observed under acidic condition. Limited swelling of these hydrogels as well as lack of porous structure as deduced from scanning electron microscopy analysis might explain the poor drug release. To enhance the drug releasing capacity of these hydrogels that might stem from the increased porosity, reactive carbonate group bearing cryogels were synthesized. Compared to the bulk hydrogels, cryogels were highly porous in structure and also possessed much higher swelling capacity (1150-1500%). As a result of these distinctions, a 7-fold enhancement in drug release was observed for the cryogel system compared to the relating hydrogel. In vitro studies demonstrated that the anticancer drug doxorubicin conjugated through carbamate linkers to the cryogels was released and proved effective against MDA-MB-231 human breast cancer cells. Overall, a novel class of slow releasing nontoxic hydrogel and cryogel scaffolds with potential applications as anticancer drug reservoirs was realized.

  15. An investigation of effects of modification processes on physical properties and mechanism of drug release for sustaining drug release from modified rice.

    Science.gov (United States)

    Ngo, Vuong Duy; Luu, Thinh Duc; Van Vo, Toi; Tran, Van-Thanh; Duan, Wei; Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh

    2016-10-01

    The aim of this study was to investigate the effect of modification processes on physical properties and explain the mechanism of sustained drug release from modified rice (MR). Various types of Vietnamese rice were introduced in the study as the matrices of sustained release dosage form. Rice was thermally modified in water for a determined temperature at different times with a simple process. Then tablets containing MR and isradipine, the model drug, were prepared to investigate the capability of sustained drug release. Scanning electron microscopy (SEM) was used to determine different morphologies between MR formulations. Flow property of MR was analyzed by Hausner ratio and Carr's indices. The dissolution rate and swelling/erosion behaviors of tablets were evaluated at pH 1.2 and pH6.8 at 37±0.5°C. The matrix tablet containing MR showed a sustained release as compared to the control. The SEM analyses and swelling/erosion studies indicated that the morphology as well as swelling/erosion rate of MR were modulated by modification time, drying method and incubation. It was found that the modification process was crucial because it could highly affect the granule morphologies and hence, leading to the change of flowability and swelling/erosion capacity for sustained release of drug.

  16. In vitro release of diclofenac diethylamine from gels: evaluation of generic semisolid drug products in Brazil

    Directory of Open Access Journals (Sweden)

    Karin Goebel

    2013-06-01

    Full Text Available In order for the pharmacological action of a topical dermal drug product to occur, the drug must first be released from the vehicle to be available to penetrate the skin layers and reach the site of action. Drug release is mainly dependent on the characteristics of the formulation. Currently, to register a generic or a similar drug product in Brazil performance testing of topical drug products for local action is not required. In this context, this aim of this study was to evaluate the in vitro release of commercial diclofenac diethylamine gel products available on the Brazilian pharmaceutical market, using the vertical diffusion cell method. Factors which may influence the test, such as the type of membrane used, and the effect of the formulation characteristics on the diffusion rate were evaluated. Brazilian legislation currently allows generic drug products to contain excipients other than the reference drug, which may affect the drug release from the vehicle. Only one of the four generic drug products tested could be considered equivalent to the reference Cataflam Emulgel®. The cellulose acetate and polyethersulfone membranes tested were found to be interchangeable in the in vitro release studies carried out on this product.

  17. Solid lipid extrudates as sustained-release matrices: the effect of surface structure on drug release properties.

    Science.gov (United States)

    Reitz, Claudia; Strachan, Clare; Kleinebudde, Peter

    2008-11-15

    The study focused on the structural characterization of sustained-release lipid matrices prepared by solid lipid extrusion. Drug-containing lipid extrudates were locally analyzed in order to identify differences between the chemical and structural composition of surface and core elements. Independent of the lipid the dissolution from the outer extrudate surfaces was slower compared with dissolution from surfaces prepared by cutting the extrudate. The burst effect was higher for the cross-sections indicating more drug was exposed on these surfaces. The release from glycerol trimyristate (Dynasan 114) extrudates was slower compared with glycerol palmitostearate (Precirol ATO 5) extrudates. By solid-state analysis using DSC, ATR-FTIR and SEM measurements the differences between surface material and core material could be attributed mainly to morphological differences. Chemical differences between the core and the outer surface were not relevant. The differences between the surfaces might be explained by the friction induced temperature increase during extrusion in the die plate. The obtained results and a proposed scheme were used to explain the influence of different formulation/processing parameters, such as drug particle size and milling on the drug dissolution behaviour. Small drug particles and intact extrudates are a means of minimizing the burst release.

  18. Reliability of a Novel Model for Drug Release from 2D HPMC-Matrices

    Directory of Open Access Journals (Sweden)

    Rumiana Blagoeva

    2010-04-01

    Full Text Available A novel model of drug release from 2D-HPMC matrices is considered. Detailed mathematical description of matrix swelling and the effect of the initial drug loading are introduced. A numerical approach to solution of the posed nonlinear 2D problem is used on the basis of finite element domain approximation and time difference method. The reliability of the model is investigated in two steps: numerical evaluation of the water uptake parameters; evaluation of drug release parameters under available experimental data. The proposed numerical procedure for fitting the model is validated performing different numerical examples of drug release in two cases (with and without taking into account initial drug loading. The goodness of fit evaluated by the coefficient of determination is presented to be very good with few exceptions. The obtained results show better model fitting when accounting the effect of initial drug loading (especially for larger values.

  19. Natural melanin: a potential pH-responsive drug release device.

    Science.gov (United States)

    Araújo, Marco; Viveiros, Raquel; Correia, Tiago R; Correia, Ilídio J; Bonifácio, Vasco D B; Casimiro, Teresa; Aguiar-Ricardo, Ana

    2014-07-20

    This work proposes melanin as a new nanocarrier for pH-responsive drug release. Melanin is an abundant natural polymer that can be easily extracted from cuttlefish as nanoparticles with a suitable size range for drug delivery. However, despite its high potentiality, the application of this biopolymer in the pharmaceutical and biomedical fields is yet to be explored. Herein, melanin nanoparticles were impregnated with metronidazole, chosen as model antibiotic drug, using supercritical carbon dioxide. The drug release profile was investigated at acidic and physiologic pH, and the dominant mechanism was found to follow a non-Fickian transport. Drug release from melanin shows a strong pH dependency, which allied to its biocompatibility and lack of cytotoxicity envisages its potential application as nanocarrier in formulations for colon and intestine targeted drug delivery.

  20. A novel drug delivery system of gold nanorods with doxorubicin and study of drug release by single molecule spectroscopy.

    Science.gov (United States)

    Mirza, Agha Zeeshan

    2015-01-01

    The work presented here describes the fabrication of a novel drug delivery system, which consists of gold nanorods and doxorubicin, with the attachment of thioctic acid and folic acid, for the targeted release of drug to cancer cells. Doxorubicin, the potent anticancer drug, is widely used to treat various cancers. Gold nanorods were functionalized chemically to generate active groups for the attachment of drug molecules and subsequently attached to folic acid. The resulting nanostructure was characterized by UV-visible-NIR spectrophotometry, TEM techniques, zeta potential measurement and subsequently used to target folate receptor-expressing cancers cells for the delivery of doxorubicin. We generated a release profile for the release of doxorubicin from the nanostructures in KB cells using single-molecule fluorescence intensity images and fluorescence lifetime images. The results indicated that the nanorods were able to enter the target cells because of the attachment of folic acid and used as a carriers for the targeted delivery of doxorubicin.

  1. Experimental and Mathematical Studies on the Drug Release Properties of Aspirin Loaded Chitosan Nanoparticles

    Directory of Open Access Journals (Sweden)

    Yixiang Shi

    2014-01-01

    Full Text Available The study of drug release dynamic is aiming at understanding the process that drugs release in human body and its dynamic characteristics. It is of great significance since these characteristics are closely related to the dose, dosage form, and effect of the drugs. The Noyes-Whitney function is used to represent how the solid material is dissolved into solution, and it is well used in study of drug dynamic. In this research, aspirin (acetylsalicylic acid (ASA has been encapsulated with different grades of chitosan (CS varying in molecular weight (Mw for the purpose of controlled release. The encapsulation was accomplished by ionic gelation technology based on assembly of positively charged chitosan and negatively charged sodium tripolyphosphate (TPP. The encapsulation efficiency, loading capacity, and drug release behavior of aspirin loaded chitosan nanoparticles (CS-NPs were studied. It was found that the concentration of TPP and Aspirin, molecular weights of chitosan have important effect on the drug release patterns from chitosan nanoparticles. The results for simulation studies show that the Noyes-Whitney equation can be successfully used to interpret the drug release characteristics reflected by our experimental data.

  2. Fused-filament 3D printing of drug products: Microstructure analysis and drug release characteristics of PVA-based caplets.

    Science.gov (United States)

    Goyanes, Alvaro; Kobayashi, Masanori; Martínez-Pacheco, Ramón; Gaisford, Simon; Basit, Abdul W

    2016-11-30

    Fused deposition modeling (FDM) 3-Dimensional (3D) printing is becoming an increasingly important technology in the pharmaceutical sciences, since it allows the manufacture of personalized oral dosage forms by deposition of thin layers of material. Here, a filament extruder was used to obtain filaments of polyvinyl alcohol (PVA) containing paracetamol or caffeine appropriate for 3D printing. The filaments were used to manufacture caplets for oral administration by FDM 3D printing, with the aim of evaluating the effect of the internal structure (micropore volume), drug loading and composition on drug dissolution behaviour. Micropore volume of the caplets was primarily determined by the presence of large pores due to gaps in the printed layers/net while printing, and the porosity of the caplets was 10 fold higher than the porosity of the extruded filament. Dynamic dissolution drug release tests on the caplets in biorelevant bicarbonate media revealed distinctive release profiles, which were dependent on drug solubility and drug loading. Porosity of the caplets did not help to predict the different drug release profiles. This study confirms the potential of 3D printing to fabricate caplets and helps to elucidate which factors influence drug release from this type of new dosage form. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. An investigation of effects of modification processes on physical properties and mechanism of drug release for sustaining drug release from modified rice

    Energy Technology Data Exchange (ETDEWEB)

    Ngo, Vuong Duy; Luu, Thinh Duc; Van Vo, Toi [Pharmaceutical Engineering Laboratory, Biomedical Engineering Department, International University, Vietnam National University, Ho Chi Minh City (Viet Nam); Tran, Van-Thanh [Faculty of Pharmacy, University of Medicine and Pharmacy, Ho Chi Minh City (Viet Nam); Duan, Wei [School of Medicine, Deakin University, Pigdons Road, Waurn Ponds, Victoria (Australia); Tran, Phuong Ha-Lien, E-mail: phuong.tran1@deakin.edu.au [School of Medicine, Deakin University, Pigdons Road, Waurn Ponds, Victoria (Australia); Tran, Thao Truong-Dinh, E-mail: ttdthao@hcmiu.edu.vn [Pharmaceutical Engineering Laboratory, Biomedical Engineering Department, International University, Vietnam National University, Ho Chi Minh City (Viet Nam)

    2016-10-01

    The aim of this study was to investigate the effect of modification processes on physical properties and explain the mechanism of sustained drug release from modified rice (MR). Various types of Vietnamese rice were introduced in the study as the matrices of sustained release dosage form. Rice was thermally modified in water for a determined temperature at different times with a simple process. Then tablets containing MR and isradipine, the model drug, were prepared to investigate the capability of sustained drug release. Scanning electron microscopy (SEM) was used to determine different morphologies between MR formulations. Flow property of MR was analyzed by Hausner ratio and Carr's indices. The dissolution rate and swelling/erosion behaviors of tablets were evaluated at pH 1.2 and pH 6.8 at 37 ± 0.5 °C. The matrix tablet containing MR showed a sustained release as compared to the control. The SEM analyses and swelling/erosion studies indicated that the morphology as well as swelling/erosion rate of MR were modulated by modification time, drying method and incubation. It was found that the modification process was crucial because it could highly affect the granule morphologies and hence, leading to the change of flowability and swelling/erosion capacity for sustained release of drug. - Highlights: • Modification process affected granule morphologies and flowability of modified rice. • Modification process affected swelling/erosion capacity for drug sustained release. • Freeze-drying could decrease the erosion as well as increase the swelling rate.

  4. Co-extrusion as manufacturing technique for multilayer mini-matrices with dual drug release.

    Science.gov (United States)

    Dierickx, L; Remon, J P; Vervaet, C

    2013-11-01

    The aim of this work was to develop by means of co-extrusion a multilayered dosage form characterized by a dual release profile of the same drug. Co-extrudates consisted of two concentric polymer matrices: a core having a lipophilic character and a coat with a hydrophilic character. Diclofenac sodium (DS) was incorporated as model drug in both layers. Several polymers were screened on the basis of their processability via hot melt extrusion (HME) and in vitro drug release. Polymer combinations with suitable properties (i.e., similar extrusion temperature, appropriate drug release profile) were processed via co-extrusion. (Co-) extruded samples were characterized in terms of solid state (XRD, SEM), in vitro drug release, core/coat adhesion, and bioavailability. Based on the polymer screening, two polymer combinations were selected for co-extrusion: ethylcellulose (core) combined with Soluplus® (coat) and polycaprolactone (core) with PEO (coat). These combinations were successfully co-extruded. XRD revealed that DS remained crystalline during extrusion in ethylcellulose, Soluplus®, polycaprolactone, and PEO. The polycaprolactone/PEO combination could be processed at a lower temperature (70 °C), vs. 140 °C for ethylcellulose/Soluplus®. The maximum drug load in core and coat depended on the extrusion temperature and the die dimensions, while adhesion between core and coat was mainly determined by the drug load and by the extrusion temperature. In vitro drug release from the co-extruded formulations was reflected in the in vivo behavior: formulations with a higher DS content in the coat (i.e., faster drug release) resulted in higher Cmax and higher AUC values. Co-extrusion is a viable method to produce in a single step a multilayer dosage form with dual drug release.

  5. A Review of In Vitro Drug Release Test Methods for Nano-Sized Dosage Forms

    Directory of Open Access Journals (Sweden)

    Susan D’Souza

    2014-01-01

    Full Text Available This review summarizes the methods used to study real-time (37°C drug release from nanoparticulate drug delivery systems and establish an IVIVC. Since no compendial standards exist, drug release is currently assessed using a variety of methods including sample and separate (SS, continuous flow (CF, dialysis membrane (DM methods, and a combination thereof, as well as novel techniques like voltametry and turbidimetry. This review describes the principle of each method along with their advantages and disadvantages, including challenges with set-up and sampling. The SS method allows direct measurement of drug release with simple set-up requirements, but sampling is cumbersome. With the CF method, sampling is straightforward but the set-up is time consuming. Set-up as well as sampling is easier with the DM, but it may not be suitable for drugs that bind to the membrane. Novel methods offer the possibility of real-time drug release measurement but may be restricted to certain types of drugs. Of these methods, Level A IVIVCs have been obtained with dialysis, alone or in combination with the sample and separate technique. Future efforts should focus on developing mathematical models that describe drug release mechanisms as well as facilitate formulation development of nano-sized dosage forms.

  6. Ibuprofen-loaded poly(lactic-co-glycolic acid films for controlled drug release

    Directory of Open Access Journals (Sweden)

    Pang JM

    2011-04-01

    Full Text Available Jianmei Pang1, Yuxia Luan1, Feifei Li1, Xiaoqing Cai1, Jimin Du2, Zhonghao Li31School of Pharmaceutical Science, Shandong University, Jinan, Shandong Province, PR China; 2School of Chemistry and Chemical Engineering, Anyang Normal University, Henan Province, PR China; 3School of Materials Science and Engineering, Shandong University, Jinan, Shandong Province, PR ChinaAbstract: Ibuprofen- (IBU loaded biocompatible poly(lactic-co-glycolic acid (PLGA films were prepared by spreading polymer/ibuprofen solution on the nonsolvent surface. By controlling the weight ratio of drug and polymer, different drug loading polymer films can be obtained. The synthesized ibuprofen-loaded PLGA films were characterized with scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry. The drug release behavior of the as-prepared IBU-loaded PLGA films was studied to reveal their potential application in drug delivery systems. The results show the feasibility of the as-obtained films for controlling drug release. Furthermore, the drug release rate of the film could be controlled by the drug loading content and the release medium. The development of a biodegradable ibuprofen system, based on films, should be of great interest in drug delivery systems.Keywords: ibuprofen, controlled release, poly(lactic-co-glycolic acid, films

  7. A drug release study from hydroxypropylmethylcellulose (HPMC) matrices using QSPR modeling.

    Science.gov (United States)

    Ghafourian, Taravat; Gafourian, Taravat; Safari, Arezoo; Adibkia, Khosro; Parviz, Fatemeh; Nokhodchi, Ali

    2007-12-01

    This investigation is aimed at characterization of the mode of release from two different substitution types of HPMC and the effect of chemical structure of drugs using the QSPR (Quantitative - Structure-Property Relationship) technique. To this end, release profiles of HPMC matrices of several drugs containing the same formulation and compressed at a constant pressure were studied. QSPR method was used to establish statistically significant relationships between release parameters and the structural descriptors. Structural descriptors consisted of molecular mechanical, quantum mechanical and graph-theoretical parameters, as well as the partition coefficient and the aqueous solubility of the drugs. The results showed that the most important factors determining the release profile from both HPMC K4M and HPMC E4M matrices were the aqueous solubility of drugs (which could be substituted efficiently by dipole moment) and the size of the drug molecules. Comparison of drug release from matrices prepared using the two grades of HPMC showed very distinct differences for some drugs, as evaluated by the similarity factor. The results indicated that the source of the difference could be sought in the drug properties (as exemplified by the aqueous solubility and surface area) as well as the rate of erosion (that depends mainly on the polymer type).

  8. Influence of polymethacrylates and compritol on release profile of a highly water soluble drug metformin hydrochloride

    Directory of Open Access Journals (Sweden)

    Sunita Dahiya

    2015-01-01

    Full Text Available Aims: The present investigation studied effect of polymethacrylates Eudragit RSPO, Eudragit RLPO and compritol 888 ATO on release profile of highly water soluble drug metformin hydrochloride (MET. Materials and Methods: The solid dispersions were prepared using drug:polymer ratios 1:1 and 1:5 by coevaporation and coprecipitation techniques. Solid dispersions were characterized by infrared Spectroscopy (IR, differential scanning calorimetry (DSC, X-ray diffractometry (XRD as well as content uniformity, in vitro dissolution studies in 0.1 N HCl pH 1.2, phosphate buffer pH 6.8. Results and Discussion: Results of the studies suggested that there were progressive disappearance or changes of prominent peaks in IR, X-ray diffraction and thermotropic drug signals in coevaporates and coprecipitates with increased amount of polymers. Moreover, the in vitro release of highly water soluble MET could be extended at higher drug:polymer ratios. Conclusion: It was summarized that Eudragit RLPO had greater capacity of drug release than Eudragit RSPO and Comproitol 888 and its coevaporates in 1:5 drug:polymer ratio (F11 displayed extended drug release with comparatively higher dissolution rates (92.15 % drug release at 12 hour following near Zero order kinetics (r² =0.9822.

  9. Swelling and Drug Release Characteristics of Poly (methacrylic acid-co-poloxamer) hydrogels

    Institute of Scientific and Technical Information of China (English)

    XUHui; LINYan-nan; DINGPing-tian; TIANMei-juan; ZHENGJun-min

    2003-01-01

    Poly (methacrylie acid co-poloxamer) hydrogel networks were synthesized by free-radical solution polymerization, and the dynamic swelling and in vitro release properties of model drugs, dextromethorphan hydrobromide (DMP) and vitamin B12 (VB12) were studied. These gels exhibited pH-dependant swelling and sustained drug release properties, and the water uptake rate and drug release rate in neutral or basic media were higher than that in acidic media. The results showed that the water uptake followed non-Fickian or zero order process in neutral or basic media, and the release of model drugs from hydrogels of appropriate composition was of zero order kinetics over a period of several hours.

  10. Hildebrand solubility parameter to predict drug release from hydroxypropyl methylcellulose gels.

    Science.gov (United States)

    Bustamante, P; Navarro-Lupión, J; Peña, M A; Escalera, B

    2011-07-29

    An equation including the Hildebrand solubility parameter δ of the drugs is used for the first time to model drug release from hydroxypropyl methylcellulose (HPMC) gels: l nM = -21.578 + 2.102 δ-0.037 δ(2)+0.48 ln t + 1.028 ln C(i) (r(2) = 0.94 for a total of 286 cases). The experimentally determined release data of six drugs having different polarity (caffeine, theophylline, paracetamol, salicylic acid, naproxen and diclofenac) at several initial concentrations C(i) were included in the equation. In general, the amount of drug delivered is linear at the first 5-6h of the release profiles and the zero order constants K(o) increase as the solubility parameter of the drugs become larger. The Peppas exponential law M/M(∞) = Kt(n) is applicable to larger fractional release, until 67-87% (48-51 h) for the less polar drugs (diclofenac and naproxen, lower δ values) and more than 80% (26-28 h) for the more polar drugs (higher δ values, theophylline, salicylic acid, caffeine and paracetamol). The Peppas release rate (lnK) shows a parabolic relationship with the drug solubility parameter. The diffusional exponent n varies between 0.40 and 0.58 indicating that drug release is mainly controlled by diffusion. An extended form of the Peppas equation is also tested for each drug including all the initial concentrations: lnM = a + b ln t + c ln C(i) (r(2) = 0.88-0.94). The logarithm of the octanol-water partition coefficients can also be used in combination with the drug concentrations. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Surface Modifications of Titanium Implants by Multilayer Bioactive Coatings with Drug Delivery Potential: Antimicrobial, Biological, and Drug Release Studies

    Science.gov (United States)

    Ordikhani, Farideh; Zustiak, Silviya Petrova; Simchi, Abdolreza

    2016-04-01

    Recent strategies to locally deliver antimicrobial agents to combat implant-associated infections—one of the most common complications in orthopedic surgery—are gaining interest. However, achieving a controlled release profile over a desired time frame remains a challenge. In this study, we present an innovative multifactorial approach to combat infections which comprises a multilayer chitosan/bioactive glass/vancomycin nanocomposite coating with an osteoblastic potential and a drug delivery capacity. The bioactive drug-eluting coating was prepared on the surface of titanium foils by a multistep electrophoretic deposition technique. The adopted deposition strategy allowed for a high antibiotic loading of 1038.4 ± 40.2 µg/cm2. The nanocomposite coating exhibited a suppressed burst release with a prolonged sustained vancomycin release for up to 6 weeks. Importantly, the drug release profile was linear with respect to time, indicating a zero-order release kinetics. An in vitro bactericidal assay against Staphylococcus aureus confirmed that releasing the drug reduced the risk of bacterial infection. Excellent biocompatibility of the developed coating was also demonstrated by in vitro cell studies with a model MG-63 osteoblast cell line.

  12. Drug Release from Inert Spherical Matrix Systems Using Monte Carlo Simulations.

    Science.gov (United States)

    Villalobos, Rafael; Garcia, Erika V; Quintanar, David; Young, Paul M

    2017-01-01

    Computational approaches for predicting release properties from matrix devices have recently been purposed as an approach to better understand and predict such systems. The objective of this research is to study the behavior of drug delivery from inert spherical matrix systems of different size by means of computer simulation. To simulate the matrix medium, a simple cubic lattice was used, which was sectioned to make a spherical macroscopic system. The sites within the system were randomly occupied by drug-particles or excipient-particles in accordance with chosen drug/excipient ratios. Then, the drug was released from the matrix system simulating a diffusion process. When the released fraction was processed until 90% release, the Weibull equation suitably expressed the release profiles. On the basis of the analysis of release equations, it was found that close to the percolation threshold an anomalous released occurs, while in the systems with an initial drug load greater than 0.45, the released was Fickian type. It was also possible to determine the amount of drug trapped in the matrix, which was found to be a function of the initial drug load. The relationship between the two mentioned variables was adequately described by a model that involves the error function. Based on the these results and by means of a non-linear regression to the previous model, it was possible to determine the drug percolation threshold in these matrix devices. It was found that the percolation threshold is consistent with the value predicted by the percolation theory. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Controlled Release of Drugs FromHydrogel Based Matrices Systems: Experiments and Modeling

    OpenAIRE

    LAMBERTI, G.; Cascone, S.; Titomanlio, G.; Barba, A.A.

    2012-01-01

    Hydrogels are materials largely used in the formulation of pharmaceuticals since, in principle, they could produce a release system of zero-order kinetics, which is of great therapeutic interest. In this paper, a model was proposed for the description of the main transport phenomena involved in the drug release process from hydrogel matrices (water diffusion, polymer swelling, drug diffusion and polymer dissolution); the model predictions are successfully compared with a large set of exper...

  14. Laser-activated nano-biomaterials for tissue repair and controlled drug release

    Energy Technology Data Exchange (ETDEWEB)

    Matteini, P; Ratto, F; Rossi, F; Pini, R [Institute of Applied Physics ' Nello Carrara' , National Research Council, via Madonna del Piano 10 50019 Sesto Fiorentino (Italy)

    2014-07-31

    We present recent achievements of minimally invasive welding of biological tissue and controlled drug release based on laser-activated nano-biomaterials. In particular, we consider new advancements in the biomedical application of near-IR absorbing gold nano-chromophores as an original solution for the photothermal repair of surgical incisions and as nanotriggers of controlled drug release from hybrid biopolymer scaffolds. (laser biophotonics)

  15. Composite films of poly(vinyl alcohol)-chitosan-bacterial cellulose for drug controlled release.

    Science.gov (United States)

    Pavaloiu, Ramona-Daniela; Stoica-Guzun, Anicuta; Stroescu, Marta; Jinga, Sorin Ion; Dobre, Tanase

    2014-07-01

    Mono and multilayer composite films of poly(vinyl alcohol)-chitosan-bacterial cellulose (PVA/chitosan/BC) have been prepared to achieve controlled release of ibuprofen sodium salt (IbuNa) as model drug. The composite films have been characterized by Fourier transformed infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Surface morphology was investigated by scanning electron microscopy (SEM). Equilibrium swelling was measured in water at two different pH values and in vitro release of IbuNa in pH 1.2 and pH 7.4 media was studied. The release experiments revealed that drug release is pH sensitive. The release kinetics of IbuNa could be described by the Fickian model of diffusion with a good agreement. The IbuNa release rate was decreasing for all the films as the BC concentration was increased in the films composition, the decrease being higher for the multilayer films.

  16. Drug Toxicity Deaths after Release from Incarceration in Ontario, 2006-2013: Review of Coroner's Cases.

    Directory of Open Access Journals (Sweden)

    Emily Groot

    Full Text Available There is an increased risk of death due to drug toxicity after release from incarceration. The purpose of this study was to describe the timing, rate and circumstances of drug toxicity deaths following release from incarceration. This information can be used to help design potential preventive interventions.We reviewed coroner's files to identify deaths in adults in Ontario between 2006 and 2013 caused by drug toxicity (n = 6,978 and these records were matched with provincial correctional records to identify individuals who died within one year of being released from incarceration (n = 702. Twenty percent (n = 137 of the 702 deaths occurred within one week of release. The majority (77%, n = 538 of deaths after release involved one or more opioids. Of the deaths involving opioids, intervention by another person may have been possible in 318 cases.Between 2006 and 2013 in Ontario, one in ten drug toxicity deaths in adults occurred within one year of release from provincial incarceration. These findings may help to inform the implemention and assessment of interventions aimed at reducing drug toxicity deaths following release from incarceration.

  17. Mathematical Models for Controlled Drug Release Through pH-Responsive Polymeric Hydrogels.

    Science.gov (United States)

    Manga, Ramya D; Jha, Prateek K

    2017-02-01

    Hydrogels consisting of weakly charged acidic/basic groups are ideal candidates for carriers in oral delivery, as they swell in response to pH changes in the gastrointestinal tract, resulting in drug entrapment at low pH conditions of the stomach and drug release at high pH conditions of the intestine. We have developed 1-dimensional mathematical models to study the drug release behavior through pH-responsive hydrogels. Models are developed for 3 different cases that vary in the level of rigor, which together can be applied to predict both in vitro (drug release from carrier) and in vivo (drug concentration in the plasma) behavior of hydrogel-drug formulations. A detailed study of the effect of hydrogel and drug characteristics and physiological conditions is performed to gain a fundamental insight into the drug release behavior, which may be useful in the design of pH-responsive drug carriers. Finally, we describe a successful application of these models to predict both in vitro and in vivo behavior of docetaxel-loaded micelle in a pH-responsive hydrogel, as reported in a recent experimental study. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  18. A novel sustained release drug-resin complex-based microbeads of ciprofloxacin HCl.

    Science.gov (United States)

    Jain, Sunil K; Prajapati, Neeraj; Rajpoot, Kuldeep; Kumar, Amrish

    2016-12-01

    Objective A novel multiparticulate system for the gastro-mucoadhesive delivery of ciprofloxacin HCl (CFN) was developed with the help of ion-exchange resin to deal with urinary tract (UT) infections effectively. Materials and methods An optimized complex (resinate) of CFN with sodium polystyrene sulfonate USP resin was prepared and entrapped within microbeads of sodium alginate and pectin. The developed systems were evaluated for drug entrapment efficiency, percentage of mucoadhesion and in vitro release patterns in simulated gastric fluid (pH 1.2). Results and discussion The interaction of the resin complex and polycation via alginate was consequently supported the formation of polyelectrolyte complex membrane. The in vitro drug release studies demonstrate that formulation without drug-resin complex (NRB) released the drug more swiftly than formulation containing drug-resin complex (DRC). This controlled release pattern of drug, resin complex containing microbeads was owed to complexation between drug and resin. Conclusion Preliminary results from the study suggested that this drug-resin complex-entrapped microbeads can be used to incorporate other antibiotic drugs and could be effective against UT infection. Such developed formulation could be subjected to in vivo studies in future in order to prove their efficacy for such type of infections.

  19. [Sustained release of the antitumor drug paclitaxel from poly(3-hydroxybutyrate)-based microspheres].

    Science.gov (United States)

    Bonartsev, A P; Iaovlev, S G; Filatova, E V; Soboleva, G M; Makhina, T K; Bonartseva, G A; Shaĭtan, K V; Popov, V O; Kirpichnikov, M P

    2011-01-01

    Development of systems of medicines with sustained action on the basis of biodegradable polymers is a promising trend in modem pharmacology. Polyhydroxyalkanoates (POA) attract increasing attention due to their biodegradability and high biocompatibility, which make them suitable for development of novel drug dosage forms. We obtained microspheres on the basis of poly(3-hydroxybutyrate) (PHB) loaded with the antitumor drug paclitaxel. Morphology, drug release kinetics and effect on tumor cells in vitro of microspheres were studied. The data on the kinetics of drug release, biocompatibility and biological activity of the biopolymer microspheres in vitro showed that the studied system of prolonged drug release had lower toxicity and higher efficiency compared to the traditional dosage forms of paclitaxel.

  20. Electrospun micelles/drug-loaded nanofibers for time-programmed multi-agent release.

    Science.gov (United States)

    Yang, Guang; Wang, Jie; Li, Long; Ding, Shan; Zhou, Shaobing

    2014-07-01

    Combined therapy with drugs of different therapeutic effects is an effective way in the treatment of diseases and damaged tissues or organs. However, how to precisely control the release order, dose, and time of the drugs using vehicles is still a challenging task. In this work, for the first time, a study to develop a nanoscale multi-drug delivery system based on polymer micelle-enriched electrospun nanofibers is presented. The multi-drug delivery system is achieved, first, by the fabrication of hydrophobic curcumin encapsulated micelles assembled from biodegradable mPEG-PCL copolymer and, second, by the blending of the micelle powder with hydrophilic doxorubicin in polyvinyl alcohol solution, followed by simply electrospinning this combination. Due to the different domains of the two drugs within the nanofibers, the release behaviors show a time-programmed release, and can be temporally and spatially regulated. In vitro tumor cell inhibition assay indicates that the delivery system possesses great potential in cancer chemotherapy.

  1. Poly(lactic acid)/chitosan hybrid nanoparticles for controlled release of anticancer drug.

    Science.gov (United States)

    Wang, Wenlong; Chen, Shu; Zhang, Liang; Wu, Xi; Wang, Jiexin; Chen, Jian-Feng; Le, Yuan

    2015-01-01

    Poly(lactic acid) (PLA) is a kind of non-toxic biological materials with excellent absorbability, biocompatibility and biodegradability, which can be used for drug release, tissue engineering and surgical treatment applications. In this study, we prepared chitosan modified PLA nanoparticles as carriers for encapsulation of docetaxel by anti-solvent precipitation method. The morphology, particle size, zeta potential and composition of the PLA/chitosan were characterized by SEM, DLS, FTIR and XPS. As-prepared PLA/chitosan particles exhibited average size of 250 nm and showed very narrow distribution with polydispersity index of 0.098. Their large surface charge-ability was confirmed by zeta potential value of 53.9 mV. Docetaxel was released from PLA/chitosan nanoparticles with 40% initial burst release in 5 h and 70% cumulative release within 24 h, while from PLA nanoparticles 65% of docetaxel was released in 5h. In vitro drug release study demonstrated that PLA/chitosan nanoparticles prolonged drug release and decreased the burst release over the unmodified PLA nanoparticles. These results illustrated high potential of chitosan modified PLA nanoparticles for usage as anticancer drug carriers.

  2. A novel and alternative approach to controlled release drug delivery system based on solid dispersion technique

    Directory of Open Access Journals (Sweden)

    Tapan Kumar Giri

    2012-12-01

    Full Text Available The solid dispersion method was originally used to improve the dissolution properties and the bioavailability of poorly water soluble drugs by dispersing them into water soluble carriers. In addition to the above, dissolution retardation through solid dispersion technique using water insoluble and water swellable polymer for the development of controlled release dosage forms has become a field of interest in recent years. Development of controlled release solid dispersion has a great advantage for bypassing the risk of a burst release of drug; since the structure of the solid dispersion is monolithic where drug molecules homogeneously disperse. Despite the remarkable potential and extensive research being conducted on controlled release solid dispersion system, commercialization and large scale production are limited. The author expects that recent technological advances may overcome the existing limitations and facilitate the commercial utilization of the techniques for manufacture of controlled release solid dispersions. This article begins with an overview of the different carriers being used for the preparation of controlled release solid dispersion and also different techniques being used for the purpose. Kinetics of drug release from these controlled release solid dispersions and the relevant mathematical modeling have also been reviewed in this manuscript.

  3. Sustained and controlled release of lipophilic drugs from a self-assembling amphiphilic peptide hydrogel

    DEFF Research Database (Denmark)

    Briuglia, Maria-Lucia; Urquhart, Andrew; Lamprou, Dimitrios A.

    2014-01-01

    . In this work, we have investigated the diffusion properties of Pindolol, Quinine and Timolol maleate from RADA16 in PBS and in BSS-PLUS at 37°C. A sustained, controlled, reproducible and efficient drug release has been detected for all the systems, which allows to understand the dependence of release kinetics...

  4. Development of a cell-based bioassay for phospholipase A2-triggered liposomal drug release

    DEFF Research Database (Denmark)

    Arouri, Ahmad; Trojnar, Jakub; Schmidt, Steffen

    2015-01-01

    models, the pattern of sPLA2-assisted drug release is unknown due to the lack of a suitable bio-relevant model. We report here on the development of a novel bioluminescence living-cell-based luciferase assay for the monitoring of sPLA2-triggered release of luciferin from liposomes. To this end, we...

  5. Stimuli-free programmable drug release for combination chemo-therapy

    Science.gov (United States)

    Fan, Li; Jin, Boquan; Zhang, Silu; Song, Chaojun; Li, Quan

    2016-06-01

    Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug binding to FAT1-expressing colon cancer cells. The loaded dual drugs were demonstrated to be delivered in a sequential manner with specific time intervals between their peak releases, which maximize the synergistic effect of the chemotherapeutics. These features led to significantly enhanced drug efficacy and reduced system toxicity. The tumor weight decreased by 1/350, together with a moderate increase in rats' body weight, which were observed when adopting the dual drug loaded nanoparticles, as compared to those of the control groups. The present system provides a simple and feasible method for the design of targeting and combination chemotherapy with programmed drug release.Combinational chemotherapy capable of targeted delivery and programmable multi-drug release leads to enhanced drug efficacy, and is highly desired for cancer treatment. However, effective approaches for achieving both features in a single treatment are limited. In the present work, we demonstrated programmed delivery of both chemotherapeutic and immunotherapeutic agents with tumor cell targeting capability by using SiO2 based self-decomposable nanoparticulate systems. The programmable drug delivery is realized by manipulating drug loading configurations instead of relying on external stimuli. Both in vitro and in vivo results showed specific drug

  6. NIR-driven Smart Theranostic Nanomedicine for On-demand Drug Release and Synergistic Antitumour Therapy

    Science.gov (United States)

    Zhao, Pengfei; Zheng, Mingbin; Luo, Zhenyu; Gong, Ping; Gao, Guanhui; Sheng, Zonghai; Zheng, Cuifang; Ma, Yifan; Cai, Lintao

    2015-09-01

    Smart nanoparticles (NPs) that respond to external and internal stimulations have been developing to achieve optimal drug release in tumour. However, applying these smart NPs to attain high antitumour performance is hampered by limited drug carriers and inefficient spatiotemporal control. Here we report a noninvasive NIR-driven, temperature-sensitive DI-TSL (DOX/ICG-loaded temperature sensitive liposomes) co-encapsulating doxorubicin (DOX) and indocyanine green (ICG). This theranostic system applies thermo-responsive lipid to controllably release drug, utilizes the fluorescence (FL) of DOX/ICG to real-time trace the distribution of NPs, and employs DOX/ICG to treat cancer by chemo/photothermal therapy. DI-TSL exhibits uniform size distribution, excellent FL/size stability, enhanced response to NIR-laser, and 3 times increased drug release through laser irradiation. After endocytosis by MCF-7 breast adenocarcinoma cells, DI-TSL in cellular endosomes can cause hyperthermia through laser irradiation, then endosomes are disrupted and DI-TSL ‘opens’ to release DOX simultaneously for increased cytotoxicity. Furthermore, DI-TSL shows laser-controlled release of DOX in tumour, enhanced ICG and DOX retention by 7 times and 4 times compared with free drugs. Thermo-sensitive DI-TSL manifests high efficiency to promote cell apoptosis, and completely eradicate tumour without side-effect. DI-TSL may provide a smart strategy to release drugs on demand for combinatorial cancer therapy.

  7. Microfluidic synthesis of microfibers for magnetic-responsive controlled drug release and cell culture.

    Directory of Open Access Journals (Sweden)

    Yung-Sheng Lin

    Full Text Available This study demonstrated the fabrication of alginate microfibers using a modular microfluidic system for magnetic-responsive controlled drug release and cell culture. A novel two-dimensional fluid-focusing technique with multi-inlets and junctions was used to spatiotemporally control the continuous laminar flow of alginate solutions. The diameter of the manufactured microfibers, which ranged from 211 µm to 364 µm, could be well controlled by changing the flow rate of the continuous phase. While the model drug, diclofenac, was encapsulated into microfibers, the drug release profile exhibited the characteristic of a proper and steady release. Furthermore, the diclofenac release kinetics from the magnetic iron oxide-loaded microfibers could be controlled externally, allowing for a rapid drug release by applying a magnetic force. In addition, the successful culture of glioblastoma multiforme cells in the microfibers demonstrated a good structural integrity and environment to grow cells that could be applied in drug screening for targeting cancer cells. The proposed microfluidic system has the advantages of ease of fabrication, simplicity, and a fast and low-cost process that is capable of generating functional microfibers with the potential for biomedical applications, such as drug controlled release and cell culture.

  8. 3D printing of tablets containing multiple drugs with defined release profiles.

    Science.gov (United States)

    Khaled, Shaban A; Burley, Jonathan C; Alexander, Morgan R; Yang, Jing; Roberts, Clive J

    2015-10-30

    We have employed three-dimensional (3D) extrusion-based printing as a medicine manufacturing technique for the production of multi-active tablets with well-defined and separate controlled release profiles for three different drugs. This 'polypill' made by a 3D additive manufacture technique demonstrates that complex medication regimes can be combined in a single tablet and that it is viable to formulate and 'dial up' this single tablet for the particular needs of an individual. The tablets used to illustrate this concept incorporate an osmotic pump with the drug captopril and sustained release compartments with the drugs nifedipine and glipizide. This combination of medicines could potentially be used to treat diabetics suffering from hypertension. The room temperature extrusion process used to print the formulations used excipients commonly employed in the pharmaceutical industry. Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and X-ray powder diffraction (XRPD) were used to assess drug-excipient interaction. The printed formulations were evaluated for drug release using USP dissolution testing. We found that the captopril portion showed the intended zero order drug release of an osmotic pump and noted that the nifedipine and glipizide portions showed either first order release or Korsmeyer-Peppas release kinetics dependent upon the active/excipient ratio used.

  9. CHEMICAL MODIFICATION AND CHARACTERIZATION OF PECTIN AS A POTENTIAL DRUG RELEASE RETARDANT

    Directory of Open Access Journals (Sweden)

    Harika Puppala Satya Krishna

    2011-02-01

    Full Text Available The present study deals with the chemical modification of pectin by acetylation of their free hydroxyl groups to yield high ester pectin and to evaluate its solubility and swelling behaviour along with the effect on the release pattern of the drug. Modified pectins were prepared by acetylation process using various strengths of 20%, 40% and 60% v/v acetyl chloride in ethanol. The prepared modified pectins were subjected to various physico-chemical characteristics like solubility, gelling studies, acid value, saponification value and ester value. FTIR studies were carried out to confirm the chemical modification of pectin. Matrix tablets of tramadol were formulated using various strengths of modified pectins in different concentrations and its impact on drug release was studied. All the formulated batches were subjected to weight variation, hardness, friability, drug content and the values obtained were within the acceptable range. The in-vitro drug release characteristics from the formulated tablets were compared with commercial sustained release tablet of tramadol. The optimized tablet formulation F4 sustained the drug release over a period of 8hours as comparable to the marketed product. Thus the synthesized modified pectin proved to be an ideal drug release retarding polymer.

  10. Drug-nanoencapsulated PLGA microspheres prepared by emulsion electrospray with controlled release behavior

    Science.gov (United States)

    Yao, Shenglian; Liu, Huiying; Yu, Shukui; Li, Yuanyuan; Wang, Xiumei; Wang, Luning

    2016-01-01

    The development of modern therapeutics has raised the requirement for controlled drug delivery system which is able to efficiently encapsulate bioactive agents and achieve their release at a desired rate satisfying the need of the practical system. In this study, two kind of aqueous model drugs with different molecule weight, Congo red and albumin from bovine serum (BSA) were nano-encapsulated in poly (dl-lactic-co-glycolic acid) (PLGA) microspheres by emulsion electrospray. In the preparation process, the aqueous phase of drugs was added into the PLGA chloroform solution to form the emulsion solution. The emulsion was then electrosprayed to fabricate drug-nanoencapsulated PLGA microspheres. The morphology of the PLGA microspheres was affected by the volume ratio of aqueous drug phase and organic PLGA phase (Vw/Vo) and the molecule weight of model drugs. Confocal laser scanning microcopy showed the nanodroplets of drug phase were scattered in the PLGA microspheres homogenously with different distribution patterns related to Vw/Vo. With the increase of the volume ratio of aqueous drug phase, the number of nanodroplets increased forming continuous phase gradually that could accelerate drug release rate. Moreover, BSA showed a slower release rate from PLGA microspheres comparing to Congo red, which indicated the drug release rate could be affected by not only Vw/Vo but also the molecule weight of model drug. In brief, the PLGA microspheres prepared using emulsion electrospray provided an efficient and simple system to achieve controlled drug release at a desired rate satisfying the need of the practices. PMID:27699061

  11. Poly(lactide-co-glycolide)-methoxy-poly(ethylene glycol) nanoparticles: drug loading and release properties.

    Science.gov (United States)

    Katsikogianni, Georgia; Avgoustakis, Konstantinos

    2006-01-01

    In this work, the drug loading and in vitro release properties of PLGA-mPEG nanoparticles were studied. Three methyl-xanthine derivatives differing significantly in aqueous solubility, i.e., caffeine, theophylline, and theobromine, were employed as model drugs. Two different PLGA-mPEG copolymer compositions, namely PLGA(40)mPEG(5) and PLGA(136)mPEG(5), were included in the study. The nanoparticles were prepared by a double emulsion technique. The drug release properties of the nanoparticles in phosphate buffered saline (PBS) and in human plasma were determined. An increase of the drug proportion in the feed led to increased drug loading. The composition of the PLGA-mPEG copolymer (PLGA/mPEG molar ratio) did not appear to affect drug loading and encapsulation. Caffeine exhibited higher loading in the nanoparticles than theobromine and this exhibited a little higher loading than theophylline. Solid-state solubility of the drug in PLGA-mPEG did not affect drug loading. Drug loading and encapsulation in the PLGA-mPEG nanoparticles appeared to be governed by the partition coefficient of the drug between the organic phase and the external aqueous phase employed in nanoparticle preparation. Relatively low loading and encapsulation values were obtained, suggesting that the physical entrapment of drugs in PLGA-mPEG nanoparticles could only be an option in the development of formulations of potent drugs. Only the release of the least water-soluble theobromine was efficiently sustained by its entrapment in the nanoparticles, indicating that the physical entrapment of drugs provides the means for the development of controlled-release PLGA-mPEG nanoparticulate formulations only in the case of drugs with low aqueous solubility.

  12. Spherical mesoporous silica nanoparticles for loading and release of the poorly water-soluble drug telmisartan.

    Science.gov (United States)

    Zhang, Yanzhuo; Zhi, Zhuangzhi; Jiang, Tongying; Zhang, Jinghai; Wang, Zhanyou; Wang, Siling

    2010-08-03

    The purpose of this study was to develop mesoporous silica nanoparticles (MSNs) loaded with a poorly water-soluble drug, intended to be orally administered, able to improve the dissolution rate and enhance the drug loading capacity. Spherical MSNs were synthesized using an organic template method in an oil/water phase, and large pore diameter MSNs were functionalized with aminopropyl groups through postsynthesis. MSNs as well as the resulting functionalized MSNs were investigated as matrices for loading and release of the model drug telmisartan (TEL). The effects of different pore sizes and surface chemical groups on TEL uptake and release were systematically studied using scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption, X-ray diffraction (XRD), Fourier transformation infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and HPLC. The total pore volume and the pore diameter of MSNs were the two main factors limiting the maximum drug load capacity. MSNs allow a very high drug loading of about 60% in weight. The release rate of TEL from MSNs with a pore diameter of 12.9 nm was found to be effectively increased and the release rate of TEL from the functionalized MSNs was effectively controlled compared with that from the unmodified MSNs. We believe that the present study will help in the design of oral drug delivery systems for the dissolution enhancement and/or sustained release of poorly water-soluble drugs.

  13. Inorganically modified diatomite as a potential prolonged-release drug carrier.

    Science.gov (United States)

    Janićijević, Jelena; Krajišnik, Danina; Calija, Bojan; Dobričić, Vladimir; Daković, Aleksandra; Krstić, Jugoslav; Marković, Marija; Milić, Jela

    2014-09-01

    Inorganic modification of diatomite was performed with the precipitation product of partially neutralized aluminum sulfate solution at three different mass ratios. The starting and the modified diatomites were characterized by SEM-EDS, FTIR, thermal analysis and zeta potential measurements and evaluated for drug loading capacity in adsorption batch experiments using diclofenac sodium (DS) as a model drug. In vitro drug release studies were performed in phosphate buffer pH6.8 from comprimates containing: the drug adsorbed onto the selected modified diatomite sample (DAMD), physical mixture of the drug with the selected modified diatomite sample (PMDMD) and physical mixture of the drug with the starting diatomite (PMDD). In vivo acute toxicity testing of the modified diatomite samples was performed on mice. High adsorbent loading of the selected modified diatomite sample (~250mg/g in 2h) enabled the preparation of comprimates containing adsorbed DS in the amount near to its therapeutic dose. Drug release studies demonstrated prolonged release of DS over a period of 8h from both DAMD comprimates (18% after 8h) and PMDMD comprimates (45% after 8h). The release kinetics for DAMD and PMDMD comprimates fitted well with Korsmeyer-Peppas and Bhaskar models, indicating that the release mechanism was a combination of non-Fickian diffusion and ion exchange process. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Multifunctionalization of magnetic nanoparticles for controlled drug release: a general approach.

    Science.gov (United States)

    Latorre, Alfonso; Couleaud, Pierre; Aires, Antonio; Cortajarena, Aitziber L; Somoza, Álvaro

    2014-07-23

    In this study, a general approach for the multifunctionalization of magnetic nanoparticles (MNPs) with drugs (Doxorubicin and Gemcitabine) and targeting moieties (Nucant pseudopeptide) for controlled and selective release is described. The functionalization is achieved by the formation of disulfide bonds between MNPs and drugs derivatives synthesized in this work. Our strategy consists in the introduction of a pyridyldisulfide moiety to the drugs that react efficiently with sulfhydryl groups of pre-activated MNPs. This approach also allows the quantification of the covalently immobilized drug by measuring the amount of the 2-pyridinethione released during the process. The linkers developed here allow the release of drugs without any chemical modification. This process is triggered under highly reducing environment, such as that present inside the cells. Complete release of drugs is achieved within 5-8 h under intracellular conditions whereas negligible percentage of release is observed in extracellular conditions. We propose here a modular general approach for the functionalization of nanoparticles that can be used for different types of drugs and targeting agents.

  15. Fabrication of core-shell micro/nanoparticles for programmable dual drug release by emulsion electrospraying

    Energy Technology Data Exchange (ETDEWEB)

    Wang Yazhou, E-mail: yazhou_wang@cqu.edu.cn; Zhang Yiqiong; Wang Bochu, E-mail: wangbc2000@126.com; Cao Yang [Chongqing University, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering (China); Yu Qingsong [University of Missouri, Department of Mechanical and Aerospace Engineering (United States); Yin Tieying [Chongqing University, Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering (China)

    2013-06-15

    The study aimed at constructing a novel drug delivery system for programmable multiple drug release controlled with core-shell structure. The core-shell structure consisted of chitosan nanoparticles as core and polyvinylpyrrolidone micro/nanocoating as shell to form core-shell micro/nanoparticles, which was fabricated by ionic gelation and emulsion electrospray methods. As model drug agents, Naproxen and rhodamine B were encapsulated in the core and shell regions, respectively. The core-shell micro/nanoparticles thus fabricated were characterized and confirmed by scanning electron microscope, transmission electron microscope, and fluorescence optical microscope. The core-shell micro/nanoparticles showed good release controllability through drug release experiment in vitro. It was noted that a programmable release pattern for dual drug agents was also achieved by adjusting their loading regions in the core-shell structures. The results indicate that emulsion electrospraying technology is a promising approach in fabrication of core-shell micro/nanoparticles for programmable dual drug release. Such a novel multi-drug delivery system has a potential application for the clinical treatment of cancer, tuberculosis, and tissue engineering.

  16. Experimental and numerical evaluation of drug release from nanofiber mats to brain tissue.

    Science.gov (United States)

    Nakielski, Paweł; Kowalczyk, Tomasz; Zembrzycki, Krzysztof; Kowalewski, Tomasz A

    2015-02-01

    Drug delivery systems based on nanofibrous mats appear to be a promising healing practice for preventing brain neurodegeneration after surgery. One of the problems encountered during planning and constructing optimal delivery system based on nanofibrous mats is the estimation of parameters crucial for predicting drug release dynamics. This study describes our experimental setup allowing for spatial and temporary evaluation of drug release from nanofibrous polymers to obtain data necessary to validate appropriate numerical models. We applied laser light sheet method to illuminate released fluorescent drug analog and CCD camera for imaging selected cross-section of the investigated volume. Transparent hydrogel was used as a brain tissue phantom. The proposed setup allows for continuous observation of drug analog (fluorescent dye) diffusion for time span of several weeks. Images captured at selected time intervals were processed to determine concentration profiles and drug release kinetics. We used presented method to evaluate drug release from several polymers to validate numerical model used for optimizing nanofiber system for neuroprotective dressing.

  17. A predictive model for the release of slightly water-soluble drugs from HPMC matrices.

    Science.gov (United States)

    Fu, X C; Wang, G P; Wang, Y H; Liang, W Q

    2004-08-01

    A model to predict the fraction of slightly water-soluble drug released as a function of release time (t, h), HPMC concentration (C(H), w/w), drug solubility in distilled water at 37 degrees C (C(s), g/100 mL), and volume of drug molecule (V, nm3) was derived when theophyline, tinidazole, and propylthiouracil were selected as model drugs. The model is log (M(t)/M(infinity)) = 0.8683 logt-0.1930C(s) logt + 0.5406V logt-1.227C(H) + 0.1594C(s) + 0.4423C(H)C(s) - 0.8655 (n = 130, r = 0.9969), where Mt is the amount of drug released at time t, Minfinity is the amount of drug released over a very long time, which corresponds in principle to the initial loading, n is the number of samples, and r is the correlation coefficient. The model was validated using sulfamethoxazole and satisfactory results were obtained. The model can be used to predict the release fraction of variousslightly water-soluble drugs from HPMC matrices having different polymer levels.

  18. Synthesis of attapulgite/N-isopropylacrylamide and its use in drug release

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaomo [Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials, School of Chemistry and Chemical Engineering, Huaiyin Normal University, Huaian 223300 (China); Faculty of Chemistry, Northeast Normal University, Changchun 130024, Jilin (China); Zhong, Hui, E-mail: huizhong@hytc.edu.cn [Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials, School of Chemistry and Chemical Engineering, Huaiyin Normal University, Huaian 223300 (China); Faculty of Chemistry, Northeast Normal University, Changchun 130024, Jilin (China); Li, Xiaorong, E-mail: lxr206206@163.com [Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials, School of Chemistry and Chemical Engineering, Huaiyin Normal University, Huaian 223300 (China); Jia, Feifei [Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials, School of Chemistry and Chemical Engineering, Huaiyin Normal University, Huaian 223300 (China); Faculty of Chemistry, Northeast Normal University, Changchun 130024, Jilin (China); Cheng, Zhipeng; Zhang, Lili; Yin, Jingzhou; An, Litao [Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials, School of Chemistry and Chemical Engineering, Huaiyin Normal University, Huaian 223300 (China); Guo, Liping, E-mail: guolp078@nenu.edu.cn [Faculty of Chemistry, Northeast Normal University, Changchun 130024, Jilin (China)

    2014-12-01

    Environmentally sensitive hydrogels as one of the most potential drug delivery systems have gained considerable interest in recent years. In the present study, we synthesized a newly temperature-responsive composite hydrogel based on attapulgite (ATP) and poly (N-isopropylacrylamide) (PNIPAM) as the localized drug carriers for drug delivery. The as-prepared ATP/PNIPAM hydrogel has large aperture which significantly improved the quantity of adsorption of drugs, exhibiting the excellent properties of drug release. The scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and X-ray diffraction (XRD) were used to characterize the ATP/PNIPAM. The swelling/deswelling behaviors and the release of ciprofloxacin lactate were studied. When the temperature was below the low critical solution temperature (LCST), the swelling property of hydrogels was excellent and the swelling rate was large. And, the drug release rate increased with the increase of the content of attapulgite in the composite hydrogel when it was put in the buffer solution (pH 7.38) at 37.0 °C. Therefore, the composite hydrogels might be very useful for its application in biomedical fields. - Highlights: • Attapulgite/N-isopropylacrylamide hydrogels were synthesized and characterized. • The swelling property of hydrogels was excellent when temperature was below 34.0 °C. • The composite hydrogels were used for the release of ciprofloxacin lactate. • The drug release rate increased with the increase of the content of attapulgite.

  19. [Evolution of oral drug forms of metoprolol: advantages of long acting modified release forms with modified release].

    Science.gov (United States)

    Leonova, M V; Maneshina, O A; Belousov, Iu B

    2010-01-01

    Review oral modified release drug forms of beta-adrenoblocker metoprolol which is used in arterial hypertension and ischemic heart disease is presented. Metoprolol has salts such as tartrate which is used for production of immediate release (IR) and sustained release (SR) forms and succinate used for production of controlled release form (CR/XL). Metoprolol SR has monolith matrix type, metoprolol CR/XL-system of multiple pellets. Effect of metoprolol tartrate (IR) on mortality was demonstrated in a number of studies in patients with arterial hypertension (AH) (MAPHY), myocardial infarction (SMT, GMT, MIAMI), dilated cardiomyopathy and heart failure (MDC). Studies of efficacy of metoprolol SR are scarce. Antihypertensive efficacy of metoprolol SR in patients with AH did not exceed that of a metoprolol IR or CR/XL. First retrospective analysis of efficacy of metoprolol tartrate and succinate (CR/XL) in patients after myocardial infarction allowed to obtain comparable results of 34% mortality lowering. In a prospective study in patients with chronic heart failure (COMET) metoprolol tartrate IR was not superior to carvedilol when mortality lowering was concerned. At the same time administration of controlled release metoprolol (CR/XL) in 2 large clinical trials (RESOLVD, MERITAHF) was advantageous in patients with chronic heart failure relative to lowering of mortality and rate of hospitalizations. A novel controlled release form of metoprolol has been created as a tartrate salt on the basis of pellet technology (CD/ERT) and its bioequivalence to metoprolol CR/XL has been proved.

  20. Numerical modelling and experimental investigation of drug release from layered silicone matrix systems.

    Science.gov (United States)

    Snorradóttir, Bergthóra S; Jónsdóttir, Fjóla; Sigurdsson, Sven Th; Thorsteinsson, Freygardur; Másson, Már

    2013-07-16

    Medical devices and polymeric matrix systems that release drugs or other bioactive compounds are of interest for a variety of applications. The release of the drug can be dependent on a number of factors such as the solubility, diffusivity, dissolution rate and distribution of the solid drug in the matrix. Achieving the goal of an optimal release profile can be challenging when relying solely on traditional experimental work. Accurate modelling complementing experimentation is therefore desirable. Numerical modelling is increasingly becoming an integral part of research and development due to the significant advances in computer simulation technology. This work focuses on numerical modelling and investigation of multi-layered silicone matrix systems. A numerical model that can be used to model multi-layered systems was constructed and validated by comparison with experimental data. The model could account for the limited dissolution rate and effect of the drug distribution on the release profiles. Parametric study showed how different factors affect the characteristics of drug release. Multi-layered medical silicone matrices were prepared in special moulds, where the quantity of drug in each layer could be varied, and release was investigated with Franz-diffusion cell setup. Data for long-term release was fitted to the model and the full depletion of the system predicted. The numerical model constructed for this study, whose input parameters are the diffusion, effective dissolution rate and dimensional solubility coefficients, does not require any type of steady-state approximation. These results indicate that numerical model can be used as a design tool for development of controlled release systems such as drug-loaded medical devices.

  1. Rhamnogalacturonan-I based microcapsules for targeted drug release

    DEFF Research Database (Denmark)

    Svagan, Anna J.; Kusic, Anja; De Gobba, Cristian;

    2016-01-01

    Drug targeting to the colon via the oral administration route for local treatment of e.g. inflammatory bowel disease and colonic cancer has several advantages such as needle-free administration and low infection risk. A new source for delivery is plant-polysaccharide based delivery platforms...... such as Rhamnogalacturonan-I (RG-I). In the gastro-intestinal tract the RG-I is only degraded by the action of the colonic microflora. For assessment of potential drug delivery properties, RG-I based microcapsules (~1 μm in diameter) were prepared by an interfacial poly-addition reaction. The cross-linked capsules were...

  2. Drug Release Kinetics, Cell Uptake, and Tumor Toxicity of Hybrid VVVVVVKK Peptide-Assembled Polylactide Nanoparticles

    Science.gov (United States)

    Jabbari, Esmaiel; Yang, Xiaoming; Moeinzadeh, Seyedsina; He, Xuezhong

    2013-01-01

    An exciting approach to tumor delivery is encapsulation of the drug in self-assembled polymer-peptide nanoparticles. The objective of this work was to synthesize a conjugate of low molecular weight polylactide (LMW PLA) and V6K2 peptide, and investigate self-assembly, drug release kinetics, cell uptake and toxicity, drug pharmacokinetics, and tumor cell invasion with Doxorubicin (DOX) or paclitaxel (PTX). The results for PLA-V6K2 self-assembled NPs were compared with those of polyethylene glycol stabilized PLA (PLA-EG) NPs. The size of PLA-V6K2 and PLA-EG NPs were 100±20 and 130±50 nm, respectively, with polydispersity index of 1.04 and 1.14. The encapsulation efficiency of DOX in PLA-V6K2 and PLA-EG NPs was 44±9% and 55±5%, respectively, and that of PTX was >90 for both NP types. The release of DOX and PTX from PLA-V6K2 was slower than that of PLA-EG and the release rate was relatively constant with time. Based on molecular dynamic simulation, the less hydrophobic DOX was distributed in the lactide core as well as the peptide shell while the hydrophobic PTX was localized mainly to the lactide core. PLA-V6K2 NPs had significantly higher cell uptake by 4T1 mouse breast carcinoma cells compared to PLA-EG NPs, which was attributed to the electrostatic interactions between the peptide and negatively charged moieties on the cell membrane. PLA-V6K2 NPs showed no toxicity to marrow stromal cells. DOX loaded PLA-V6K2 NPs showed higher toxicity to 4T1 cells and the DNA damage response and apoptosis was delayed compared to the free DOX. DOX or PTX encapsulated in PLA-V6K2 NPs significantly reduced invasion of 4T1 cells compared to those cells treated with the drug in PLA-EG NPs. Invasion of 4T1 cells treated with DOX in PLA-V6K2 and PLA-EG NPs was 5±1% and 30±5%, respectively, and that of PTX was 11±2% and 40±7%. The AUC of DOX in PLA-V6K2 NPs was 67% and 21% higher than those of free DOX and PLA-EG NPs, respectively. DOX loaded PLA-V6K2 NPs injected in C3He

  3. The effects of cyclodextrins on drug release from fatty suppository bases : I. In vitro observations

    NARCIS (Netherlands)

    Frijlink, H.W.; Eissens, Anko; Schoonen, Adelbert; Lerk, C.F.

    1991-01-01

    The effect of cyclodextrins on suppository drug release was investigated. Complexes of several lipophilic drugs with β- and/or γ-cyclodextrin were prepared using the coprecipitation method. The formation of true complexes was confirmed by DSC and an 'ether-wash' method. Witepsol H15 suppositories we

  4. Evaluating the effects of crystallinity in new biocompatible polyester nanocarriers on drug release behavior.

    Science.gov (United States)

    Karavelidis, Vassilios; Karavas, Evangelos; Giliopoulos, Dimitrios; Papadimitriou, Sofia; Bikiaris, Dimitrios

    2011-01-01

    Four new polyesters based on 1,3-propanediol and different aliphatic dicarboxylic acids were used to prepare ropinirole HCl-loaded nanoparticles. The novelty of this study lies in the use of polyesters with similar melting points but different degrees of crystallinity, varying from 29.8% to 67.5%, as drug nanocarriers. Based on their toxicity to human umbilical vein endothelial cells, these aliphatic polyesters were found to have cytotoxicity similar to that of polylactic acid and so may be considered as prominent drug nanocarriers. Drug encapsulation in polyesters was performed via an emulsification/solvent evaporation method. The mean particle size of drug-loaded nanoparticles was 164-228 nm, and the drug loading content was 16%-23%. Wide angle X-ray diffraction patterns showed that ropinirole HCl existed in an amorphous state within the nanoparticle polymer matrices. Drug release diagrams revealed a burst effect for ropinirole HCl in the first 6 hours, probably due to release of drug located on the nanoparticle surface, followed by slower release. The degree of crystallinity of the host polymer matrix seemed to be an important parameter, because higher drug release rates were observed in polyesters with a low degree of crystallinity.

  5. Study of anti-cancer drug release (tamoxifen of the nanofibers made of polycaprolactone -chitosan

    Directory of Open Access Journals (Sweden)

    Zahra Saeidi

    2016-12-01

    Full Text Available Breast cancer is a kind of cancer that begins than breast tissue. That in a kind of it, breast skin is quite involved. Than symptoms of the breast cancer is a dimple on the skin and peeling of skin and on the chest and..Natural polymers in terms of the environmental characteristics and their compatibility with the human body have vast applications in the industry: cosmetics, wound dressing, delivery of medicine scaffold, and so on.In this study, the cancer drug (tamoxifen used to complete the PCL-chitosan nanofibers made of a biocompatible polymer packag that deliver drugs will be examine. For this purpose, first the nanofibers made of PCL-chitosan-containing drugs (tamoxifen with optimal concentration of the drug was produced by electrospinning. The surface morphology of nanofibers microscopy (SEM were studied. Using infrared spectrometer instrument (FTIR evaluated the drug in nano-fibers. The effects of drug release and antimicrobial from nanofibers with standard (AATCC100 measurement and determined. According to antimicrobial test the nano-fiber manufacturing against Gram-positive and Gram-negative bacteria, Escherichia coli and Staphylococcus Cocos considerable influence along. Based on the results of tests it was found that nano-fiber PCL-chitosan-containing drug with a ratio of 70-30 and a concentration of 1 gr and 0.3 gr, speed And release better itself show compared to concentrations and the other ratios. The test results of drug release indicate a total release rate was high.

  6. Design Project on Controlled-Release Drug Delivery Devices: Implementation, Management, and Learning Experiences

    Science.gov (United States)

    Xu, Qingxing; Liang, Youyun; Tong, Yen Wah; Wang, Chi-Hwa

    2010-01-01

    A design project that focuses on the subject of controlled-release drug delivery devices is presented for use in an undergraduate course on mass transfer. The purpose of the project is to introduce students to the various technologies used in the fabrication of drug delivery systems and provide a practical design exercise for understanding the…

  7. Assembling and releasing performance of supramolecular hydrogels formed from simple drug molecule as the hydrogelator

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    A simple drug compound, 4-oxo-4-(2-pyridinylamino) butanoic acid (defined as AP), was able to gel water at 4 wt%concentration under various conditions. In the superstructure, AP molecules assembled into fibrous aggregates driving by hydrogen bonds and π-π stacking interaction. The gels with different backbone structures released drug molecules in different speeds.

  8. The effects of particle properties on nanoparticle drug retention and release in dynamic minoxidil foams.

    Science.gov (United States)

    Zhao, Yanjun; Brown, Marc B; Jones, Stuart A

    2010-01-04

    Nanocarriers may act as useful tools to deliver therapeutic agents to the skin. However, balancing the drug-particle interactions; to ensure adequate drug loading, with the drug-vehicle interactions; to allow efficient drug release, presents a significant challenge using traditional semi-solid vehicles. The aim of this study was to determine how the physicochemical properties of nanoparticles influenced minoxidil release pre and post dose application when formulated as a simple aqueous suspension compared to dynamic hydrofluoroalkane (HFA) foams. Minoxidil loaded lipid nanoparticles (LN, 1.4 mg/ml, 50 nm) and polymeric nanoparticles with a lipid core (PN, 0.6 mg/ml, 260 nm) were produced and suspended in water to produce the aqueous suspensions. These aqueous suspensions were emulsified with HFA using pluronic surfactant to generate the foams. Approximately 60% of the minoxidil loaded into the PN and 80% of the minoxidil loaded into the LN was released into the external aqueous phase 24h after production. Drug permeation was superior from the PN, i.e. it was the particle that retained the most drugs, irrespective of the formulation method. Premature drug release, i.e. during storage, resulted in the performance of the topical formulation being dictated by the thermodynamic activity of the solubilised drug not the particle properties.

  9. 76 FR 27888 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor-Diphtheria...

    Science.gov (United States)

    2011-05-13

    ... drug regulations to reflect approval of a new animal drug application (NADA) filed by Pfizer, Inc. The NADA provides for the veterinary prescription use of gonadotropin releasing factor-diphtheria toxoid...-5755, filed NADA 141-322 that provides for the veterinary prescription use of IMPROVEST...

  10. 77 FR 4227 - Implantation or Injectable Dosage Form New Animal Drugs; Gonadotropin Releasing Factor Analog...

    Science.gov (United States)

    2012-01-27

    ... drug regulations to reflect approval of a supplemental new animal drug application (NADA) filed by Pfizer, Inc. The supplemental NADA extends the slaughter interval for intact male swine injected with..., filed a supplement to NADA 141-322 for IMPROVEST (gonadotropin releasing factor analog-diphtheria...

  11. The effects of cyclodextrins on drug release from fatty suppository bases : I. In vitro observations

    NARCIS (Netherlands)

    Frijlink, H.W.; Eissens, Anko; Schoonen, Adelbert; Lerk, C.F.

    The effect of cyclodextrins on suppository drug release was investigated. Complexes of several lipophilic drugs with β- and/or γ-cyclodextrin were prepared using the coprecipitation method. The formation of true complexes was confirmed by DSC and an 'ether-wash' method. Witepsol H15 suppositories

  12. Optimization of biodegradable sponges as controlled release drug matrices. I. Effect of moisture level on chitosan sponge mechanical properties.

    Science.gov (United States)

    Foda, Nagwa H; El-laithy, Hanan M; Tadros, Mina I

    2004-04-01

    Cross-linked chitosan sponges as controlled release drug carrier systems were developed. Tramadol hydrochloride, a centrally acting analgesic, was used as a model drug. The sponges were prepared by freeze-drying 1.25% and 2.5% (w/w) high and low M.wt. chitosan solutions, respectively, using glutaraldehyde as a cross-linking agent. The hardness of the prepared sponges was a function of glutaraldehyde concentration and volume where the optimum concentration that offered accepted sponge consistency was 5%. Below or above 5%, very soft or very hard and brittle sponges were obtained, respectively. The determined drug content in the prepared sponges was uniform and did not deviate markedly from the calculated amount. Scanning electron microscopy (SEM) was used to characterize the internal structures of the sponges. The SEM photos revealed that cross-linked high M.wt. chitosan sponges have larger size surface pores that form connections (channels) with the interior of the sponge than cross-linked low M.wt. ones. Moreover, crystals of the incorporated Tramadol hydrochloride were detected on the lamellae and within pores in both chitosan sponges. Differences in pore size and dissolution medium uptake capacity were crucial factors for the more delayed drug release from cross-linked low M.wt. chitosan sponges over high M.wt. ones at pH 7.4. Kinetic analysis of the release data using linear regression followed the Higuchi diffusion model over 12 hours. Setting storage conditions at room temperature under 80-92% relative humidity resulted in soft, elastic, and compressible sponges.

  13. Optical suppression of drug-evoked phasic dopamine release.

    Science.gov (United States)

    McCutcheon, James E; Cone, Jackson J; Sinon, Christopher G; Fortin, Samantha M; Kantak, Pranish A; Witten, Ilana B; Deisseroth, Karl; Stuber, Garret D; Roitman, Mitchell F

    2014-01-01

    Brief fluctuations in dopamine concentration (dopamine transients) play a key role in behavior towards rewards, including drugs of abuse. Drug-evoked dopamine transients may result from actions at both dopamine cell bodies and dopamine terminals. Inhibitory opsins can be targeted to dopamine neurons permitting their firing activity to be suppressed. However, as dopamine transients can become uncoupled from firing, it is unknown whether optogenetic hyperpolarization at the level of the soma is able to suppress dopamine transients. Here, we used in vivo fast-scan cyclic voltammetry to record transients evoked by cocaine and raclopride in nucleus accumbens (NAc) of urethane-anesthetized rats. We targeted halorhodopsin (NpHR) specifically to dopamine cells by injecting Cre-inducible virus into ventral tegmental area (VTA) of transgenic rats that expressed Cre recombinase under control of the tyrosine hydroxylase promoter (TH-Cre(+) rats). Consistent with previous work, co-administration of cocaine and raclopride led to the generation of dopamine transients in NAc shell. Illumination of VTA with laser strongly suppressed the frequency of transients in NpHR-expressing rats, but not in control rats. Laser did not have any effect on amplitude of transients. Thus, optogenetics can effectively reduce the occurrence of drug-evoked transients and is therefore a suitable approach for studying the functional role of such transients in drug-associated behavior.

  14. Optical suppression of drug-evoked phasic dopamine release

    Directory of Open Access Journals (Sweden)

    James Edgar Mccutcheon

    2014-09-01

    Full Text Available Brief fluctuations in dopamine concentration (dopamine transients play a key role in behavior towards rewards, including drugs of abuse. Drug-evoked dopamine transients may result from actions at both dopamine cell bodies and dopamine terminals. Inhibitory opsins can be targeted to dopamine neurons permitting their firing activity to be suppressed. However, as dopamine transients can become uncoupled from firing, it is unknown whether optogenetic hyperpolarization at the level of the soma is able to suppress dopamine transients. Here, we used in vivo fast-scan cyclic voltammetry to record transients evoked by cocaine and raclopride in nucleus accumbens (NAc of urethane-anesthetized rats. We targeted halorhodopsin (NpHR specifically to dopamine cells by injecting Cre-inducible virus into ventral tegmental area (VTA of transgenic rats that expressed Cre recombinase under control of the tyrosine hydroxylase promoter (TH-Cre+ rats. Consistent with previous work, co-administration of cocaine and raclopride led to the generation of dopamine transients in NAc shell. Illumination of VTA with laser strongly suppressed the frequency of transients in NpHR-expressing rats, but not in control rats. Laser did not have any effect on amplitude of transients. Thus, optogenetics can effectively reduce the occurrence of drug-evoked transients and is therefore a suitable approach for studying the functional role of such transients in drug-associated behavior.

  15. Effects of poly lactic-co-glycolic acid-Nogo A antibody delayed-release microspheres on regeneration of injured spinal cord in rats

    Institute of Scientific and Technical Information of China (English)

    Hai Lan; Yueming Song

    2009-01-01

    microsphere group was significantly less than model and Nogo A antibody alone groups (P0.05). Ten weeks after injury, microsphere group showed a significantly greater expression of neurofilament 200 than model and Nogo A antibody alone groups (P0.05). At postoperative weeks 5 and 6, the score of BBB locomotor rating scale in microsphere group was significantly greater than the model group (P< 0.05), and at postoperative weeks 7-10, the score was much greater than model and Nogo A antibody alone groups (P<0.05).CONCLUSION: Nogo A antibody delayed-release microspheres decreased Nogo A expression, increased neurofilament 200 expression in the injured spinal cord of rats, and promoted recovery of motor function through sustained drug release over a long-term period.

  16. Characterization of drug-release kinetics in trabecular bone from titania nanotube implants

    Directory of Open Access Journals (Sweden)

    Aw MS

    2012-09-01

    Full Text Available Moom Sinn Aw,1 Kamarul A Khalid,2,3 Karan Gulati,1 Gerald J Atkins,2 Peter Pivonka,4 David M Findlay,2 Dusan Losic11School of Chemical Engineering, 2Discipline of Orthopaedics and Trauma, The University of Adelaide, Adelaide, SA, Australia; 3Department of Orthopaedics, Traumatology and Rehabilitation, Faculty of Medicine, International Islamic University Malaysia, Kuantan, Pahang, Malaysia; 4Engineering Computational Biology Group, School of Computer Science and Software Engineering, The University of Western Australia, Perth, WA, AustraliaPurpose: The aim of this study was to investigate the application of the three-dimensional bone bioreactor for studying drug-release kinetics and distribution of drugs in the ex vivo cancellous bone environment, and to demonstrate the application of nanoengineered titanium (Ti wires generated with titania nanotube (TNT arrays as drug-releasing implants for local drug deliveryMethods: Nanoengineered Ti wires covered with a layer of TNT arrays implanted in bone were used as a drug-releasing implant. Viable bovine trabecular bone was used as the ex vivo bone substrate embedded with the implants and placed in the bone reactor. A hydrophilic fluorescent dye (rhodamine B was used as the model drug, loaded inside the TNT–Ti implants, to monitor drug release and transport in trabecular bone. The distribution of released model drug in the bone was monitored throughout the bone structure, and concentration profiles at different vertical (0–5 mm and horizontal (0–10 mm distances from the implant surface were obtained at a range of release times from 1 hour to 5 days.Results: Scanning electron microscopy confirmed that well-ordered, vertically aligned nanotube arrays were formed on the surface of prepared TNT–Ti wires. Thermogravimetric analysis proved loading of the model drug and fluorescence spectroscopy was used to show drug-release characteristics in-vitro. The drug release from implants inserted into bone ex

  17. Externally controlled drug release using a gold nanorod contained composite membrane.

    Science.gov (United States)

    Kim, Kibeom; Jo, Min-Chul; Jeong, Sundo; Palanikumar, L; Rotello, Vincent M; Ryu, Ja-Hyoung; Park, Myoung-Hwan

    2016-06-09

    Versatile drug delivery devices using nanoporous membranes consisting of gold nanorods and dendrimers have been demonstrated to provide light-triggered on-demand pulsatile release from a reservoir containing highly enriched therapeutics for a real patient's needs. The drug release rate is directly correlated with the temperature increase and irradiated energy of a near-IR laser in both static and fluidic devices. This biocompatible platform for on-demand control was further confirmed by in vitro experiments. Interestingly, different responses to stimuli were obtained from each drug in the absence and presence of NIR light, indicating the versatile potential of our on-demand drug delivery system in less-invasive therapies requiring multi-drug delivery strategies. The enhanced delivery system will improve therapeutic efficacy and reduce side effects through regulation of plasma drug profiles.

  18. Investigation into the Effect of Ethylcellulose Viscosity Variation on the Drug Release of Metoprolol Tartrate and Acetaminophen Extended Release Multiparticulates-Part I.

    Science.gov (United States)

    Mehta, R; Teckoe, J; Schoener, C; Workentine, S; Ferrizzi, D; Rajabi-Siahboomi, A

    2016-12-01

    Ethylcellulose is one of the most commonly used polymers to develop reservoir type extended release multiparticulate dosage forms. For multiparticulate extended release dosage forms, the drug release is typically governed by the properties of the barrier membrane coating. The ICH Pharmaceutical Development Guideline (ICH Q8) requires an understanding of the influence of critical material attributes and critical process parameters on the drug release of a pharmaceutical product. Using this understanding, it is possible to develop robust formulations with consistent drug release characteristics. Critical material attributes for ethylcellulose were evaluated, and polymer molecular weight variation (viscosity) was considered to be the most critical attribute that can impact drug release. To investigate the effect of viscosity variation within the manufacturer's specifications of ethylcellulose, extended release multiparticulate formulations of two model drugs, metoprolol tartrate and acetaminophen, were developed using ETHOCEL™ as the rate controlling polymer. Quality by Design (QbD) samples of ETHOCEL Std. 10, 20, and 100 Premium grades representing the low, medium, and high molecular weight (viscosity) material were organically coated onto drug layered multiparticulates to a 15% weight gain (WG). The drug release was found to be similar (f 2 > 50) for both metoprolol tartrate and acetaminophen multiparticulates at different coating weight gains of ethylcellulose, highlighting consistent and robust drug release performance. The use of ETHOCEL QbD samples also serves as a means to develop multiparticulate dosage formulations according to regulatory guidelines.

  19. Evaluation of drug release from coated pellets based on isomalt, sugar, and microcrystalline cellulose inert cores.

    Science.gov (United States)

    Kállai, Nikolett; Luhn, Oliver; Dredán, Judit; Kovács, Kristóf; Lengyel, Miléna; Antal, István

    2010-03-01

    The objective of the present study was to investigate the effect of the pellet core materials isomalt, sugar, and microcrystalline cellulose on the in vitro drug release kinetics of coated sustained-release pellets as well as to evaluate the influence of different ratios of polymethacrylate copolymers exhibiting different permeability characteristics on the drug release rate. For characterization of the drug release process of pellets, the effect of osmolality was studied using glucose as an osmotically active agent in the dissolution medium. The pellet cores were layered with diclofenac sodium as model drug and coated with different ratios of Eudragit RS30D and Eudragit RL30D (ERS and ERL; 0:1 and 0.5:0.5 and 1:0 ratio) in a fluid bed apparatus. Physical characteristics such as mechanical strength, shape, and size proved that the inert cores were adequate for further processing. The in vitro dissolution tests were performed using a USP Apparatus I (basket method). The results demonstrated that, besides the ratio of the coating polymers (ERS/ERL), the release mechanism was also influenced by the type of starter core used. Sugar- and isomalt-type pellet cores demonstrated similar drug release profiles.

  20. Formulation and evaluation of dorzolamide hydrochloride-loaded nanoparticles as controlled release drug delivery system

    Directory of Open Access Journals (Sweden)

    Azza A Hasan

    2012-01-01

    Full Text Available This study aimed to prepare anti-glaucomatous dorzolamide hydrochloride-(Dorzo loaded nanoparticles as a controlled release system. Eudragit RS 100 (RS and/or RL 100 (RL were used in formulations by an opportunely adapted Quasi-emulsion solvent diffusion technique. The formulations were evaluated in terms of particle size, zeta potential, drug entrapment, and release profile. All formulations showed tiny particle size varying from 114 to 395 nm for RS and 65 to 277 nm for RL. Positive zeta potential was +19 to +32 mV for RS and +23 to +42 mV for RL formulations. It was demonstrated that increasing polymer concentration lead to increase the percentage of drug entrapped in all batches, to a certain extent (drug: polymer 1:4. Nanoparticles prepared using RL showed lower entrapment efficiency than RS. In contrast, increasing the stirring rate resulted in an increase in the percentage of Dorzo entrapped. A prolonged drug release was shown by all the formulations. Increasing the polymer concentration caused a decrease in the release rate. Moreover, it was evident that increasing RL content increased the amount of Dorzo released. Dorzo-loaded nanoparticles could represent promising drug ophthalmic carriers, due to small particle size, positive zeta potential, and sustained release profile; hence, expecting prolonged corneal contact time, more therapeutically efficient, decreased frequency of administration per day, and better patient compliance.

  1. [Release characteristics in vitro and pharmacokinetics of da chuanxiong fang multiunit drug delivery system in rats].

    Science.gov (United States)

    Wei, Yuan-feng; Zhang, Ning; Lin, Xiao; Feng, Yi

    2011-09-01

    The drug release characteristics ofDa Chuanxiong Fang multiunit drug delivery system (DCXFMDDS) in vivo and in vitro were evaluated. Ferulic acid (FA) and senkyunolide I (SI) were used as marker components, which were two of the effective components of Da Chuanxiong Fang. And their contents were determined by HPLC. Drug release characteristics in vitro of DCXFMDDS and Da Chuanxiong pills and pharmacokinetics characteristics of DCXFMDDS and Da Chuanxiong Fang active fraction (DCXFAF) in rats were compared. It was obvious that FA released from the DCXFMDDS in a sustained fashion but SI in a fast fashion both in vitro and in vivo. The releasing process and the releasing mechanism of FA and SI from DCXFMDDS were different, but the AUC value indicated that compared with DCXFAF the extent of absorption of FA and SI from DCXFMDDS was increased. Though from the same multiunit drug delivery system, FA an SI had different drug release characteristics both in vitro and in vivo, and that may be one of the reason why DCXFMDDS has the good properties such as rapid and long-lasting effect and high efficiency.

  2. Swelling and drug releasing properties of poly(N-isopropylacrylamide) thermo-sensitive copolymer gels

    Institute of Scientific and Technical Information of China (English)

    Chunyue PAN; Qingde LONG; Dian YU; Yanping RAO; Nianqian WU; Xingcui LI

    2008-01-01

    A series of N,isopropylacrylamide (NIPAAm)copolymer gels with different hydrophilicities were prepared from NIPAAm, hydrophilic acrylamide (AAm) and hydrophobic butyl methacrylate (BMA). The swelling and thermo,responsive properties of PNIPAAm P (NIPAm,co,BMA) and P(NIPAm,co,AAm) copolymer hydrogels were investigated. The drug loading and releasing behaviors for two kinds of model drug with different hydrophilicities were studied. The result shows that the copolymer gels present negative thermo,sensitivities. The lower critical solution temperature (LCST), equilibrium swelling degree and the initial swelling rate increase as the hydrophilicity of gels increases when the temperature is below the LCST. With increasing gel hydrophilicity the loading ratio for sodium salicylate increases, while for salicylic acid, the reverse is observed. The initial drug releasing rate of sodium salicylate and salicylic acid also increase with increasing gel hydrophilicity. The initial drug releasing rate of sodium salicylate is significantly higher than that of salicylic acid. For salicylic acid which is less hydrophilic, the equilibrium releasing ratio at high temperature is lower than that at low temperature while for sodium salicylate which is more hydrophilic, the equilibrium releasing ratio at high temperature is almost the same as that at low temperature. Equilibrium releasing ratios of the three gels are significantly different from each other for salicylic acid when the temperature is below LCST while the equilibrium releasing ratios of the three gels are all 100% for sodium salicylate.

  3. Polymer excipients enable sustained drug release in low pH from mechanically strong inorganic geopolymers.

    Science.gov (United States)

    Jämstorp, Erik; Yarra, Tejaswi; Cai, Bing; Engqvist, Håkan; Bredenberg, Susanne; Strømme, Maria

    2012-01-01

    Improving acid resistance, while maintaining the excellent mechanical stability is crucial in the development of a sustained and safe oral geopolymer dosage form for highly potent opioids. In the present work, commercially available Methacrylic acid-ethyl acrylate copolymer, Polyethylene-glycol (PEG) and Alginate polymer excipients were included in dissolved or powder form in geopolymer pellets to improve the release properties of Zolpidem, herein acting as a model drug for the highly potent opioid Fentanyl. Scanning electron microscopy, compression strength tests and drug release experiments, in gastric pH 1 and intestinal pH 6.8 conditions, were performed. The polymer excipients, with an exception for PEG, reduced the drug release rate in pH 1 due to their ability to keep the pellets in shape, in combination with the introduction of an insoluble excipient, and thereby maintain a barrier towards drug diffusion and release. Neither geopolymer compression strength nor the release in pH 6.8 was considerably impaired by the incorporation of the polymer excipients. The geopolymer/polymer composites combine high mechanical strength and good release properties under both gastric and intestinal pH conditions, and are therefore promising oral dosage forms for sustained release of highly potent opioids.

  4. Evaluation of drug delivery profiles in geometric three-layered tablets with various mechanical properties, in vitro-in vivo drug release, and Raman imaging.

    Science.gov (United States)

    Choi, Du Hyung; Kim, Ki Hyun; Park, Jun Sang; Jeong, Seong Hoon; Park, Kinam

    2013-12-28

    Even though various multi-layered tablets have been developed for sustained release formulations, evaluations of mechanical properties during dissolution with drug release and imaging in the tablets have been limited. A novel geometric system consisting of an inner immediate release layer and two extended release barrier layers with swellable hydrophilic polymers was suggested as a once-a-day formulation. To evaluate drug release mechanisms with geometric properties, various mechanical characteristics during swelling were investigated to comprehend the relationship among in vitro drug release, human pharmacokinetics, and geometric characteristics. Imaging of drug movement was also studied in real-time using Raman spectroscopy. Drug delivery in the tablets might be divided into three processes through the geometric properties. When exposed to aqueous environments, the drug in the mid-layer was released until wrapped by the swollen barrier layers. Then, the drug in the mid-layer was mainly delivered to the barrier layers and a small amount of the drug was delivered to the contact region of the swollen barrier layers. Finally, the delivered drug to the barrier layers was consistently released out in response to the characteristics of the polymer of the barrier layers. Using Raman spectroscopy, these processes were confirmed in real-time analysis. Moreover, in vitro drug release profiles and human pharmacokinetics showed consistent results suggesting that drug release might be dependent on the various geometric properties and be modified consistently during the formulation development. © 2013.

  5. Triggered drug release from dynamic microspheres via a protein conformational change.

    Science.gov (United States)

    King, William J; Pytel, Nicholas J; Ng, Kelvin; Murphy, William L

    2010-06-11

    In this study we formed and characterized dynamic hydrogel microspheres in which a protein conformational change was used to control microsphere volume changes and the release of an encapsulated drug. In particular, a specific biochemical ligand, trifluoperazine, induced calmodulin's nanometer scale conformation change, which translated to a 48.7% microsphere volume decrease. This specific, ligand-induced volume change triggered the release of a model drug, vascular endothelial growth factor (VEGF), at pre-determined times. After release from the microspheres, 85.6 +/- 10.5% of VEGF was in its native conformation. Taken together, these results suggest that protein conformational change could serve as a useful mechanism to control drug release from dynamic hydrogels.

  6. Review on Medusa:a polymer-based sustained release technology for protein and peptide drugs.

    Science.gov (United States)

    Chan, Y-P; Meyrueix, R; Kravtzoff, R; Nicolas, F; Lundstrom, K

    2007-07-01

    The polymer-based Medusa system (Flamel Technologies) has been designed for slow release of therapeutic proteins and peptides. The Medusa II consists of a poly L-glutamate backbone grafted with hydrophobic alpha-tocopherol molecules, creating a colloidal suspension of nanoparticles (10 - 50 nm) in water. The sustained drug release is based on reversible drug interactions with hydrophobic nanodomains within the nanoparticles. In vivo, it is suggested that the therapeutic protein is displaced by endogenous proteins present in physiological fluids, leading to a slow drug release. The peak concentration is dramatically decreased and the protein release substantially extended. The Medusa technology has been applied to subcutaneous injection for several therapeutic proteins, such as IL-2 and IFN-alpha(2b), in animal models (rats, dogs, monkeys) and clinical trials in renal cancer (IL-2) and hepatitis C (IFN-alpha(2b)) patients.

  7. Controlled release of simvastatin from biomimetic β-TCP drug delivery system.

    Directory of Open Access Journals (Sweden)

    Joshua Chou

    Full Text Available Simvastatin have been shown to induce bone formation and there is currently a urgent need to develop an appropriate delivery system to sustain the release of the drug to increase therapeutic efficacy whilst reducing side effects. In this study, a novel drug delivery system for simvastatin by means of hydrothermally converting marine exoskeletons to biocompatible beta-tricalcium phosphate was investigated. Furthermore, the release of simvastatin was controlled by the addition of an outer apatite coating layer. The samples were characterized by x-ray diffraction analysis, fourier transform infrared spectroscopy, scanning electron microscopy and mass spectroscopy confirming the conversion process. The in-vitro dissolution of key chemical compositional elements and the release of simvastatin were measured in simulated body fluid solution showing controlled release with reduction of approximately 25% compared with un-coated samples. This study shows the potential applications of marine structures as a drug delivery system for simvastatin.

  8. In Vitro Cytotoxicity and Protein Drug Release Properties of Chitosan/Heparin Microspheres

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Chitosan/heparin microspheres were prepared using the water-in-oil emulsification solvent evaporation technique. The microsphere diameters were controlled by selecting the fabrication process parameters. Scanning electron micrographs showed that the chitosan/heparin microspheres were regular and the surface morphology was smooth. Fourier transform infrared showed that the chitosan amino groups reacted with heparin carboxylic groups to form acylamides in the microspheres. Analysis of the microsphere cytotoxicity showed that they had no cytotoxic effect and behaved very similar to the negative control (polystyrene).To analyze the protein drug release profiles of the microspheres, bovine serum albumin was loaded as a model drug into the microspheres and released in vitro. Marked retardation was observed in the BSA release profiles. The results show that chitosan/heparin microspheres may provide a useful controlled release protein drug system for used in pharmaceutics.

  9. Rosin and rosin derivatives as hydrophobic matrix materials for controlled release of drugs.

    Science.gov (United States)

    Pathak, Y V; Dorle, A K

    1990-09-01

    The evaluation of rosin, a rosin hard paraffin adduct, and four rosin esters as hydrophobic matrix materials for the controlled release of drugs is reported, using aspirin as a drug model. Aspirin matrix tablets were prepared using a wet granulation (nonaqueous) method, and were evaluated for various pharmaceutical parameters. Dissolution studies in pH 7.2 phosphate buffer showed that all formulations had hardness greater than 6 kg/cm2 and disintegration time greater than 150 min. Release of aspirin from the formulations obeyed a diffusion controlled first order kinetic and linear to the square root of time function. Two of the resin ester formulations had a T80% of more than 4 hr. The results suggest that these esters may find application in the development of sustained release formulations for the local treatment of dental diseases, or--as tablet matrices suitably coated with acid resistant material--in the development of oral sustained release drug delivery systems.

  10. Release of a Poorly Soluble Drug from Hydrophobically Modified Poly (Acrylic Acid in Simulated Intestinal Fluids.

    Directory of Open Access Journals (Sweden)

    Patrik Knöös

    Full Text Available A large part of new pharmaceutical substances are characterized by a poor solubility and high hydrophobicity, which might lead to a difference in drug adsorption between fasted and fed patients. We have previously evaluated the release of hydrophobic drugs from tablets based on Pemulen TR2 and showed that the release can be manipulated by adding surfactants. Here we further evaluate the possibility to use Pemulen TR2 in controlled release tablet formulations containing a poorly soluble substance, griseofulvin. The release is evaluated in simulated intestinal media that model the fasted state (FaSSIF medium or fed state (FeSSIF. The rheology of polymer gels is studied in separate experiments, in order to gain more information on possible interactions. The release of griseofulvin in tablets without surfactant varied greatly and the slowest release were observed in FeSSIF. Addition of SDS to the tablets eliminated the differences and all tablets showed a slow linear release, which is of obvious relevance for robust drug delivery. Comparing the data from the release studies and the rheology experiment showed that the effects on the release from the different media could to a large extent be rationalised as a consequence of the interactions between the polymer and the surfactants in the media. The study shows that Pemulen TR2 is a candidate for controlled release formulations in which addition of surfactant provides a way to eliminate food effects on the release profile. However, the formulation used needs to be designed to give a faster release rate than the tablets currently investigated.

  11. Externally controlled drug release using a gold nanorod contained composite membrane

    Science.gov (United States)

    Kim, Kibeom; Jo, Min-Chul; Jeong, Sundo; Palanikumar, L.; Rotello, Vincent M.; Ryu, Ja-Hyoung; Park, Myoung-Hwan

    2016-06-01

    Versatile drug delivery devices using nanoporous membranes consisting of gold nanorods and dendrimers have been demonstrated to provide light-triggered on-demand pulsatile release from a reservoir containing highly enriched therapeutics for a real patient's needs. The drug release rate is directly correlated with the temperature increase and irradiated energy of a near-IR laser in both static and fluidic devices. This biocompatible platform for on-demand control was further confirmed by in vitro experiments. Interestingly, different responses to stimuli were obtained from each drug in the absence and presence of NIR light, indicating the versatile potential of our on-demand drug delivery system in less-invasive therapies requiring multi-drug delivery strategies. The enhanced delivery system will improve therapeutic efficacy and reduce side effects through regulation of plasma drug profiles.Versatile drug delivery devices using nanoporous membranes consisting of gold nanorods and dendrimers have been demonstrated to provide light-triggered on-demand pulsatile release from a reservoir containing highly enriched therapeutics for a real patient's needs. The drug release rate is directly correlated with the temperature increase and irradiated energy of a near-IR laser in both static and fluidic devices. This biocompatible platform for on-demand control was further confirmed by in vitro experiments. Interestingly, different responses to stimuli were obtained from each drug in the absence and presence of NIR light, indicating the versatile potential of our on-demand drug delivery system in less-invasive therapies requiring multi-drug delivery strategies. The enhanced delivery system will improve therapeutic efficacy and reduce side effects through regulation of plasma drug profiles. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00362a

  12. Magnetic field activated lipid-polymer hybrid nanoparticles for stimuli-responsive drug release.

    Science.gov (United States)

    Kong, Seong Deok; Sartor, Marta; Hu, Che-Ming Jack; Zhang, Weizhou; Zhang, Liangfang; Jin, Sungho

    2013-03-01

    Stimuli-responsive nanoparticles (SRNPs) offer the potential of enhancing the therapeutic efficacy and minimizing the side-effects of chemotherapeutics by controllably releasing the encapsulated drug at the target site. Currently controlled drug release through external activation remains a major challenge during the delivery of therapeutic agents. Here we report a lipid-polymer hybrid nanoparticle system containing magnetic beads for stimuli-responsive drug release using a remote radio frequency (RF) magnetic field. These hybrid nanoparticles show long-term stability in terms of particle size and polydispersity index in phosphate-buffered saline (PBS). Controllable loading of camptothecin (CPT) and Fe(3)O(4) in the hybrid nanoparticles was demonstrated. RF-controlled drug release from these nanoparticles was observed. In addition, cellular uptake of the SRNPs into MT2 mouse breast cancer cells was examined. Using CPT as a model anticancer drug the nanoparticles showed a significant reduction in MT2 mouse breast cancer cell growth in vitro in the presence of a remote RF field. The ease of preparation, stability, and controllable drug release are the strengths of the platform and provide the opportunity to improve cancer chemotherapy.

  13. Multi-Drug-Loaded Microcapsules with Controlled Release for Management of Parkinson's Disease.

    Science.gov (United States)

    Baek, Jong-Suep; Choo, Chee Chong; Qian, Cheng; Tan, Nguan Soon; Shen, Zexiang; Loo, Say Chye Joachim

    2016-07-01

    Parkinson's disease (PD) is a progressive disease of the nervous system, and is currently managed through commercial tablets that do not sufficiently enable controlled, sustained release capabilities. It is hypothesized that a drug delivery system that provides controlled and sustained release of PD drugs would afford better management of PD. Hollow microcapsules composed of poly-l-lactide (PLLA) and poly (caprolactone) (PCL) are prepared through a modified double-emulsion technique. They are loaded with three PD drugs, i.e., levodopa (LD), carbidopa (CD), and entacapone (ENT), at a ratio of 4:1:8, similar to commercial PD tablets. LD and CD are localized in both the hollow cavity and PLLA/PCL shell, while ENT is localized in the PLLA/PCL shell. Release kinetics of hydrophobic ENT is observed to be relatively slow as compared to the other hydrophilic drugs. It is further hypothesized that encapsulating ENT into PCL as a surface coating onto these microcapsules can aid in accelerating its release. Now, these spray-coated hollow microcapsules exhibit similar release kinetics, according to Higuchi's rate, for all three drugs. The results suggest that multiple drug encapsulation of LD, CD, and ENT in gastric floating microcapsules could be further developed for in vivo evaluation for the management of PD.

  14. A novel system for three-pulse drug release based on "tablets in capsule" device.

    Science.gov (United States)

    Li, Bin; Zhu, JiaBi; Zheng, Chunli; Gong, Wen

    2008-03-20

    The objective of the present study was to obtain programmed drug delivery from a novel system, which contains a water-soluble cap, impermeable capsule body, and two multi-layered tablets. Types of materials for the modulating barrier and its weight can significantly affect the lag time (defined as the time when drug released 8% of the single pulse dosage). We chose sodium alginate and hydroxy-propyl methyl cellulose (HPMC E5) as the candidate modulating barrier material. Through adjusting ratio of sodium alginate and lactose, lag time was controllable between the first two pulsatile release. Linear relationship was observed between the ratio and the lag time. Through adjusting the ratio of HPMC E5/lactose, lag time between the second and the third pulse can be successfully modulated. In further studies, drug release rate of the second pulsatile dose can be improved by adding a separating layer between the third and the modulating barrier layer in the three-layered tablet. To evaluate contribution of bulking agent to drug release rate, lactose, sodium chloride, and effervescent blend were investigated. No superiority was found using sodium chloride and effervescent blend. However, lactose favored it. The results reveal that programmed drug delivery to achieve pulsatile drug release for three times daily can be obtained from these tablets in capsule system by systemic formulation approach.

  15. Pore geometry of ceramic device: The key factor of drug release kinetics

    Directory of Open Access Journals (Sweden)

    Čolović B.

    2013-01-01

    Full Text Available Release kinetics of tigecycline, a potential antibiotic in treatment of osteomyelitis, from calcium hydroxyapatite (CHA, as one of the most important ceramic materials in bone tissue engineering, was investigated in this study. Tigecycline, in solid state, was mixed with CHA powder and the obtained mixture was compressed into tablets using two different pressures. These tablets were immersed in a phosphate-buffered saline solution and tigecycline release was measured by a UV-VIS spectrophotometer. The total release time was 5 or 28 days, depending on the pressure applied during compression. It was shown that there is a close relationship between pore sizes and drug release rate. The drug release kinetics was interpreted on the base of pore sizes and pore size distribution. [Projekat Ministarstva nauke Republike Srbije, br. 172026

  16. Novel Gelatin-Adriamycin Sustained Drug Release System for Intravesical Therapy of Bladder Cancer

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    To reduce recurrence in the patients with bladder cancer after tumor removal through open surgery or transurethral resection, a form of gelatin-adriamycin sustained drug release system was developed and its release kinetics both in vitro and in vivo, its efficacy in inhibiting BIU-87 bladder tumor cell growth in vitro and its safety in vivo were studied. The results showed that this system controlled adriamycin release over a period of 21 days in vitro and significantly inhibited BIU-87 cell growth. When this system was injected into rabbit bladder, it sustained adriamycin release for 12 days and the released drug could diffuse 1 cm around the injection point. No major complications were observed except minor acute nonspecific cystitis that could be tolerated well by the animals. This study suggests the possibility of applying this system locally in treating bladder cancer.

  17. Entrapment and Sustained Release of Hydrophobic Drugs with Different Molecular Weights from PHBHHx-PEG Nanoparticles

    Institute of Scientific and Technical Information of China (English)

    FAN Fan; LU Xiao-yun; REN Kai; MA Jian-gang

    2014-01-01

    Biodegradable polymeric nanoparticles are more and more frequently used in drug delivery systems, which represent one of the most rapidly developing areas. In our previous study, a novel natural hybrid polyester, polyethylene glycol 200 (PEG200) end-capped poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx-PEG) was directly produced by Aeromonas hydrophila fermentation. In this study, the performance of the novel biodegradable PHBHHx-PEG copolyester as a sustained release carrier for hydrophobic drugs with different molecular weights and the in vitro sustained release profile were investigated. 5-Fluorouracil (5-Fu, Mw=130.1), TGX221 (Mw=364.4), and Rapamycin (RAP, Mw=914.2) were used as the model drugs. PHBHHx-PEG nanoparticles entrapped with 5-Fu, TGX221 and RAP were fabricated by a modified emulsification/solvent evaporation method, respectively. The average diameter of 5-Fu, TGX221, and RAP loaded PHBHHx-PEG nanoparticles was between 198.2-217.4 nm, and the entrapment efficiency of the three drugs was 62.5%, 93.4% and 91.9%, respectively. The in vitro release profiles of 5-Fu, TGX221 and RAP from PHBHHx-PEG nanoparticles were different. 5-Fu showed faster release rate and an obvious initial burst release phase. TGX221 and RAP were demonstrated to be released more slowly and steadily. The release percentages of 5-Fu, TGX221 and RAP were 97.7%, 85.1%and 74.7%after releasing for 72 h. PHBHHx-PEG is a kind of promising material as a carrier for the entrapment and delivery of hydrophobic drugs especially for those drugs with high molecular weight.

  18. Extracellular control of intracellular drug release for enhanced safety of anti-cancer chemotherapy

    Science.gov (United States)

    Zhu, Qian; Qi, Haixia; Long, Ziyan; Liu, Shang; Huang, Zhen; Zhang, Junfeng; Wang, Chunming; Dong, Lei

    2016-06-01

    The difficulty of controlling drug release at an intracellular level remains a key challenge for maximising drug safety and efficacy. We demonstrate herein a new, efficient and convenient approach to extracellularly control the intracellular release of doxorubicin (DOX), by designing a delivery system that harnesses the interactions between the system and a particular set of cellular machinery. By simply adding a small-molecule chemical into the cell medium, we could lower the release rate of DOX in the cytosol, and thereby increase its accumulation in the nuclei while decreasing its presence at mitochondria. Delivery of DOX with this system effectively prevented DOX-induced mitochondria damage that is the main mechanism of its toxicity, while exerting the maximum efficacy of this anti-cancer chemotherapeutic agent. The present study sheds light on the design of drug delivery systems for extracellular control of intracellular drug delivery, with immediate therapeutic implications.

  19. Molecular weight-dependent degradation and drug release of surface-eroding poly(ethylene carbonate)

    DEFF Research Database (Denmark)

    Bohr, Adam; Wang, Yingya; Harmankaya, Necati

    2017-01-01

    .7 macrophages) and in vivo (subcutaneous implantation in rats). All investigated samples degraded by means of surface erosion (mass loss, but constant molecular weight), which was accompanied by a predictable, erosion-controlled drug release pattern. Accordingly, the obtained in vitro degradation half-lives...... physicochemical characterization of diverse PEC (molecular weights: 85, 110, 133, 174 and 196kDa), the degradation and drug release behavior of rifampicin- and bovine serum albumin-loaded PEC films was investigated in vitro (in the presence and absence of cholesterol esterase), in cell culture (RAW264...... correlated well with the observed in vitro half-times of drug delivery (R2=0.96). Here, the PEC of the highest molecular weight resulted in the fastest degradation/drug release. When incubated with macrophages or implanted in animals, the degradation rate of PEC films superimposed the results of in vitro...

  20. Quality of Life is Improved and Kidney Function Preserved in Patients with Nephropathic Cystinosis Treated for 2 Years with Delayed-Release Cysteamine Bitartrate

    NARCIS (Netherlands)

    Langman, C.B.; Greenbaum, L.A.; Grimm, P.; Sarwal, M.; Niaudet, P.; Deschenes, G.; Cornelissen, E.A.M.; Morin, D.; Cochat, P.; Elenberg, E.; Hanna, C.; Gaillard, S.; Bagger, M.J.; Rioux, P.

    2014-01-01

    OBJECTIVES: To determine the long-term effects of delayed-release cysteamine bitartrate (DR-CYS) based on our previous work that established the short-term noninferiority of DR-CYS every 12 hours compared with immediate-release cysteamine bitartrate every 6 hours. STUDY DESIGN: We conducted a prospe

  1. Prospective strategies to delay the evolution of anti-malarial drug resistance: weighing the uncertainty

    Directory of Open Access Journals (Sweden)

    McKenzie F Ellis

    2010-07-01

    Full Text Available Abstract Background The evolution of drug resistance in malaria parasites highlights a need to identify and evaluate strategies that could extend the useful therapeutic life of anti-malarial drugs. Such strategies are deployed to best effect before resistance has emerged, under conditions of great uncertainty. Methods Here, the emergence and spread of resistance was modelled using a hybrid framework to evaluate prospective strategies, estimate the time to drug failure, and weigh uncertainty. The waiting time to appearance was estimated as the product of low mutation rates, drug pressure, and parasite population sizes during treatment. Stochastic persistence and the waiting time to establishment were simulated as an evolving branching process. The subsequent spread of resistance was simulated in simple epidemiological models. Results Using this framework, the waiting time to the failure of artemisinin combination therapy (ACT for malaria was estimated, and a policy of multiple first-line therapies (MFTs was evaluated. The models quantify the effects of reducing drug pressure in delaying appearance, reducing the chances of establishment, and slowing spread. By using two first-line therapies in a population, it is possible to reduce drug pressure while still treating the full complement of cases. Conclusions At a global scale, because of uncertainty about the time to the emergence of ACT resistance, there was a strong case for MFTs to guard against early failure. Our study recommends developing operationally feasible strategies for implementing MFTs, such as distributing different ACTs at the clinic and for home-based care, or formulating different ACTs for children and adults.

  2. NAIL AS A PROMISING DRUG DELIVERY SYSTEM FOR CONTROLLED RELEASE

    OpenAIRE

    G. Sai Krishna*, P. Prem Kumar, K. Bala Murugan

    2013-01-01

    ABSTRACT: The effectiveness of topical therapies is limited by minimal drug permeability through the nail plate. Nail permeability is however quite low and limits topical therapy to early/mild disease states such as onychomycosis (fungal infections of the nail). Current research on nail permeation that focuses on altering the nail plate barrier by means of chemical treatments, penetration enhancers as well as physical and mechanical methods is reviewed also the recent research into ungual dru...

  3. NAIL AS A PROMISING DRUG DELIVERY SYSTEM FOR CONTROLLED RELEASE

    OpenAIRE

    G. Sai Krishna*, P. Prem Kumar, K. Bala Murugan

    2013-01-01

    ABSTRACT: The effectiveness of topical therapies is limited by minimal drug permeability through the nail plate. Nail permeability is however quite low and limits topical therapy to early/mild disease states such as onychomycosis (fungal infections of the nail). Current research on nail permeation that focuses on altering the nail plate barrier by means of chemical treatments, penetration enhancers as well as physical and mechanical methods is reviewed also the recent research into ungual dru...

  4. Interaction between DNA and Drugs Having Protonable Basic Groups: Characterization through Affinity Constants, Drug Release Kinetics, and Conformational Changes.

    Science.gov (United States)

    Alarcón, Liliana P; Baena, Yolima; Manzo, Rubén H

    2017-01-04

    This paper reports the in vitro characterization of the interaction between the phosphate groups of DNA and the protonated species of drugs with basic groups through the determination of the affinity constants, the reversibility of the interaction, and the effect on the secondary structure of the macromolecule. Affinity constants of the counterionic condensation DNA-drug were in the order of 10⁶. The negative electrokinetic potential of DNA decreased with the increase of the proportion of loading drugs. The drugs were slowly released from the DNA-drug complexes and had release kinetics consistent with the high degree of counterionic condensation. The circular dichroism profile of DNA was not modified by complexation with atenolol, lidocaine, or timolol, but was significantly altered by the more lipophilic drugs benzydamine and propranolol, revealing modifications in the secondary structure of the DNA. The in vitro characterization of such interactions provides a physicochemical basis that would contribute to identify the effects of this kind of drugs in cellular cultures, as well as side effects observed under their clinical use. Moreover, this methodology could also be projected to the fields of intracellular DNA transfection and the use of DNA as a carrier of active drugs.

  5. Interaction between DNA and Drugs Having Protonable Basic Groups: Characterization through Affinity Constants, Drug Release Kinetics, and Conformational Changes

    Directory of Open Access Journals (Sweden)

    Liliana P. Alarcón

    2017-01-01

    Full Text Available This paper reports the in vitro characterization of the interaction between the phosphate groups of DNA and the protonated species of drugs with basic groups through the determination of the affinity constants, the reversibility of the interaction, and the effect on the secondary structure of the macromolecule. Affinity constants of the counterionic condensation DNA–drug were in the order of 106. The negative electrokinetic potential of DNA decreased with the increase of the proportion of loading drugs. The drugs were slowly released from the DNA–drug complexes and had release kinetics consistent with the high degree of counterionic condensation. The circular dichroism profile of DNA was not modified by complexation with atenolol, lidocaine, or timolol, but was significantly altered by the more lipophilic drugs benzydamine and propranolol, revealing modifications in the secondary structure of the DNA. The in vitro characterization of such interactions provides a physicochemical basis that would contribute to identify the effects of this kind of drugs in cellular cultures, as well as side effects observed under their clinical use. Moreover, this methodology could also be projected to the fields of intracellular DNA transfection and the use of DNA as a carrier of active drugs.

  6. Colorectal distention induces acute and delayed visceral hypersensitivity: role of peripheral corticotropin-releasing factor and interleukin-1 in rats.

    Science.gov (United States)

    Nozu, Tsukasa; Kumei, Shima; Miyagishi, Saori; Takakusaki, Kaoru; Okumura, Toshikatsu

    2015-12-01

    Most studies evaluating visceral sensation measure visceromotor response (VMR) to colorectal distention (CRD). However, CRD itself induces visceral sensitization, and little is known about the detailed characteristics of this response. The present study tried to clarify this question. VMR was determined by measuring abdominal muscle contractions as a response to CRD in rats. The CRD set consisted of two isobaric distentions (60 mmHg for 10 min twice, with a 30-min rest), and the CRD set was performed on two separate days, i.e., days 1 and 3, 8. On day 1, VMR to the second CRD was increased as compared with that to the first CRD, which is the acute sensitization. VMR to the first CRD on day 3 returned to the same level as that to the first CRD on day 1, and total VMR, i.e., the whole response to the CRD set, was not different between day 1 and day 3. However, total VMR was significantly increased on day 8 as compared with that on day 1, suggesting CRD induced the delayed sensitization. Intraperitoneally administered astressin (200 µg/kg), a corticotropin-releasing factor receptor antagonist, at the end of the first CRD blocked the acute sensitization, but anakinra (20 mg/kg, intraperitoneally), an interleukin-1 receptor antagonist, did not modify it. Astressin (200 µg/kg, twice before CRD on day 8) did not alter the delayed sensitization, but anakinra (20 mg/kg, twice) abolished it. CRD induced both acute sensitization and delayed sensitization, which were mediated through peripheral corticotropin-releasing factor and interleukin-1 pathways, respectively.

  7. The synthesis and application involving regulation of the insoluble drug release from mesoporous silica nanotubes

    Science.gov (United States)

    Li, Jia; Wang, Yan; Zheng, Xin; Zhang, Ying; Sun, Changshan; Gao, Yikun; Jiang, Tongying; Wang, Siling

    2015-03-01

    Mesoporous silica nanotubes (SNT) were synthesized using hard template carbon nanotubes (CNT) with the aid of cetyltrimethyl ammonium bromide (CTAB) in a method, which was simple and inexpensive. Scanning electron microscopy, transmission electron microscopy and specific surface area analysis were employed to characterize the morphology and structure of SNT, and the formation mechanism of SNT was also examined by Fourier transform infrared spectroscopy. There are few published reports of the mesoporous SNT with large specific surface area applied in the drug delivery systems to improve the amount of drug loading. In addition, the structure of SNT allows investigators to control the drug particle size in the pore channels and significantly increase the drug dissolution rate. The insoluble drug, cilostazol, was chosen as a model drug to be loaded into SNT and we developed a simple and efficient method for regulating the drug release by using a gelatin coating with different thicknesses around the SNT. The release rate was adjusted by the amount of gelatin surrounding the SNT, with an increased barrier leading to a reduction in the release rate. A model developed on the basis of the Weibull modulus was established to fit the release results.

  8. Magnetic hyperthermia controlled drug release in the GI tract: solving the problem of detection

    Science.gov (United States)

    Bear, Joseph C.; Patrick, P. Stephen; Casson, Alfred; Southern, Paul; Lin, Fang-Yu; Powell, Michael J.; Pankhurst, Quentin A.; Kalber, Tammy; Lythgoe, Mark; Parkin, Ivan P.; Mayes, Andrew G.

    2016-09-01

    Drug delivery to the gastrointestinal (GI) tract is highly challenging due to the harsh environments any drug- delivery vehicle must experience before it releases it’s drug payload. Effective targeted drug delivery systems often rely on external stimuli to effect release, therefore knowing the exact location of the capsule and when to apply an external stimulus is paramount. We present a drug delivery system for the GI tract based on coating standard gelatin drug capsules with a model eicosane- superparamagnetic iron oxide nanoparticle composite coating, which is activated using magnetic hyperthermia as an on-demand release mechanism to heat and melt the coating. We also show that the capsules can be readily detected via rapid X-ray computed tomography (CT) and magnetic resonance imaging (MRI), vital for progressing such a system towards clinical applications. This also offers the opportunity to image the dispersion of the drug payload post release. These imaging techniques also influenced capsule content and design and the delivered dosage form. The ability to easily change design demonstrates the versatility of this system, a vital advantage for modern, patient-specific medicine.

  9. Magnetic hyperthermia controlled drug release in the GI tract: solving the problem of detection

    Science.gov (United States)

    Bear, Joseph C.; Patrick, P. Stephen; Casson, Alfred; Southern, Paul; Lin, Fang-Yu; Powell, Michael J.; Pankhurst, Quentin A.; Kalber, Tammy; Lythgoe, Mark; Parkin, Ivan P.; Mayes, Andrew G.

    2016-01-01

    Drug delivery to the gastrointestinal (GI) tract is highly challenging due to the harsh environments any drug- delivery vehicle must experience before it releases it’s drug payload. Effective targeted drug delivery systems often rely on external stimuli to effect release, therefore knowing the exact location of the capsule and when to apply an external stimulus is paramount. We present a drug delivery system for the GI tract based on coating standard gelatin drug capsules with a model eicosane- superparamagnetic iron oxide nanoparticle composite coating, which is activated using magnetic hyperthermia as an on-demand release mechanism to heat and melt the coating. We also show that the capsules can be readily detected via rapid X-ray computed tomography (CT) and magnetic resonance imaging (MRI), vital for progressing such a system towards clinical applications. This also offers the opportunity to image the dispersion of the drug payload post release. These imaging techniques also influenced capsule content and design and the delivered dosage form. The ability to easily change design demonstrates the versatility of this system, a vital advantage for modern, patient-specific medicine. PMID:27671546

  10. Magnetically Vectored Nanocapsules for Tumor Penetration and Remotely Switchable On-Demand Drug Release

    Science.gov (United States)

    Kong, Seong Deok

    Hollow-sphere nanocapsules containing intentionally trapped magnetic nanoparticles and defined anticancer drugs provide a powerful magnetic vector under moderate gradient magnetic fields, and enable the nanocapsules to penetrate into the midst of tumors and allow a controlled on-off switchable release of the anticancer drug cargo by remotely applied Radio Frequency (RF) magnetic field. This imageable smart drug delivery system is compact because the drug molecules and magnetic nanoparticles can all be self-contained within 80~150 nm capsules. In vitro as well as in vivo results indicate that the nanocapsules are effective in reducing tumor cell growth. In Chapter 1, the concept of Drug Delivery Systems (DDSs) and the impact of nanotechnology on Drug Delivery Systems were introduced. Triggered drug release using magnetothermally-responsive nanomaterials, magnetic nanoparticles for nanomedicine, and ordered mesoporous materials in the context of Drug Delivery System were discussed. In Chapter 2, creation of remotely controllable, On-Off switchable drug release methodology was described. In this thesis work, triggerable nanocapsules which contain magnetic nanoparticles responsive to external radio frequency (RF) magnetic field have been successfully created. This is in contrast to the regular hollow nanospheres for slow passive release of drugs. The new nanocapsule material consists of bio-inert, bio-compatible or bio-degradable material that we can be selected from a variety of materials depending on specific medical applications. In Chapter 3, study and utilization of magnetic vector for guided tumor penetration was discussed. In the presence of a moderate gradient magnetic field, a powerful magnetic vector is created that allows these nanocapsules to cross cell membranes or blood-tissue barriers and penetrate into the midst of tumors, thus overcoming the well-known problem of limited access of anti-cancer drugs to cancer cells in the interior of a tumor tissue. In

  11. Mathematical modeling of drug release from bioerodible microparticles: effect of gamma-irradiation.

    Science.gov (United States)

    Faisant, N; Siepmann, J; Richard, J; Benoit, J P

    2003-09-01

    Bioerodible polymers used in controlled drug delivery systems, such as poly(lactic-co-glycolic acid) (PLGA) undergo radiolytic degradation during gamma-irradiation. In spite of the considerable practical importance, yet only little knowledge is available on the consequences of this sterilization method on the resulting drug release patterns in a quantitative way. The major objectives of the present study were: (i) to monitor the effects of different gamma-irradiation doses on the physicochemical properties of drug-free and drug-loaded, PLGA-based microparticles; (ii) to analyze the obtained experimental results using adequate mathematical models; (iii) to get further insight into the occurring physical and chemical phenomena; and (iv) to relate the applied gamma-irradiation dose in a quantitative way to the resulting drug release rate. 5-Fluorouracil-loaded, PLGA-based microparticles were prepared with an oil-in-water solvent extraction method and exposed to gamma-irradiation doses ranging from 0 to 33 kGy. Size exclusion chromatography, differential scanning calorimetry, scanning electron microscopy, particle size analysis, determination of the actual drug loading and in vitro drug release kinetics were used to study the effects of the gamma-irradiation dose on the physicochemical properties of the microparticles. Two mathematical models-a simplified and a more comprehensive one-were used to analyze the experimental results. The simplified model considers drug diffusion based on Fick's second law for spherical geometry and a Higuchi-like pseudo-steady-state approach. The complex model combines Monte Carlo simulations (describing polymer erosion) with partial differential equations quantifying drug diffusion with time-, position- and direction-dependent diffusivities. Interestingly, exponential relationships between the gamma-irradiation dose and the initial drug diffusivity within the microparticles could be established. Based on this knowledge both models were

  12. Role of Gonadotropin-releasing Hormone Stimulation Test in Diagnosing Gonadotropin Deficiency in Both Males and Females with Delayed Puberty

    Institute of Scientific and Technical Information of China (English)

    Qi-Hong Sun; Yu Zheng; Xiao-Lin Zhang; Yi-Ming Mu

    2015-01-01

    Background:Delayed puberty can result either from constitutional delay of growth and puberty (CDP) or idiopathic hypogonadotropic hypogonadism (IHH).Gonadotropin-releasing hormone (GnRH) stimulation test has been generally accepted as a current method for diagnosing delayed puberty.The objective of this research was to assess the cut-off values and the efficacy of GnRH stimulation test in the diagnosis of delayed puberty in both males and females.Methods:A study of 91 IHH,27 CDP patients,6 prepubertal children,and 20 pubertal adults was undertaken.Blood samples were obtained at 0,30,60,and 120 min after GnRH administration and the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured.For each parameter,the sensitivities and specificities were estimated,and the receiver operating characteristic (ROC) curves were constructed.Results:The ROC curves indicated that a serum basal LH <0.6 IU/L or peak LH <9.74 IU/L resulted in moderate sensitivity (73.8% or 80.0%) and specificity (90.9% or 86.4%) in the diagnosis of HH in males.Serum basal LH <0.85 IU/L or basal FSH <2.43 IU/L resulted in moderate sensitivity (80.0% or 100.0%) and specificity (75.0% or 50.0%) in the diagnosis of HH in females.Conclusions:Our data suggest that isolated use of the gonadorelin stimulation test is almost sufficient to discriminate between HH and CDP in males,but unnecessary in females.The most useful predictor is serum basal or peak LH to differentiate these two disorders in males,but serum basal LH or FSH in females.

  13. The synthesis and application involving regulation of the insoluble drug release from mesoporous silica nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jia, E-mail: ydlijia@163.com [School of Pharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016 (China); Wang, Yan, E-mail: wangyan6505@163.com [School of Pharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016 (China); Zheng, Xin, E-mail: 33682150@qq.com [School of Pharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016 (China); Zhang, Ying, E-mail: yzhang7704@sina.com [College of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016 (China); Sun, Changshan, E-mail: freescs@163.com [School of Pharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016 (China); Gao, Yikun, E-mail: 174913818@qq.com [School of Medical Devices, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016 (China); Jiang, Tongying, E-mail: jiangtongyingsy@163.com [School of Pharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016 (China); Wang, Siling, E-mail: silingwang@syphu.edu.cn [School of Pharmaceutics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016 (China)

    2015-03-01

    Highlights: • Mesoporous silica nanotubes (SNT) were synthesized by using CNT as hard template, and the formation of the SNT shows that CTAB played a significant effect on the coating process. • The tube mesoporous silica materials which were seldom reported were applied in the drug delivery system to improve the loading amount and the drug dissolution. • The release rate could be controlled by the gelatin layer on the silica surface and the mechanism was illustrated. - Abstract: Mesoporous silica nanotubes (SNT) were synthesized using hard template carbon nanotubes (CNT) with the aid of cetyltrimethyl ammonium bromide (CTAB) in a method, which was simple and inexpensive. Scanning electron microscopy, transmission electron microscopy and specific surface area analysis were employed to characterize the morphology and structure of SNT, and the formation mechanism of SNT was also examined by Fourier transform infrared spectroscopy. There are few published reports of the mesoporous SNT with large specific surface area applied in the drug delivery systems to improve the amount of drug loading. In addition, the structure of SNT allows investigators to control the drug particle size in the pore channels and significantly increase the drug dissolution rate. The insoluble drug, cilostazol, was chosen as a model drug to be loaded into SNT and we developed a simple and efficient method for regulating the drug release by using a gelatin coating with different thicknesses around the SNT. The release rate was adjusted by the amount of gelatin surrounding the SNT, with an increased barrier leading to a reduction in the release rate. A model developed on the basis of the Weibull modulus was established to fit the release results.

  14. PLGA implants: How Poloxamer/PEO addition slows down or accelerates polymer degradation and drug release.

    Science.gov (United States)

    Hamoudi-Ben Yelles, M C; Tran Tan, V; Danede, F; Willart, J F; Siepmann, J

    2017-03-08

    The aim of this study was to evaluate the impact of the addition of small amounts of hydrophilic polymers (Poloxamer 188 and PEO 200kDa) to PLGA-based implants loaded with prilocaine. Special emphasis was placed on the importance of the type of preparation technique: direct compression of milled drug-polymer powder blends versus compression of drug loaded microparticles (prepared by spray-drying). The implants were thoroughly characterized before and upon exposure to phosphate buffer pH7.4, e.g. using optical and scanning electron microscopy, X-ray diffraction, DSC and GPC. Interestingly, the addition of Poloxamer/PEO to the PLGA implants had opposite effects on the resulting drug release kinetics, depending on the type of preparation method: in the case of implants prepared by compression of milled drug-polymer powder blends, drug release was accelerated, whereas it was slowed down when the implants were prepared by compression of drug loaded PLGA microparticles. These phenomena could be explained by the swelling/disintegration behavior of the implants upon exposure to the release medium. Systems consisting of compressed microparticles remained intact and autocatalytic effects were of major importance. The presence of a hydrophilic polymer facilitated water penetration into these devices, slowing down PLGA degradation and drug release. In contrast, implants consisting of compressed drug-polymer powder blends rapidly (at least partially) disintegrated and autocatalysis was much less important. In these cases, the addition of a hydrophilic polymer facilitated ester bond cleavage, leading to accelerated PLGA degradation and drug release.

  15. Controlled drug release from antibiotic-loaded layered double hydroxide coatings on porous titanium implants in a mouse model.

    Science.gov (United States)

    Badar, Muhammad; Rahim, Muhammad Imran; Kieke, Marc; Ebel, Thomas; Rohde, Manfred; Hauser, Hansjörg; Behrens, Peter; Mueller, Peter P

    2015-06-01

    As an alternative to degradable organic coatings the possibility of using layered double hydroxides (LDHs) to generate implant coatings for controlled drug delivery was evaluated in vivo and in vitro. Coatings prepared from LDH suspensions dissolved slowly and appeared compatible with cultured cells. LDH coatings loaded with an antibiotic resulted in antibacterial effects in vitro. The LDH coating prolonged the drug release period and improved the proliferation of adherent cells in comparison to pure drug coatings. However, during incubation in physiological solutions the LDH coatings became brittle and pieces occasionally detached from the surface. For stress protection porous titanium implants were investigated as a substrate for the coatings. The pores prevented premature detachment of the coatings. To evaluate the coated porous implants in vivo a mouse model was established. To monitor bacterial infection of implants noninvasive in vivo imaging was used to monitor luminescently labeled Pseudomonas aeruginosa. In this model porous implants with antibiotic-loaded LDH coatings could antagonize bacterial infections for over 1 week. The findings provide evidence that delayed drug delivery from LDH coatings could be feasible in combination with structured implant surfaces.

  16. Piroxicam loaded alginate beads obtained by prilling/microwave tandem technique: morphology and drug release.

    Science.gov (United States)

    Aquino, Rita P; Auriemma, Giulia; d'Amore, Matteo; D'Ursi, Anna Maria; Mencherini, Teresa; Del Gaudio, Pasquale

    2012-07-01

    This paper presents a tandem technique, based on the combination of prilling and microwave (MW) assisted treatments, to produce biodegradable alginate carriers of piroxicam with different drug controlled release behaviours. Results showed that alginate/piroxicam beads demonstrated high encapsulation efficiency and very narrow dimensional distribution. Beads dried by MW retained shape and size distribution of the hydrated particles while drying rate was strongly increased compared to convective drying processes. Moreover, different MW irradiation regimes promoted interactions between the drug and alginate matrix, affected drug polymorphism as well as inner and surface matrix structure leading to different piroxicam release profiles. High level MW irradiation led to beads with highly porous and swellable matrix able to release piroxicam in few minutes in the intestine while convective drying produced gastro-resistant beads that exhibit sustained piroxicam release (total release in 5.5h) in intestinal environment. On these results the tandem technique prilling/MW irradiation appears to be promising to obtain alginate carrier with tailored NSAIDs release depending on drug characteristics and MW irradiation.

  17. Controlled drug-release system based on pH-sensitive chloride-triggerable liposomes.

    Science.gov (United States)

    Wehunt, Mark P; Winschel, Christine A; Khan, Ali K; Guo, Tai L; Abdrakhmanova, Galya R; Sidorov, Vladimir

    2013-03-01

    New pH-sensitive lipids were synthesized and utilized in formulations of liposomes suitable for controlled drug release. These liposomes contain various amounts of NaCl in the internal aqueous compartments. The release of the drug model is triggered by an application of HCl cotransporter and exogenous physiologically relevant NaCl solution. HCl cotransporter allows an uptake of HCl by liposomes to the extent of their being proportional to the transmembrane Cl(-) gradient. Therefore, each set of liposomes undergoes internal acidification, which, ultimately, leads to the hydrolysis of the pH-sensitive lipids and content release at the desired time. The developed system releases the drug model in a stepwise fashion, with the release stages separated by periods of low activity. These liposomes were found to be insensitive to physiological concentrations of human serum albumin and to be nontoxic to cells at concentrations exceeding pharmacological relevance. These results render this new drug-release model potentially suitable for in vivo applications.

  18. Antibiotic-loaded chitosan-Laponite films for local drug delivery by titanium implants: cell proliferation and drug release studies.

    Science.gov (United States)

    Ordikhani, Farideh; Dehghani, Mehdi; Simchi, Arash

    2015-12-01

    In this study, chitosan-Laponite nanocomposite coatings with bone regenerative potential and controlled drug-release capacity are prepared by electrophoretic deposition technique. The controlled release of a glycopeptide drug, i.e. vancomycin, is attained by the intercalation of the polymer and drug macromolecules into silicate galleries. Fourier-transform infrared spectrometry reveals electrostatic interactions between the charged structure of clay and the amine and hydroxyl groups of chitosan and vancomycin, leading to a complex positively-charged system with high electrophoretic mobility. By applying electric field the charged particles are deposited on the surface of titanium foils and uniform chitosan films containing 25-55 wt% Laponite and 937-1655 µg/cm(2) vancomycin are obtained. Nanocomposite films exhibit improved cell attachment with higher cell viability. Alkaline phosphatase assay reveals enhanced cell proliferation due the gradual dissolution of Laponite particles into the culture medium. In-vitro drug-release studies show lower release rate through a longer period for the nanocomposite compared to pristine chitosan.

  19. Spatiotemporally and Sequentially-Controlled Drug Release from Polymer Gatekeeper-Hollow Silica Nanoparticles

    Science.gov (United States)

    Palanikumar, L.; Jeena, M. T.; Kim, Kibeom; Yong Oh, Jun; Kim, Chaekyu; Park, Myoung-Hwan; Ryu, Ja-Hyoung

    2017-04-01

    Combination chemotherapy has become the primary strategy against cancer multidrug resistance; however, accomplishing optimal pharmacokinetic delivery of multiple drugs is still challenging. Herein, we report a sequential combination drug delivery strategy exploiting a pH-triggerable and redox switch to release cargos from hollow silica nanoparticles in a spatiotemporal manner. This versatile system further enables a large loading efficiency for both hydrophobic and hydrophilic drugs inside the nanoparticles, followed by self-crosslinking with disulfide and diisopropylamine-functionalized polymers. In acidic tumour environments, the positive charge generated by the protonation of the diisopropylamine moiety facilitated the cellular uptake of the particles. Upon internalization, the acidic endosomal pH condition and intracellular glutathione regulated the sequential release of the drugs in a time-dependent manner, providing a promising therapeutic approach to overcoming drug resistance during cancer treatment.

  20. Spatiotemporally and Sequentially-Controlled Drug Release from Polymer Gatekeeper–Hollow Silica Nanoparticles

    Science.gov (United States)

    Palanikumar, L.; Jeena, M. T.; Kim, Kibeom; Yong Oh, Jun; Kim, Chaekyu; Park, Myoung-Hwan; Ryu, Ja-Hyoung

    2017-01-01

    Combination chemotherapy has become the primary strategy against cancer multidrug resistance; however, accomplishing optimal pharmacokinetic delivery of multiple drugs is still challenging. Herein, we report a sequential combination drug delivery strategy exploiting a pH-triggerable and redox switch to release cargos from hollow silica nanoparticles in a spatiotemporal manner. This versatile system further enables a large loading efficiency for both hydrophobic and hydrophilic drugs inside the nanoparticles, followed by self-crosslinking with disulfide and diisopropylamine-functionalized polymers. In acidic tumour environments, the positive charge generated by the protonation of the diisopropylamine moiety facilitated the cellular uptake of the particles. Upon internalization, the acidic endosomal pH condition and intracellular glutathione regulated the sequential release of the drugs in a time-dependent manner, providing a promising therapeutic approach to overcoming drug resistance during cancer treatment. PMID:28436438

  1. Spatiotemporally and Sequentially-Controlled Drug Release from Polymer Gatekeeper-Hollow Silica Nanoparticles.

    Science.gov (United States)

    Palanikumar, L; Jeena, M T; Kim, Kibeom; Yong Oh, Jun; Kim, Chaekyu; Park, Myoung-Hwan; Ryu, Ja-Hyoung

    2017-04-24

    Combination chemotherapy has become the primary strategy against cancer multidrug resistance; however, accomplishing optimal pharmacokinetic delivery of multiple drugs is still challenging. Herein, we report a sequential combination drug delivery strategy exploiting a pH-triggerable and redox switch to release cargos from hollow silica nanoparticles in a spatiotemporal manner. This versatile system further enables a large loading efficiency for both hydrophobic and hydrophilic drugs inside the nanoparticles, followed by self-crosslinking with disulfide and diisopropylamine-functionalized polymers. In acidic tumour environments, the positive charge generated by the protonation of the diisopropylamine moiety facilitated the cellular uptake of the particles. Upon internalization, the acidic endosomal pH condition and intracellular glutathione regulated the sequential release of the drugs in a time-dependent manner, providing a promising therapeutic approach to overcoming drug resistance during cancer treatment.

  2. Comparison of ionic and non-ionic drug release from multi-membrane spherical aerogels.

    Science.gov (United States)

    Veronovski, Anja; Knez, Zeljko; Novak, Zoran

    2013-09-15

    The presented research was oriented towards the preparation of dry biodegradable alginate aerogels with multi-membranes using a multi-step sol-gel process with potential applications as carriers during oral drug delivery. First alginate spherical hydrogels were formed in CaCl2 or BaCl2 solutions by ionic cross-linking. These cores were further immersed into alginate sodium solution, filtered through a sieve, and dropped into the salt solution again. Multi-membrane hydrogels were obtained by repeating the above process. They were further converted into aerogels by supercritical drying. The effect of the number of membranes was investigated regarding the loading and release of the model drugs nicotinic acid and theophylline. Moreover, the efficiencies of Ba(2+) and Ca(2+) metal ions for forming tridimensional networks that retain and extend drug release were also investigated. Nicotinic acid release was prolonged by adding membranes around the core and using Ca(2+) for cross-linking. However, retarded theophylline release was only obtained by using Ba(2+) for cross-linking. Namely, by increasing the number of membranes and BaCl2 concentration drug release became linear versus time in all studied cases. In the case of nicotinic acid loading increased by adding membranes around the core, however, for theophylline the opposite results were obtained due to the different nature of the model drugs.

  3. Drug release from liposome coated hydrogels for soft contact lenses: the blinking and temperature effect.

    Science.gov (United States)

    Paradiso, P; Colaço, R; Mata, J L G; Krastev, R; Saramago, B; Serro, A P

    2016-05-18

    In this article, liposome-based coatings aiming to control drug release from therapeutic soft contact lenses (SCLs) materials are analyzed. A PHEMA based hydrogel material loaded with levofloxacin is used as model system for this research. The coatings are formed by polyelectrolyte layers containing liposomes of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and DMPC + cholesterol (DMPC + CHOL). The effect of friction and temperature on the drug release is investigated. The aim of the friction tests is to simulate the blinking of the eyelid in order to verify if the SCLs materials coated with liposomes are able to keep their properties, in particular the drug release ability. It was observed that under the study conditions, friction did not affect significantly the drug release from the liposome coated PHEMA material. In contrast, increasing the temperature of release leads to an increase of the drug diffusion rate through the hydrogel. This phenomenon is recorded both in the control and in the coated samples. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2016.

  4. Swallowing a cellular automaton pill: predicting drug release from a matrix tablet

    CERN Document Server

    Buchla, Ezra; Najera, Aisha; Radunskaya, Ami

    2012-01-01

    Matrix tablets are drug delivery devices designed to release a drug in a controlled manner over an extended period of time. We develop a cellular automaton (CA) model for the dissolution and release of a water-soluble drug and excipient from a matrix tablet of water-insoluble polymer. Cells of the CA are occupied by drug, excipient, water or polymer and the CA updating rules simulate the dissolution of drug and excipient and the subsequent diffusion of the dissolved substances. In addition we simulate the possible fracture of brittle drug and excipient powders during the tablet compression and the melting of the polymer during a possible thermal curing process. Different stirring mechanisms that facilitate the transport of dissolved drug in the fluid in which the tablet is immersed are modeled in the water cells adjacent to the boundary of the tablet. We find that our simulations can reproduce experimental drug release profiles. Our simulation tool can be used to streamline the formulation and production of s...

  5. Sustained Release and Cytotoxicity Evaluation of Carbon Nanotube-Mediated Drug Delivery System for Betulinic Acid

    Directory of Open Access Journals (Sweden)

    Julia M. Tan

    2014-01-01

    Full Text Available Carbon nanotubes (CNTs have been widely utilized as a novel drug carrier with promising future applications in biomedical therapies due to their distinct characteristics. In the present work, carboxylic acid-functionalized single-walled carbon nanotubes (f-SWCNTs were used as the starting material to react with anticancer drug, BA to produce f-SWCNTs-BA conjugate via π-π stacking interaction. The conjugate was extensively characterized for drug loading capacity, physicochemical properties, surface morphology, drug releasing characteristics, and cytotoxicity evaluation. The results indicated that the drug loading capacity was determined to be around 20 wt% and this value has been verified by thermogravimetric analysis. The binding of BA onto the surface of f-SWCNTs was confirmed by FTIR and Raman spectroscopies. Powder XRD analysis showed that the structure of the conjugate was unaffected by the loading of BA. The developed conjugate was found to release the drug in a controlled manner with a prolonged release property. According to the preliminary in vitro cytotoxicity studies, the conjugate was not toxic in a standard fibroblast cell line, and anticancer activity was significantly higher in A549 than HepG2 cell line. This study suggests that f-SWCNTs could be developed as an efficient drug carrier to conjugate drugs for pharmaceutical applications in cancer chemotherapies.

  6. Immobilization and controlled release of drug using plasma polymerized thin film

    Energy Technology Data Exchange (ETDEWEB)

    Myung, Sung-Woon [Department of Dental Materials, School of Dentistry, MRC Center, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju (Korea, Republic of); Jung, Sang-Chul [Department of Environmental Engineering, Sunchon National University, Sunchon 540-742 (Korea, Republic of); Kim, Byung-Hoon, E-mail: kim5055@chosun.ac.kr [Department of Dental Materials, School of Dentistry, MRC Center, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju (Korea, Republic of)

    2015-06-01

    In this study, plasma polymerization of acrylic acid was employed to immobilize drug and control its release. Doxorubicin (DOX) was immobilized covalently on the glass surface deposited with plasma polymerized acrylic acid (PPAAc) thin film containing the carboxylic group. At first, the PPAAc thin film was coated on a glass surface at a pressure of 1.33 Pa and radio frequency (RF) discharge power of 20 W for 10 min. DOX was immobilized on the PPAAc deposition in a two environment of phosphate buffer saline (PBS) and dimethyl sulfoxide (DMSO) solutions. The DOX immobilized surface was characterized by scanning electron microscope, atomic force microscope and attenuated total reflection Fourier transform infrared spectroscopy. The DOX molecules were more immobilized in PBS than DMSO solution. The different immobilization and release profiles of DOX result from the solubility of hydrophobic DOX in aqueous and organic solutions. Second, in order to control the release of the drug, PPAAc thin film was covered over DOX dispersed layer. Different thicknesses and cross-linked PPAAc thin films by adjusting deposition time and RF discharge power were covered on the DOX layer dispersed. PPAAc thin film coated DOX layer reduced the release rate of DOX. The thickness control of plasma deposition allows controlling the release rate of drug. - Highlights: • Doxorubicin was immobilized on the surface of plasma polymerized acrylic acid thin film. • Release profile of doxorubicin was affected by aqueous and organic solutions. • Plasma polymerized acrylic acid thin film can be used to achieve controlled release.

  7. Melt-processed polymeric cellular dosage forms for immediate drug release.

    Science.gov (United States)

    Blaesi, Aron H; Saka, Nannaji

    2015-12-28

    The present immediate-release solid dosage forms, such as the oral tablets and capsules, comprise granular matrices. While effective in releasing the drug rapidly, they are fraught with difficulties inherent in processing particulate matter. By contrast, liquid-based processes would be far more predictable; but the standard cast microstructures are unsuited for immediate-release because they resist fluid percolation and penetration. In this article, we introduce cellular dosage forms that can be readily prepared from polymeric melts by incorporating the nucleation, growth, and coalescence of microscopic gas bubbles in a molding process. We show that the cell topology and formulation of such cellular structures can be engineered to reduce the length-scale of the mass-transfer step, which determines the time of drug release, from as large as the dosage form itself to as small as the thickness of the cell wall. This allows the cellular dosage forms to achieve drug release rates over an order of magnitude faster compared with those of cast matrices, spanning the entire spectrum of immediate-release and beyond. The melt-processed polymeric cellular dosage forms enable predictive design of immediate-release solid dosage forms by tailoring microstructures, and could be manufactured efficiently in a single step.

  8. Influence of drug distribution and solubility on release from geopolymer pellets--a finite element method study.

    Science.gov (United States)

    Jämstorp, Erik; Strømme, Maria; Bredenberg, Susanne

    2012-05-01

    This study investigates the influence of drug solubility and distribution on its release from inert geopolymer pellets of three different sizes (1.5 × 1.5, 3 × 6, and 6 × 6 mm), having the same geopolymer composition and containing highly potent opioid fentanyl, sumatriptan, theophylline, or saccharin. Scanning electron microscopy, nitrogen sorption, drug solubility, permeation, and release experiments were performed, and estimates of the drug diffusion coefficients and solubilities in the geopolymer matrix were derived with the aid of finite element method (FEM). FEM was further employed to investigate the effect of a nonuniform drug distribution on the drug release profile. When inspecting the release profiles for each drug, it was observed that their solubilities in the geopolymer matrix imposed a much greater influence on the drug release rate than their diffusion coefficients. Concentrating the initial drug load in FEM into nonuniformly distributed drug regions inside the matrix created drug release profiles that more closely resembled experimental data than an FEM-simulated uniform drug distribution did. The presented FEM simulations and visualization of drug release from geopolymers under varying initial and dynamic conditions should open up for more systematic studies of additional factors that influence the drug release profile from porous delivery vehicles.

  9. Controlled drug release from lung-targeted nanocarriers via chemically mediated shell permeabilisation.

    Science.gov (United States)

    Chen, Hanpeng; Woods, Arcadia; Forbes, Ben; Jones, Stuart

    2016-09-25

    Nanocarriers can aid therapeutic agent administration to the lung, but controlling drug delivery from these systems after deposition in the airways can be problematic. The aim of this study was to evaluate if chemically mediated shell permeabilisation could help manipulate the rate and extent of nanocarrier drug release. Rifampicin was loaded into lipid shell (loading efficiency 41.0±11.4%, size 50nm) and polymer shell nanocarriers (loading efficiency 25.9±2.3%, size 250nm). The drug release at pH 7.4 (lung epithelial pH) and 4.2 (macrophage endosomal pH) with and without the chemical permeabilisers (Pluronic L62D - lipid nanocarriers; H(+)- polymer nanocarriers) was then tested. At pH 7.4 the presence of the permeabilisers increased nanocarrier drug release rate (from 3.2μg/h to 6.8μg/h for lipid shell nanocarriers, 2.3μg/h to 3.4μg/h for polymer shell nanocarriers) and drug release extent (from 50% to 80% for lipid shell nanocarriers, from 45% to 76% for polymer shell nanocarriers). These effects were accompanied by lipid nanocarrier distension (from 50 to 240nm) and polymer shell hydrolysis. At pH 4.2 the polymer nanocarriers did not respond to the permeabiliser, but the lipid nanocarrier maintained a robust drug release enhancement response and hence they demonstrated that the manipulation of controlled drug release from lung-targeted nanocarriers was possible through chemically mediated shell permeabilisation.

  10. Delays in new drug applications in Japan and industrial R&D strategies.

    Science.gov (United States)

    Hirai, Y; Kinoshita, H; Kusama, M; Yasuda, K; Sugiyama, Y; Ono, S

    2010-02-01

    The gap between Japan and both the United States (US) and the European Union (EU) with regard to access to new drugs is becoming a major issue in Japan. We analyzed the time lags involved in new drug application (NDA) and biological license application submissions in Japan, the US, and the EU in order to identify the causes of delayed access. The time lag related to submission of applications ("submission lag") was longer for in-licensed products and for non-Japanese companies. Factors related to costs of clinical studies and potential volumes of sales were not associated with the submission lag. A bridging strategy (extrapolative use of foreign clinical data in the clinical data package based on International Conference on Harmonisation guideline E5) seemed to reduce submission lag, but the association between the two diminished when the cause-and-effect relationship was specifically investigated. These results suggest that multinational companies are likely to place more emphasis on the choice of development strategies that successfully lead to their goal rather than on direct costs and expected sales when deciding to introduce their pharmaceutical products in Japan. Our findings indicate that the clinical development guidances that helps pharmaceutical companies decide on investment and strategies are also the key to narrowing the gap in access to new drugs.

  11. In vitro drug release studies on guar gum-based colon targeted oral drug delivery systems of 5-fluorouracil.

    Science.gov (United States)

    Krishnaiah, Y S R; Satyanarayana, V; Dinesh Kumar, B; Karthikeyan, R S

    2002-08-01

    Intravenous administration of 5-fluorouracil for colon cancer therapy produces severe systemic side-effects due to its cytotoxic effect on normal cells. The broad objective of the present study was to develop novel tablet formulations for site-specific delivery of 5-fluorouracil to the colon without the drug being released in the stomach or small intestine using guar gum as a carrier. Fast-disintegrating 5-fluorouracil core tablets were compression coated with 60% (FHV-60), 70% (FHV-70) and 80% (FHV-80) of guar gum, and were subjected to in vitro drug release studies. The amount of 5-fluorouracil released from the compression-coated tablets in the dissolution medium at different time intervals was estimated by a HPLC method. Guar gum compression-coated tablets released only 2.5-4% of the 5-fluorouracil in simulated GI fluids. When the dissolution study was continued in simulated colonic fluids (4% w/v rat caecal content medium) the compression-coated FHV-60, FHV-70 and FHV-80 tablets released another 70, 55 and 41% of the 5-fluorouracil respectively. The results of the study show that compression-coated tablets containing 80% (FHV-80) of guar gum are most likely to provide targeting of 5-fluorouracil for local action in the colon, since they released only 2.38% of the drug in the physiological environment of the stomach and small intestine. The FHV-80 formulation showed no change either in physical appearance, drug content or dissolution pattern after storage at 40 degrees C/RH 75% for 6 months. The differential scanning calorimetric study showed that 5-fluorouracil did not interact with the formulation excipients used in the study.

  12. Natural Non-Mulberry Silk Nanoparticles for Potential-Controlled Drug Release.

    Science.gov (United States)

    Wang, Juan; Yin, Zhuping; Xue, Xiang; Kundu, Subhas C; Mo, Xiumei; Lu, Shenzhou

    2016-12-01

    Natural silk protein nanoparticles are a promising biomaterial for drug delivery due to their pleiotropic properties, including biocompatibility, high bioavailability, and biodegradability. Chinese oak tasar Antheraea pernyi silk fibroin (ApF) nanoparticles are easily obtained using cations as reagents under mild conditions. The mild conditions are potentially advantageous for the encapsulation of sensitive drugs and therapeutic molecules. In the present study, silk fibroin protein nanoparticles are loaded with differently-charged small-molecule drugs, such as doxorubicin hydrochloride, ibuprofen, and ibuprofen-Na, by simple absorption based on electrostatic interactions. The structure, morphology and biocompatibility of the silk nanoparticles in vitro are investigated. In vitro release of the drugs from the nanoparticles depends on charge-charge interactions between the drugs and the nanoparticles. The release behavior of the compounds from the nanoparticles demonstrates that positively-charged molecules are released in a more prolonged or sustained manner. Cell viability studies with L929 demonstrated that the ApF nanoparticles significantly promoted cell growth. The results suggest that Chinese oak tasar Antheraea pernyi silk fibroin nanoparticles can be used as an alternative matrix for drug carrying and controlled release in diverse biomedical applications.

  13. Natural Non-Mulberry Silk Nanoparticles for Potential-Controlled Drug Release

    Science.gov (United States)

    Wang, Juan; Yin, Zhuping; Xue, Xiang; Kundu, Subhas C.; Mo, Xiumei; Lu, Shenzhou

    2016-01-01

    Natural silk protein nanoparticles are a promising biomaterial for drug delivery due to their pleiotropic properties, including biocompatibility, high bioavailability, and biodegradability. Chinese oak tasar Antheraea pernyi silk fibroin (ApF) nanoparticles are easily obtained using cations as reagents under mild conditions. The mild conditions are potentially advantageous for the encapsulation of sensitive drugs and therapeutic molecules. In the present study, silk fibroin protein nanoparticles are loaded with differently-charged small-molecule drugs, such as doxorubicin hydrochloride, ibuprofen, and ibuprofen-Na, by simple absorption based on electrostatic interactions. The structure, morphology and biocompatibility of the silk nanoparticles in vitro are investigated. In vitro release of the drugs from the nanoparticles depends on charge-charge interactions between the drugs and the nanoparticles. The release behavior of the compounds from the nanoparticles demonstrates that positively-charged molecules are released in a more prolonged or sustained manner. Cell viability studies with L929 demonstrated that the ApF nanoparticles significantly promoted cell growth. The results suggest that Chinese oak tasar Antheraea pernyi silk fibroin nanoparticles can be used as an alternative matrix for drug carrying and controlled release in diverse biomedical applications. PMID:27916946

  14. Evaluating the link between self-assembled mesophase structure and drug release.

    Science.gov (United States)

    Phan, Stephanie; Fong, Wye-Khay; Kirby, Nigel; Hanley, Tracey; Boyd, Ben J

    2011-12-12

    Lipid-based liquid crystalline materials are of increasing interest for use as drug delivery systems. The intricate nanostructure of the reversed bicontinuous cubic (V(2)) and inverse hexagonal (H(2)) liquid crystal matrices have been shown to provide diffusion controlled release of actives of varying size and polarity. In this study, we extend the understanding of release to other self-assembled phases, the micellar cubic phase (I(2)) and inverse micelles (L(2)). The systems are comparable as they were all prepared from the one lipid, glyceryl monooleate (GMO), which sequentially forms all four phases with increasing hexadecane (HD) content in excess water. Phase identity was confirmed by small angle X-ray scattering (SAXS). SAXS data indicated that four mesophases were formed with increasing HD content at 25°C: V(2) phase (Pn3m space group) formed at 0-4% (w/w) HD, H(2) phase formed at 4-25% (w/w) HD, I(2) phase (Fd3m space group) formed at 25-40% (w/w) HD and finally L(2) phase formed at >40% (w/w) HD. Analogous compositions using phytantriol rather than GMO as the core lipid did not produce the I(2) phase, with only V(2) to H(2) to L(2) transitions being apparent with increasing HD concentration. In order to relate the liquid crystal phase structure to drug release rate, in vitro release tests were conducted by incorporating radio-labelled glucose as a model hydrophilic drug into the four GMO-based mesophases. It was found that the drug release followed first-order diffusion kinetics and was fastest from V(2) followed by L(2), H(2), and I(2). Drug release was shown to be significantly faster from bicontinuous cubic phase than the other mesophases, indicating that the state of the water compartments, whether open or closed, has a great influence on the rate of drug release. It is envisioned that liquid crystalline mesophases with slower release characteristics will more likely have potential applications as sustained release drug delivery systems, and hence

  15. Mechanism of drug release from silica-gelatin aerogel-Relationship between matrix structure and release kinetics.

    Science.gov (United States)

    Veres, Péter; Kéri, Mónika; Bányai, István; Lázár, István; Fábián, István; Domingo, Concepción; Kalmár, József

    2017-01-17

    Specific features of a silica-gelatin aerogel (3 wt.% gelatin content) in relation to drug delivery has been studied. It was confirmed that the release of both ibuprofen (IBU) and ketoprofen (KET) is about tenfold faster from loaded silica-gelatin aerogel than from pure silica aerogel, although the two matrices are structurally very similar. The main goal of the study was to understand the mechanistic background of the striking difference between the delivery properties of these closely related porous materials. Hydrated and dispersed silica-gelatin aerogel has been characterized by NMR cryoporometry, diffusiometry and relaxometry. The pore structure of the silica aerogel remains intact when it disintegrates in water. In contrast, dispersed silica-gelatin aerogel develops a strong hydration sphere, which reshapes the pore walls and deforms the pore structure. The drug release kinetics was studied on a few minutes time scale with 1s time resolution. Simultaneous evaluation of all relevant kinetic and structural information confirmed that strong hydration of the silica-gelatin skeleton facilitates the rapid desorption and dissolution of the drugs from the loaded aerogel. Such a driving force is not operative in pure silica aerogels.

  16. Smart electrospun nanofibers for controlled drug release: recent advances and new perspectives.

    Science.gov (United States)

    Weng, Lin; Xie, Jingwei

    2015-01-01

    In biological systems, chemical molecules or ions often release upon certain conditions, at a specific location, and over a desired period of time. Electrospun nanofibers that undergo alterations in the physicochemical characteristics corresponding to environmental changes have gained considerable interest for various applications. Inspired by biological systems, therapeutic molecules have been integrated with these smart electrospun nanofibers, presenting activation-modulated or feedback-regulated control of drug release. Compared to other materials like smart hydrogels, environment-responsive nanofiber-based drug delivery systems are relatively new but possess incomparable advantages due to their greater permeability, which allows shorter response time and more precise control over the release rate. In this article, we review the mechanisms of various environmental parameters functioning as stimuli to tailor the release rates of smart electrospun nanofibers. We also illustrate several typical examples in specific applications. We conclude this article with a discussion on perspectives and future possibilities in this field.

  17. Degradation and drug release in calcium polyphosphate bioceramics: an MRI-based characterization.

    Science.gov (United States)

    Bray, J M; Filiaggi, M J; Bowen, C V; Beyea, S D

    2012-10-01

    Degradable, bioceramic bone implants made of calcium polyphosphate (CPP) hold potential for controlled release of therapeutic agents in the treatment of localized bone disease. Magnetic resonance imaging techniques for non-invasively mapping fluid distribution, T(1) and T(2) relaxation times and the apparent diffusion coefficient were performed in conjunction with a drug elution protocol to resolve free and bound water components within the material microstructure in two CPP formulations (G1 and G2). The T(2) maps provided the most accurate estimates of free and bound water, and showed that G1 disks contained a detectable free water component at all times, with drug release dominated by a Fickian diffusion mechanism. Drug release from G2 disks was characterized by a combined diffusional/structural relaxation mechanism, which may be related to the gradual infiltration of a free water component associated with swelling and/or chemical degradation.

  18. 49 CFR 40.323 - May program participants release drug or alcohol test information in connection with legal...

    Science.gov (United States)

    2010-10-01

    ... PROGRAMS Confidentiality and Release of Information § 40.323 May program participants release drug or... information pertaining to an employee's drug or alcohol test without the employee's consent in certain legal... the drug or alcohol test information sought is relevant to the case and issues an order directing...

  19. Kinetic models for the release of the anticancer drug doxorubicin from biodegradable polylactide/metal oxide-based hybrids

    CSIR Research Space (South Africa)

    Mhlanga, N

    2015-01-01

    Full Text Available For decades, studies on drug-release kinetics have been an important topic in the field of drug delivery because they provide important insights into the mechanism of drug release from carriers. In this work, polylactide (PLA), doxorubicin (DOX...

  20. PREPARATION AND DRUG RELEASE CHARACTERISTICS OF PINGYANGMYCIN GELATIN MICROSPHERES FOR EMBOLIZATION THERAPY

    Institute of Scientific and Technical Information of China (English)

    吴红; 张镇西; 吴道澄; 于开涛; 李晓晔

    2003-01-01

    Objective: To prepare Pingyangmycin gelatin microspheres (PYM-GMS) for carotid artery embolization therapy and to study the release characteristics in vivo and in vitro. Methods: PYM-GMS was prepared by optical double-phase emulsified condensation polymerization. Through UV-spectrophotometer drug content and encapsulation rate were measured. The characteristics of drug release in vitro which could simulate the actual state in vivo were tested by HPLC. Three ways of vein drop, artery perfusion and artery embolization were contrasted. Under the supervision of X-ray, PYM-GMS were perfused into the external carotid artery of rabbits by superselective artery embolization. Blood samples were tested at different time and analyzed statistically. Results: The roundness of PYM-GMS was 1.02±0.005. The mean diameter was 85.6 (m, 78% of them ranging from 50(200 (m, which fitted the use of embolization. PYM content and encapsulation rate were 6.8% and 91.3% respectively. 70% of the drug was released in 3 h in the simulated environment in vivo and total drug was released after more than 6 h. After artery embolization with small dosage of PYM-GMS, the local drug concentration was 8 times higher than the blood drug concentration and the high level of local drug concentration was kept for more than 120 min. Conclusion: External carotid artery embolization with PYM-GMS, which significantly reduced the circulating drug level and employment dosage, could prolong the duration higher drug concentration and suit the purpose of targeted tumor therapy.

  1. TiO2 nanotubes as animal drug delivery system and in vitro controlled release.

    Science.gov (United States)

    Lai, Shuting; Zhang, Wei; Liu, Fang; Wu, Cui; Zeng, Dongping; Sun, Yongxue; Xu, Yuehua; Fang, Yueping; Zhou, Wuyi

    2013-01-01

    The enrofloxacin hydrochloride (Enro), an anti-inflammatory drug for the animals, was loaded on the TNTs through physical absorption due to the high specific surface area and excellent surface activity of the TiO2 nanotubes. The samples were characterized by XRD, BET, TEM, TG and FTIR. The in vitro controlled release behavior at different temperatures was studied in detail. The results showed that the obtained TNTs were uniform and mainly amorphous crystal phase with a diameter of 10-15 nm and a length of 350-400 nm. By investigating the effect of the hydrothermal reaction process of the obtained TiO2 nanotubes and the drug loading frequency on the loading content of Enro drugs, the results indicated that the increasing loading frequency of the drug was available for the drug loading and the maximum loading content of drug reached to 33.28%. Enro-TNTs performed a better release profile at low temperature than at high temperature in PBS solution. The Higuchi square root models are suitable to explain the in vitro drug release behavior of Enro from Enro-TNTs.

  2. Charge-Reversal APTES-Modified Mesoporous Silica Nanoparticles with High Drug Loading and Release Controllability.

    Science.gov (United States)

    Wang, Yifeng; Sun, Yi; Wang, Jine; Yang, Yang; Li, Yulin; Yuan, Yuan; Liu, Changsheng

    2016-07-13

    In this study, we demonstrate a facile strategy (DL-SF) for developing MSN-based nanosystems through drug loading (DL, using doxorubicin as a model drug) followed by surface functionalization (SF) of mesoporous silica nanoparticles (MSNs) via aqueous (3-aminopropyl)triethoxysilane (APTES) silylation. For comparison, a reverse functionalization process (i.e., SF-DL) was also studied. The pre-DL process allows for an efficient encapsulation (encapsulation efficiency of ∼75%) of an anticancer drug [doxorubicin (DOX)] inside MSNs, and post-SF allows in situ formation of an APTES outer layer to restrict DOX leakage under physiological conditions. This method makes it possible to tune the DOX release rate by increasing the APTES decoration density through variation of the APTES concentration. However, the SF-DL approach results in a rapid decrease in drug loading capacity with an increase in APTES concentration because of the formation of the APTES outer layer hampers the inner permeability of the DOX drug, resulting in a burst release similar to that of undecorated MSNs. The resulting DOX-loaded DL-SF MSNs present a slightly negatively charged surface under physiological conditions and become positively charged in and extracellular microenvironment of solid tumor due to the protonation effect under acidic conditions. These merits aid their maintenance of long-term stability in blood circulation, high cellular uptake by a kind of skin carcinoma cells, and an enhanced intracellular drug release behavior, showing their potential in the delivery of many drugs beyond anticancer chemotherapeutics.

  3. Modeling drug release from functionalized magnetic nanoparticles actuated by non-heating low frequency magnetic field

    Science.gov (United States)

    Golovin, Y.; Golovin, D.; Klyachko, N.; Majouga, A.; Kabanov, A.

    2017-02-01

    Various plausible acceleration mechanisms of drug release from nanocarriers composed of a single-domain magnetic nanoparticle core with attached long macromolecule chains activated by low frequency non-heating alternating magnetic field (AMF) are discussed. The most important system characteristics affecting the AMF exposure impact are determined. Impact of several reasonable mechanisms is estimated analytically or obtained using numerical modeling. Some conditions providing manifold release acceleration as a result from exposure in AMF are found.

  4. The influence of metoprolol dosage release formulation on the pharmacokinetic drug interaction with paroxetine

    OpenAIRE

    Stout, Stephen M.; Nielsen, Jace; Welage, Lynda S; Shea, Michael; Brook, Robert; Kerber, Kevin; Bleske, Barry E

    2010-01-01

    Studies have demonstrated an influence of dosage release formulations on drug interactions and enantiomeric plasma concentrations. Metoprolol is a commonly used β-adrenergic antagonist metabolized by CYP2D6. The CYP2D6 inhibitor paroxetine has previously been shown to interact with metoprolol tartrate. This open-label, randomized, 4 phase crossover study assessed the potential differential effects of paroxetine on stereoselective pharmacokinetics of immediate release (IR) tartrate and extende...

  5. One Step Preparation of Controlled Drug Release Systems in Supercritical Carbon Dioxide

    Institute of Scientific and Technical Information of China (English)

    CAO Liqin; WANG Chengwei; CHEN Liuping

    2009-01-01

    Drug delivery systems based on copolymers of N-isopropylacrylamide were fn-st prepared by a one step method, in which supercritical carbon dioxide was simultaneously used as a polymerization medium and an impregnation agent. The obtained microspheres were characterized by scanning electronic microscopy (SEM), differential scan-ning calorimetry (DSC), transmission electron microscopy (TEM) and X-ray diffraction (XRD). The release effect of the in situ prepared microgels impregnated with ibuprofen was presented through in vitro release simulation.

  6. Coatings of Eudragit® RL and L-55 Blends: Investigations on the Drug Release Mechanism.

    Science.gov (United States)

    Wulff, Robert; Leopold, Claudia S

    2016-04-01

    In a previous study, generally lower drug release rates from RL:L55 blend coated pellets in neutral/basic release media than in acidic release media were reported. The aim of this study was to obtain information on the drug release mechanism of solid dosage forms coated with blends of Eudragit® RL (RL) and Eudragit® L-55 (L55). Swelling experiments with free films were analyzed spectroscopically and gravimetrically to identify the physicochemical cause for this release behavior. With Raman spectroscopy, the swelling of copolymer films could be monitored. IR spectroscopic investigations on RL:L55 blends immersed in media at pH 6.8 confirmed the formation of interpolyelectrolyte complexes (IPECs) that were not detectable after swelling in hydrochloric acid pH 1.2. Further investigations revealed that these IPECs decreased the extent of ion exchange between the quaternary ammonium groups of RL and the swelling media. This is presumably the reason for the previously reported decreased drug permeability of RL:L55 coatings in neutral/basic media as ion exchange is the determining factor in drug release from RL coated dosage forms. Gravimetric erosion studies confirmed that L55 was not leached out of the film blends during swelling in phosphate buffer pH 6.8. In contrast to all other investigated films, the 4:1 (RL:L55) blend showed an extensive swelling within 24 h at pH 6.8 which explains the reported sigmoidal release behavior of 4:1 blend coated pellets. These results help to understand the release behavior of RL:L55 blend coated solid dosage forms.

  7. Photoactive Fluoropolymer Surfaces that Release Sensitizer Drug Molecules

    Science.gov (United States)

    Ghosh, Goutam; Minnis, Mihaela; Ghogare, Ashwini A.; Abramova, Inna; Cengel, Keith; Busch, Theresa M.; Greer, Alexander

    2015-01-01

    We describe a physical-organic study of two fluoropolymers bearing a photoreleasable PEGylated photosensitizer which generates 1O2(1Δg) [chlorin e6 methoxy tri(ethylene glycol) triester]. The surfaces are Teflon/polyvinylalcohol (PVA) nanocomposite and fluorinated silica. The relative efficiency of these surfaces to photorelease the PEGylated sensitizer [shown previously to be phototoxic to ovarian cancer cells (Kimani, S. et al J. Org. Chem 2012, 77, 10638)] was slightly higher for the nanocomposite. In the presence of red light and O2, 1O2 is formed, which cleaves an ethene linkage to liberate the sensitizer in 68–92% yields. The fluoropolymers were designed to deal with multiple problems. Namely, their success relied not only high O2 solubility and drug repellency, but that the C−F bonds physically quench little 1O2 for its productive use away from the surface. The results obtained here indicate that Teflon-like surfaces have potential uses of delivering sensitizer and singlet oxygen for applications in tissue repair and photodynamic therapy (PDT). PMID:25686407

  8. Photoactive fluoropolymer surfaces that release sensitizer drug molecules.

    Science.gov (United States)

    Ghosh, Goutam; Minnis, Mihaela; Ghogare, Ashwini A; Abramova, Inna; Cengel, Keith A; Busch, Theresa M; Greer, Alexander

    2015-03-12

    We describe a physical-organic study of two fluoropolymers bearing a photoreleasable PEGylated photosensitizer that generates (1)O2((1)Δg) [chlorin e6 methoxy tri(ethylene glycol) triester]. The surfaces are Teflon/poly(vinyl alcohol) (PVA) nanocomposite and fluorinated silica. The relative efficiency of these surfaces to photorelease the PEGylated sensitizer [shown previously to be phototoxic to ovarian cancer cells (Kimani, S. et al. J. Org. Chem 2012, 77, 10638)] was slightly higher for the nanocomposite. In the presence of red light and O2, (1)O2 is formed, which cleaves an ethene linkage to liberate the sensitizer in 68-92% yield. The fluoropolymers were designed to deal with multiple problems. Namely, their success relied not only on high O2 solubility and drug repellency but also on the C-F bonds, which physically quench little (1)O2, for singlet oxygen's productive use away from the surface. The results obtained here indicate that Teflon-like surfaces have potential uses in delivering sensitizer and singlet oxygen for applications in tissue repair and photodynamic therapy (PDT).

  9. Effects of amphiphilic chitosan-g-poly(ε-caprolactone) polymer additives on paclitaxel release from drug eluting implants

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Weibin [Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092 (China); Gu, Chunhua [Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Jiang, Han [Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092 (China); Zhang, Mengru [Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China); Lang, Meidong, E-mail: mdlang@ecust.edu.cn [Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, Shanghai 200237 (China)

    2014-12-01

    Bioresorbable polymer stents have been proposed as promising medical implants to avoid long-term safety concerns and other potential issues caused by traditional materials. As an important member, poly(ε-caprolactone) (PCL) was used as the implant matrix with different drug loadings. To better regulate drug release rate, the hydrophilicity of PCL was adjusted by addition of amphiphilic graft copolymers, chitosan-g-poly(ε-caprolactone) (CP). The in vitro release results indicated that the improvement of bulk hydrophilicity could accelerate drug release better than that of surface coating. The optimum additive amount was 25% with CP9. Further study showed that the effect of aspirin molecules displayed no obvious difference to that of CP macromolecules on drug release rate. Moreover, these release profiles were fitted with mathematical models. The similarities were evaluated with similarity factors. Scanning electron microscopy (SEM) images displayed surface/cross-section morphologies of pure PCL and modified implants before and after release. - Highlights: • The improvement of bulk hydrophilicity better accelerated drug release. • The higher weight ratio of CP implants had, the faster the drug released. • The shorter PCL chain in CP graft coploymers, the faster the drug released. • The optimum additive amount was 25% with CP9. • Drug release profile conformed to controllable Fick diffusional release mechanism.

  10. Nanosized sustained-release drug depots fabricated using modified tri-axial electrospinning.

    Science.gov (United States)

    Yang, Guang-Zhi; Li, Jiao-Jiao; Yu, Deng-Guang; He, Mei-Feng; Yang, Jun-He; Williams, Gareth R

    2017-01-27

    Nanoscale drug depots, comprising a drug reservoir surrounded by a carrier membrane, are much sought after in contemporary pharmaceutical research. Using cellulose acetate (CA) as a filament-forming polymeric matrix and ferulic acid (FA) as a model drug, nanoscale drug depots in the form of core-shell fibers were designed and fabricated using a modified tri-axial electrospinning process. This employed a solvent mixture as the outer working fluid, as a result of which a robust and continuous preparation process could be achieved. The fiber-based depots had a linear morphology, smooth surfaces, and an average diameter of 0.62±0.07μm. Electron microscopy data showed them to have clear core-shell structures, with the FA encapsulated inside a CA shell. X-ray diffraction and IR spectroscopy results verified that FA was present in the crystalline physical form. In vitro dissolution tests revealed that the fibers were able to provide close to zero-order release over 36h, with no initial burst release and minimal tailing-off. The release properties of the depot systems were much improved over monolithic CA/FA fibers, which exhibited a significant burst release and also considerable tailing-off at the end of the release experiment. Here we thus demonstrate the concept of using modified tri-axial electrospinning to design and develop new types of heterogeneous nanoscale biomaterials.

  11. Physicochemical and drug release characteristics of acetylated starches of five Lagenaria siceraria cultivars.

    Science.gov (United States)

    Kulkarni, Sameer D; Sinha, Barij N; Kumar, K Jayaram

    2015-01-01

    Modified starches play a crucial role in the pharmaceutical industries in controlling the drug release at a pre-determined rate. The effect of acetylation on the physicochemical and drug release characteristics of the starches from five different Indian L. siceraria cultivars was investigated. Starches isolated from the seeds of L. siceraria were subjected to varying degrees of acetylation. Using a range of characterization methods including amylose content, elemental analysis, light transmittance, swelling power, scanning electron microscopy, FT-IR and X-ray diffraction, the effect of acetylation was determined. The swelling power of starch acetates improved significantly (P siceraria starch. Modification in the crystalline structure of starch acetate retarded the drug release, which is controlled by water uptake. The starch acetates from all the cultivars showed better sustained release properties with the increase in degree of substitution. Drug release through the swellable matrix was found to be controlled by fickian diffusion from the gel layer as indicated by Korsmeyer-Peppas models (R(2)) 0.9885-0.9984.

  12. Winter warming delays dormancy release, advances budburst, alters carbohydrate metabolism and reduces yield in a temperate shrub

    DEFF Research Database (Denmark)

    Pagter, Majken; Andersen, Uffe Brandt; Andersen, Lillie

    2015-01-01

    winter warming modifies phenological traits in a woody perennial known to have a large chilling requirement and to be sensitive to spring frost. Warming delayed dormancy release more in the cultivar ‘Narve Viking’ than in the cultivar ‘Titania’, but advanced budburst and flowering predominantly...... in ‘Titania’. Since ‘Narve Viking’ has a higher chilling requirement than ‘Titania’, this indicates that, in high-chillingrequiring genotypes, dormancy responses may temper the effect of warming on spring phenology. Winter Warming significantly reduced fruit yield the following summer in both cultivars...... at elevated temperature showed decreased levels of sucrose in stems of both cultivars and flower buds of ‘Narve Viking’, which, in buds, was associated with increased concentrations of glucose and fructose. Hence, winter warming influences carbohydrate metabolism, but it remains to be elucidated whether...

  13. Oral controlled release drug delivery system and Characterization of oral tablets; A review

    Directory of Open Access Journals (Sweden)

    Muhammad Zaman

    2016-01-01

    Full Text Available Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes diffusion controlled drug delivery systems; dissolution controlled drug delivery systems, osmotically controlled drug delivery systems, ion-exchange controlled drug delivery systems, hydrodynamically balanced systems, multi-Particulate drug delivery systems and microencapsulated drug delivery system. The systems are formulated using different natural, semi-synthetic and synthetic polymers. The purpose of the review is to provide information about the orally controlled drug delivery system, polymers which are used to formulate these systems and characterizations of one of the most convenient dosage form which is the tablets. 

  14. The effect of porosity on drug release kinetics from vancomycin microsphere/calcium phosphate cement composites.

    Science.gov (United States)

    Schnieders, Julia; Gbureck, Uwe; Vorndran, Elke; Schossig, Michael; Kissel, Thomas

    2011-11-01

    The influence of porosity on release profiles of antibiotics from calcium phosphate composites was investigated to optimize the duration of treatment. We hypothesized, that by the encapsulation of vancomycin-HCl into biodegradable microspheres prior admixing to calcium phosphate bone cement, the influence of porosity of the cement matrix on vancomycin release could be reduced. Encapsulation of vancomycin into a biodegradable poly(lactic co-glycolic acid) copolymer (PLGA) was performed by spray drying; drug-loaded microparticles were added to calcium phosphate cement (CPC) at different powder to liquid ratios (P/L), resulting in different porosities of the cement composites. The effect of differences in P/L ratio on drug release kinetics was compared for both the direct addition of vancomycin-HCl to the cement liquid and for cement composites modified with vancomycin-HCl-loaded microspheres. Scanning electron microscopy (SEM) was used to visualize surface and cross section morphology of the different composites. Brunauer, Emmett, and Teller-plots (BET) was used to determine the specific surface area and pore size distribution of these matrices. It could be clearly shown, that variations in P/L ratio influenced both the porosity of cement and vancomycin release profiles. Antibiotic activity during release study was successfully measured using an agar diffusion assay. However, vancomycin-HCl encapsulation into PLGA polymer microspheres decreased porosity influence of cement on drug release while maintaining antibiotic activity of the embedded substance.

  15. Controlled poorly soluble drug release from solid self-microemulsifying formulations with high viscosity hydroxypropylmethylcellulose.

    Science.gov (United States)

    Yi, Tao; Wan, Jiangling; Xu, Huibi; Yang, Xiangliang

    2008-08-07

    The objective of this work was the development of a controlled release system based on self-microemulsifying mixture aimed for oral delivery of poorly water-soluble drugs. HPMC-based particle formulations were prepared by spray drying containing a model drug (nimodipine) of low water solubility and hydroxypropylmethylcellulose (HPMC) of high viscosity. One type of formulations contained nimodipine mixed with HPMC and the other type of formulations contained HPMC and nimodipine dissolved in a self-microemulsifying system (SMES) consisting of ethyl oleate, Cremophor RH 40 and Labrasol. Based on investigation by transmission electron microscopy (TEM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction, differences were found in the particle structure between both types of formulations. In vitro release was performed and characterized by the power law. Nimodipine release from both types of formulations showed a controlled release profile and the two power law parameters, n and K, correlated to the viscosity of HPMC. The parameters were also influenced by the presence of SMES. For the controlled release solid SMES, oil droplets containing dissolved nimodipine diffused out of HPMC matrices following exposure to aqueous media. Thus, it is possible to control the in vitro release of poorly soluble drugs from solid oral dosage forms containing SMES.

  16. Mimicking Biological Delivery Through Feedback-Controlled Drug Release Systems Based on Molecular Imprinting.

    Science.gov (United States)

    Kryscio, David R; Peppas, Nicholas A

    2009-06-01

    Intelligent drug delivery systems (DDS) are able to rapidly detect a biological event and respond appropriately by releasing a therapeutic agent; thus, they are advantageous over their conventional counterparts. Molecular imprinting is a promising area that generates a polymeric network which can selectively recognize a desired analyte. This field has been studied for a variety of applications over a long period of time, but only recently has it been investigated for biomedical and pharmaceutical applications. Recent work in the area of molecularly imprinted polymers in drug delivery highlights the potential of these recognitive networks as environmentally responsive DDS that can ultimately lead to feedback controlled recognitive release systems.

  17. Kinetic models for the release of the anticancer drug doxorubicin from biodegradable polylactide/metal oxide-based hybrids.

    Science.gov (United States)

    Mhlanga, Nikiwe; Ray, Suprakas Sinha

    2015-01-01

    For decades, studies on drug-release kinetics have been an important topic in the field of drug delivery because they provide important insights into the mechanism of drug release from carriers. In this work, polylactide (PLA), doxorubicin (DOX), and metal oxide (MO) (titanium dioxide, magnetic iron oxide, and zinc oxide) spheres were synthesised using the solvent-evaporation technique and were tested for sustained drug release. The efficacy of a dosage system is determined by its ability to deliver the drug at a sustained rate, afford an increased plasma half-life, a minimum exposure of toxic drugs to healthy cells and a high drug pay load. Mathematical models were used to elucidate the release mechanism of the drug from the spheres. The release fitted a zero-order model with a correlation coefficient in the range of 0.9878-0.9891 and the release mechanism followed an anomalous release, meaning drug release was afforded through both diffusion and the dissolution of PLA. Therefore, PLA/DOX/MO released the same amount of drug per unit time. Consequently, the potential for PLA use as a carrier was ascertained. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Obtaining of Sol-Gel Ketorolac-Silica Nanoparticles: Characterization and Drug Release Kinetics

    Directory of Open Access Journals (Sweden)

    T. M. López Goerne

    2013-01-01

    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are among most commonly prescribed medications worldwide. NSAIDs play an important role due to their pronounced analgesic potency, anti-inflammatory effects, and lesser side effects compared to opioids. However, adverse effects including gastrointestinal and cardiovascular effects seriously complicate their prolonged use. In the present work we prepare SiO2-based nanoparticles with ketorolac, for controlled release proposes. The nanomaterials were prepared by the sol-gel technology at acidic conditions and two different water/alcoxide ratios were used. FTIR spectroscopy was performed in order to characterize the solids and drug-SiO2 interactions. Thermal analysis and nitrogen adsorption isotherms showed thermal stability of the drug and confirmed the presence of particles with high surface area. Transmission electron micrographies of the samples showed the nanosize particles (20 nm forming aggregates. Drug release profiles were collected by means of UV-Vis spectroscopy and kinetic analysis was developed. Release data were fitted and 1 : 8 sample showed a sustained release over ten hours; 90% of the drug was delivered at the end of the time.

  19. Optimization of matrix tablets controlled drug release using Elman dynamic neural networks and decision trees.

    Science.gov (United States)

    Petrović, Jelena; Ibrić, Svetlana; Betz, Gabriele; Đurić, Zorica

    2012-05-30

    The main objective of the study was to develop artificial intelligence methods for optimization of drug release from matrix tablets regardless of the matrix type. Static and dynamic artificial neural networks of the same topology were developed to model dissolution profiles of different matrix tablets types (hydrophilic/lipid) using formulation composition, compression force used for tableting and tablets porosity and tensile strength as input data. Potential application of decision trees in discovering knowledge from experimental data was also investigated. Polyethylene oxide polymer and glyceryl palmitostearate were used as matrix forming materials for hydrophilic and lipid matrix tablets, respectively whereas selected model drugs were diclofenac sodium and caffeine. Matrix tablets were prepared by direct compression method and tested for in vitro dissolution profiles. Optimization of static and dynamic neural networks used for modeling of drug release was performed using Monte Carlo simulations or genetic algorithms optimizer. Decision trees were constructed following discretization of data. Calculated difference (f(1)) and similarity (f(2)) factors for predicted and experimentally obtained dissolution profiles of test matrix tablets formulations indicate that Elman dynamic neural networks as well as decision trees are capable of accurate predictions of both hydrophilic and lipid matrix tablets dissolution profiles. Elman neural networks were compared to most frequently used static network, Multi-layered perceptron, and superiority of Elman networks have been demonstrated. Developed methods allow simple, yet very precise way of drug release predictions for both hydrophilic and lipid matrix tablets having controlled drug release.

  20. Sustained drug release by contact lenses for glaucoma treatment-a review.

    Science.gov (United States)

    Carvalho, I M; Marques, C S; Oliveira, R S; Coelho, P B; Costa, P C; Ferreira, D C

    2015-03-28

    In the context of ocular pharmacology, there is a growing need for innovative delivery platforms for a convenient and sustained drug release into the eye, especially for chronic diseases that require the adoption of a strict insurmountable treatment regimen for a large part of the affected population, as in the case of glaucoma. Due to the large residence time of the contact lenses in the eye, its use for sustained drug delivery is quite promising. However, and despite the numerous therapeutic advantages arising from its use, the low affinity shown by most ophthalmic drugs for conventional contact lenses hinders the practical application of this technology. In this paper we elaborated a review of the various methods exploited so far to improve the contact lenses' characteristics as mechanisms for controlled and prolonged drug release for topical treatment of ocular diseases, with particular emphasis on the treatment of glaucoma.

  1. Molecular weight-dependent degradation and drug release of surface-eroding poly(ethylene carbonate)

    DEFF Research Database (Denmark)

    Bohr, Adam; Wang, Yingya; Harmankaya, Necati

    2017-01-01

    Poly(ethylene carbonate) (PEC) is a unique biomaterial showing significant potential for controlled drug delivery applications. The current study investigated the impact of the molecular weight on the biological performance of drug-loaded PEC films. Following the preparation and thorough...... physicochemical characterization of diverse PEC (molecular weights: 85, 110, 133, 174 and 196 kDa), the degradation and drug release behavior of rifampicin- and bovine serum albumin-loaded PEC films was investigated in vitro (in the presence and absence of cholesterol esterase), in cell culture (RAW264.......7 macrophages) and in vivo (subcutaneous implantation in rats). All investigated samples degraded by means of surface erosion (mass loss, but constant molecular weight), which was accompanied by a predictable, erosion-controlled drug release pattern. Accordingly, the obtained in vitro degradation half...

  2. Drug-releasing nano-engineered titanium implants: therapeutic efficacy in 3D cell culture model, controlled release and stability.

    Science.gov (United States)

    Gulati, Karan; Kogawa, Masakazu; Prideaux, Matthew; Findlay, David M; Atkins, Gerald J; Losic, Dusan

    2016-12-01

    There is an ongoing demand for new approaches for treating localized bone pathologies. Here we propose a new strategy for treatment of such conditions, via local delivery of hormones/drugs to the trauma site using drug releasing nano-engineered implants. The proposed implants were prepared in the form of small Ti wires/needles with a nano-engineered oxide layer composed of array of titania nanotubes (TNTs). TNTs implants were inserted into a 3D collagen gel matrix containing human osteoblast-like, and the results confirmed cell migration onto the implants and their attachment and spread. To investigate therapeutic efficacy, TNTs/Ti wires loaded with parathyroid hormone (PTH), an approved anabolic therapeutic for the treatment of severe bone fractures, were inserted into 3D gels containing osteoblast-like cells. Gene expression studies revealed a suppression of SOST (sclerostin) and an increase in RANKL (receptor activator of nuclear factor kappa-B ligand) mRNA expression, confirming the release of PTH from TNTs at concentrations sufficient to alter cell function. The performance of the TNTs wire implants using an example of a drug needed at relatively higher concentrations, the anti-inflammatory drug indomethacin, is also demonstrated. Finally, the mechanical stability of the prepared implants was tested by their insertion into bovine trabecular bone cores ex vivo followed by retrieval, which confirmed the robustness of the TNT structures. This study provides proof of principle for the suitability of the TNT/Ti wire implants for localized bone therapy, which can be customized to cater for specific therapeutic requirements.

  3. A poly({epsilon}-caprolactone) device for sustained release of an anti-glaucoma drug

    Energy Technology Data Exchange (ETDEWEB)

    Natu, Madalina V; De Sousa, HermInio C; Gil, M H [Department of Chemical Engineering, University of Coimbra, Polo II, Pinhal de Marrocos, 3030-290, Coimbra (Portugal); Gaspar, Manuel N; Fontes Ribeiro, Carlos A [Institute of Pharmacology and Experimental Therapeutics, University of Coimbra, Azinhaga de Santa Comba, Celas, 3000-354, Coimbra (Portugal); Correia, IlIdio J; Silva, Daniela, E-mail: hgil@eq.uc.pt [Centro de Investigacao em Ciencias da Saude, Faculdade de Ciencias da Saude, Universidade da Beira Interior, Covilha (Portugal)

    2011-04-15

    Implantable dorzolamide-loaded discs were prepared by blending poly({epsilon}-caprolactone), PCL, with poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide), Lu. By blending, crystallinity, water uptake and mass loss were modified relative to the pure polymers. Burst was diminished by coating the discs with a PCL shell. All samples presented burst release except PCL-coated samples that showed controlled release during 18 days. For PCL-coated samples, barrier control of diffusion coupled with partition control from the core slowed down the release, while for 50/50 Lu/PCL-coated samples, the enhancement in the porosity of the core diminished partition control of drug release. Nonlinear regression analysis suggested that a degradation model fully describes the release curve considering a triphasic release mechanism: the instantaneous diffusion (burst), diffusion and polymer degradation stages. The MTT test indicated that the materials are not cytotoxic for corneal endothelial cells. A good in vitro-in vivo correlation was obtained, with similar amounts of drug released in vitro and in vivo. The discs decreased intraocular pressure (IOP) in normotensive rabbit eyes by 13.0% during 10 days for PCL-coated and by 13.0% during 4 days for 50/50 Lu/PCL-coated samples. The percentages of IOP decrease are similar to those obtained by dorzolamide eyedrop instillation (11.0%).

  4. Biointerfacing polymeric microcapsules for in vivo near-infrared light-triggered drug release

    Science.gov (United States)

    Shao, Jingxin; Xuan, Mingjun; Si, Tieyan; Dai, Luru; He, Qiang

    2015-11-01

    Seeking safe and effective water-soluble drug carriers is of great significance in nanomedicine. To achieve this goal, we present a novel drug delivery system based on biointerfacing hollow polymeric microcapsules for effectively encapsulating water-soluble antitumor drug and gold nanorod (GNR) functionalization for triggered release of therapeutic drugs on-demand using low power near-infrared (NIR) radiation. The surface of polymeric microcapsules is covered with fluidic lipid bilayers to decrease the permeability of the wall of polymeric capsules. The temperature increase upon NIR illumination deconstructs the structure of the lipid membrane and polyelectrolyte multilayers, which in turn results in the rapid release of encapsulated water-soluble drug. In vivo antitumor tests demonstrate that this microcapsule has the effective ability of inhibiting tumor growth and preventing metastases. Real time in vivo fluorescence imaging results confirm that capsules can be excreted gradually from the animal body which in turn demonstrates the biocompatibility and biodegradation of these biointerfacing GNR-microcapsules. This intelligent system provides a novel anticancer platform with the advantages of controlled release, biological friendliness and credible biosafety.Seeking safe and effective water-soluble drug carriers is of great significance in nanomedicine. To achieve this goal, we present a novel drug delivery system based on biointerfacing hollow polymeric microcapsules for effectively encapsulating water-soluble antitumor drug and gold nanorod (GNR) functionalization for triggered release of therapeutic drugs on-demand using low power near-infrared (NIR) radiation. The surface of polymeric microcapsules is covered with fluidic lipid bilayers to decrease the permeability of the wall of polymeric capsules. The temperature increase upon NIR illumination deconstructs the structure of the lipid membrane and polyelectrolyte multilayers, which in turn results in the rapid

  5. Synthesis of Some Streoregular Polydiacetylenes and the Slow Release of Drug Using Some Linear Polymers

    Directory of Open Access Journals (Sweden)

    *Mohammad S. Al-Ajely

    2012-09-01

    Full Text Available Some polydiacetylenes have been synthesized using UV light in topochemical polymerization technique. Some diacetylene compounds were reacted with benzocaine and procaine in an attempt to be used as biosensors in topochemical polymerization process (In vivo. The linear (Amorphous polymer was allowed to react with some commercial antibiotics and were studied as slow drug release polymers. Externally treatment of the drug containing polymers to groups of infected rabbits revealed that these polymers are effective against certain types of micro organisms.

  6. A combination of chondroitinase ABC, glial cell line-derived neurotrophic factor, and Nogo A antibody delayed-release microspheres for the treatment of spinal cord injury

    Institute of Scientific and Technical Information of China (English)

    Yu Zhang; Yueming Song

    2011-01-01

    The purpose of this study was to evaluate the effect of poly(lactide-co-glycolic acid) delayed-release microspheres, which were prepared using glial cell line-derived neurotrophic factor (GDNF), on the delayed-release, controllability, and protection of GDNF activity. The present study is the first to combine chondroitinase ABC, GDNF, and Nogo A antibody delayed-release microspheres for the treatment of spinal cord injury. Results show that the combined therapy of chondroitinase ABC,GDNF, and Nogo A antibody microspheres can increase the immunoreaction of neurofilament 200in the injured spinal cord, and this therapeutic effect was better than chondroitinase ABC, GDNF, or Nogo A antibody microspheres administered singularly.

  7. Neuroblastoma-targeted nanocarriers improve drug delivery and penetration, delay tumor growth and abrogate metastatic diffusion.

    Science.gov (United States)

    Cossu, Irene; Bottoni, Gianluca; Loi, Monica; Emionite, Laura; Bartolini, Alice; Di Paolo, Daniela; Brignole, Chiara; Piaggio, Francesca; Perri, Patrizia; Sacchi, Angelina; Curnis, Flavio; Gagliani, Maria Cristina; Bruno, Silvia; Marini, Cecilia; Gori, Alessandro; Longhi, Renato; Murgia, Daniele; Sementa, Angela Rita; Cilli, Michele; Tacchetti, Carlo; Corti, Angelo; Sambuceti, Gianmario; Marchiò, Serena; Ponzoni, Mirco; Pastorino, Fabio

    2015-11-01

    Selective tumor targeting is expected to enhance drug delivery and to decrease toxicity, resulting in an improved therapeutic index. We have recently identified the HSYWLRS peptide sequence as a specific ligand for aggressive neuroblastoma, a childhood tumor mostly refractory to current therapies. Here we validated the specific binding of HSYWLRS to neuroblastoma cell suspensions obtained either from cell lines, animal models, or Schwannian-stroma poor, stage IV neuroblastoma patients. Binding of the biotinylated peptide and of HSYWLRS-functionalized fluorescent quantum dots or liposomal nanoparticles was dose-dependent and inhibited by an excess of free peptide. In animal models obtained by the orthotopic implant of either MYCN-amplified or MYCN single copy human neuroblastoma cell lines, treatment with HSYWLRS-targeted, doxorubicin-loaded Stealth Liposomes increased tumor vascular permeability and perfusion, enhancing tumor penetration of the drug. This formulation proved to exert a potent antitumor efficacy, as evaluated by bioluminescence imaging and micro-PET, leading to (i) delay of tumor growth paralleled by decreased tumor glucose consumption, and (ii) abrogation of metastatic spreading, accompanied by absence of systemic toxicity and significant increase in the animal life span. Our findings are functional to the design of targeted nanocarriers with potentiated therapeutic efficacy towards the clinical translation.

  8. Catanionic aggregates formed from drugs and lauric or capric acids enable prolonged release from gels.

    Science.gov (United States)

    Dew, Noel; Bramer, Tobias; Edsman, Katarina

    2008-07-15

    The aim of this study was to add to the range of charged surfactants that can be used to form catanionic aggregates with oppositely charged surface active drug substances; and to apply these aggregates to prolong drug release from gels. The surfactants used in this study, lauric and capric acids are of natural origin-unlike traditionally used, synthetic, surfactants. The mixtures of drug substances and oppositely charged surfactants were studied visually and with cryogenic transmission electron microscopy. Drug release from gels was studied with a modified USP paddle method. This study shows that lauric and capric acids are as, or even more, active in forming catanionic aggregates than traditionally used surfactants such as sodium dodecyl sulfate. It is shown that the length of the hydrophobic part of the surfactant plays an important role in the formation of pharmaceutically interesting catanionic aggregates. As seen in previous studies, using catanionic vesicles prolongs the drug release from gels and decreases the apparent diffusion coefficient by a factor of 10-50, compared to a gel containing only drug substance.

  9. Targeted and controlled anticancer drug delivery and release with magnetoelectric nanoparticles

    Science.gov (United States)

    Rodzinski, Alexandra; Guduru, Rakesh; Liang, Ping; Hadjikhani, Ali; Stewart, Tiffanie; Stimphil, Emmanuel; Runowicz, Carolyn; Cote, Richard; Altman, Norman; Datar, Ram; Khizroev, Sakhrat

    2016-02-01

    It is a challenge to eradicate tumor cells while sparing normal cells. We used magnetoelectric nanoparticles (MENs) to control drug delivery and release. The physics is due to electric-field interactions (i) between MENs and a drug and (ii) between drug-loaded MENs and cells. MENs distinguish cancer cells from normal cells through the membrane’s electric properties; cancer cells have a significantly smaller threshold field to induce electroporation. In vitro and in vivo studies (nude mice with SKOV-3 xenografts) showed that (i) drug (paclitaxel (PTX)) could be attached to MENs (30-nm CoFe2O4@BaTiO3 nanostructures) through surface functionalization to avoid its premature release, (ii) drug-loaded MENs could be delivered into cancer cells via application of a d.c. field (~100 Oe), and (iii) the drug could be released off MENs on demand via application of an a.c. field (~50 Oe, 100 Hz). The cell lysate content was measured with scanning probe microscopy and spectrophotometry. MENs and control ferromagnetic and polymer nanoparticles conjugated with HER2-neu antibodies, all loaded with PTX were weekly administrated intravenously. Only the mice treated with PTX-loaded MENs (15/200 μg) in a field for three months were completely cured, as confirmed through infrared imaging and post-euthanasia histology studies via energy-dispersive spectroscopy and immunohistochemistry.

  10. Investigation of release pattern of a drug with low solubility through asymmetric membrane capsules

    Directory of Open Access Journals (Sweden)

    P K Sahoo

    2013-01-01

    Full Text Available Asymmetric membrane capsules are a type of osmotic drug delivery systems. They are nondisintegrating capsules, which utilize osmotic pressure to drive the drug outwards for controlled delivery. Preceded by systems such as elementary osmotic pump, controlled porosity osmotic pump, single composition osmotic tablet this system has the advantage of simple and easy fabrication as it obviates the necessity of drilling an orifice into the drug delivery system. Moreover; it seems to be a low-cost alternative. The cellulose acetate capsule shell, on coming in contact with the aqueous medium shows in situ pore formation due to leaching of pore formers, which have been incorporated into the shell forming solution. Until date, a number of osmotic agents to the likes of sodium chloride, mannitol has been used to build up osmotic pressure inside the cell. The system is endowed with high water flux, which is a plus point for delivery of poorly soluble drugs like cephalexin in terms of increasing release rates. Studies envisaged in this research include the effect of different concentrations of different pore formers on in vitro drug release as well as the effect of modification of inner contents of the capsule. The system was successful in producing a gradual release of drug for 12 h.

  11. Delayed release pancrelipase for the treatment of pancreatic exocrine insufficiency associated with cystic fibrosis

    Directory of Open Access Journals (Sweden)

    Susan S Baker

    2008-10-01

    Full Text Available Susan S BakerDepartment of Pediatrics, University at Buffalo, Buffalo, NY, USAAbstract: Pancreatic enzyme replacement therapy (PERT is the only treatment for malabsorption in cystic fi brosis (CF caused by pancreatic insufficiency (PI. PI occurs in approximately 85% of patients with CF. PERT overcomes some, but not all the signs and symptoms of malabsorption. Clinical parameters such as growth, abdominal pain, diarrhea and gassiness, commonly used to adjust PERT dosing, are shown not to be good indicators of their effectiveness. The FDA does not provide oversight of preparations of pancreatic enzymes consistent with the oversight it provides for all other drugs. The FDA intends to rectify this situation. Measures of the effectiveness of PERT are limited to the coefficient of fat absorption, a difficult and unpleasant exercise for patients.Keywords: pancrelipase, cystic fibrosis, malabsorption, pancreatic enzymes

  12. Delayed release pancrelipase for treatment of pancreatic exocrine insufficiency associated with chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Devi Mukkai Krishnamurty

    2009-07-01

    Full Text Available Devi Mukkai Krishnamurty,1 Atoosa Rabiee,2 Sanjay B Jagannath,1 Dana K Andersen2Johns Hopkins University School of Medicine; 1Department of Medicine; 2Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA; 2Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, MD, USAAbstract: Pancreatic enzyme supplements (PES are used in chronic pancreatitis (CP for correction of pancreatic exocrine insufficiency (PEI as well as pain and malnutrition. The use of porcine pancreatic enzymes for the correction of exocrine insufficiency is governed by the pathophysiology of the disease as well as pharmacologic properties of PES. Variability in bioequivalence of PES has been noted on in vitro and in vivo testing and has been attributed to the differences in enteric coating and the degree of micro-encapsulation. As a step towards standardizing pancreatic enzyme preparations, the Food and Drug Administration now requires the manufacturers of PES to obtain approval of marketed formulations by April 2010. In patients with treatment failure, apart from evaluating drug and dietary interactions and compliance, physicians should keep in mind that patients may benefit from switching to a different formulation. The choice of PES (enteric coated versus non-enteric coated and the need for acid suppression should be individualized. There is no current standard test for evaluating adequacy of therapy in CP patients and studies have shown that optimization of therapy based on symptoms may be inadequate. Goals of therapy based on overall patient presentation and specific laboratory tests rather than mere correction of steatorrhea are needed.Keywords: pancreatic exocrine insufficiency, chronic pancreatitis, pancreatic enzyme supplement

  13. On the exfoliating polymeric cellular dosage forms for immediate drug release.

    Science.gov (United States)

    Blaesi, Aron H; Saka, Nannaji

    2016-06-01

    The most prevalent pharmaceutical dosage forms at present-the oral immediate-release tablets and capsules-are granular solids. Though effective in releasing drug rapidly, development and manufacture of such dosage forms are fraught with difficulties inherent to particulate processing. Predictable dosage form manufacture could be achieved by liquid-based processing, but cast solid dosage forms are not suitable for immediate drug release due to their resistance to fluid percolation. To overcome this limitation, we have recently introduced cellular dosage forms that can be readily prepared from polymeric melts. It has been shown that open-cell structures comprising polyethylene glycol 8000 (PEG 8k) excipient and a drug exfoliate upon immersion in a dissolution medium. The drug is then released rapidly due to the large specific surface area of the exfoliations. In this work, we vary the molecular weight of the PEG excipient and investigate its effect on the drug release kinetics of structures with predominantly open-cell topology. We demonstrate that the exfoliation rate decreases substantially if the excipient molecular weight is increased from 12 to 100kg/mol, which causes the drug dissolution time to increase by more than a factor of ten. A model is then developed to elucidate the exfoliation behavior of cellular structures. Diverse transport processes are considered: percolation due to capillarity, diffusion of dissolution medium through the cell walls, and viscous flow of the saturated excipient. It is found that the lower exfoliation rate and the longer dissolution time of the dosage forms with higher excipient molecular weight are primarily due to the greater viscosity of the cell walls after fluid penetration.

  14. Analyzing the impact of different excipients on drug release behavior in hot-melt extrusion formulations using FTIR spectroscopic imaging.

    Science.gov (United States)

    Pudlas, Marieke; Kyeremateng, Samuel O; Williams, Leonardo A M; Kimber, James A; van Lishaut, Holger; Kazarian, Sergei G; Woehrle, Gerd H

    2015-01-25

    The drug release performance of hot-melt extrudate formulations is mainly affected by its composition and interactions between excipients, drug and the dissolution media. For targeted formulation development, it is crucial to understand the role of these interactions on the drug release performance of extrudate formulations. Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopic imaging was used with an in-situ flow-cell device to analyze the impact of different excipients on drug release from extrudates. The compositions differed in the type of polymer (copovidone and Soluplus®), the salt or acid form of ibuprofen and the addition of sodium carbonate. For comparison, conventional USP (United States Pharmacopeia) Apparatus 2 dissolution studies were performed. FTIR imaging revealed that differences in the drug release rate were mainly due to drug-polymer interactions. Ibuprofen acid showed interactions with the matrix polymer and exhibited a slower drug release compared to non-interacting ibuprofen salt. Addition of sodium carbonate to the ibuprofen acid containing formulations enhanced the drug release rate of these systems by interfering with the drug-polymer interactions. In addition, drug release rates also depended on the polymer type, showing faster drug release rates for extrudate formulations containing copovidone compared to Soluplus®. FTIR imaging revealed that the stronger the drug-polymer interaction in the formulations, the slower the drug release. The addition of sodium carbonate improved release as it reduces drug-polymer interactions and allows for the formation of the more water-soluble ibuprofen salt.

  15. A randomized, crossover pharmacodynamic study of immediate-release omeprazole/sodium bicarbonate and delayed-release lansoprazole in healthy adult volunteers.

    Science.gov (United States)

    Pratha, Vijayalakshmi S; McGraw, Thomas; Tobin, William

    2016-06-01

    Proton pump inhibitors (PPIs) effectively block gastric acid secretion and are the treatment of choice for heartburn. PPIs differ, however, in onset of action and bioavailability. In this single-center, open-label, three-way crossover study, onset of action of immediate-release omeprazole 20 mg/sodium bicarbonate 1100 mg (IR-OME) and delayed-release (DR) lansoprazole 15 mg was evaluated in 63 healthy fasting adults. Subjects were randomized to once daily IR-OME, or DR-lansoprazole, or no treatment for 7 days. The primary efficacy endpoint was the earliest time where a statistically significant difference was observed between IR-OME and DR-lansoprazole in median intragastric pH scores for three consecutive 5-min intervals on day 7. Secondary endpoints compared effects of active treatments on days 1 and 7 (e.g., time to sustained inhibition, percentage of time with pH >4). A significant difference in median intragastric pH favoring IR-OME was observed on day 7 starting at the 10- to 15-min interval postdosing (P = 0.024) and sustaining through the 115- to 120-min interval (P = 0.017). On day 1, IR-OME achieved sustained inhibition of intragastric acidity significantly faster than DR-lansoprazole. IR-OME maintained pH >4 significantly longer than DR-lansoprazole over a 24-h period (P = 0.007) on day 7. Overall, results of this study demonstrate IR-OME is safe and well tolerated and that treatment with IR-OME results in significantly faster onset of action and better gastric acid suppression at steady state than DR-lansoprazole.

  16. Drug release characteristics from chitosan-alginate matrix tablets based on the theory of self-assembled film.

    Science.gov (United States)

    Li, Liang; Wang, Linlin; Shao, Yang; Ni, Rui; Zhang, Tingting; Mao, Shirui

    2013-06-25

    The aim of this study was to better understand the underlying drug release characteristics from chitosan-alginate matrix tablets containing different types of drugs. Theophylline, paracetamol, metformin hydrochloride and trimetazidine hydrochloride were used as model drugs exhibiting significantly different solubilities (12, 16, 346 and >1000 mg/ml at 37 °C in water). A novel concept raised was that drugs were released from chitosan-alginate matrix tablets based on the theory of a self-assembled film-controlled release system. The film was only formed on the surface of tablets in gastrointestinal environment and originated from chitosan-alginate polyelectrolyte complex, confirmed by differential scanning calorimetry characterization. The formed film could decrease the rate of polymer swelling to a degree, also greatly limit the erosion of tablets. Drugs were all released through diffusion in the hydrated matrix and polymer relaxation, irrespective of the drug solubility. The effects of polymer level and initial drug loading on release depended on drug properties. Drug release was influenced by the change of pH. In contrast, the impact of ionic strength of the release medium within the physiological range was negligible. Importantly, hydrodynamic conditions showed a key factor determining the superiority of the self-assembled film in controlling drug release compared with conventional matrix tablets. The new insight into chitosan-alginate matrix tablets can help to broaden the application of this type of dosage forms.

  17. Monitoring the hydrolyzation of aspirin during the dissolution testing for aspirin delayed-release tablets with a fiber-optic dissolution system

    Institute of Scientific and Technical Information of China (English)

    Yan Wang; Ping-Ping Xu; Xin-Xia Li; Kun Nie; Ming-Fu Tuo; Bin Kong; Jian Chen

    2012-01-01

    The purpose of this study was to investigate the hydrolyzation of aspirin during the process of dissolution testing for aspirin delayed-release tablets. Hydrolysis product of salicylic acid can result in adverse effects and affect the determination of dissolution rate assaying. In this study, the technique of differential spectra was employed, which made it possible to monitor the dissolution testing in situ. The results showed that the hydrolyzation of aspirin made the percentage of salicylic acid exceed the limit of free salicylic acid (4.0), and the hydrolyzation may affect the quality detection of aspirin delayed-release tablets.

  18. Correction of misleading information in prescription drug television advertising: The roles of advertisement similarity and time delay.

    Science.gov (United States)

    Aikin, Kathryn J; Southwell, Brian G; Paquin, Ryan S; Rupert, Douglas J; O'Donoghue, Amie C; Betts, Kevin R; Lee, Philip K

    Prescription drug television advertisements containing potentially consequential misinformation sometimes appear in the United States. When that happens, the U.S. Food and Drug Administration can request that companies distribute corrective advertisements to address misinformation and inaccurate claims. Previous research has demonstrated effectiveness in corrective advertising for various products. The present article builds on that work with a randomized experimental study (n = 6454) of corrective advertising investigating the extent to which visual similarity matters between violative and corrective ads and the extent to which time delay matters between violative and corrective advertisement exposure. Our study sample included overweight or obese U.S. adults recruited from an existing online consumer panel representative of the U.S. adult population. We created a brand for a fictitious prescription weight-loss drug and produced corresponding direct-to-consumer (DTC) television ads. All participants viewed the same violative ad, but were randomly assigned to view corrective ads with different levels of visual similarity and exposure time delay using a 4 × 4 between-subjects factorial design. Results suggest corrective ad exposure can influence consumer perceptions of drug efficacy, risks, and benefits previously established by violative ads that overstated drug efficacy, broadened drug indication, and omitted important risk information. Corrective ads also can weaken consumer intentions to consider and investigate a drug. However, ad similarity does not appear to affect consumer perceptions and preferences. Although we found that the effects of violative ad exposure tend to diminish over time, the length of the delay between violative and corrective ad exposure has limited influence. An exception to this was observed with regard to recall of drug benefits and risks, where the impact of corrective ad exposure increases with greater time delay. These results

  19. Amphiphilic Beads as Depots for Sustained Drug Release Integrated into Fibrillar Scaffolds

    Science.gov (United States)

    Gaharwar, Akhilesh K.; Mihaila, Silvia M.; Kulkarni, Ashish A.; Patel, Alpesh; Di Luca, Andrea; Reis, Rui L.; Gomes, Manuela E.; van Blitterswijk, Clemens; Moroni, Lorenzo; Khademhosseini, Ali

    2014-01-01

    Native extracellular matrix (ECM) is a complex fibrous structure loaded with bioactive cues that affects the surrounding cells. A promising strategy to mimicking native tissue architecture for tissue engineering applications is to engineer fibrous scaffolds using electrospinning. By loading appropriate bioactive cues within these fibrous scaffolds, various cellular functions such as cell adhesion, proliferation and differentiation can be regulated. Here, we report on the encapsulation and sustained release of model hydrophobic drug (dexamethasone (Dex)) within beaded fibrillar scaffold of poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT), a polyether-ester multiblock copolymer to direct differentiation of human mesenchymal stem cells (hMSCs). The amphiphilic beads act as depots for sustained drug release that is integrated into the fibrillar scaffolds. The entrapment of Dex within the beaded structure results in sustained release of drug over the period of 28 days. This is mainly attributed to the diffusion driven release of Dex from the amphiphilic electrospun scaffolds. In vitro results indicate that hMSCs cultured on Dex containing beaded fibrillar scaffolds exhibit an increase in osteogenic differentiation potential, as evidenced by increased alkaline phosphatase (ALP) activity, compared to the direct infusion of Dex in culture medium. The formation of mineralized matrix is also significantly enhanced due to the controlled Dex release from the fibrous scaffolds. This approach can be used to engineer scaffolds with appropriate chemical cues to direct tissue regeneration. PMID:24794894

  20. Layered double hydroxides as supports for intercalation and sustained release of antihypertensive drugs

    Science.gov (United States)

    Xia, Sheng-Jie; Ni, Zhe-Ming; Xu, Qian; Hu, Bao-Xiang; Hu, Jun

    2008-10-01

    Zn/Al layered double hydroxides (LDHs) were intercalated with the anionic antihypertensive drugs Enalpril, Lisinopril, Captopril and Ramipril by using coprecipitation or ion-exchange technique. TG-MS analyses suggested that the thermal stability of Ena -, Lis - (arranged with monolayer, resulted from X-ray diffraction (XRD) and Fourier transform infrared spectra (FT-IR) analysis was enhanced much more than Cap - and Ram - (arranged with bilayer). The release studies show that the release rate of all samples markedly decreased in both pH 4.25 and 7.45. However, the release time of Ena -, Lis - were much longer compared with Cap -, Ram - in both pH 4.25 and 7.45, it is possible that the intercalated guests, arranged with monolayer in the interlayer, show lesser repulsive force and strong affinity with the LDH layers. And the release data followed both the Higuchi-square-root law and the first-order equation well. Based on the analysis of batch release, intercalated structural models as well as the TG-DTA results, we conclude that for drug-LDH, stronger the affinity between intercalated anions and the layers is, better the thermal property and the stability to the acid attack of drug-LDH, and the intercalated anions are easier apt to monolayer arrangement within the interlayer, were presented.

  1. Oil-in-microgel strategy for enzymatic-triggered release of hydrophobic drugs.

    Science.gov (United States)

    Busatto, C A; Labie, H; Lapeyre, V; Auzely-Velty, R; Perro, A; Casis, N; Luna, J; Estenoz, D A; Ravaine, V

    2017-05-01

    Polymer microgels have received considerable attention due to their great potential in the biomedical field as drug delivery systems. Hyaluronic acid (HA) is a naturally occurring glycosaminoglycan composed of N-acetyl-d-glucosamine and d-glucuronic acid. This polymer is biodegradable, nontoxic, and can be chemically modified. In this work, a co-flow microfluidic strategy for the preparation of biodegradable HA microgels encapsulating hydrophobic drugs is presented. The approach relies on: (i) generation of a primary oil-in-water (O/W) nanoemulsion by the ultrasonication method, (ii) formation of a double oil-in-water-in-oil emulsion (O/W/O) using microfluidics, and (iii) cross-linking of microgels by photopolymerization of HA precursors modified with methacrylate groups (HA-MA) present in the aqueous phase of the droplets. The procedure is used for the encapsulation and controlled release of progesterone. Degradability and encapsulation/release studies in PBS buffer at 37°C in presence of different concentrations of hyaluronidase are performed. It is demonstrated that enzymatic degradation can be used to trigger the release of progesterone from microgels. This method provides precise control of the release system and can be applied for the encapsulation and controlled release of different types of hydrophobic drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. The effects of cyclodextrins on drug release from fatty suppository bases : III. Application of cyclodextrin derivatives

    NARCIS (Netherlands)

    Frijlink, H.W.; Paiotti, S.; Eissens, Anko; Lerk, C.F.

    1992-01-01

    The complexation of both n-butyl-4-aminobenzoate and diazepam with dimethyl-beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin, respectively, was studied. Solid complexes were prepared by freeze-drying. The complexes were incorporated in fatty suppositories and drug release was studied, both in v

  3. Magnetic field activated drug release system based on magnetic PLGA microspheres for chemo-thermal therapy.

    Science.gov (United States)

    Fang, Kun; Song, Lina; Gu, Zhuxiao; Yang, Fang; Zhang, Yu; Gu, Ning

    2015-12-01

    Controlled drug delivery systems have been extensively investigated for cancer therapy in order to obtain better specific targeting and therapeutic efficiency. Herein, we developed doxorubicin-loaded magnetic PLGA microspheres (DOX-MMS), in which DOX was encapsulated in the core and high contents (28.3 wt%) of γ-Fe2O3 nanoparticles (IOs) were electrostatically assembled on the surface of microsphere to ensure the high sensitivity to response of an external alternating current magnetic field (ACMF). The IOs in PLGA shell can both induce the heat effect and trigger shell permeability enhancement to release drugs when DOX-MMs was activated by ACMF. Results show that the cumulative drug release from DOX-MMs exposed to ACMF for 30 min (21.6%) was significantly higher (approximately 7 times higher) than that not exposed to ACMF (2.8%). The combination of hyperthermia and enhanced DOX release from DOX-MMS is beneficial for in vitro 4T1 breast cancer cell apoptosis as well as effective inhibition of tumor growth in 4T1 tumor xenografts. Therefore, the DOX-MMS can be optimized as powerful delivery system for efficient magnetic responsive drug release and chemo-thermal therapy.

  4. Synthesis, characterization and drug release properties of 3D chitosan/clinoptilolite biocomposite cryogels.

    Science.gov (United States)

    Dinu, Maria Valentina; Cocarta, Ana Irina; Dragan, Ecaterina Stela

    2016-11-20

    Three-dimensional (3D) biocomposites based on chitosan (CS) and clinoptilolite (CPL) were prepared by cryogelation and their potential application as drug carriers was investigated. Variation of CPL content from 0 to 33wt.% allowed the formation of biocomposites with heterogeneous morphologies consisting of randomly distributed pores. The further increase of CPL content led to ordered porous architectures where parallel pore channels were observed. The CPL content had a strong influence on water uptake, as well as on the cumulative release of diclofenac sodium (DS) and indomethacin (IDM). It was demonstrated that the drug delivery preferentially takes place in phosphate buffer saline (pH 7.4) in comparison to simulated gastric fluid (pH 1.2), where only a reduced drug release was observed. The drug release mechanism dominating these systems is described as a pseudo-Fickian diffusion, but it changes to non-Fickian release when 33wt.% of CPL was entrapped into the CS matrix or when IDM was loaded into biocomposites.

  5. Drug Release Kinetics from Polymer Matrix through Fractal Approximation of Motion

    Directory of Open Access Journals (Sweden)

    S. Băcăiţă

    2012-01-01

    Full Text Available The present paper analyzes the process of drug release from polymer matrix. This process has been considered as fractal polymer process. Since complexity of physical processes is replaced by fractality, the paper studies the process through fractal approach. In drug dynamics, fractal “diffusion” equation can be obtained through fractal approximation of motion. All experimental release curves have been best demonstrated by Weibull relation (which was, in its turn, also demonstrated. Weibull parameters are related to the fractal dimension of drug release kinetics from a polymer matrix. Such a dimension can characterize and measure the complexity of the system. In the above-mentioned context, some experimental results of our researchers are presented and analyzed by comparing them with Peppas relation, a basic law in the description of drug release kinetics. Consequently, experimental data for Weibull relation are better correlated with certain resulting factors. At the same time, some conclusions regarding the phenomena involved in the process are considered as being based on the approach.

  6. Thermosensitive hydrogel for periodontal application: in vitro drug release, antibacterial activity and toxicity evaluation.

    Science.gov (United States)

    Pakzad, Yousef; Ganji, Fariba

    2016-02-01

    Injectable thermosensitive chitosan hydrogel is an attractive temperature-induced sol-gel solution that is widely used in drug delivery and biomedical applications. In this study, an injectable antimicrobial delivery system for periodontal treatment based on chitosan/gelatin/β-glycerolphosphate solution has been developed. The result of thermal and mechanical evaluations of chitosan/gelatin/β-glycerolphosphate hydrogel showed that adding gelatin to chitosan/β-glycerolphosphate solution significantly decreased gelling time and increased gel strength at 37℃. The antimicrobial agents chosen for release studies were metronidazole with a low molecular weight and vancomycin hydrochloride with a high molecular weight. The initial burst and total in vitro drug release for metronidazole was 13% and 67%, respectively. The initial burst and total drug release for vancomycin hydrochloride was relatively low at 3% and 23%, respectively. The momentary and total percentage of metronidazole accumulated in the phosphate buffer revealed that chitosan/gelatin/β-glycerolphosphate can develop and maintain sustained release of metronidazole in concentrations that are effective for eliminating pathogenic bacteria over time. Cytotoxicity evaluations show that chitosan/gelatin/β-glycerolphosphate thermosensitive hydrogel is a drug carrier with no cytotoxic effects.

  7. Regulating the antibiotic drug release from β-tricalcium phosphate ceramics by atmospheric plasma surface engineering.

    Science.gov (United States)

    Canal, C; Modic, M; Cvelbar, U; Ginebra, M-P

    2016-10-20

    Calcium phosphate (CaP) ceramics are of interest in bone substitution due to their good biocompatibility and bioresorbability. Currently certain CaPs in the market are loaded with antibiotics in order to prevent infections but further control is needed over antibiotic release patterns. Cold plasmas have emerged as a useful means of modifying the interactions with drugs through surface modification of polymer materials. In this work we explore the possibility of using atmospheric pressure plasmas as a tool for the surface modification of these CaP materials with newly populated bonds and charges, with views on enabling higher loading and controlled drug release. Herein the surface modification of β-tricalcium phosphate ceramics is investigated using an atmospheric pressure helium plasma jet as a tool for tuning the controlled release of the antibiotic doxycycline hyclate, employed as a drug model. The surface chemistry is tailored mainly by plasma jet surface interaction with an increasing O/C ratio without changes in the topography as well as by build-up of surface charges. With this surface tailoring it is demonstrated that the atmospheric plasma jet is a new promising tool that leads to the design of a control for drug release from bioceramic matrices.

  8. The effects of cyclodextrins on drug release from fatty suppository bases : III. Application of cyclodextrin derivatives

    NARCIS (Netherlands)

    Frijlink, H.W.; Paiotti, S.; Eissens, Anko; Lerk, C.F.

    1992-01-01

    The complexation of both n-butyl-4-aminobenzoate and diazepam with dimethyl-beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin, respectively, was studied. Solid complexes were prepared by freeze-drying. The complexes were incorporated in fatty suppositories and drug release was studied, both in

  9. Comparison of two hydrogel formulations for drug release in ophthalmic lenses.

    Science.gov (United States)

    Paradiso, P; Galante, R; Santos, L; Alves de Matos, A P; Colaço, R; Serro, A P; Saramago, B

    2014-08-01

    In the present work two types of polymers were investigated as drug releasing contact lens materials: a poly-hydroxyethylmethacrylate (pHEMA) based hydrogel and a silicone hydrogel. The silicone hydrogel resulted from the addition of TRIS, a hydrophobic monomer containing silicon (3-tris(trimethylsilyloxy)silylpropyl 2-methylprop-2-enoate), to pHEMA. Both hydrogels were loaded with an antibiotic (levofloxacin) and an antiseptic (chlorhexidine) by soaking in the drug solutions. The hydrogel properties were determined to be within the range demanded for lens materials. The release profiles of both drugs from the hydrogels were obtained and eventual drug/polymer interactions were assessed with the help of Raman spectra. A mathematical model, developed to mimic the eye conditions, was applied to the experimental results in order to predict the in vivo efficacy of the studied systems. The release profiles were compared with those resulting from the application of commercial eyedrops. The pHEMA based hydrogel demonstrated to be the best material to achieve a controlled release of levofloxacin. In the case of chlorhexidine, the silicone hydrogel seems to lead to better results. In both cases, our results suggest that these materials are adequate for the preparation of daily disposable therapeutic contact lenses.

  10. An integrated device for magnetically-driven drug release and in situ quantitative measurements: Design, fabrication and testing

    Energy Technology Data Exchange (ETDEWEB)

    Bruvera, I.J. [Aragon Institute of Nanoscience (INA), University of Zaragoza, 50018 (Spain); Hernández, R.; Mijangos, C. [Instituto de Ciencia y Tecnología de Polímeros, CSIC, Juan Cierva 3, E-28006 Madrid (Spain); Goya, G.F., E-mail: goya@unizar.es [Aragon Institute of Nanoscience (INA), University of Zaragoza, 50018 (Spain); Condensed Matter Physics Department, Science Faculty, University of Zaragoza, 50009 (Spain)

    2015-03-01

    We have developed a device capable of remote triggering and in situ quantification of therapeutic drugs, based on magnetically-responsive hydrogels of poly (N-isopropylacrylamide) and alginate (PNiPAAm). The heating efficiency of these hydrogels measured by their specific power absorption (SPA) values showed that the values between 100 and 300 W/g of the material were high enough to reach the lower critical solution temperature (LCST) of the polymeric matrix within few minutes. The drug release through application of AC magnetic fields could be controlled by time-modulated field pulses in order to deliver the desired amount of drug. Using B12 vitamin as a concept drug, the device was calibrated to measure amounts of drug released as small as 25(2)×10{sup −9} g, demonstrating the potential of this device for very precise quantitative control of drug release. - Highlights: • A device for magnetically driven drug release was developed and constructed. • Thermally responsive PNiPAAm and Fe3O4 nanoparticles were usedas drug reservoir. • The device allowed repetitive, remote and precisely controlled drug release. • By in situ spectrometry we could detect released drug quantities as small as 25 ng. • Released drug was controlled through magnetic ac field parameters H, f and time.

  11. Drug release from extruded solid lipid matrices: theoretical predictions and independent experiments.

    Science.gov (United States)

    Güres, Sinan; Siepmann, Florence; Siepmann, Juergen; Kleinebudde, Peter

    2012-01-01

    The aim of this study was to use a mechanistically realistic mathematical model based on Fick's second law to quantitatively predict the release profiles from solid lipid extrudates consisting of a ternary matrix. Diprophylline was studied as a freely water-soluble model drug, glycerol tristearate as a matrix former and polyethylene glycol or crospovidone as a pore former (blend ratio: 50:45:5%w/w/w). The choice of these ratios is based on former studies. Strains with a diameter of 0.6, 1, 1.5, 2.7 and 3.5mm were prepared using a twin-screw extruder at 65 °C and cut into cylinders of varying lengths. Drug release in demineralised water was measured using the USP 32 basket apparatus. Based on SEM pictures of extrudates before and after exposure to the release medium as well as on DSC measurements and visual observations, an analytical solution of Fick's second law of diffusion was identified in order to quantify the resulting diprophylline release kinetics from the systems. Fitting the model to one set of experimentally determined diprophylline release kinetics from PEG containing extrudates allowed determining the apparent diffusion coefficient of this drug (or water) in this lipid matrix. Knowing this value, the impact of the dimensions of the cylinders on drug release could be quantitatively predicted. Importantly, these theoretical predictions could be confirmed by independent experimental results. Thus, diffusion is the dominant mass transport mechanism controlling drug release in this type of advanced drug delivery systems. In contrast, theoretical predictions of the impact of the device dimensions in the case of crospovidone containing extrudates significantly underestimated the real diprophylline release rates. This could be attributed to the disintegration of this type of dosage forms when exceeding a specific minimal device diameter. Thus, mathematical modelling can potentially significantly speed up the development of solid lipid extrudates, but care has

  12. Understanding drug-related mortality in released prisoners: a review of national coronial records

    Directory of Open Access Journals (Sweden)

    Andrews Jessica Y

    2012-04-01

    Full Text Available Abstract Background The prisoner population is characterised by a high burden of disease and social disadvantage, and ex-prisoners are at increased risk of death following release. Much of the excess mortality can be attributed to an increased risk of unnatural death, particularly from drug overdose; however, relatively few studies have investigated the circumstances surrounding drug-related deaths among released prisoners. This study aimed to explore and compare the circumstances of death for those who died from accidental drug-related causes to those who died from all other reportable causes. Methods A nationwide search of the Australian National Coroners Information System (NCIS was conducted to identify reportable deaths among ex-prisoners from 2000 to 2007. Using a structured coding form, NCIS records for these cases were interrogated to explore causes and circumstances of death. Results Coronial records for 388 deceased ex-prisoners were identified. Almost half of these deaths were a result of accidental drug-related causes (45%. The majority of accidental drug-related deaths occurred in a home environment, and poly-substance use at or around the time of death was common, recorded in 72% of drug-related deaths. Ex-prisoners who died of accidental drug-related causes were on average younger and less likely to be Indigenous, born in Australia, married, or living alone at or around the time of death, compared with those who died from all other reportable causes. Evidence of mental illness or self-harm was less common among accidental drug-related deaths, whereas evidence of previous drug overdose, injecting drug use, history of heroin use and history of drug withdrawal in the previous six months were more common. Conclusions Drug-related deaths are common among ex-prisoners and often occur in a home (vs. public setting. They are often associated with use of multiple substances at or around the time of death, risky drug-use patterns, and even

  13. Effect of methyl cellulose on gelation behavior and drug release from poloxamer based ophthalmic formulations.

    Science.gov (United States)

    Dewan, Mitali; Bhowmick, Biplab; Sarkar, Gunjan; Rana, Dipak; Bain, Mrinal Kanti; Bhowmik, Manas; Chattopadhyay, Dipankar

    2015-01-01

    The effect of weight average molecular weight (Mw) of methyl cellulose (MC) on the gelation behavior of Poloxamer 407 (PM) and in vitro release of Ketorolac Tromethamine (KT) from different ophthalmic formulations based on PM is examined. A drop of gelation temperature of PM is observed using MC of various M(w) by test tube tilting method, UV-vis spectroscopy, viscometry and rheometry. It is also observed that the viscosity and gel strength of all the formulations are increased with the increase in Mw of MC. PM with highest Mw of MC provides best drug release property among all the formulations. It is evident from this investigation that there is a distinct effect of M(w) of MC on the gelation behavior of PM as well as on the drug release profile of KT from PM-MC based ophthalmic formulations.

  14. Basic butylated methacrylate copolymer/kappa-carrageenan interpolyelectrolyte complex: preparation, characterization and drug release behaviour.

    Science.gov (United States)

    Prado, H J; Matulewicz, M C; Bonelli, P; Cukierman, A L

    2008-09-01

    The formation of a novel interpolyelectrolyte complex (IPEC) between basic butylated methacrylate copolymer and kappa-carrageenan was investigated and the product formed was characterized. Turbidity measurements and elemental analyses pointed to a 1:1 interaction of the repeating units. These results and FT-IR confirmed IPEC formation. Electronic microscopy images, particle size determination by image analysis and N(2) (77K) adsorption measurements were consistent with a porous material. This IPEC formed presented very good flowability and compactibility. Two maxima were observed in the swelling behaviour as a function of pH. The performance of the IPEC as a matrix for controlled release of drugs was evaluated, using ibuprofen as a model drug. Release profiles were properly represented by a mathematical model, which indicates that the system releases ibuprofen in a zero-order manner. These profiles could be controlled by conveniently modifying the proportion of the IPEC in the tablets.

  15. STUDY OF THE PROLONGED RELEASE OF A DRUG FROM ENCAPSULATED GRANULES PREPARED WITH BEESWAX

    Directory of Open Access Journals (Sweden)

    N. A. Elechi* and H. C. Mital

    2012-06-01

    Full Text Available The in vitro dissolution studies of encapsulated sodium salicylate granules coated with beeswax is presented. The factors investigated were the effects of concentration, presence of a hydrophilic fatty material, polyethylene glycol 6000 (PEG 6000, and technique (pan-coating, fusion and granulation on the sustained release of drug when coated with beeswax. Comparison of release rates was based on the use of a parameter, t70% (time for 70% of drug to be released. The greater the concentration of beeswax, ranging from 13.04 to 28.75%, the more prolonged the release. The presence of PEG 6000 at a concentration of 1:9 beeswax in the coating fluid significantly (p<0.05 increased the release rate, and at a concentration of 1:1 nullified the sustained release effect of beeswax. The t70% for the fusion, granulated and pan-coated batches were in the increasing order of 25min., 1hr.35min. and 2hr.45min, respectively.

  16. Biodegradable gelatin-ciprofloxacin-montmorillonite composite hydrogels for controlled drug release and wound dressing application.

    Science.gov (United States)

    Kevadiya, Bhavesh D; Rajkumar, Shalini; Bajaj, Hari C; Chettiar, Shiva Shankaran; Gosai, Kalpeshgiri; Brahmbhatt, Harshad; Bhatt, Adarsh S; Barvaliya, Yogesh K; Dave, Gaurav S; Kothari, Ramesh K

    2014-10-01

    This work reports intercalation of a sparingly soluble antibiotic (ciprofloxacin) into layered nanostructure silicate, montmorillonite (MMT) and its reaction with bone derived polypeptide, gelatin that yields three-dimensional composite hydrogel. Drug intercalation results in changes in MMT layered space and drug loaded MMT and gelatin creates 3D morphology with biodegradable composite hydrogels. These changes can be correlated with electrostatic interactions between the drug, MMT and the gelatin polypeptides as confirmed by X-ray diffraction patterns, thermal, spectroscopic analyses, computational modeling and 3D morphology revealed by SEM and TEM analysis. No significant changes in structural and functional properties of drug was found after intercalation in MMT layers and composite hydrogels. In vitro drug release profiles showed controlled release up to 150h. The drug loaded composite hydrogels were tested on lung cancer cells (A549) by MTT assay. The results of in vitro cell migration and proliferation assay were promising as composite hydrogels induced wound healing progression. In vitro biodegradation was studied using proteolytic enzymes (lysozyme and protease K) at physiological conditions. This new approach of drug intercalation into the layered nanostructure silicate by ion-exchange may have significant applications in cost-effective wound dressing biomaterial with antimicrobial property.

  17. Influence of Hydrothermal Treatment on Physicochemical Properties and Drug Release of Anti-Inflammatory Drugs of Intercalated Layered Double Hydroxide Nanoparticles

    Directory of Open Access Journals (Sweden)

    Zi Gu

    2014-05-01

    Full Text Available The synthesis method of layered double hydroxides (LDHs determines nanoparticles’ performance in biomedical applications. In this study, hydrothermal treatment as an important synthesis technique has been examined for its influence on the physicochemical properties and the drug release rate from drug-containing LDHs. We synthesised MgAl–LDHs intercalated with non-steroidal anti-inflammatory drugs (i.e., naproxen, diclofenac and ibuprofen using a co-precipitation method with or without hydrothermal treatment (150 °C, 4 h. After being hydrothermally treated, LDH–drug crystallites increased in particle size and crystallinity, but did not change in the interlayer anion orientation, gallery height and chemical composition. The drug release patterns of all studied LDH–drug hybrids were biphasic and sustained. LDHs loaded with diclofenac had a quicker drug release rate compared with those with naproxen and ibuprofen, and the drug release from the hydrothermally-treated LDH–drug was slower than the freshly precipitated LDH–drug. These results suggest that the drug release of LDH–drugs is influenced by the crystallite size of LDHs, which can be controlled by hydrothermal treatment, as well as by the drug molecular physicochemical properties.

  18. Effect of processing methods on drug release profiles of anti-restenotic self-assembled monolayers

    Science.gov (United States)

    Stoebner, Susan E.; Mani, Gopinath

    2012-04-01

    The use of anti-restenotic self-assembled monolayers (ARSAMs) has been previously demonstrated for delivering drugs from stents without polymeric carriers. ARSAMs have been prepared by coating an anti-restenotic drug (paclitaxel - PAT) on -COOH terminated phosphonic acid self-assembled monolayers (SAMs) coated Co-Cr alloy specimens. This study investigates the effect of different processing methods on the percentage of drug release from ARSAMs. The different methods that were used in this study to process ARSAMs include room temperature (RT) treatment, heat treatment (HT), cold treatment (CT) and quenching. The changes in polymorphism, chemical structure, morphology, and distribution of PAT on SAMs coated specimens were investigated using differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and atomic force microscopy (AFM), respectively. DSC showed dihydrate, dehydrated dihydrate, semi-crystalline, and mixed (amorphous and dihydrate) forms of PAT for RT, HT, CT, and quenched specimens, respectively. FTIR showed that the chemical structure of PAT was unaltered in all the specimens processed by various methods employed in this study. SEM showed a mixture of spherical, ovoid, and bean-shaped morphologies of PAT on RT, HT, and CT while particle-like and needle-shaped morphologies of PAT were observed on quenched specimens. AFM showed PAT was uniformly distributed on RT, HT and CT specimens while particle-like PAT was well distributed and needle-shaped PAT was sparsely distributed on quenched specimens. CT specimens showed greater density of PAT crystals when compared to other methods. Thus, this study demonstrated that processing methods have significant influence on the polymorphism, morphology, and distribution of PAT on SAMs coated Co-Cr alloy specimens. The in vitro drug elution studies for up to 56 days showed sustained release for all the different groups of specimens. CT showed lesser

  19. In situ generation of sodium alginate/hydroxyapatite nanocomposite beads as drug-controlled release matrices.

    Science.gov (United States)

    Zhang, J; Wang, Q; Wang, A

    2010-02-01

    In order to find a new way to slow down the release of drugs and to solve the burst release problem of drugs from traditionally used hydrogel matrices, a series of novel pH-sensitive sodium alginate/hydroxyapatite (SA/HA) nanocomposite beads was prepared by the in situ generation of HA micro-particles in the beads during the sol-gel transition process of SA. The SA/HA nanocomposites were characterized by Fourier transform IR spectroscopy, X-ray fluorescence spectrometry, scanning electron microscopy and field emission SEM in order to reveal their composition and surface morphology as well as the role that the in situ generated HA micro-particles play. The factors influencing the swelling behavior, drug loading and controlled release behavior of the SA/HA nanocomposite beads were also investigated using diclofenac sodium (DS) as the model drug. The HA micro-particles act as inorganic crosslinkers in the nanocomposites, which could contract and restrict the movability of the SA polymer chains, and then change the surface morphology and decrease the swell ratio. Meanwhile, the entrapment efficiency of DS was improved, and the burst release of DS was overcome. The factors (including concentration of Ca(2+), reaction time and temperature) affecting the growth of HA micro-particles have a clear influence on the entrapment efficiency and release rate of DS. In this work, the nanocomposite beads prepared under optimum condition could prolong the release of DS for 8h more compared with the pristine SA hydrogel beads.

  20. Folic acid conjugated magnetic drug delivery system for controlled release of doxorubicin

    Science.gov (United States)

    Andhariya, Nidhi; Upadhyay, Ramesh; Mehta, Rasbindu; Chudasama, Bhupendra

    2013-01-01

    Targeting tumors by means of their vascular endothelium is a promising strategy, which utilizes targets that are easily accessible, stable, and do not develop resistance against therapeutic agents. Folate receptor is a highly specific tumor marker, frequently over expressed in cancer tumors. In the present study, an active drug delivery system, which can effectively target cancer cells by means of folate receptor-mediated endocytosis, have ability to escape from opsonization and capability of magnetic targeting to withstand the drag force of the body fluid have been designed and synthesized. The core of the drug delivery system is of mono-domain magnetic particles of magnetite. Magnetite nanoparticles are shielded with PEG, which prevents their phagocytosis by reticuloendothelial system. These PEG shielded magnetite nanoparticles are further decorated with an antitumor receptor—folic acid and loaded with an antineoplastic agent doxorubicin. An in vitro drug loading and release kinetics study reveals that the drug delivery system can take 52 % of drug load and can release doxorubicin over a sustained period of 7 days. The control and sustained release over a period of several days may find its practical utilities in chemotherapy where frequent dosing is not possible.

  1. Folic acid conjugated magnetic drug delivery system for controlled release of doxorubicin

    Energy Technology Data Exchange (ETDEWEB)

    Andhariya, Nidhi, E-mail: nidhiandhariya@gmail.com [Thapar University, School of Physics and Materials Science (India); Upadhyay, Ramesh [Charotar University of Science and Technology, P.D. Patel Institute of Applied Sciences (India); Mehta, Rasbindu [Maharaja Krishnakumarsinhji Bhavnagar University, Department of Physics (India); Chudasama, Bhupendra, E-mail: bnchudasama@gmail.com [Thapar University, School of Physics and Materials Science (India)

    2013-01-15

    Targeting tumors by means of their vascular endothelium is a promising strategy, which utilizes targets that are easily accessible, stable, and do not develop resistance against therapeutic agents. Folate receptor is a highly specific tumor marker, frequently over expressed in cancer tumors. In the present study, an active drug delivery system, which can effectively target cancer cells by means of folate receptor-mediated endocytosis, have ability to escape from opsonization and capability of magnetic targeting to withstand the drag force of the body fluid have been designed and synthesized. The core of the drug delivery system is of mono-domain magnetic particles of magnetite. Magnetite nanoparticles are shielded with PEG, which prevents their phagocytosis by reticuloendothelial system. These PEG shielded magnetite nanoparticles are further decorated with an antitumor receptor-folic acid and loaded with an antineoplastic agent doxorubicin. An in vitro drug loading and release kinetics study reveals that the drug delivery system can take 52 % of drug load and can release doxorubicin over a sustained period of 7 days. The control and sustained release over a period of several days may find its practical utilities in chemotherapy where frequent dosing is not possible.

  2. Improved antimicrobial property and controlled drug release kinetics of silver sulfadiazine loaded ordered mesoporous silica

    Directory of Open Access Journals (Sweden)

    Suman Jangra

    2016-09-01

    Full Text Available The present study deals with the loading of silver sulfadiazine into ordered mesoporous silica material by post-impregnation method and its effect on the in vitro release kinetics and antimicrobial property of the drug. The formulated SBA-15 silica material with rope-like morphology and SBA-15-silver sulfadiazine (SBA-AgSD were characterized by UV–visible spectrophotometer, small and wide-angle powder X-ray diffraction (PXRD, field emission scanning electron microscope (FESEM and high resolution transmission electron microscope (HRTEM. Thermo-gravimetric analysis of SBA-AgSD revealed a high loading amount of 52.87%. Nitrogen adsorption–desorption analysis confirmed the drug entrapment into host material by revealing a reduced surface area (214 m2/g and pore diameter (6.7 nm of the SBA-AgSD. The controlled release of silver sulfadiazine drug from the mesoporous silica to simulated gastric, intestinal and body fluids was evaluated. The Korsmeyer–Peppas model fits the drug release data with the non-Fickian diffusion model and zero order kinetics of SBA-AgSD. The antibacterial performance of the SBA-AgSD was evaluated with respect to Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa. The controlled drug delivery of the SBA-AgSD revealed improved antibacterial activity, thus endorsing its applicability in effective wound dressing.

  3. Drug release from core-shell PVA/silk fibroin nanoparticles fabricated by one-step electrospraying.

    Science.gov (United States)

    Cao, Yang; Liu, Fengqiu; Chen, Yuli; Yu, Tao; Lou, Deshuai; Guo, Yuan; Li, Pan; Wang, Zhigang; Ran, Haitao

    2017-09-20

    Silk fibroin (SF), a FDA-approved natural protein, is renowned for its great biocompatibility, biodegradability, and mechanical properties. SF-based nanoparticles provide new options for drug delivery with their tunable drug loading and release properties. To take advantage of the features of carrier polymers, we present a one-step electrospraying method that combines SF, polyvinyl alcohol (PVA) and therapeutic drugs without an emulsion process. A distinct core-shell structure was obtained with the PVA core and silk shell after the system was properly set up. The model drug, doxorubicin, was encapsulated in the core with a greater than 90% drug encapsulation efficiency. Controllable drug release profiles were achieved by alternating the PVA/SF ratio. Although the initial burst release of the drug was minimized by the SF coating, a large number of drug molecules remained entrapped by the carrier polymers. To promote and trigger drug release on demand, low intensity focused ultrasound (US) was applied. The US was especially advantageous for accelerating the drug diffusion and release. The apoptotic activity of MDA-MB-231 cells incubated with drug-loaded nanoparticles was found to increase with time. In addition, we also observed PVA/SF nanoparticles that could elicit a drug release in response to pH.

  4. Development of hydroxyapatite bone cement for controlled drug release via tetracycline hydrochloride

    Indian Academy of Sciences (India)

    Sayed Mahmood Rabiee

    2013-02-01

    The purpose of this work was to study the preparation and characterization of drug–hydroxyapatite cement. The hydroxyapatite (HA) cement has been synthesized by using tricalcium phosphate, calcium carbonate and dicalcium phosphate anhydrous with sodium hydrogen phosphate as liquid phase. The effect of added tetracycline hydrochloride (TCH) as drug on final phases, microstructure, setting behaviour and compressive strength has been studied. The drug release rate was first order within the first day and then was zero order. No obvious difference could be detected in XRD patterns of the TCH–HA cement with various amounts of drug. By increasing the drug concentration, mechanical strength of cement was decreased and its setting time was increased. The results of this study demonstrate the potential of using HA cement as a carrier for drug delivery.

  5. Dendronized Mesoporous Silica Nanoparticles Provide an Internal Endosomal Escape Mechanism for Successful Cytosolic Drug Release

    CERN Document Server

    Weiss, Veronika; Torrano, Adriano A; Strobel, Claudia; Mackowiak, Stephan A; Gatzenmeier, Tim; Hilger, Ingrid; Braeuchle, Christoph; Bein, Thomas

    2015-01-01

    Mesoporous silica nanoparticles (MSNs) attract increasing interest in the field of gene and drug delivery due to their versatile features as a multifunctional drug delivery platform. Here, we describe poly(amidoamine) (PAMAM) dendron-functionalized MSNs that fulfill key prerequisites for a controllable intracellular drug release. In addition to high loading capacity, they offer 1) low cytotoxicity, showing no impact on the metabolism of endothelial cells, 2) specific cancer cell targeting due to receptor-mediated cell uptake, 3) a redox-driven cleavage of disulfide bridges allowing for stimuli-responsive cargo release, and most importantly, 4) a specific internal trigger based on the high buffering capacity of PAMAM dendrons to provide endosomal escape.

  6. The systems containing clays and clay minerals from modified drug release: a review.

    Science.gov (United States)

    Rodrigues, Luís Alberto de Sousa; Figueiras, Ana; Veiga, Francisco; de Freitas, Rivelilson Mendes; Nunes, Lívio César Cunha; da Silva Filho, Edson Cavalcanti; da Silva Leite, Cleide Maria

    2013-03-01

    Clays are materials commonly used in the pharmaceutical industry, either as ingredients or as active ingredients. It was observed that when they are administered concurrently, they may interact with drugs reducing their absorption. Therefore, such interactions can be used to achieve technological and biopharmaceutical advantages, regarding the control of release. This review summarizes bibliographic (articles) and technological (patents) information on the use of systems containing clays and clay minerals in modified drug delivery. In this area, formulations such natural clay, commercial clay, synthetic clay, composites clay-polymers, nanocomposites clay-polymers, films and hidrogels composites clay-polymers are used to slow/extend or vectorize the release of drugs and consequently they increase their bioavailability. Finally, this review summarizes the fields of technology and biopharmaceutical applications, where clays are applied.

  7. Effect of amine functionalization of spherical MCM-41 and SBA-15 on controlled drug release

    Science.gov (United States)

    Szegedi, A.; Popova, M.; Goshev, I.; Mihály, J.

    2011-05-01

    MCM-41 and SBA-15 silica materials with spherical morphology and different particle sizes were synthesized and modified by post-synthesis method with 3-aminopropyltriethoxysilane (APTES). A comparative study of the adsorption and release of a model drug, ibuprofen, were carried out. The modified and drug loaded mesoporous materials were characterized by XRD, TEM, N 2 physisorption, thermal analysis, elemental analysis and FT-IR spectroscopy. Surface modification with amino groups resulted in high degree of ibuprofen loading and slow rate of release for MCM-41, whereas it was the opposite for SBA-15. The adsorbed drug content and the delivery rate can be predetermined by the choice of mesoporous material with the appropriate structural characteristics and surface functionality.

  8. Hierarchical porous bioactive glasses/PLGA-magnetic SBA-15 for dual-drug release.

    Science.gov (United States)

    Ma, Jie; Lin, Huiming; Li, Xiaofeng; Bian, Chunhui; Xiang, Di; Han, Xiao; Wu, Xiaodan; Qu, Fengyu

    2014-06-01

    The hierarchical porous bioglass combined with magnetic SBA-15 was synthesized. The bioactive glass materials possess a hierarchical porous structure with the macroporous (50μm) and the mesoporous (3.86nm) structures derived from the plant template (cattail stem) and triblock polyethylene oxide-propylene oxide block copolymer (P123), respectively. Magnetic SBA-15 was synthesized by adopting the post assembly method using Fe(NO3)3 as iron source and ethylene glycol as reduction. After coating PLGA, PLGA-IBU-magnetic SBA-15 also possessed super-paramagnetism and the corresponding saturation magnetizations (Ms) could reach 2.6emug(-1). Metformin HCl (MH) and ibuprofen (IBU) were used as model drugs, and the drug release kinetics was studied. MH and IBU could release 60% and 85% from the sample respectively. The system shows excellent dual-drug controlled delivery performance and good bioactivity in vitro that leads to good potential application on bone regeneration.

  9. The delayed-release combination of doxylamine and pyridoxine (Diclegis®/Diclectin ®) for the treatment of nausea and vomiting of pregnancy.

    Science.gov (United States)

    Madjunkova, Svetlana; Maltepe, Caroline; Koren, Gideon

    2014-06-01

    Nausea and vomiting of pregnancy (NVP) affects up to 85 % of all pregnancies. Effective treatment can greatly improve a woman's quality of life, reduce the risk for maternal and fetal complications, and reduce healthcare costs. Unfortunately, many women receive either no pharmacological treatment or are recommended therapies for which fetal safety and efficacy have not been established. First-line treatment of NVP, as recommended by several leading healthcare and professional organizations, is the combination of doxylamine and pyridoxine. This combination, formulated as a 10 mg/10 mg delayed-release tablet, was approved by the US Food and Drug Administration (FDA) for the treatment of NVP in April 2013 under the brand name Diclegis(®), and has been on the Canadian market since 1979, currently under the brand name Diclectin(®). The efficacy of Diclegis(®)/Diclectin(®) has been demonstrated in several clinical trials, and, more importantly, studies on more than 200,000 women exposed to doxylamine and pyridoxine in the first trimester of pregnancy have demonstrated no increased fetal risk for congenital malformations and other adverse pregnancy outcomes. The present review aims to present the scientific evidence on the effectiveness and fetal safety of Diclegis(®)/Diclectin(®) for the treatment of NVP to justify its use as first-line treatment for NVP.

  10. Use of Placket-Burman statistical design to study effect of formulation variables on the release of drug from hot melt sustained release extrudates.

    Science.gov (United States)

    Jain, Satishkumar P; Singh, Pirthi Pal; Javeer, Sharad; Amin, Purnima D

    2010-06-01

    The present paper was focused on exploiting Plackett-Burman design to screen the effect of nine factors--poly (ethylene oxide) molecular weight (X(1)), poly (ethylene oxide) amount (X(2)), ethylcellulose amount (X(4)), drug solubility (X(5)), drug amount (X(6)), sodium chloride amount (X(7)), citric acid amount (X(8)), polyethylene glycol amount (X(9)), and glycerin amount (X(11)) on the release of drugs from the extended release extrudates, i.e., release rate and release mechanism. The experiments were carried out according to a nine-factor 12-run statistical model and subjected to an 8-h dissolution study in phosphate buffer pH 6.8. The significance of the model was indicated by the ANOVA and the residual analysis. Poly (ethylene oxide) amount, ethylcellulose amount and drug solubility had significant effect on the T90 values whereas poly (ethylene oxide) amount and ethylcellulose amount had significant effect on the n value.

  11. Mesoporous silica-based dosage forms improve release characteristics of poorly soluble drugs: case example fenofibrate.

    Science.gov (United States)

    Dressman, Jennifer B; Herbert, Elisabeth; Wieber, Alena; Birk, Gudrun; Saal, Christoph; Lubda, Dieter

    2016-05-01

    Mesoporous silica-based dosage forms offer the potential for improving the absorption of poorly soluble drugs after oral administration. In this investigation, fenofibrate was used as a model drug to study the ability of monomodal ('PSP A') and bimodal ('PSP B') porous silica to improve release by a 'spring' effect in in vitro biorelevant dissolution tests. Also investigated was the addition of various polymers to provide a 'parachute' effect, that is, to keep the drug in solution after its release. Loading fenofibrate onto PSP A or PSP B porous silica substantially improved the dissolution profile of fenofibrate under fasted state conditions compared with both pure drug and the marketed product, TriCor® 145 mg. Adding a polymer such as hydroxypropyl methylcellulose acetate succinate, polyvinylpyrrolidone or copovidon (HPMCAS, PVP or PVPVA) sustains the higher release of fenofibrate from the PSP A silica, resulting in a combination 'spring and parachute' effect - loading the drug onto the silica causes a 'spring' effect while the polymer enhances the spring effect (HPMCAS, PVP) and adds a sustaining 'parachute'. Interestingly, a silica to polymer ratio of 4:1 w/w appears to have an optimal effect for fenofibrate (HPMCAS, PVP). Dissolution results under conditions simulating the fasted state in the small intestine with the PSP A or the PSP B silica with HPMCAS added in a 4:1 w/w ratio show very substantial improvement over the marketed, nanosized product (TriCor® 145 mg). Further experiments to determine whether the highly positive effects on fenofibrate release observed with the silica prototypes investigated to date can be translated to further poorly soluble drugs and to what extent they translate into improved in-vivo performance are warranted. © 2015 Royal Pharmaceutical Society.

  12. Protein corona change the drug release profile of nanocarriers: the "overlooked" factor at the nanobio interface.

    Science.gov (United States)

    Behzadi, Shahed; Serpooshan, Vahid; Sakhtianchi, Ramin; Müller, Beate; Landfester, Katharina; Crespy, Daniel; Mahmoudi, Morteza

    2014-11-01

    The emergence of nanocarrier systems in drug delivery applications has ushered in rapid development of new classes of therapeutic agents which can provide an essential breakthrough in the fight against refractory diseases. However, successful clinical application of nano-drug delivery devices has been limited mainly due to the lack of control on sustained release of therapeutics from the carriers. A wide range of sophisticated approaches employs the formation of crosslinkable, non-crosslinkable, stimuli-responsive polymer nanocarriers in order to enhance their delivery efficiency. Despite the extensive research conducted on the development of various nanocarriers, the effect of the biological milieu on the drug release profile of these constructs is not yet fully investigated. In particular, the formation of a protein corona on the surface of nanocarriers, when they interact with living organisms in vivo is largely decisive for their biological function. Using a number of synthetized (i.e., superparamagnetic iron oxide nanoparticles and polymeric nanocapsules) and commercialized nanocarriers (i.e., Abraxane®, albumin-bound paclitaxel drug), this study demonstrates that the protein corona can shield the nanocarriers and, consequently, alters the release profile of the drugs from the nanocarriers. More specifically, the protein corona could significantly reduce the burst effect of either protein conjugated nanocarriers or carriers with surface loaded drug (i.e., SPIONs). However, the corona shell only slightly changed the release profile of polymeric nanocapsules. Therefore, the intermediary, buffer effect of the protein shells on the surface of nanoscale carriers plays a crucial role in their successful high-yield applications in vivo.

  13. Water soluble drug releasing soft contact lens in response to pH of tears

    Science.gov (United States)

    Kim, G.; Noh, H.

    2016-06-01

    Human tear characteristics including pH and compositions can vary significantly depending on physical and environmental factors. Contact lenses directly contact with human tears can be swelled or de-swelled depending on the pH of the solution due to the nature of the hydrogel. For examples, anionic hydrogels, when the solution's pH is low, is shrunken due to the electric attraction force within the hydrogel network; the opposite phenomenon appears when the solution is basic. The purpose of this study was to evaluate the extent of water soluble drug, hydroxyl propyl methyl cellulose, released from contact lens according to the pH of the artificial tears. Artificial tears are prepared by mixing lysozyme, albumin, sodium chloride, potassium chloride, and calcium chloride following physiological concentrations. Hydrogel contact lens was thermally polymerized using HEMA, EGDMA, and AIBN. The prepared hydrogel lens was immersed in drug for 3 hours and the eluted drug mass was measured as a function of the time. As a result, the drug was released from the lens for 12 hours in all the pH of artificial tears. At the lower pH of artificial tears (pH 5.8), the total amount of dye emitted from the lens was increased than the total amount of dye emitted at the basic tear (pH 8.4). Also, initial burst at acidic tears was increased within 1 hour. Release pattern of water-soluble drug from hydrogel lens turned out to be different depending on the pH of the artificial tears. When designing drug releasing contact lens, physiological pH of tears should be considered.

  14. In vitro release of two anti-muscarinic drugs from soft contact lenses

    Directory of Open Access Journals (Sweden)

    Hui A

    2017-09-01

    Full Text Available Alex Hui,1 Magdalena Bajgrowicz-Cieslak,2 Chau-Minh Phan,3 Lyndon Jones3 1School of Optometry and Vision Science, UNSW Sydney, Sydney, NSW, Australia; 2Department of Mechanics, Material Science and Engineering, Wroclaw University of Technology, Wroclaw, Poland; 3Centre for Contact Lens Research, School of Optometry & Vision Science, University of Waterloo, Waterloo, ON, Canada Abstract: The purpose of this study was to investigate the release of the anti-myopia drugs atropine sulfate and pirenzepine dihydrochloride from commercially available soft contact lenses. Standard ultraviolet (UV absorbance–concentration curves were generated for atropine and pirenzepine. Ten commercially available contact lenses, including four multifocal lenses, were loaded by soaking in atropine or pirenzepine solutions at two different concentrations (10 mg/mL and 1 mg/mL. The release of the drugs into phosphate-buffered saline was determined over the course of 24 hours at 34°C using UV absorbance. Materials with surface charge released the greatest amount of atropine when loaded with either concentration when compared to the other lens types (p<0.05, releasing upward of 1.026±0.035 mg/lens and 0.979±0.024 mg/lens from etafilcon A and ocufilcon A, respectively. There were no significant differences in the amount of atropine or pirenzepine released from the multifocal and non-multifocal lenses made from the same lens materials. Narafilcon A material demonstrated prolonged release of up to 8 hours when loaded with pirenzepine, although the overall dose delivered from the lens into the solution was among the lowest of the materials investigated. The rest of the lenses reached a plateau within 2 hours of release, suggesting that they were unable to sustain drug release into the solution for long periods of time. Given that no single method of myopia control has yet shown itself to be completely effective in preventing myopia progression, a combination of

  15. Gradual reduction of testosterone using a gonadotropin-releasing hormone vaccination delays castration resistance in a prostate cancer model

    Science.gov (United States)

    Barranco, Jesús A. Junco; Millar, Robert P.; Fuentes, Franklin; Bover, Eddy; Pimentel, Eulogio; Basulto, Roberto; Calzada, Lesvia; Morán, Rolando; Rodríguez, Ayni; Garay, Hilda; Reyes, Osvaldo; Castro, Maria D.; Bringas, Ricardo; Arteaga, Niurka; Toudurí, Henio; Rabassa, Mauricio; Fernández, Yairis; Serradelo, Andrés; Hernández, Eduardo; Guillén, Gerardo E.

    2016-01-01

    In a previous study aimed to design a novel prostate cancer vaccine, the authors of the present study demonstrated the advantage of combining the adjuvants Montanide ISA 51 with very small size proteoliposomes (VSSP) to promote a significant humoral immune response to gonadotropin-releasing hormone (GnRH) in healthy animals. The present study compared the efficacy of this vaccine formulation versus the standard treatment currently available in terms of preventing the development of tumors in DD/S mice injected with Shionogi carcinoma (SC) 115 cells. The results demonstrated that 5 non-vaccinated control mice exhibited a fast tumor growth, and succumbed to the disease within 19–31 days. Mice immunized with the GnRH/Montanide ISA 51/VSSP vaccine exhibited a moderate decline in testosterone levels that was associated with a decrease in anti-GnRH antibody titers, which lead to a sustained tumor growth inhibition. In total, 2 mice in the immunized group exhibited complete remission of the tumor for the duration of the present study. In addition, castrated mice, which were used as a control for standard hormonal therapy, exhibited an accelerated decrease in tumor size. However, tumor relapse was observed between days 50 and 54, and between days 65 and 85, following the injection of SC 155 cells. Therefore, these mice were sacrificed at day 90. The present study concludes that the slow and moderate reduction of testosterone levels observed using the GnRH-based vaccine may delay the appearance of castration resistance in a Shionogi prostate cancer model. These findings suggest that this vaccine may be used to delay castration resistance in patients with prostate cancer. PMID:27446378

  16. Modeling the Release Kinetics of Poorly Water-Soluble Drug Molecules from Liposomal Nanocarriers

    Directory of Open Access Journals (Sweden)

    Stephan Loew

    2011-01-01

    Full Text Available Liposomes are frequently used as pharmaceutical nanocarriers to deliver poorly water-soluble drugs such as temoporfin, cyclosporine A, amphotericin B, and paclitaxel to their target site. Optimal drug delivery depends on understanding the release kinetics of the drug molecules from the host liposomes during the journey to the target site and at the target site. Transfer of drugs in model systems consisting of donor liposomes and acceptor liposomes is known from experimental work to typically exhibit a first-order kinetics with a simple exponential behavior. In some cases, a fast component in the initial transfer is present, in other cases the transfer is sigmoidal. We present and analyze a theoretical model for the transfer that accounts for two physical mechanisms, collisions between liposomes and diffusion of the drug molecules through the aqueous phase. Starting with the detailed distribution of drug molecules among the individual liposomes, we specify the conditions that lead to an apparent first-order kinetic behavior. We also discuss possible implications on the transfer kinetics of (1 high drug loading of donor liposomes, (2 attractive interactions between drug molecules within the liposomes, and (3 slow transfer of drugs between the inner and outer leaflets of the liposomes.

  17. Pharmaceutical equivalence by design for generic drugs: modified-release products.

    Science.gov (United States)

    Raw, André Sirota; Lionberger, Robert; Yu, Lawrence X

    2011-07-01

    The Office of Generic Drugs has ensured the high quality of generic products based upon two requirements: pharmaceutical equivalence and bioequivalence to the reference listed drug (RLD). This paradigm has been used with success toward ensuring quality generic drug products that provide the same therapeutic benefit as the RLD. Drug products have increased in design complexity; as a result, approaches to ensure therapeutic equivalence must evolve to provide assurance of quality generic drug products. The Food and Drug Administration quality by design initiative (QbD) provides an enhanced evaluation approach by introducing the concept of a quality target product profile (QTPP). The QTPP introduces, within the context of the current regulatory framework, the quality concept of "pharmaceutical equivalence by design." This article illustrates through several examples how this QbD element in the evaluation of modified-release drug products enhances the current framework to ensure generic drug product equivalence. It achieves this by complementing the traditional paradigm, "equivalence by testing," where product equivalence is based upon inferences from a limited bioequivalence study, to one that also considers whether the drug product was developed to be an equivalent to the RLD, using appropriate quality surrogates that target "pharmaceutical equivalence by design."

  18. Modeling the Release Kinetics of Poorly Water-Soluble Drug Molecules from Liposomal Nanocarriers

    Science.gov (United States)

    Loew, Stephan; Fahr, Alfred; May, Sylvio

    2011-01-01

    Liposomes are frequently used as pharmaceutical nanocarriers to deliver poorly water-soluble drugs such as temoporfin, cyclosporine A, amphotericin B, and paclitaxel to their target site. Optimal drug delivery depends on understanding the release kinetics of the drug molecules from the host liposomes during the journey to the target site and at the target site. Transfer of drugs in model systems consisting of donor liposomes and acceptor liposomes is known from experimental work to typically exhibit a first-order kinetics with a simple exponential behavior. In some cases, a fast component in the initial transfer is present, in other cases the transfer is sigmoidal. We present and analyze a theoretical model for the transfer that accounts for two physical mechanisms, collisions between liposomes and diffusion of the drug molecules through the aqueous phase. Starting with the detailed distribution of drug molecules among the individual liposomes, we specify the conditions that lead to an apparent first-order kinetic behavior. We also discuss possible implications on the transfer kinetics of (1) high drug loading of donor liposomes, (2) attractive interactions between drug molecules within the liposomes, and (3) slow transfer of drugs between the inner and outer leaflets of the liposomes. PMID:21773045

  19. Diffusion-Based Design of Multi-Layered Ophthalmic Lenses for Controlled Drug Release.

    Science.gov (United States)

    Pimenta, Andreia F R; Serro, Ana Paula; Paradiso, Patrizia; Saramago, Benilde; Colaço, Rogério

    2016-01-01

    The study of ocular drug delivery systems has been one of the most covered topics in drug delivery research. One potential drug carrier solution is the use of materials that are already commercially available in ophthalmic lenses for the correction of refractive errors. In this study, we present a diffusion-based mathematical model in which the parameters can be adjusted based on experimental results obtained under controlled conditions. The model allows for the design of multi-layered therapeutic ophthalmic lenses for controlled drug delivery. We show that the proper combination of materials with adequate drug diffusion coefficients, thicknesses and interfacial transport characteristics allows for the control of the delivery of drugs from multi-layered ophthalmic lenses, such that drug bursts can be minimized, and the release time can be maximized. As far as we know, this combination of a mathematical modelling approach with experimental validation of non-constant activity source lamellar structures, made of layers of different materials, accounting for the interface resistance to the drug diffusion, is a novel approach to the design of drug loaded multi-layered contact lenses.

  20. Controlled release of cortisone drugs from block copolymers synthetized by ATRP

    Science.gov (United States)

    Valenti, G.; La Carta, S.; Mazzotti, G.; Rapisarda, M.; Perna, S.; Di Gesù, R.; Giorgini, L.; Carbone, D.; Recca, G.; Rizzarelli, P.

    2016-05-01

    Diseases affecting posterior eye segment, like macular edema, infection and neovascularization, may cause visual impairment. Traditional treatments, such as steroidal-drugs intravitreal injections, involve chronic course of therapy usually over a period of years. Moreover, they can require frequent administrations of drug in order to have an adequately disease control. This dramatically reduce patient's compliance. Efforts have been made to develop implantable devices that offer an alternative therapeutic approach to bypass many challenges of conventional type of therapy. Implantable drug delivery systems (DDS) have been developed to optimize therapeutic properties of drugs and ensure their slow release in the specific site. Polymeric materials can play an essential role in modulating drug delivery and their use in such field has become indispensable. During last decades, acrylic polymers have obtained growing interest. Biocompatibility and chemical properties make them extremely versatile, allowing their use in many field such as biomedical. In particular, block methacrylate copolymer with a balance of hydrophilic and hydrophobic properties can be suitable for prolonged DDS in biomedical devices. In this work, we focused on the realization of a system for controlled and long term release of betamethasone 17,21-dipropionate (BDP), a cortisone drug, from methacrylic block copolymers, to be tested in the treatment of the posterior eye's diseases. Different series of methyl methacrylate/hydroxyethyl methacrylate (MMA/HEMA) block and random copolymers, with different monomer compositions (10-60% HEMA), were synthetized by Atom Transfer Radical Polymerization (ATRP) to find the best hydrophilic/hydrophobic ratio, able to ensure optimal kinetic release. Copolymer samples were characterized by NMR spectroscopy (1H-NMR, 13C-NMR, CosY), SEC, TGA and DSC. Monitoring of drug release from films loaded with BDP was carried out by HPLC analysis. Evaluation of different kinetic

  1. Controlled release of cortisone drugs from block copolymers synthetized by ATRP

    Energy Technology Data Exchange (ETDEWEB)

    Valenti, G.; La Carta, S.; Rapisarda, M.; Carbone, D.; Recca, G.; Rizzarelli, P., E-mail: paola.rizzarelli@cnr.it [Istituto per i Polimeri, Compositi e Biomateriali, Consiglio Nazionale delle Ricerche Via P. Gaifami 18, 95129 Catania (Italy); Mazzotti, G.; Giorgini, L. [Dipartimento di Chimica Industriale «Toso Montanari», Università di Bologna Via Risorgimento 4, 40136 Bologna (Italy); Perna, S. [ST Microelectronics Srl, Stradale Primosole, 50–95121 Catania (Italy); Di Gesù, R. [Merck Serono S.p.A., Via L. Einaudi, 11–00012 Guidonia Montecelio, Rome (Italy)

    2016-05-18

    Diseases affecting posterior eye segment, like macular edema, infection and neovascularization, may cause visual impairment. Traditional treatments, such as steroidal-drugs intravitreal injections, involve chronic course of therapy usually over a period of years. Moreover, they can require frequent administrations of drug in order to have an adequately disease control. This dramatically reduce patient’s compliance. Efforts have been made to develop implantable devices that offer an alternative therapeutic approach to bypass many challenges of conventional type of therapy. Implantable drug delivery systems (DDS) have been developed to optimize therapeutic properties of drugs and ensure their slow release in the specific site. Polymeric materials can play an essential role in modulating drug delivery and their use in such field has become indispensable. During last decades, acrylic polymers have obtained growing interest. Biocompatibility and chemical properties make them extremely versatile, allowing their use in many field such as biomedical. In particular, block methacrylate copolymer with a balance of hydrophilic and hydrophobic properties can be suitable for prolonged DDS in biomedical devices. In this work, we focused on the realization of a system for controlled and long term release of betamethasone 17,21-dipropionate (BDP), a cortisone drug, from methacrylic block copolymers, to be tested in the treatment of the posterior eye’s diseases. Different series of methyl methacrylate/hydroxyethyl methacrylate (MMA/HEMA) block and random copolymers, with different monomer compositions (10–60% HEMA), were synthetized by Atom Transfer Radical Polymerization (ATRP) to find the best hydrophilic/hydrophobic ratio, able to ensure optimal kinetic release. Copolymer samples were characterized by NMR spectroscopy ({sup 1}H-NMR, {sup 13}C-NMR, CosY), SEC, TGA and DSC. Monitoring of drug release from films loaded with BDP was carried out by HPLC analysis. Evaluation of

  2. Aptamer/Graphene Quantum Dots Nanocomposite Capped Fluorescent Mesoporous Silica Nanoparticles for Intracellular Drug Delivery and Real-Time Monitoring of Drug Release.

    Science.gov (United States)

    Zheng, Fen-Fen; Zhang, Peng-Hui; Xi, Yu; Chen, Jing-Jia; Li, Ling-Ling; Zhu, Jun-Jie

    2015-12-01

    Great challenges in investigating the release of drug in complex cellular microenvironments necessitate the development of stimuli-responsive drug delivery systems with real-time monitoring capability. In this work, a smart drug nanocarrier based on fluorescence resonance energy transfer (FRET) is fabricated by capping graphene quantum dots (GQDs, the acceptor) onto fluorescent mesoporous silica nanoparticles (FMSNs, the donor) via ATP aptamer for real-time monitoring of ATP-triggered drug release. Under extracellular conditions, the fluorescence of FMSNs remains in the "off" state in the low ATP level which is unable to trigger the release of drug. Once specifically recognized and internalized into the target tumor cells by AS1411 aptamer, in the ATP-rich cytoplasm, the conformation switch of the ATP aptamer causes the shedding of the GQDs from the nanocarriers, leading to the release of the loaded drugs and consequently severe cytotoxicity. Simultaneously, the fluorescence of FMSNs turns "on" along with the dissociation of GQDs, which allows real-time monitoring of the release of drug from the pores. Such a drug delivery system features high specificity of dual-target recognition with AS1411 and ATP aptamer as well as high sensitivity of the FRET-based monitoring strategy. Thus, the proposed multifunctional ATP triggered FRET-nanocarriers will find potential applications for versatile drug-release monitoring, efficient drug transport, and targeted cancer therapeutics.

  3. Enhanced Oral Bioavailability of Efavirenz by Solid Lipid Nanoparticles: In Vitro Drug Release and Pharmacokinetics Studies

    Directory of Open Access Journals (Sweden)

    Praveen Kumar Gaur

    2014-01-01

    Full Text Available Solid lipid nanoparticle is an efficient lipid based drug delivery system which can enhance the bioavailability of poorly water soluble drugs. Efavirenz is a highly lipophilic drug from nonnucleoside inhibitor category for treatment of HIV. Present work illustrates development of an SLN formulation for Efavirenz with increased bioavailability. At first, suitable lipid component and surfactant were chosen. SLNs were prepared and analyzed for physical parameters, stability, and pharmacokinetic profile. Efavirenz loaded SLNs were formulated using Glyceryl monostearate as main lipid and Tween 80 as surfactant. ESLN-3 has shown mean particle size of 124.5±3.2 nm with a PDI value of 0.234, negative zeta potential, and 86% drug entrapment. In vitro drug release study has shown 60.6–98.22% drug release in 24 h by various SLN formulations. Optimized SLNs have shown good stability at 40°C ± 2°C and 75±5% relative humidity (RH for 180 days. ESLN-3 exhibited 5.32-fold increase in peak plasma concentration (Cmax⁡ and 10.98-fold increase in AUC in comparison to Efavirenz suspension (ES.

  4. CONTROLLED RELEASE IN SITU FORMING GATIFLOXACIN HCl HYDROGEL FOR OPHTHALMIC DRUG DELIVERY

    Directory of Open Access Journals (Sweden)

    Pawar Sagar D

    2012-06-01

    Full Text Available Recently, controlled drug delivery has become the standard in modern Pharmaceutical design and an intensive research have been undertaken in achieving much better drug product effectiveness, reliability and safety. This interest has been sparked by the advantages shown by in situ forming polymeric delivery systems such as ease of administration and reduced frequency of administration, improved patient compliance and comfort. In situ hydrogels are instilled as drops into the eye and undergoes a sol to gel transition in the cul-de-sac, improved ocular bioavailability by increasing the duration of contact with corneal tissue, thereby reducing the frequency of administration. The purpose of the present work was to develop an ophthalmic drug delivery system using the three different gelling agents with different mechanisms for in situ gelation of Gatifloxacin hydrochloride, a fluoroquinolone antibiotic. Polyox – a pH sensitive gelling agent and sodium alginate is an ion sensitive gelling agent and Poloxamer – a temperature sensitive gelling agent were employed for the formation of in situ hydrogel along with HPMC K4M as viscofying agent. The promising formulations were evaluated for pH, drug content, in vitro gelation, in vitro drug release, in vivo drug release, ocular irritation.

  5. Will targeting oropharyngeal gonorrhoea delay the further emergence of drug-resistant Neisseria gonorrhoeae strains?

    Science.gov (United States)

    Lewis, D A

    2015-06-01

    Gonorrhoea is an important sexually transmitted infection associated with serious complications and enhanced HIV transmission. Oropharyngeal infections are often asymptomatic and will only be detected by screening. Gonococcal culture has low sensitivity (gonorrhoea, and, although not yet approved commercially, nucleic acid amplification tests (NAAT) are the assay of choice. Screening for oropharyngeal gonorrhoea should be performed in high-risk populations, such as men-who-have-sex-with-men(MSM). NAATs have a poor positive predictive value when used in low-prevalence populations. Gonococci have repeatedly thwarted gonorrhoea control efforts since the first antimicrobial agents were introduced. The oropharyngeal niche provides an enabling environment for horizontal transfer of genetic material from commensal Neisseria and other bacterial species to Neisseria gonorrhoeae. This has been the mechanism responsible for the generation of mosaic penA genes, which are responsible for most of the observed cases of resistance to extended-spectrum cephalosporins (ESC). As antimicrobial-resistant gonorrhoea is now an urgent public health threat, requiring improved antibiotic stewardship, laboratory-guided recycling of older antibiotics may help reduce ESC use. Future trials of antimicrobial agents for gonorrhoea should be powered to test their efficacy at the oropharynx as this is the anatomical site where treatment failure is most likely to occur. It remains to be determined whether a combination of frequent screening of high-risk individuals and/or laboratory-directed fluoroquinolone therapy of oropharyngeal gonorrhoea will delay the further emergence of drug-resistant N. gonorrhoeae strains.

  6. Study of mesoporous silica/magnetite systems in drug controlled release.

    Science.gov (United States)

    Souza, K C; Ardisson, J D; Sousa, E M B

    2009-02-01

    Ordered mesoporous materials like SBA-15 have a network of channels and pores with well-defined size in the nanoscale range. This particular silica matrix pore architecture makes them suitable for hosting a broad variety of compounds in very promising materials in a range of applications, including drug release magnetic carriers. In this work, magnetic nanoparticles embedded into mesoporous silica were prepared in two steps: first, magnetite was synthesized by oxidation-precipitation method, and next, the magnetic nanoparticles were coated with mesoporous silica by using nonionic block copolymer surfactants as structure-directing agents. The materials were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), N(2) adsorption, and scanning electron microscopy (SEM). The influence of magnetic nanoparticles on drug release kinetics was studied with cisplatin, carboplatin, and atenolol under in vitro conditions in the absence and in the presence of an external magnetic field (0.25 T) by using NdFeB permanent magnet. The constant external magnetic field did not affect drug release significantly. The low-frequency alternating magnetic field had a large influence on the cisplatin release profile.

  7. Effect of mechanical and electrical behavior of gelatin hydrogels on drug release and cell proliferation.

    Science.gov (United States)

    Biswal, Dibyajyoti; Anupriya, B; Uvanesh, K; Anis, Arfat; Banerjee, Indranil; Pal, Kunal

    2016-01-01

    The present study was aimed to explore the effect of the mechanical and the electrical properties of the gelatin hydrogels on the mammalian cell proliferation and drug release properties. FTIR analysis of the hydrogels suggested that gelatin retained its secondary protein structure. A decrease in the diffusion constant of the water molecules was observed with the increase in the gelatin concentration in the hydrogels. The mechanical and the electrical stabilities of the hydrogels were enhanced with the increase in the gelatin content. Stress relaxation and creep studies were modeled using Weichert and Burger׳s models, respectively. The relaxation time (stress relaxation study) did not follow a concentration-dependent relationship and was found to affect the MG-63 cell (human osteoblast) proliferation. The impedance profile of the hydrogels was modeled using a (RQ)Q model. Release of ciprofloxacin from the hydrogels was inversely dependent on the rate of swelling. The release of the drug was not only dependent on the Fickian diffusion but also on the relaxation process of the gelatin chains. The inhomogeneous constant of the constant phase element representing the hydrogel-electrode interface indicated improved cell proliferation rate with a decrease in the inhomogeneous constant. In gist, the rate of cell proliferation could be related to the relaxation time (stress relaxation) and the inhomogeneous constant of the sample-electrode constant phase element (electrical study) properties, whereas, the drug release properties can be related to the bulk resistance of the formulations.

  8. Chitosan/alginate based multilayers to control drug release from ophthalmic lens.

    Science.gov (United States)

    Silva, Diana; Pinto, Luís F V; Bozukova, Dimitriya; Santos, Luís F; Serro, Ana Paula; Saramago, Benilde

    2016-11-01

    In this study we investigated the possibility of using layer-by-layer deposition, based in natural polymers (chitosan and alginate), to control the release of different ophthalmic drugs from three types of lens materials: a silicone-based hydrogel recently proposed by our group as drug releasing soft contact lens (SCL) material and two commercially available materials: CI26Y for intraocular lens (IOLs) and Definitive 50 for SCLs. The optimised coating, consisting in one double layer of (alginate - CaCl2)/(chitosan+glyoxal) topped with a final alginate-CaCl2 layer to avoid chitosan degradation by tear fluid proteins, proved to have excellent features to control the release of the anti-inflammatory, diclofenac, while keeping or improving the physical properties of the lenses. The coating leads to a controlled release of diclofenac from SCL and IOL materials for, at least, one week. Due to its high hydrophilicity (water contact angle≈0) and biocompatibility, it should avoid the use of further surface treatments to enhance the useŕs comfort. However, the barrier effect of this coating is specific for diclofenac, giving evidence to the need of optimizing the chemical composition of the layers in view of the desired drug.

  9. Evaluation of chitosan–anionic polymers based tablets for extended-release of highly water-soluble drugs

    Directory of Open Access Journals (Sweden)

    Yang Shao

    2015-02-01

    Full Text Available The objective of this study is to develop chitosan–anionic polymers based extended-release tablets and test the feasibility of using this system for the sustained release of highly water-soluble drugs with high drug loading. Here, the combination of sodium valproate (VPS and valproic acid (VPA were chosen as the model drugs. Anionic polymers studied include xanthan gum (XG, carrageenan (CG, sodium carboxymethyl cellulose (CMC-Na and sodium alginate (SA. The tablets were prepared by wet granulation method. In vitro drug release was carried out under simulated gastrointestinal condition. Drug release mechanism was studied. Compared with single polymers, chitosan–anionic polymers based system caused a further slowdown of drug release rate. Among them, CS–xanthan gum matrix system exhibited the best extended-release behavior and could extend drug release for up to 24 h. Differential scanning calorimetry (DSC and Fourier transform infrared spectroscopy (FTIR studies demonstrated that polyelectrolyte complexes (PECs were formed on the tablet surface, which played an important role on retarding erosion and swelling of the matrix in the later stage. In conclusion, this study demonstrated that it is possible to develop highly water-soluble drugs loaded extended-release tablets using chitosan–anionic polymers based system.

  10. Electrospun tri-layered zein/PVP-GO/zein nanofiber mats for providing biphasic drug release profiles.

    Science.gov (United States)

    Lee, Hoik; Xu, Gang; Kharaghani, Davood; Nishino, Masayoshi; Song, Kyung Hun; Lee, Jung Soon; Kim, Ick Soo

    2017-10-05

    Simple sequential electrospinning was utilized to create a functional tri-layered nanofiber mesh that achieves time-regulated biphasic drug release behavior. A tri-layered nanofiber mesh -composed of zein and poly(vinylpyrrolidone) (PVP) as the top/bottom and middle layers, respectively - was constructed through sequential electrospinning with ketoprofen (KET) as the model drug. PVP was blended with graphene oxide (GO) to improve the drug release functionality of PVP nanofiber as well as its mechanical properties. Scanning electron microscopy confirmed that the resultant nanofibers had a linear morphology, smooth surface, and tri-layered structure. In addition, X-ray diffraction patterns, differential scanning calorimetric analyses, and Fourier transform infrared spectra verified that the drugs were uniformly dispersed throughout the nanofiber due to good compatibility between the polymer and KET induced by hydrogen interaction. In vitro release test of the tri-layered structure, each component of which had distinct release features, successfully demonstrated time-regulated biphasic drug release. Also, it was confirmed that the drug release rate and duration can be controlled by designing a morphological feature - namely, mesh thickness - which was achieved by simply regulating the spinning time of the first and third layer. This multilayered electrospun nanofiber mesh fabricated by sequential electrospinning could provide a useful method of controlling drug release behavior over time, which will open new routes for practical applications and stimulate further research in the development of effective drug release carriers. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Polymer grafted-magnetic halloysite nanotube for controlled and sustained release of cationic drug.

    Science.gov (United States)

    Fizir, Meriem; Dramou, Pierre; Zhang, Kai; Sun, Cheng; Pham-Huy, Chuong; He, Hua

    2017-11-01

    In this research, novel polymer grafted-magnetic halloysite nanotubes with norfloxacin loaded (NOR-MHNTs) and controlled-release, was achieved by surface-initiated precipitation polymerization. The magnetic halloysite nanotubes exhibited better adsorption of NOR (72.10mgg(-1)) compared with the pristine HNTs (30.80mgg(-1)). Various parameters influencing the drug adsorption of the MHNTs for NOR were studied. Polymer grafted NOR-MHNTs has been designed using flexible docking in computer simulation to choose optimal monomers. NOR-MHNTs/poly (methacrylic acid or acrylamide-co-ethylene glycol dimethacrylate) nanocomposite were synthesized using NOR-MHNTs, methacrylic acid (MAA) or acrylamide (AM), ethylene glycol dimethacrylate (EGDMA) and AIBN as nanotemplate, monomers, cross linker and initiator, respectively. The magnetic nanocomposites were characterized by FTIR, TEM, XRD and VSM. The magnetic nanocomposites show superparamagnetic property and fast magnetic response (12.09emug(-1)). The copolymerization of monomers and cross linker led to a better sustained release of norfloxacin (>60h) due to the strong interaction formed between monomers and this cationic drug. The cumulative release rate of NOR is closely related to the cross linker amount. In conclusion, combining the advantages of the high adsorption capacity and magnetic proprieties of this biocompatible clay nanotube and the advantages of polymer shell in the enhancement of controlled-sustained release of cationic drug, a novel formulation for the sustained-controlled release of bioactive agents is developed and may have considerable potential application in targeting drug delivery system. Copyright © 2017. Published by Elsevier Inc.

  12. Technetium-99m-labeled nanofibrillar cellulose hydrogel for in vivo drug release.

    Science.gov (United States)

    Laurén, Patrick; Lou, Yan-Ru; Raki, Mari; Urtti, Arto; Bergström, Kim; Yliperttula, Marjo

    2014-12-18

    Nanoscale celluloses have recently gained an increasing interest in modern medicine. In this study, we investigated the properties of plant derived nanofibrillar cellulose (NFC) as an injectable drug releasing hydrogel in vivo. We demonstrated a reliable and efficient method of technetium-99m-NFC labeling, which enables us to trace the in vivo localization of the hydrogel. The release and distribution of study compounds from the NFC hydrogel after subcutaneous injection in the pelvic region of BALB/c mice were examined with a multimodality imaging device SPECT/CT. The drug release profiles were simulated by 1-compartmental models of Phoenix® WinNonlin®. The NFC hydrogel remained intact at the injection site during the study. The study compounds are more concentrated at the injection site when administered with the NFC hydrogel compared with saline solutions. In addition, the NFC hydrogel reduced the elimination rate of a large compound, technetium-99m-labeled human serum albumin by 2 folds, but did not alter the release rate of a small compound (123)I-β-CIT (a cocaine analogue). In conclusion, the NFC hydrogels is easily prepared and readily injected, and it has potential use as a matrix for controlled release or local delivery of large compounds. The interactions between NFC and specific therapeutic compounds are possible and should be investigated further.

  13. Interpolymer Complexation Between Polyox and Carbopol, and Its Effect on Drug Release From Matrix Tablets.

    Science.gov (United States)

    Zhang, Feng; Lubach, Joseph; Na, Watson; Momin, Samad

    2016-08-01

    Interaction between Polyox N12K and Carbopol 907 was pH dependent. A hydrogen bond-induced complexation began between pH 5.0 and 6.0 in an aqueous medium, and the interpolymer complex started to precipitate when the pH fell to 4.0. This complex was amorphous with a glass transition temperature of 3.17°C. The molar ratio between ethylene oxide and acrylic acid units in the complex was 1.3:1. About 46% of the COOH groups in Carbopol 907 were H bonded to ether oxygen in Polyox. Theophylline release from tablets containing both polymers was a function of dissolution media pH, due to the pH-dependent interactions. In 0.01 N HCl, an insoluble tablet matrix formed in situ. 93% drug was released over 27 h via Fickian diffusion. In acetate buffer pH 4.0, the insoluble tablet matrix formed in situ disintegrated into tiny gel particles. Gel erosion controlled drug release at pH 4.0. These 2 polymers were unable to complex in a phosphate buffer pH 6.8. Therefore, the tablet matrix dissolved, and drug release followed the anomalous transport mechanism at pH 6.8. The release profiles in an acetate buffer pH 4.0 and phosphate buffer pH 6.8 were statistically same, and a sustained release over 12 h was achieved.

  14. Development of a cell-based bioassay for phospholipase A2-triggered liposomal drug release.

    Science.gov (United States)

    Arouri, Ahmad; Trojnar, Jakub; Schmidt, Steffen; Hansen, Anders H; Mollenhauer, Jan; Mouritsen, Ole G

    2015-01-01

    The feasibility of exploiting secretory phospholipase A2 (sPLA2) enzymes, which are overexpressed in tumors, to activate drug release from liposomes precisely at the tumor site has been demonstrated before. Although the efficacy of the developed formulations was evaluated using in vitro and in vivo models, the pattern of sPLA2-assisted drug release is unknown due to the lack of a suitable bio-relevant model. We report here on the development of a novel bioluminescence living-cell-based luciferase assay for the monitoring of sPLA2-triggered release of luciferin from liposomes. To this end, we engineered breast cancer cells to produce both luciferase and sPLA2 enzymes, where the latter is secreted to the extracellular medium. We report on setting up a robust and reproducible bioassay for testing sPLA2-sensitive, luciferin remote-loaded liposomal formulations, using 1,2-distearoyl-sn-glycero-3-phosphatidylcholine/1,2-distearoyl-sn-glycero-3-phosphatidylglycerol (DSPC/DSPG) 7:3 and DSPC/DSPG/cholesterol 4:3:3 as initial test systems. Upon their addition to the cells, the liposomes were degraded almost instantaneously by sPLA2 releasing the encapsulated luciferin, which provided readout from the luciferase-expressing cells. Cholesterol enhanced the integrity of the formulation without affecting its susceptibility to sPLA2. PEGylation of the liposomes only moderately broadened the release profile of luciferin. The provided bioassay represents a useful tool for monitoring active drug release in situ in real time as well as for testing and optimizing of sPLA2-sensitive lipid formulations. In addition, the bioassay will pave the way for future in-depth in vitro and in vivo studies.

  15. Thermo-Responsive Injectable MPEG-Polyester Diblock Copolymers for Sustained Drug Release

    Directory of Open Access Journals (Sweden)

    Hoon Hyun

    2014-10-01

    Full Text Available Thermo-responsive diblock copolymers composed of hydrophilic methoxy poly(ethylene glycol (MPEG and hydrophobic biodegradable polyesters were prepared for application as injectable drug delivery systems, because they show a thermo-responsive sol-to-gel transition, especially around body temperature, when dispersed in aqueous solutions. The thermogelling hydrogels formed by hydrophobic aggregation could be varied by changing the components of the hydrophobic polyester part. For the polyester block in the present study, 95 mol% of ε-caprolactone (CL was used for the main polyester chain and 5 mol% of p-dioxanone (DO was copolymerized randomly by the MPEG initiator in the presence of HCl as the catalyst. By adding a small portion of DO into the poly ε-caprolactone (PCL chains, the temperature range of gelation, the intensity of viscosity and the drug release behavior were changed. The MPEG-b-poly(ε-caprolactone-ran-p-dioxanone (MPEG-b-PCDO hydrogel showed the enhanced drug release in vitro and in vivo compared to MPEG-b-PCL hydrogel. Therefore, MPEG-polyester hydrogels may serve as minimally invasive and therapeutic, injectable hydrogel systems with adjustable temperature-responsive and biodegradable windows, as well as sustained release of drugs over a certain time period.

  16. Preparation and drug releasing property of magnetic chitosan-5-fluorouracil nano-particles

    Institute of Scientific and Technical Information of China (English)

    WANG Dong-sheng; LI Jian-guo; LI He-ping; TANG Fa-qing

    2009-01-01

    In order to synthesize the targeting drug carrier system, magnetic chitosan-5-fluorouracil nano-particles were prepared by using 5-fluorouracil (5-Fu) as model drug, Fe_3O_4 nano-particles as kernel, chitosan as enveloping material and glutaraldehyde as cross linking agent through ultrasonic technique. The morphology of the magnetic chitosan-5-Fu nano-particles was observed with a transmission electron microscope(TEM). The results showed that magnetic chitosan-5-Fu nano-particles were prepared in spherical structure with a size range of 50-60 nm. The delivering capacity and drug releasing properties of magnetic chitosan-5-Fu nano-particles were investigated by UV-vis spectrum analysis. The results showed that the loading capacity was 13.4% and the cumulative release percentage in the phosphate buffer (pH=7.2) solutions was 68% in 30 h. These data indicate that the wrapped drug of magnetic chitosan-5-Fu nano-particles was slowly-released. The magnetic response of magnetic chitosan-5-Fu nano-particles was studied by UV-vis spectrometer to detect the changes of solution absorbance. Without external magnetic field, the nano-particle deposition rate was slow. When being subjected to 8 mT magnetic field, the particle sedimentation rate was increased rapidly. The results showed that magnetic chitosan-5-Fu nano-particles have a magnetic stability and strong targeting characteristics.

  17. Ampicillin-Ester Bonded Branched Polymers: Characterization, Cyto-, Genotoxicity and Controlled Drug-Release Behaviour

    Directory of Open Access Journals (Sweden)

    Ewa Oledzka

    2014-06-01

    Full Text Available The development and characterization of novel macromolecular conjugates of ampicillin using branched biodegradable polymers has been described in this study. The conjugates have been prepared coupling the β-lactam antibiotic with branched polymer matrices based on the natural oligopeptide core. The cyto- and genotoxicity of the synthesized polymers were evaluated with a bacterial luminescence test, two protozoan assays and Salmonella typhimurium TA1535. The presence of a newly formed covalent bond between the drug and the polymer matrices was confirmed by 1H-NMR and FTIR studies. A drug content (15.6 and 10.2 mole % in the macromolecular conjugates has been determined. The obtained macromolecular products have been subjected to further in vitro release studies. The total percentage of ampicillin released after 21 days of incubation was nearly 60% and 14% and this resulted from the different physicochemical properties of the polymeric matrices. This is the first report on the application of branched biodegradable polymeric matrices for the covalent conjugation of ampicillin. The obtained results showed that the synthesized macromolecular drug-conjugates might slowly release the active drug molecule and improve the pharmacokinetics of ampicillin.

  18. Deeper insight into the drug release mechanisms in Eudragit RL-based delivery systems.

    Science.gov (United States)

    Glaessl, B; Siepmann, F; Tucker, I; Rades, T; Siepmann, J

    2010-04-15

    Tartaric acid, metoprolol free base and metoprolol tartrate act as plasticisers for Eudragit RL, in the dry but also in the wet state. Fitting analytical solutions of Fick's second law of diffusion allowed for the determination of the apparent diffusivities of water and of tartaric acid, metoprolol free base and metoprolol tartrate upon exposure of thin films to 0.1M HCl, phosphate buffer pH 7.4 and distilled water. Based on these calculations, it could be shown that water penetration into the systems is predominantly controlled by pure diffusion, irrespective of the type of bulk fluid. Interestingly, the plasticising effect of metoprolol tartrate was much more pronounced than that of tartaric acid, resulting in monotonically increasing diffusion coefficients with increasing initial drug content. In contrast, the plasticising activity of metoprolol free base was very limited in the wet state, due to drug precipitation in aqueous environments. Partially observed film shrinking (after an initial system swelling) could be attributed to the leaching of the plasticising compound into the release medium, resulting in less flexible polymeric networks and squeezing out of water. Also the release of tartaric acid, metoprolol free base and metoprolol tartrate into the investigated bulk fluids was predominantly diffusion controlled. However, the precipitation of the free base in wet films rendered the mass transport mechanisms more complex, at moderate and high initial drug loadings. The obtained new insight into the underlying drug release mechanisms in Eudragit RL networks can help to facilitate the optimisation of this type of dosage forms.

  19. In situ synthesis of magnetic CaraPVA IPN nanocomposite hydrogels and controlled drug release

    Energy Technology Data Exchange (ETDEWEB)

    Mahdavinia, Gholam Reza, E-mail: grmnia@maragheh.ac.ir; Etemadi, Hossein

    2014-12-01

    In this work, the magnetic nanocomposite hydrogels that focused on targeted drug delivery were synthesized by incorporation of polyvinyl alcohol (PVA), kappa-carrageenan (Cara), and magnetite Fe{sub 3}O{sub 4} nanoparticles. The magnetic nanoparticles were obtained in situ in the presence of a mixture of polyvinyl alcohol/kappa-carrageenan (CaraPVA). The produced magnetite-polymers were cross-linked with freezing–thawing technique and subsequent with K{sup +} solution. The synthesized hydrogels were thoroughly characterized by transmittance electron microscopy (TEM), scanning electron microscopy (SEM), X-ray diffraction (XRD), thermal gravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR), and vibrating sample magnetometer (VSM) techniques. The dynamic swelling kinetic models of hydrogels were analyzed according to the first- and second-order kinetic models and were found that the experimental kinetics data followed the second-order model well. Drug loading and release efficiency were evaluated by diclofenac sodium (DS) as the model drug. The in vitro drug release studies from hydrogels exhibited significant behaviors on the subject of physiological simulated pHs and external magnetic fields. Investigation on the antibacterial activity revealed the ability of drug-loaded hydrogels to inactivate the Gram-positive Staphylococcus aureus (S. aureus) bacteria. The mucoadhesive properties of the hydrogels were studied and the hydrogels containing kappa-carrageenan showed good mucoadhesiveness in both simulated gastric and intestinal conditions. - Highlights: • In situ synthesis of magnetic kappa-carrageenan/PVA nanocomposite hydrogel. • Low salt sensitivity of magnetic nanocomposite hydrogels was observed. • The release of diclofenac sodium from hydrogels was pH-dependent. • The release of diclofenac sodium from magnetic hydrogels was affected by external magnetic field. • The hydrogels containing carrageenan component showed high

  20. Natural gums as sustained release carriers: development of gastroretentive drug delivery system of ziprasidone HCl

    Directory of Open Access Journals (Sweden)

    AJ Rajamma

    2012-10-01

    Full Text Available Abstract Background Objective of this study is to show the potential use of natural gums in the development of drug delivery systems. Therefore in this work gastro retentive tablet formulations of ziprasidone HCl were developed using simplex lattice design considering concentration of okra gum, locust bean gum and HPMC K4M as independent variables. A response surface plot and multiple regression equations were used to evaluate the effect of independent variables on hardness, flag time, floating time and drug release for 1 h, 2 h, and 8 h and for 24 h. A checkpoint batch was also prepared by considering the constraints and desirability of optimized formulation to improve its in vitro performance. Significance of result was analyzed using ANOVA and p was considered statistically significant. Results Formulation chiefly contains locust bean gum found to be favorable for hardness and floatability but combined effect of three variables was responsible for the sustained release of drug. The in vitro drug release data of check point batch (F8 was found to be sustained well compared to the most satisfactory formulation (F7 of 7 runs. The ‘n’ value was found to be between 0.5 and 1 suggesting that release of drug follows anomalous (non-fickian diffusion mechanism indicating both diffusion and erosion mechanism from these natural gums. Predicted results were almost similar to the observed experimental values indicating the accuracy of the design. In vivo floatability test indicated non adherence to the gastric mucosa and tablets remain buoyant for more than 24 h. Conclusions Study showed these eco-friendly natural gums can be considered as promising SR polymers.

  1. Histamine-releasing and allergenic properties of opioid analgesic drugs: resolving the two.

    Science.gov (United States)

    Baldo, B A; Pham, N H

    2012-03-01

    Opioid analgesics are amongst the most commonly administered drugs in hospitals. Whether natural or synthetic, they show some common structural features, morphine-like pharmacological action and binding specificity for complementary opioid receptors. Tramadol differs from the other opioid analgesics in possessing monoaminergic activity in addition to its affinity for the µ opioid receptor. Many opioids are potent histamine releasers producing a variety of haemodynamic changes and anaphylactoid reactions, but the relationship of the appearance of these effects to the histamine plasma concentration is complex and there is no direct and invariable relationship between the two. Studies of the histamine-releasing effects, chiefly centred on morphine, reveal variable findings and conclusions often due to a range of factors including differences in technical measurements, dose, mode of administration, site of injection, the anatomical distribution of histamine receptors and heterogeneity of patient responses. Morphine itself has multiple direct effects on the vasculature and other haemodynamically-active mediators released along with histamine contribute to the variable responses to opioid drug administration. Despite their heavy use and occasional apparent anaphylactic-like side-effects, immunoglobulin E antibody-mediated immediate hypersensitivity reactions to the drugs are not often encountered. Uncertainties associated with skin testing with these known histamine-releasers, and the general unavailability of opioid drug-specific immunoglobulin E antibody tests contribute to the frequent failure to adequately investigate and establish underlying mechanisms of reactions by distinguishing anaphylactoid from true anaphylactic reactions. Clinical implications for diagnosis of reactions and some speculations on the rarity of true Type 1 allergies to these drugs are presented.

  2. Preparation and release kinetics of betulinic acid/ CS drug-loaded microspheres

    Directory of Open Access Journals (Sweden)

    Zhou Hao Ran

    2016-01-01

    Full Text Available Chitosan(CS is the unique alkaline polysaccharide in nature, because of its perfect biocompatibility and degradability, it is widely used in medicine, soft release and control release. The betulinic acid is the derivative of betulin, it has many pharmacological activities, such as anti- inflammatory, antitumor, anti-malaria and anti-HIV. In this paper, the Span-80 was used as emulsifiers, the glutaraldehyde was used as crosslinker. With the method of orthogonal experiment, the preparation technology was optimized. The microspheres were characterized by SEM and its degree of crosslinking, drug-loading rate and encapsulation efficiency were tested at the same time.

  3. Designed drug-release systems having various breathable polyurethane film-backed hydrocolloid acrylated adhesive layers for moisture healing.

    Science.gov (United States)

    Chang, Ching-Hsien; Liu, Hsia-Wei; Huang, Ching-Cheng

    2014-01-01

    A series of designed drug-release systems were prepared and established for clear moisture healing. These systems were designed to have an interpenetrating polymer network (IPN) structure, which contained a breathable polyurethane film, hydrocolloidlayer, and polyacrylate adhesive layer. Breathable polyurethane film (2000 g/m(2)/24 hr) with high moisture permeability was employed as a base for new drug-release systems or wound dressings. All drug-release systems having a polyurethane film-backed hydrocolloid acrylated adhesive layer showed an increase of water uptakes with increasing time. After 114 hours, high water uptakes of drug-release systems with 20% hydrocolloid components were observed in the values of 160, 1100, and 1870% for different additional hydrocolloid components of carboxymethylcellulose, sodium alginate, and carbomer U10, respectively. New drug-release systems of polyurethane film-backed hydrocolloid/adhesive layers could be designed and established for wound care managements.

  4. Fabrication and characterization of a rapid prototyped tissue engineering scaffold with embedded multicomponent matrix for controlled drug release

    DEFF Research Database (Denmark)

    Chen, Muwan; Le, Dang Q S; Hein, San

    2012-01-01

    Bone tissue engineering implants with sustained local drug delivery provide an opportunity for better postoperative care for bone tumor patients because these implants offer sustained drug release at the tumor site and reduce systemic side effects. A rapid prototyped macroporous polycaprolactone......, this scaffold can fulfill the requirements for both bone tissue engineering and local sustained release of an anticancer drug in vitro. These results suggest that the scaffold can be used clinically in reconstructive surgery after bone tumor resection. Moreover, by changing the composition and amount...... of individual components, the scaffold can find application in other tissue engineering areas that need local sustained release of drug....

  5. Mesoporous Silica Nanoparticles as Controlled Release Drug Delivery and Gene Transfection Carriers

    Energy Technology Data Exchange (ETDEWEB)

    Igor I. Slowing; Juan L. Viveo-Escoto; Chia-Wen Wu; Victor S. Y. Lin

    2008-04-10

    In this review, we highlight the recent research developments of a series of surface-functionalized mesoporous silica nanoparticle (MSN) materials as efficient drug delivery carriers. The synthesis of this type of MSN materials is described along with the current methods for controlling the structural properties and chemical functionalization for biotechnological and biomedical applications. We summarized the advantages of using MSN for several drug delivery applications. The recent investigations of the biocompatibility of MSN in vitro are discussed. We also describe the exciting progress on using MSN to penetrate various cell membranes in animal and plant cells. The novel concept of gatekeeping is introduced and applied to the design of a variety of stimuli-responsive nanodevices. We envision that these MSN-based systems have a great potential for a variety of drug delivery applications, such as the site-specific delivery and intracellular controlled release of drugs, genes, and other therapeutic agents.

  6. Delay discounting and the use of mindful attention versus distraction in the treatment of drug addiction: a conceptual review.

    Science.gov (United States)

    Ashe, Melinda L; Newman, Michelle G; Wilson, Stephen J

    2015-01-01

    In recent decades, researchers have integrated measurements of delay discounting, how the subjective valuation of a reward changes as a function of time, into their study of addiction. Research has begun to explore the idea that delay discounting may serve as both a marker for the effectiveness of existing treatments for addiction and a potential target for novel intervention strategies. As this work is in its infancy, many potentially significant connections between the construct of delay discounting and the treatment of addiction have yet to be explored. Here, we present a conceptual review highlighting novel points of intersection between delay discounting and two approaches to treating addiction that have become increasingly popular in recent years: those that focus on the development of mindfulness skills and those that emphasize the use of distraction techniques. Viewing these two techniques through the lens of delay discounting is particularly intriguing because of the very different way that they address the experience of drug cravings in the present moment (nonjudgmentally attending to vs. shifting attention away from subjective cravings, respectively). We propose that these opposing strategies for dealing with cravings may interact with delay discounting in ways that have important implications for treatment effectiveness. © Society for the Experimental Analysis of Behavior.

  7. Oral controlled release formulation for highly water-soluble drugs: drug--sodium alginate--xanthan gum--zinc acetate matrix.

    Science.gov (United States)

    Zeng, W M

    2004-05-01

    An oral controlled release formulation matrix for highly water-soluble drugs was designed and developed to achieve a 24-hour release profile. Using ranitidine HCl as a model drug, sodium alginate formulation matrices containing xanthan gum or zinc acetate or both were investigated. The caplets for these formulations were prepared by direct compression and the in vitro release tests were carried out in simulated intestinal fluid (SIF, pH 7.5) and simulated gastric fluid (SGF, pH 1.2). The release of the drug in the sodium alginate formulation containing only xanthan gum completed within 12 hours in the SIF, while the drug release in the sodium alginate formulation containing only zinc acetate finished almost within 2 hours in the same medium. Only the sodium alginate formulation containing both xanthan gum and zinc acetate achieved a 24-hour release profile, either in the SIF or in the pH change medium. In the latter case, the caplet released in the SGF for 2 hours was immediately transferred into the SIF to continue the release test. The results showed that the presence of both xanthan gum and zinc acetate in sodium alginate matrix played a key role in controlling the drug release for 24 hours. The helical structure and high viscosity of xanthan gum might prevent zinc ions from diffusing out of the ranitidine HCl--sodium alginate--xanthan gum--zinc acetate matrix so that zinc ions could react with sodium alginate to form zinc alginate precipitate with a cross-linking structure. The cross-linking structure might control a highly water-soluble drug to release for 24 hours. Evaluation of the release data showed the release mechanism for the novel formulation might be attributed to the diffusion of the drug.

  8. Hydrophobic polymers modification of mesoporous silica with large pore size for drug release

    Energy Technology Data Exchange (ETDEWEB)

    Zhu Shenmin, E-mail: smzhu@sjtu.edu.c [Shanghai Jiao Tong University, State Key Lab of Metal Matrix Composites (China); Zhang Di; Yang Na [Fudan University, Ministry of Education, Key Lab of Molecular Engineering of Polymers (China)

    2009-04-15

    Mesostructure cellular foam (MCF) materials were modified with hydrophobic polyisoprene (PI) through free radical polymerization in the pores network, and the resulting materials (MCF-PI) were investigated as matrices for drug storage. The successful synthesis of PI inside MCF was characterized by Fourier transform infrared (FT-IR), hydrogen nuclear magnetic resonance ({sup 1}H NMR), X-ray diffraction patterns (XRD) and nitrogen adsorption/desorption measurements. It was interesting to find the resultant system held a relatively large pore size (19.5 nm) and pore volume (1.02 cm{sup 3} g{sup -1}), which would benefit for drug storage. Ibuprofen (IBU) and vancomycin were selected as model drugs and loaded onto unmodified MCF and modified MCF (MCF-PI). The adsorption capacities of these model drugs on MCF-PI were observed increase as compared to that of on pure MCF, due to the trap effects induced by polyisoprene chains inside the pores. The delivery system of MCF-PI was found to be more favorable for the adsorption of IBU (31 wt%, IBU/silica), possibly attributing to the hydrophobic interaction between IBU and PI formed on the internal surface of MCF matrix. The release of drug through the porous network was investigated by measuring uptake and release of IBU.

  9. Marbofloxacin-encapsulated microparticles provide sustained drug release for treatment of veterinary diseases.

    Science.gov (United States)

    Lee, Joohyeon; Kwon, Ho Jin; Ji, Hyunggun; Cho, Sun Hang; Cho, Eun-Haeng; Han, Hee Dong; Shin, Byung Cheol

    2016-03-01

    Fluoroquinolone antibiotics with concentration-dependent killing effects and a well-established broad spectrum of activity are used commonly to treat infectious diseases caused by bacteria. However, frequent and excessive administration of these antibiotics is a serious problem, and leads to increased number of drug-resistant bacteria. Thus, there is an urgent need for novel fluoroquinolone antibiotic formulations that minimize the risk of resistance while maximizing their efficacy. In this study, we developed intramuscularly injectable polymeric microparticles (MPs) that encapsulated with marbofloxacin (MAR) and were composed of poly(D,L-lactide-co-glycolic acid) (PLGA) and poloxamer (POL). MAR-encapsulated MP (MAR-MP) had a spherical shape with particle size ranging from 80 μm to 120 μm. Drug loading efficiency varied from 55 to 85% (w/w) at increasing amount of hydrophilic agent, POL. Drug release from MAR-MP demonstrated a significant and sustained increase at increased ratios of POL to PLGA. These results indicate that MAR-MP is an improved drug delivery carrier for fluoroquinolone antibiotics, which can reduce the number of doses needed and sustain a high release rate of MAR for 2-3 days. As a novel and highly effective drug delivery platform, MAR-MP has great potential for use in a broad range of applications for the treatment of various veterinary diseases.

  10. Reconciling Estimates of the Value to Firms of Reduced Regulatory Delay in the Marketing of Their New Drugs.

    Science.gov (United States)

    Wilmoth, Daniel R

    2015-12-01

    The prescription drug user fee program provides additional resources to the U.S. Food and Drug Administration at the expense of regulated firms. Those resources accelerate the review of new drugs. Faster approvals allow firms to realize profits sooner, and the program is supported politically by industry. However, published estimates of the value to firms of reduced regulatory delay vary dramatically. It is shown here that this variation is driven largely by differences in methods that correspond to differences in implicit assumptions about the effects of reduced delay. Theoretical modeling is used to derive an equation describing the relationship between estimates generated using different methods. The method likely to yield the most accurate results is identified. A reconciliation of published estimates yields a value to a firm for a one-year reduction in regulatory delay at the time of approval of about $60 million for a typical drug. Published 2015. This article is a U.S. Government work and is in the public domain in the U.S.A.

  11. Nanoengineered drug-releasing Ti wires as an alternative for local delivery of chemotherapeutics in the brain

    Directory of Open Access Journals (Sweden)

    Gulati K

    2012-04-01

    Full Text Available Karan Gulati1,2, Moom Sinn Aw1, Dusan Losic1,21Ian Wark Research Institute, The University of South Australia, Adelaide, SA, Australia; 2School of Chemical Engineering, The University of Adelaide, Adelaide, SA, AustraliaAbstract: The blood–brain barrier (BBB blocks the passage of active molecules from the blood which makes drug delivery to the brain a challenging problem. Oral drug delivery using chemically modified drugs to enhance their transport properties or remove the blocking of drug transport across the BBB is explored as a common approach to address these problems, but with limited success. Local delivery of drugs directly to the brain interstitium using implants such as polymeric wafers, gels, and catheters has been recognized as a promising alternative particularly for the treatment of brain cancer (glioma and neurodegenerative disorders. The aim of this study was to introduce a new solution by engineering a drug-releasing implant for local drug delivery in the brain, based on titanium (Ti wires with titania nanotube (TNT arrays on their surfaces. Drug loading and drug release characteristics of this system were explored using two drugs commonly used in oral brain therapy: dopamine (DOPA, a neurotransmitter agent; and doxorubicin (DOXO, an anticancer drug. Results showed that TNT/Ti wires could provide a considerable amount of drugs (>170 µg to 1000 µg with desirable release kinetics and controllable release time (1 to several weeks and proved their feasibility for use as drug-releasing implants for local drug delivery in the brain.Purpose: In this report, a new drug-releasing platform in the form of nanoengineered Ti wires with TNT arrays is proposed as an alternative for local delivery of chemotherapeutics in the brain to bypass the BBB. To prove this concept, drug loading and release characteristics of two drugs important for brain therapy (the neurotransmitter DOPA and the anticancer drug DOXO were explored.Methods: Titania

  12. Silk fibroin/copolymer composite hydrogels for the controlled and sustained release of hydrophobic/hydrophilic drugs.

    Science.gov (United States)

    Zhong, Tianyi; Jiang, Zhijuan; Wang, Peng; Bie, Shiyu; Zhang, Feng; Zuo, Baoqi

    2015-10-15

    In the present study, a composite system for the controlled and sustained release of hydrophobic/hydrophilic drugs is described. Composite hydrogels were prepared by blending silk fibroin (SF) with PLA-PEG-PLA copolymer under mild aqueous condition. Aspirin and indomethacin were incorporated into SF/Copolymer hydrogels as two model drugs with different water-solubility. The degradation of composite hydrogels during the drug release was mainly caused by the hydrolysis of copolymers. SF with stable β-sheet-rich structure was not easily degraded which maintained the mechanical integrity of composite hydrogel. The hydrophobic/hydrophilic interactions of copolymers with model drugs would significantly alter the morphological features of composite hydrogels. Various parameters such as drug load, concentration ratio, and composition of copolymer were considered in vitro drug release. Aspirin as a hydrophilic drug could be controlled release from composite hydrogel at a constant rate for 5 days. Its release was mainly driven by diffusion-based mechanism. Hydrophobic indomethacin could be encapsulated in copolymer nanoparticles distributing in the composite hydrogel. Its sustained release was mainly degradation controlled which could last up to two weeks. SF/Copolymer hydrogel has potential as a useful composite system widely applying for controlled and sustained release of various drugs.

  13. Smart nanocarriers for pH-triggered targeting and release of hydrophobic drugs.

    Science.gov (United States)

    Cajot, S; Van Butsele, K; Paillard, A; Passirani, C; Garcion, E; Benoit, J P; Varshney, S K; Jérôme, C

    2012-12-01

    The use of hybrid pH-sensitive micelles based mainly on the (PEO)(129)(P2VP)(43)(PCL)(17) ABC miktoarm star copolymer as potential triggered drug delivery systems was investigated. Co-micellization of this star copolymer with a second copolymer labeled by a targeting ligand, i.e. biotin, on the pH sensitive block (poly-2-vinylpyridine) is considered here in order to impart possible active targeting of the tumor cells. Two architectures were studied for these labeled copolymers, i.e. a miktoarm star or a linear ABC terpolymer, and the respective hybrid micelles are compared in terms of cytotoxicity (cells viability) and cellular uptake (using fluorescent dye loaded micelles). Finally, the triggered drug release in the cytosol of tumor cells was investigated by studying, on the one hand, the lysosomal integrity after internalization and, on the other hand, the release profile in function of the pH.

  14. Preparation and Characterization of Keratin Blended Films using Biopolymers for Drug Controlled Release Application

    Directory of Open Access Journals (Sweden)

    Ansaya Thonpho

    2016-08-01

    Full Text Available Keratin solution was separately blended with collagen, gelatin, sericin and starch for films preparation. All the blended films had smooth surfaces without phase separation, except the keratin/starch blend film. The native keratin film showed small particles embedded in all the film surfaces that resulted in them being rough. The structure of the native keratin film changed from beta-sheet to random coil at high blend ratio of other substances. This result increased the dissolution of the films especially the keratin/starch blend. The results relate directly to the decreased thermal stability of this film. However, the changes in structure did not affect the chlorhexidine release pattern. It is possible that the interaction between the drug and blending substances, and the substances to water molecules are the main factor influencing the drug release pattern from the films.

  15. Drug release profiles of modified MCM-41 with superparamagnetic behavior correlated with the employed synthesis method.

    Science.gov (United States)

    Cuello, Natalia I; Elías, Verónica R; Mendieta, Silvia N; Longhi, Marcela; Crivello, Mónica E; Oliva, Marcos I; Eimer, Griselda A

    2017-09-01

    Mesoporous materials with superparamagnetic properties were successfully synthesized by two different methods: direct incorporation (DI) and wet impregnation (WI). The synthetized solids were evaluated as host of drugs for delivery systems and their physicochemical properties were characterized by XRD, ICP, N2 adsorption-desorption, spectroscopies of UV-Vis DR, FT-IR and their magnetic properties were measured. Indomethacin (IND) was incorporated into the materials and the kinetic of the release profiles was studied by applying the Pepas and Sahlin model. In this sense, materials modified by DI, particularly that with hydrothermal treatment, showed the higher adsorption capacity and slower release rate. This behavior could be associated to the synthesis method used that allowed a high percentage of silanol groups available in the solids surface, which can interact with the IND molecule. This feature coupled with the superparamagnetic behavior; make these materials very interesting for drug delivery systems. Copyright © 2017. Published by Elsevier B.V.

  16. A bacterial protein enhances the release and efficacy of liposomal cancer drugs.

    Science.gov (United States)

    Cheong, Ian; Huang, Xin; Bettegowda, Chetan; Diaz, Luis A; Kinzler, Kenneth W; Zhou, Shibin; Vogelstein, Bert

    2006-11-24

    Clostridium novyi-NT is an anaerobic bacterium that can infect hypoxic regions within experimental tumors. Because C. novyi-NT lyses red blood cells, we hypothesized that its membrane-disrupting properties could be exploited to enhance the release of liposome-encapsulated drugs within tumors. Here, we show that treatment of mice bearing large, established tumors with C. novyi-NT plus a single dose of liposomal doxorubicin often led to eradication of the tumors. The bacterial factor responsible for the enhanced drug release was identified as a previously unrecognized protein termed liposomase. This protein could potentially be incorporated into diverse experimental approaches for the specific delivery of chemotherapeutic agents to tumors.

  17. Selective Release of anti–TB Drugs Complex from Smart Copolymeric Bioactive nano–carriers

    Directory of Open Access Journals (Sweden)

    Alejandro Arredondo–Peñaranda

    2014-07-01

    Full Text Available Smart nano–copolymeric matrices have been employed to load and release anti tuberculosis (anti – TB drugs combinated complexes of Ethambutol (EMB, Isoniazid (INH, Rifampicin (RMP and Pyrazinamide (PZA. Copolymeric nanocarriers were synthesized using a microemulsion polymerization method previously reported. These nanocarriers can show selective swelling–collapse response under changes in local environments such a temperature, pH, solvent composition and electrical stimuli. The employ of these kinds of systems permits a controlled and selective delivery and release on specific human tissues. High Performance Liquid Chromatography technique was used to allow the detection of combinated mixtures of different active principles of anti–TB drugs using an acetonitrile mobile phase at 0.5 mL/min of flow rate whit a Spherisorb ODS2, C18 column. The results obtained suggest that the employ of smart nanohydrogels is a novel method in several tuberculosis therapies.

  18. Distribution of blood derivatives by registered blood establishments that qualify as health care entities; Prescription Drug Marketing Act of 1987; Prescription Drug Amendments of 1992; delay of applicability date. Final rule; delay of applicability date.

    Science.gov (United States)

    2006-11-13

    The Food and Drug Administration (FDA) is further delaying, until December 1, 2008, the applicability date of a certain requirement of a final rule published in the Federal Register of December 3, 1999 (64 FR 67720) (the final rule). The final rule implements the Prescription Drug Marketing Act of 1987 (PDMA), as modified by the Prescription Drug Amendments of 1992 (PDA), and the Food and Drug Administration Modernization Act of 1997 (the Modernization Act). The provisions of the final rule became effective on December 4, 2000, except for certain provisions whose effective or applicability dates were delayed in five subsequent Federal Register notices, until December 1, 2006. The provision with the delayed applicability date would prohibit wholesale distribution of blood derivatives by registered blood establishments that meet the definition of a "health care entity." In the Federal Register of February 1, 2006 (71 FR 5200), FDA published a proposed rule specific to the distribution of blood derivatives by registered blood establishments that qualify as health care entities (the proposed rule). The proposed rule would amend certain limited provisions of the final rule to allow certain registered blood establishments that qualify as health care entities to distribute blood derivatives. In response to the proposed rule, FDA received substantive comments. As explained in the SUPPLEMENTARY INFORMATION section of this document, further delaying the applicability of Sec. 203.3(q) (21 CFR 203.3(q)) to the wholesale distribution of blood derivatives by health care entities is necessary to give the agency additional time to address comments on the proposed rule, consider whether regulatory changes are appropriate, and, if so, to initiate such changes.

  19. Biomimetic synthesized chiral mesoporous silica: Structures and controlled release functions as drug carrier

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jing; Xu, Lu, E-mail: xl2013109@163.com; Yang, Baixue; Bao, Zhihong; Pan, Weisan; Li, Sanming, E-mail: li_sanming2013@163.com

    2015-10-01

    This work initially illustrated the formation mechanism of chiral mesoporous silica (CMS) in a brand new insight named biomimetic synthesis. Three kinds of biomimetic synthesized CMS (B-CMS, including B-CMS1, B-CMS2 and B-CMS3) were prepared using different pH or stirring rate condition, and their characteristics were tested with transmission electron microscope and small angle X-ray diffraction. The model drug indomethacin was loaded into B-CMS and drug loading content was measured using ultraviolet spectroscopy. The result suggested that pH condition influenced energetics of self-assembly process, mainly packing energetics of the surfactant, while stirring rate was the more dominant factor to determine particle length. In application, indomethacin loading content was measured to be 35.3%, 34.8% and 35.1% for indomethacin loaded B-CMS1, indomethacin loaded B-CMS2 and indomethacin loaded B-CMS3. After loading indomethacin into B-CMS carriers, surface area, pore volume and pore diameter of B-CMS carriers were reduced. B-CMS converted crystalline state of indomethacin to amorphous state, leading to the improved indomethacin dissolution. B-CMS1 controlled drug release without burst-release, while B-CMS2 and B-CMS3 released indomethacin faster than B-CMS1, demonstrating that the particle length, the ordered lever of multiple helixes, the curvature degree of helical channels and pore diameter greatly contributed to the release behavior of indomethacin loaded B-CMS. - Highlights: • Chiral mesoporous silica was synthesized using biomimetic method. • pH influenced energetics of self-assembly process of chiral mesoporous silica. • Stirring rate determined the particle length of chiral mesoporous silica. • Controlled release behaviors of chiral mesoporous silica varied based on structures.

  20. Study on drug release of and biological response to UHMWPE wear debris carrying estradiol

    Energy Technology Data Exchange (ETDEWEB)

    Qu Shuxin, E-mail: qushuxin@swjtu.edu.cn [Key Lab of Advanced Technologies of Materials, Ministry of Education, School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China); Liu Aiqin; Liu Xiaomin; Bai Yinlong; Weng Jie [Key Lab of Advanced Technologies of Materials, Ministry of Education, School of Material Science and Engineering, Southwest Jiaotong University, Chengdu 610031 (China)

    2012-12-01

    Highlights: Black-Right-Pointing-Pointer We prepared ultra-high molecular weight polyethylene (UHMWPE) loaded with 17{beta}-estradiol (E2) to treat osteolysis after artificial joint replacement. Black-Right-Pointing-Pointer We investigate the in vitro release of E2 and the cell biological response to UHMWPE-E2 wear debris. Black-Right-Pointing-Pointer The in vitro E2 release included three stages during the release process: initial burst release, celerity release and steady release. Black-Right-Pointing-Pointer The UHMWPE-E2 wear debris could promote the proliferation and ALP activity of osteoblasts and inhibit the expression of IL-6 of osteoblasts. Black-Right-Pointing-Pointer The E2 in UHMWPE-E2 would play a role in the treatment of the osteolysis after artificial hip joint replacement. - Abstract: The aim of this study is to investigate in vitro release of 17{beta}-estradiol (E2), the potential drug to treat osteolysis, and the biological response to ultra-high molecular weight polyethylene loaded with E2 (UHMWPE-E2) wear debris. The osteoblasts (MC3T3-E1) and macrophages (RAW264.7) were co-cultured with UHMWPE-E2 wear debris via inversion culture technique, respectively. MTT, ALP and ELISA assay were employed to evaluate the cell proliferation, ALP activity and the expression of interleukin-6 (IL-6). In vitro E2 release included: initial burst release, celerity release and steady release. The E2 released steadily after 40 d and lasted more than 60 d. The E2 in UHMWPE-E2 wear debris promoted the proliferation and ALP activity of MC3T3-E1 cells at the high debris dosages of 8-10 mg. In particular, the UHMWPE-E2 wear debris inhibited the expression of IL-6 of osteoblasts at all dosages in the present study. RAW264.7 cells cultured with UHMWPE-E2 and UHMWPE wear debris exhibited large sizes about 100 {mu}m in diameter. The small size wear debris presented inside of cells indicated that the wear debris activated the phagocytosis of macrophages. The results indicated

  1. Hydrophilic magnetic nanoclusters with thermo-responsive properties and their drug controlled release

    Energy Technology Data Exchange (ETDEWEB)

    Meerod, Siraprapa [Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Naresuan University, Phitsanulok 65000 (Thailand); Rutnakornpituk, Boonjira; Wichai, Uthai [Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Naresuan University, Phitsanulok 65000 (Thailand); Center of Excellence in Biomaterials, Faculty of Science, Naresuan University, Phitsanulok 65000 Thailand (Thailand); Rutnakornpituk, Metha, E-mail: methar@nu.ac.th [Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Naresuan University, Phitsanulok 65000 (Thailand); Center of Excellence in Biomaterials, Faculty of Science, Naresuan University, Phitsanulok 65000 Thailand (Thailand)

    2015-10-15

    Synthesis and drug controlled release properties of thermo-responsive magnetic nanoclusters grafted with poly(N-isopropylacrylamide) (poly(NIPAAm)) and poly(NIPAAm-co-poly(ethylene glycol) methyl ether methacrylate) (PEGMA) copolymers were described. These magnetic nanoclusters were synthesized via an in situ radical polymerization in the presence of acrylamide-grafted magnetic nanoparticles (MNPs). Poly(NIPAAm) provided thermo-responsive properties, while PEGMA played a role in good water dispersibility to the nanoclusters. The ratios of PEGMA to NIPAAm in the (co)polymerization in the presence of the MNPs were fine-tuned such that the nanoclusters with good water dispersibility, good magnetic sensitivity and thermo responsiveness were obtained. The size of the nanoclusters was in the range of 50–100 nm in diameter with about 100–200 particles/cluster. The nanoclusters were well dispersible in water at room temperature and can be suddenly agglomerated when temperature was increased beyond the lower critical solution temperature (LCST) (32 °C). The release behavior of an indomethacin model drug from the nanoclusters was also investigated. These novel magnetic nanoclusters with good dispersibility in water and reversible thermo-responsive properties might be good candidates for the targeting drug controlled release applications. - Highlights: • Nanoclusters with good water dispersibility and magnetic response were prepared. • They were grafted with thermo-responsive poly(NIPAAm) and/or poly(PEGMA). • Poly(NIPAAm) provided thermo-responsive properties to the nanoclusters. • Poly(PEGMA) provided good water dispersibilityto the nanoclusters. • Accelerated and controllable releases of a drug from the nanoclusters were shown.

  2. Smart multifunctional hollow microspheres for the quick release of drugs in intracellular lysosomal compartments.

    Science.gov (United States)

    Ke, Cherng-Jyh; Su, Tzu-Yuan; Chen, Hsin-Lung; Liu, Hao-Li; Chiang, Wei-Lun; Chu, Po-Chun; Xia, Younan; Sung, Hsing-Wen

    2011-08-22

    Prepared to self-destruct: when poly(D, L-lactic-co-glycolic acid) (PLGA) hollow microspheres containing NaHCO(3) entered the endocytic organelles of a live cell, the NaHCO(3) in the aqueous core reacted with protons that infiltrated from the compartment to generate CO(2) gas. The evolution of CO(2) bubbles led to the formation of small holes in the PLGA shell and thus rapid release of the encapsulated drug doxorubicin.

  3. Biodegradable hydrophobic-hydrophilic hybrid hydrogels: swelling behavior and controlled drug release.

    Science.gov (United States)

    Wu, Da-Qing; Chu, Chih-Chang

    2008-01-01

    The objective of this work was to investigate a new family of hydrophobic-hydrophilic biodegradable hybrid hydrogels as drug carriers. A series of hydrophobic-hydrophilic biodegradable hybrid hydrogels was formulated via photo means from hydrophobic three-arm poly (epsilon-caprolactone) maleic acid (PGCL-Ma) and hydrophilic dextran maleic acid (Dex-Ma) precursors over a wide range of the two precursors' feed ratio (PGCL-Ma/Dex-Ma at 100:0, 70:30, 50:50, 30:70 and 0:100). A low-molecular-weight and hydrophilic drug, the alpha-7 agonist cocaine methiodide, was used as the model drug for the release study from the hybrid hydrogels in pH 7.4 phosphate buffer solution at 37 degrees C. The swelling data of these hybrid hydrogels depended on the hydrophobic to hydrophilic precursors' feed ratio, and there were several-fold differences in swelling ratios between a pure hydrophilic Dex-Ma and a pure hydrophobic PGCL-Ma hydrogels. The presence of the hydrophobic PGCL-Ma component significantly reduced the initial burst swelling of the hybrid hydrogels. Depending on the two precursors' feed ratios, the swelling data during the early period obeyed either Fickian diffusion (for 50:50 PGCL-Ma/Dex-Ma hydrogel), non-Fickian or anomalous transport (for 70:30 and 100:0 PGCL-Ma/Dex-Ma), or relaxation-controlled (for 30:70 and 0:100 PGCL-Ma/Dex-Ma). A wide range of cocaine methiodide release profiles was achieved by controlling hydrophobic to hydrophilic precursors' feed ratios. Initial drug burst release was significantly reduced as the concentration of the hydrophobic PGCL-Ma component increased in the hybrid hydrogels. The bulk of cocaine methiodide released during the 160-h period was via diffusion-controlled mechanism, while degradation-controlled mechanism dominated thereafter.

  4. A new cyclopamine glucuronide prodrug with improved kinetics of drug release.

    Science.gov (United States)

    Renoux, Brigitte; Legigan, Thibaut; Bensalma, Souheyla; Chadéneau, Corinne; Muller, Jean-Marc; Papot, Sébastien

    2011-12-21

    We prepared a new glucuronide prodrug of cyclopamine designed to target selectively the Hedgehog signalling pathway of cancer cells. This prodrug includes a novel self-immolative linker bearing a hydrophilic side chain that can be easily introduced via"click chemistry". With this design, the prodrug exhibits reduced toxicity compared to the free drug on U87 glioblastoma cells. However, in the presence of β-glucuronidase, the prodrug conducts to the quick release of cyclopamine thereby restoring its antiproliferative activity.

  5. A statistical mechanical model for drug release: Investigations on size and porosity dependence

    Science.gov (United States)

    Gomes Filho, Márcio Sampaio; Oliveira, Fernando Albuquerque; Barbosa, Marco Aurélio Alves

    2016-10-01

    A lattice gas model is proposed for investigating the release of drug molecules in capsules covered with semi-permeable membranes. Release patterns in one and two dimensional systems are obtained with Monte Carlo simulations and adjusted to the semi-empirical Weibull distribution function. An analytical solution to the diffusion equation is used to complement and guide simulations in one dimension. Size and porosity dependence analysis was made on the two semi-empirical parameters of the Weibull function, which are related to characteristic time and release mechanism, and our results indicate that a simple scaling law occurs only for systems with almost impermeable membranes, represented in our model by capsules with a single leaking site.

  6. Simple measurements for prediction of drug release from polymer matrices - Solubility parameters and intrinsic viscosity

    DEFF Research Database (Denmark)

    Madsen, Claus G; Skov, Anders; Baldursdottir, Stefania;

    2015-01-01

    (dl-lactide-co-glycolide) (PLGA) were cast with bovine serum albumin (BSA) as a model drug using different solvents (acetone, dichloromethane, ethanol and water). The amount of released protein from the different matrices was correlated with the Hildebrand and Hansen solubility parameters of the solvents, and the intrinsic......PURPOSE: This study describes how protein release from polymer matrices correlate with simple measurements on the intrinsic viscosity of the polymer solutions used for casting the matrices and calculations of the solubility parameters of polymers and solvents used. METHOD: Matrices of poly...... from PLGA matrices varied depending on the solvent used for casting. The maximum amount of released BSA decreased with higher intrinsic viscosity, and increased with solubility parameter difference between the solvent and polymer used. The solvent used also had an effect on the matrix microstructure...

  7. Microstructured dextran hydrogels for burst-free sustained release of PEGylated protein drugs.

    Science.gov (United States)

    Bae, Ki Hyun; Lee, Fan; Xu, Keming; Keng, Choong Tat; Tan, Sue Yee; Tan, Yee Joo; Chen, Qingfeng; Kurisawa, Motoichi

    2015-09-01

    Hydrogels have gained significant attention as ideal delivery vehicles for protein drugs. However, the use of hydrogels for protein delivery has been restricted because their porous structures inevitably cause a premature leakage of encapsulated proteins. Here, we report a simple yet effective approach to regulate the protein release kinetics of hydrogels through the creation of microstructures, which serve as a reservoir, releasing their payloads in a controlled manner. Microstructured dextran hydrogels enable burst-free sustained release of PEGylated interferon over 3 months without compromising its bioactivity. These hydrogels substantially extend the circulation half-life of PEGylated interferon, allowing for less frequent dosing in a humanized mouse model of hepatitis C. The present approach opens up possibilities for the development of sustained protein delivery systems for a broad range of pharmaceutical and biomedical applications.

  8. A smart multifunctional nanocomposite for intracellular targeted drug delivery and self-release

    Energy Technology Data Exchange (ETDEWEB)

    Wang Chan; Tao Shengyang; Hu Tao; Yang Jingbang; Meng Changgong [School of Chemical Engineering, Dalian University of Technology, Dalian, Liaoning (China); Lv Piping; Wei Wei, E-mail: taosy@dlut.edu.cn [National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing (China)

    2011-10-14

    A multifunctional 'all-in-one' nanocomposite is fabricated using a colloid, template and surface-modification method. This material encompasses magnetic induced target delivery, cell uptake promotion and controlled drug release in one system. The nanocomposite is characterized by scanning electron microscopy, transmission electron microscopy, x-ray diffraction, N{sub 2} adsorption and vibrating sample magnetometry. The prepared material has a diameter of 350-400 nm, a high surface area of 420.29 m{sup 2} g{sup -1}, a pore size of 1.91 nm and a saturation magnetization of 32 emu g{sup -1}. Doxorubicin (DOX) is loaded in mesopores and acid-sensitive blockers are introduced onto the orifices of the mesopores by a Schiff base linker to implement pH-dependent self-release. Folate was also introduced to improve DOX targeted delivery and endocytosis. The linkers remained intact to block pores with ferrocene valves and inhibit the diffusion of DOX at neutral pH. However, in lysosomes of cancer cells, which have a weak acidic pH, hydrolysis of the Schiff base group removes the nanovalves and allows the trapped DOX to be released. These processes are demonstrated by UV-visible absorption spectra, confocal fluorescence microscopy images and methyl thiazolyl tetrazolium assays in vitro, which suggest that the smart nanocomposite successfully integrates targeted drug delivery with internal stimulus induced self-release and is a potentially useful material for nanobiomedicine.

  9. Enantioselectively controlled release of chiral drug (metoprolol) using chiral mesoporous silica materials

    Science.gov (United States)

    Guo, Zhen; Du, Yu; Liu, Xianbin; Ng, Siu-Choon; Chen, Yuan; Yang, Yanhui

    2010-04-01

    Chiral porous materials have attracted burgeoning attention on account of their potential applications in many areas, such as enantioseparation, chiral catalysis, chemical sensors and drug delivery. In this report, chiral mesoporous silica (CMS) materials with various pore sizes and structures were prepared using conventional achiral templates (other than chiral surfactant) and a chiral cobalt complex as co-template. The synthesized CMS materials were characterized by x-ray diffraction, nitrogen physisorption, scanning electron microscope and transmission electron microscope. These CMS materials, as carriers, were demonstrated to be able to control the enantioselective release of a representative chiral drug (metoprolol). The release kinetics, as modeled by the power law equation, suggested that the release profiles of metoprolol were remarkably dependent on the pore diameter and pore structure of CMS materials. More importantly, R- and S-enantiomers of metoprolol exhibited different release kinetics on CMS compared to the corresponding achiral mesoporous silica (ACMS), attributable to the existence of local chirality on the pore wall surface of CMS materials. The chirality of CMS materials on a molecular level was further substantiated by vibrational circular dichroism measurements.

  10. Enantioselectively controlled release of chiral drug (metoprolol) using chiral mesoporous silica materials

    Energy Technology Data Exchange (ETDEWEB)

    Guo Zhen; Liu Xianbin; Ng, Siu-Choon; Chen Yuan; Yang Yanhui [School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore 637459 (Singapore); Du Yu, E-mail: du_yu@jlu.edu.cn, E-mail: yhyang@ntu.edu.sg [College of Electronic Science and Engineering, Jilin University, Changchun 130012 (China)

    2010-04-23

    Chiral porous materials have attracted burgeoning attention on account of their potential applications in many areas, such as enantioseparation, chiral catalysis, chemical sensors and drug delivery. In this report, chiral mesoporous silica (CMS) materials with various pore sizes and structures were prepared using conventional achiral templates (other than chiral surfactant) and a chiral cobalt complex as co-template. The synthesized CMS materials were characterized by x-ray diffraction, nitrogen physisorption, scanning electron microscope and transmission electron microscope. These CMS materials, as carriers, were demonstrated to be able to control the enantioselective release of a representative chiral drug (metoprolol). The release kinetics, as modeled by the power law equation, suggested that the release profiles of metoprolol were remarkably dependent on the pore diameter and pore structure of CMS materials. More importantly, R- and S-enantiomers of metoprolol exhibited different release kinetics on CMS compared to the corresponding achiral mesoporous silica (ACMS), attributable to the existence of local chirality on the pore wall surface of CMS materials. The chirality of CMS materials on a molecular level was further substantiated by vibrational circular dichroism measurements.

  11. Release of small water-soluble drugs from multiblock copolymer microspheres: a feasibility study.

    Science.gov (United States)

    Sohier, J; van Dijkhuizen-Radersma, R; de Groot, K; Bezemer, J M

    2003-03-01

    Poly(ethylene glycol)-terephthalate/poly(butylene terephthalate) (PEGT/PBT) multiblock copolymer was investigated as a possible matrix for controlled delivery of small water-soluble drugs. Two molecules were selected as sustained release candidates from microspheres: leuprorelin acetate (peptide of Mw = 1270 D) and vitamin B(12) (Mw = 1355 D). First, vitamin B(12)-loaded microspheres were prepared using a double emulsion method and preparation parameters were varied (surfactant in the first emulsion and copolymer composition). The resulting microsphere structure, entrapment efficiency and release rate were eval