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Sample records for delayed release tablets

  1. 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.

  2. 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

  3. 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...

  4. 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.

  5. 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.

  6. 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.

  7. 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.

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

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    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.

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

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    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.

  10. 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.

  11. 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.

  12. Bioavailability of a dexlansoprazole delayed-release orally disintegrating tablet: effects of food and mode of administration

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    Kukulka M

    2017-02-01

    Full Text Available Michael Kukulka, Sai Nudurupati, Maria Claudia Perez Takeda Development Center Americas, Inc., Deerfield, IL, USA Background: Dexlansoprazole is a proton pump inhibitor (PPI approved for use in dual delayed-release capsule and orally disintegrating tablet (ODT formulations.Aim: To assess effects of food, water, and route of administration on the bioavailability of dexlansoprazole 30-mg ODT. Methods: Two separate open-label, phase 1, single-dose crossover studies were conducted in healthy adults. In study 1, pharmacokinetic parameters were analyzed in participants receiving dexlansoprazole ODT in a fed or fasted state with and without water. In study 2, the bioavailability of dexlansoprazole after administration via oral syringe or nasogastric (NG tube, or after swallowing intact with water was compared to ODT administration in the fasted state, swallowed without water. Blood samples for determining dexlansoprazole plasma concentrations and pharmacokinetic parameter estimates were collected before and after dosing. Results: Equivalent values for area under the plasma concentration–time curve (AUC were observed in the fed and fasted states, but the maximum observed plasma concentration (Cmax was 38% lower in the fed state; therefore, bioequivalence was not achieved. A water rinse following standard ODT administration decreased dexlansoprazole bioavailability, with lower Cmax and AUC values than when ODT was administered without a water rinse. Bioequivalence was demonstrated when comparing the alternative routes of administration, including via oral syringe or NG tube with standard ODT administration. Unlike with a water rinse, bioequivalence to standard ODT administration (i.e., without water was demonstrated when swallowing the ODT intact with water. Rates of adverse events were comparable irrespective of administration route in the fasted state (6.7%–9.3% and were 12% higher in the fed state than in the fasted state. Conclusion: The AUC

  13. Bioavailability of a dexlansoprazole delayed-release orally disintegrating tablet: effects of food and mode of administration

    Science.gov (United States)

    Kukulka, Michael; Nudurupati, Sai; Perez, Maria Claudia

    2017-01-01

    Background Dexlansoprazole is a proton pump inhibitor (PPI) approved for use in dual delayed-release capsule and orally disintegrating tablet (ODT) formulations. Aim To assess effects of food, water, and route of administration on the bioavailability of dexlansoprazole 30-mg ODT. Methods Two separate open-label, phase 1, single-dose crossover studies were conducted in healthy adults. In study 1, pharmacokinetic parameters were analyzed in participants receiving dexlansoprazole ODT in a fed or fasted state with and without water. In study 2, the bioavailability of dexlansoprazole after administration via oral syringe or nasogastric (NG) tube, or after swallowing intact with water was compared to ODT administration in the fasted state, swallowed without water. Blood samples for determining dexlansoprazole plasma concentrations and pharmacokinetic parameter estimates were collected before and after dosing. Results Equivalent values for area under the plasma concentration–time curve (AUC) were observed in the fed and fasted states, but the maximum observed plasma concentration (Cmax) was 38% lower in the fed state; therefore, bioequivalence was not achieved. A water rinse following standard ODT administration decreased dexlansoprazole bioavailability, with lower Cmax and AUC values than when ODT was administered without a water rinse. Bioequivalence was demonstrated when comparing the alternative routes of administration, including via oral syringe or NG tube with standard ODT administration. Unlike with a water rinse, bioequivalence to standard ODT administration (i.e., without water) was demonstrated when swallowing the ODT intact with water. Rates of adverse events were comparable irrespective of administration route in the fasted state (6.7%–9.3%) and were 12% higher in the fed state than in the fasted state. Conclusion The AUC from the dexlansoprazole ODT was equivalent when administered in the fed and fasted states. Equivalent systemic exposure to

  14. Multicentre study of posaconazole delayed-release tablet serum level and association with hepatotoxicity and QTc prolongation.

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    Pettit, Natasha N; Miceli, Marisa H; Rivera, Christina G; Narayanan, Prasanna P; Perissinotti, Anthony J; Hsu, Meier; Delacruz, Jennifer; Gedrimaite, Zivile; Han, Zhe; Steinbeck, Jennifer; Pisano, Jennifer; Seo, Susan K; Paskovaty, Alla

    2017-08-01

    The association of posaconazole serum concentrations and toxicity is unclear. An assessment of whether levels obtained with the delayed-release tablet (DRT) formulation are correlated with abnormal liver function test (LFT) results and/or QTc prolongation was undertaken. This was a multicentre, retrospective, observational study of adult patients with cancer between 26 November 2013 and 14 November 2014. Patients were included if they received posaconazole DRT with a posaconazole level obtained between days 5 and 14. Clinical data, including demographics, hepatotoxic medications, posaconazole levels, LFTs and QTc intervals, were obtained. Association of factors with changes in LFTs and QTc prolongation was assessed using linear and logistic regression. One hundred and sixty-six study patients were included. The median posaconazole level was 1250 (range 110-4220) ng/mL and the median time until level was 6 (range 5-14) days. There was a statistically significant increase in AST ( P  <   0.001), ALT ( P  <   0.001), alkaline phosphatase (ALK) ( P  <   0.001), total bilirubin (TBILI) ( P  <   0.001) and QTc ( P  =   0.05) from baseline. Posaconazole levels were not associated with increases in AST [β (SE) = -0.33 (2.2), P  =   0.88], log ALT [β (SE) = -0.02 (0.03), P  =   0.63], ALK [β (SE) = 2.2 (2.9), P  =   0.46] and TBILI [β (SE) = -0.01 (0.04), P  =   0.88]. For each additional hepatotoxic medication, there was a mean change in TBILI of 0.13 mg/dL ( P  =   0.02) and ALK of 7.1 U/L ( P  =   0.09). No statistically significant association between posaconazole level and QTc interval prolongation was found. We did not identify an association between posaconazole serum concentrations and LFT elevations or QTc prolongation. However, some LFTs were found to increase with more hepatotoxic medications administered.

  15. Effect of advanced blood pressure control with nifedipine delayed-release tablets on the blood pressure in patients underwent nasal endoscope surgery

    Institute of Scientific and Technical Information of China (English)

    Qing-Hua Xiao; Li Yang; Rong-Ping Chen; Wei-Dong Qiu

    2016-01-01

    Objective:To explore the effect of advanced blood pressure control with nifedipine delayed-release tablets on the blood pressure in patients underwent nasal endoscope surgery and its feasibility.Methods:A total of 80 patients who were admitted in ENT department from June, 2012 to June, 2015 for nasal endoscope surgery were included in the study and randomized into the observation group and the control group with 40 cases in each group. The patients in the observation group were given nifedipine delayed-release tablets for advanced blood pressure control before operation, and were given routine blood pressure control during operation; while the patients in the control group were only given blood pressure control during operation. The changes of blood pressure, mean central arterial pressure, and heart rate before anesthesia (T0), after intubation (T1), during operation (T2), extubation when waking (T3), 30 min after extubation (T4), and 3 h after back to wards (T5) in the two groups were compared. The intraoperative situation and the surgical field quality in the two groups were compared.Results: SBP, DBP, and MAP levels at T1-5 in the two groups were significantly lower than those at T0. SBP, DBP, and MAP levels at T2 were significantly lower than those at other timing points, and were gradually recovered after operation, but were significantly lower than those at T0. The effect taking time of blood pressure reducing, intraoperative nitroglycerin dosage, and postoperative wound surface exudation amount in the observation group were significantly less than those in the control group. The surgical field quality scores in the observation group were significantly superior to those in the control group.Conclusions:Advanced blood pressure control with nifedipine delayed-release tablets can stabilize the blood pressure during the perioperative period in patients underwent nasal endoscope surgery, and enhance the surgical field qualities.

  16. Fast dispersible/slow releasing ibuprofen tablets.

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    Fini, Adamo; Bergamante, Valentina; Ceschel, Gian Carlo; Ronchi, Celestino; de Moraes, Carlos Alberto Fonseca

    2008-05-01

    Eight formulations were developed containing ibuprofen in the form of orally disintegrating tablets. To prevent bitter taste and side effects of the drug, the drug was associated with Phospholipon 80H, a saturated lecithin, by wet granulation. The granules were then coated using different film forming agents (Kollicoat SR 30, Amprac 01, Kollidon 90F, Eudragit RD 100) obtaining four lots 1-4. Coated granules were then formulated with a sweetener (Aspartame), a mannitol-based diluent (Pearlitol SD 200) and Kollidon CL (1-4K) or Explotab (1-4E) were added as superdisintegrants and compacted under low compression force. The eight lots of tablets, 1-4K and 1-4E, were assessed if suitable as oral disintegrating tablets by determination of a range of technological parameters. Wetting and disintegregation time matched with the requirements of EP IV Ed., for almost all these formulations. Dissolution profiles suggested that the combined action of the hydrophobic lecithin and the coating delay the release of the drug from tablets with respect to when it is free or in the form of simple granules. By an appropriate combination of excipients it was thus possible to obtain orally disintegrating tablets and a delayed release of ibuprofen using simple and conventional techniques.

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

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    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.

  18. Suppressed Release of Clarithromycin from Tablets by Crystalline Phase Transition of Metastable Polymorph Form I.

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    Fujiki, Sadahiro; Watanabe, Narumi; Iwao, Yasunori; Noguchi, Shuji; Mizoguchi, Midori; Iwamura, Takeru; Itai, Shigeru

    2015-08-01

    The pharmaceutical properties of clarithromycin (CAM) tablets containing the metastable form I of crystalline CAM were investigated. Although the dissolution rate of form I was higher than that of stable form II, the release of CAM from form I tablet was delayed. Disintegration test and liquid penetration test showed that the disintegration of the tablet delayed because of the slow penetration of an external solution into form I tablet. Investigation by scanning electron microscopy revealed that the surface of form I tablet was covered with fine needle-shaped crystals following an exposure to the external solution. These crystals were identified as form IV crystals by powder X-ray diffraction. The phenomenon that CAM releases from tablet was inhibited by fine crystals spontaneously formed on the tablet surface could be applied to the design of sustained-release formulation systems with high CAM contents by minimizing the amount of functional excipients. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  19. 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%).

  20. Hydroxypropyl methylcellulose based cephalexin extended release tablets: influence of tablet formulation, hardness and storage on in vitro release kinetics.

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    Saravanan, Muniyandy; Sri Nataraj, Kalakonda; Ganesh, Kettavarampalayam Swaminath

    2003-08-01

    The object of this study was to develop hydroxypropyl methylcellulose (HPMC) based cephalexin extended release tablet, which can release the drug for six hours in predetermined rate. Twenty-one batches of cephalexin tablets were prepared by changing various physical and chemical parameters, in order to get required theoretical release profile. The influences of HPMC, microcrystalline cellulose powder (MCCP), granulation technique, wetting agent and tablet hardness on cephalexin release from HPMC based extended release tablets were studied. The formulated tablets were also characterized by physical and chemical parameters. The dissolution results showed that a higher amount of HPMC in tablet composition resulted in reduced drug release. Addition of MCCP resulted in faster drug release. Tablets prepared by dry granulation was released the drug slowly than the same prepared with a wet granulation technique. Addition of wetting agent in the tablets prepared with dry granulation technique showed slower release. An increase in tablet hardness resulted in faster drug release. Tablets prepared with a wet granulation technique and having a composition of 9.3% w/w HPMC with a hardness of 10-12 kg/cm(2) gave predicted release for 6 h. The in vitro release data was well fit in to Higuchi and Korsmeyer-Peppas model. Physical and chemical parameters of all formulated tablets were within acceptable limits. One batch among formulated twenty-one batches was successful and showed required theoretical release. The effect of storage on in vitro release and physicochemical parameters of successful batch was studied and was found to be in acceptable limits.

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

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    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.

  2. Preparation and evaluation of controlled release tablets of carvedilol

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    Varahala Setti M

    2009-01-01

    Full Text Available The objective of the present investigation is to design and evaluate controlled release tablets of carvedilol, employing synthetic polymers like polyethylene oxides, of different molecular weights as release retarding materials and to select the optimized formulation based on the pharmacokinetics of carvedilol. Matrix tablets each containing 80 mg of carvedilol were formulated employing PEO N60 K, PEO 301, and PEO 303 as release-retarding polymers and β Cyclodextrin and HP β cyclodextrin as release modulators from the matrix. Carvedilol release from the formulated tablets was very slow. Hence the release was modulated with the use of cyclodextrins. The dissolution from the matrix tablets was spread over more than 24 hours and depended on the type of polymer, its concentration and the type of cyclodextrin used. All the matrix tablets prepared using polyethylene oxides showed very good controlled release over more than 24 hours. The matrix tablets prepared using HP β cyclodextrin showed a higher dissolution rate and gave a dissolution profile that was comparable to the theoretical sustained release needed for once-a-day administration of carvedilol. The drug release mechanism from the matrix tablets was found to be quasi Fickian mechanism.

  3. Validation and Application of a New Reversed Phase HPLC Method for In Vitro Dissolution Studies of Rabeprazole Sodium in Delayed-Release Tablets

    Directory of Open Access Journals (Sweden)

    Md. Saddam Nawaz

    2013-01-01

    Full Text Available The purpose of this study was to develop and validate a new reversed phase high performance liquid chromatographic (RP-HPLC method to quantify in vitro dissolution assay of rabeprazole sodium in pharmaceutical tablet dosage form. Method development was performed on C 18, 100×4.6 mm ID, and 10 μm particle size column, and injection volume was 20 μL using a diode array detector (DAD to monitor the detection at 280 nm. The mobile phase consisted of buffer: acetonitrile at a ratio of 60 : 40 (v/v, and the flow rate was maintained at 1.0 mL/min. The method was validated in terms of suitability, linearity, specificity, accuracy, precision, stability, and sensitivity. Linearity was observed over the range of concentration 0.05–12.0 μg/mL, and the correlation coefficient was found excellent >0.999. The method was specific with respect to rabeprazole sodium, and the peak purity was found 99.99%. The method was precise and had relative standard deviations (RSD less than 2%. Accuracy was found in the range of 99.9 to 101.9%. The method was robust in different variable conditions and reproducible. This proposed fast, reliable, cost-effective method can be used as quality control tool for the estimation of rabeprazole sodium in routine dissolution test analysis.

  4. Formulation and Evaluation Of Sustained Release Matrix Tablets of Lornoxicam

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    Syed Namath Ulla

    2011-03-01

    Full Text Available Lornoxicam, a potent non-steroidal anti-inflammatory drug which has short half life, makes the development of sustained release (SR forms extremely advantageous. However, due to its weak acidic nature, its release from SR delivery systems is limited to the lower gastrointestinal tract which consequently leads to a delayed onset of its analgesic action. Therefore, the present investigation of this study was to develop Lornoxicam SR matrix tablets that provide complete drug release that starts in the stomach to rapidly alleviate the painful symptoms and continues in the intestine to maintain analgesic effect. Lornoxicam showed maximum absorption at wavelength 373 nm in 0.1N HCl and 379 nm in pH 6.8. Drug-polymer compatibility studies by FTIR gave confirmation about their purity and showed no interaction between drug and selected polymers. Various formulations were developed by using release rate controlling and gel forming polymers like HPMC (K4M, K15M, K100M by direct compression method. From among all the developed formulations, F1 formulation sustained the drug release for longer period of time as compared to other formulations. So, F1 was selected as the best formulation. It was concluded that the release followed zero order kinetics, as the correlation coefficient (R2 value was higher for zero order release, so the drug release mechanism is controlled release. The best formulation was found to be stable during stability studies for two months. Thus, best formulation satisfied physicochemical parameters and in vitro drug release profile requirements for a sustained drug delivery system.

  5. Effect of ethanol on the release of morphine sulfate from Oramorph SR tablets.

    Science.gov (United States)

    Barkin, Robert L; Shirazi, Dean; Kinzler, Eric

    2009-01-01

    Recent data have shown that rapid release of active drug (i.e., dose-dumping) can occur when modified-release formulations of pain medications, and other extended-release pharmacotherapies, are exposed to ethanol in vitro. Dose-dumping of sustained-release opioids is of particular concern because of the risk for serious and potentially fatal adverse events. Sustained-release morphine sulfate tablets (Oramorph SR, 15, 30, 60, and 100 mg; Xanodyne Pharmaceuticals, Inc., Newport, KY) were incubated in vitro at simulated physiologic conditions in media containing no ethanol or ethanol in concentrations ranging from 4%-40% v/v. Morphine sulfate release was measured over the course of 1 to 24 hours using a high-performance liquid chromatography method (United States Pharmacopeia). The sustained-release morphine sulfate tablets exhibited no evidence of active drug dose-dumping. Regardless of ethanol concentration, ethanol exposure did not increase the rate of release of morphine sulfate. Release of approximately 20%-25% of the morphine sulfate dose within 1 hour was consistent among the morphine doses tested and ethanol concentrations. Release of morphine sulfate from the 60- and 100-mg tablets exposed to the higher ethanol concentrations (20% and 40% ethanol) was slightly delayed at all time points beyond 1 hour. The results of this in vitro study suggest that ethanol concentrations as high as 40% do not substantially alter the sustained-release properties of the morphine sulfate tablets.

  6. Tablet splitting: Product quality assessment of metoprolol succinate extended release tablets.

    Science.gov (United States)

    Zhao, Na; Zidan, Ahmed; Tawakkul, Mobin; Sayeed, Vilayat A; Khan, Mansoor

    2010-11-30

    Metoprolol succinate extended release tablets comprise a multiple unit system containing metoprolol succinate in a multitude of controlled release pellets. Each pellet acts as a separate drug delivery unit and is designed to deliver metoprolol continuously over the dosage interval. Despite the flexibility that controlled release pellets may offer, segregation is one of the challenges that commonly occur during tableting for such drug delivery system. Since all commercial metoprolol succinate extended release tablets are scored, they are deemed suitable for splitting. The present study was aimed at utilizing an innovative technology to determine the dose uniformity for split tablets. Four marketed drug products consisting of innovator and generics were evaluated for effect of splitting on weight, assay and content uniformity. Novel analytical tool such as near infrared (NIR) chemical imaging was used to visualize the distribution of metoprolol succinate and functional excipients on the surfaces of the marketed tablets. The non-homogeneous distribution of directly compressed metoprolol succinate beads on the surface of the tablets as well as the split intersection explained the large variation in the split tablets' weight and content uniformity results. The obtained results indicated the usefulness of NIR chemical imaging to determine the need for content uniformity studies for certain split tablets.

  7. Release kinetics of highly porous floating tablets containing cilostazol.

    Science.gov (United States)

    Hwang, Kyu-Mok; Cho, Cheol-Hee; Tung, Nguyen-Thach; Kim, Ju-Young; Rhee, Yun-Seok; Park, Eun-Seok

    2017-02-20

    This study focuses on developing a highly porous floating tablet containing cilostazol. The underlying release mechanism of cilostazol from porous and floating tablets in dissolution media containing surfactants was investigated. The tablets were prepared by compressing granules and excipients with a sublimating agent, followed by sublimation under vacuum. The volatile material for the sublimating agent was chosen based on its flow properties using conventional methods as well as the twisted blade method. Resultant tablets could float immediately and had significantly higher tensile strengths than conventional tablets of similar porosities, holding a promising potential for increasing gastroretentive properties. Fitting the release profiles to the Korsmeyer-Peppas equation indicated Super Case II, Case II and non-Fickian kinetics, which implied that the release was affected by both floating behavior and matrix erosion. Abrupt changes in release kinetic parameters and erosional behaviors were found between the tablets containing different amounts of HPMC, indicating the existence of an excipient percolation threshold. Neither the surfactant in the media nor the porosity affected the dominant release mechanism, which was matrix erosion. Understanding the dominant release mechanism and percolation threshold allows for tuning the formulation to obtain various release profiles.

  8. Formulation and Dissolution Study of Valsartan Immediate Release Tablets

    Directory of Open Access Journals (Sweden)

    B. Brahmaiah*, K. Sasikanth, Sreekanth Nama , P.Suresh, Patan Adam Khan

    2013-06-01

    Full Text Available In the present study, design of oral immediate release tablets of Valsartan by direct compression techniquewas carried out. The main aim and objective of the work is to formulate immediate release tablets usingdifferent direct compression vehicles (DCV’S in different ratios. The main motive is to compare thedissolution profile of these formulations and conclude the best formulation which release drug at a fasterrate. To determine the best fit dissolution profile for the dosage forms. Valsartan tablets were formulated byusing microcrystalline cellulose (diluents, potato starch, acacia (binder and magnesium stearate(lubricant. The granules were compressed into tablets and were subjected to dissolution studies. Thedissolution profile of the formulation F2 was found to have better dissolution rate compared to others. TheIn-vitro dissolution studies of all the formulations were conducted and the results were obtained, it wasconcluded that formulation F2 was the best with fast release of drug compared to others.

  9. FORMULATION DEVELOPMENT OF ISOXSUPRINE HYDROCHLORIDE MODIFIED RELEASE MATRIX TABLETS

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    Ketan Patel

    2012-01-01

    Full Text Available The objective of the present investigation was to study the effect of critical formulation parameters affecting release of isoxsuprine hydrochloride from matrix tablets using combination of polyethylene oxide (PEO and dicalcium phosphate (DCP. The powder blend consisting of drug and excipients was analyzed for angle of repose, Carr’s index and Hausner’s ratio. The tablets were prepared by direct compression method. To assess the compressional behavior of the drug-excipient blend, the tablets were analyzed for friability and crushing strength. The in vitro drug release study was carried out in distilled water. The powder blend exhibited satisfactorily flow as measured by angle of repose, Carr’s index and Hausner’s ratio. The formulation ingredients showed satisfactory tableting properties (friability <1%, crushing strength ≥ 4 kgf. The drug release was modified on addition of PEO and DCP. Addition of 5 to 25% DCP in the formulation of matrix tablets caused apparent difference in the drug dissolution in distilled water. However, the difference was insignificant as analyzed by analysis of variance (ANOVA and similarity factor ( f2. The drug release from the tablets was best explained by Weibull model. Unified Weibull model was evolved to predict drug release from the formulated batches. The findings of this investigation can be extended to industry to cut down the cost of formulation and to by-pass the existing patents employing hydrophilic matrixing agents, at least for selective drugs.

  10. Desktop 3D printing of controlled release pharmaceutical bilayer tablets.

    Science.gov (United States)

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

    2014-01-30

    Three dimensional (3D) printing was used as a novel medicine formulation technique for production of viable tablets capable of satisfying regulatory tests and matching the release of standard commercial tablets. Hydroxypropyl methylcellulose (HPMC 2208) (Methocel™ K100M Premium) and poly(acrylic acid) (PAA) (Carbopol(®) 974P NF) were used as a hydrophilic matrix for a sustained release (SR) layer. Hypromellose(®) (HPMC 2910) was used as a binder while microcrystalline cellulose (MCC) (Pharmacel(®) 102) and sodium starch glycolate (SSG) (Primojel(®)) were used as disintegrants for an immediate release (IR) layer. Commercial guaifenesin bi-layer tablets (GBT) were used as a model drug (Mucinex(®)) for this study. There was a favourable comparison of release of the active guaifenesin from the printed hydrophilic matrix compared with the commercially available GBT. The printed formulations were also evaluated for physical and mechanical properties such as weight variation, friability, hardness and thickness as a comparison to the commercial tablet and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). All formulations (standard tablets and 3D printed tablets) showed Korsmeyer-Peppas n values between 0.27 and 0.44 which indicates Fickian diffusion drug release through a hydrated HPMC gel layer. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. 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.

  12. Pharmacokinetics of modified-release prednisone tablets in healthy subjects and patients with rheumatoid arthritis.

    Science.gov (United States)

    Derendorf, Hartmut; Ruebsamen, Klaus; Clarke, Lynsey; Schaeffler, Achim; Kirwan, John R

    2013-03-01

    In rheumatoid arthritis (RA), nocturnal release of proinflammatory cytokines is not adequately counteracted by endogenous glucocorticoid and is associated with symptoms of morning stiffness and pain. Taking exogenous glucocorticoid during the night reduces morning stiffness significantly more than treatment at the conventional time in the morning, although waking to take tablets is unacceptable for patients. Modified-release prednisone tablets were developed to allow administration at bedtime for programmed delivery of glucocorticoid during the night. Single-center crossover studies were conducted, each in ≤24 healthy subjects, to compare the pharmacokinetics of a single 5-mg oral dose of modified-release prednisone and conventional prednisone, as well as the effect of food on bioavailability. There was no substantial difference in pharmacokinetic parameters of the formulations apart from the programmed delay in release of glucocorticoid from the modified-release tablets (C(max) 97%, AUC(0-∞) 101%, 90% confidence intervals within the requisite range for bioequivalence). Administration after a full or light meal did not affect pharmacokinetic characteristics, but bioavailability was reduced under fasted conditions. Pharmacokinetic evaluation in 9 patients with RA confirmed that modified-release prednisone tablets taken at bedtime (around 22:00 h) with or after an evening meal result in programmed release of glucocorticoid 4 to 6 hours after intake.

  13. KINETICS STUDY ON KETOPROFEN RELEASE FROM MINI TABLETS AND MULTI-COMPARTMENT SYSTEMS.

    Science.gov (United States)

    Stawarski, Tomasz; Sieradzki, Edmund; Gałecka, Emilia; Binek, Karolina

    2016-01-01

    Thanks to multi-compartment systems it is possible to modify drug release. Two types of mini tablets containing 12.5 mg of ketoprofen were made: mini tablets of immediate (IR) and sustained (SR) release. Some of the tablets of immediate release were coated with an enteric coating, thereby obtaining a delayed release effect (IRc). For each tablet type, release profiles were tested in three media: 0.1 M HCl, phosphate buffer pH 4.5 and phosphate buffer pH 6.8. Based on the obtained results, three appropriate multi-compartment models have been constructed and tested. The factor limiting the amount of available ketoprofen at the absorption place is pH of the environment. It was observed that the increase in pH caused the increase of ketoprofen solubility. Constructed multi-compartment systems allowed to change the composition and the dose of medicinal substances easily. Thanks to this it is possible to adjust the release profile of the active substance to the individual patient, which meets the expectations of personalized medicine.

  14. Modulation of venlafaxine hydrochloride release from press coated matrix tablet

    Directory of Open Access Journals (Sweden)

    Gohel M

    2008-01-01

    Full Text Available The aim of present study was to prepare novel modified release press coated tablets of venlafaxine hydrochloride. Hydroxypropylmethylcellulose K4M and hydroxypropylmethylcellulose K100M were used as release modifier in core and coat, respectively. A 3 2 full factorial design was adopted in the optimization study. The drug to polymer ratio in core and coat were chosen as independent variables. The drug release in the first hour and drug release rate between 1 and 12 h were chosen as dependent variables. The tablets were characterized for dimension analysis, crushing strength, friability and in vitro drug release. A check point batch, containing 1:2.6 and 1:5.4 drug to polymer in core and coat respectively, was prepared. The tablets of check point batch were subjected to in vitro drug release in dissolution media with pH 5, 7.2 and distilled water. The kinetics of drug release was best explained by Korsmeyer and Peppas model (anomalous non-Fickian diffusion. The systematic formulation approach enabled us to develop modified release venlafaxine hydrochloride tablets.

  15. Modulation of venlafaxine hydrochloride release from press coated matrix tablet.

    Science.gov (United States)

    Gohel, M C; Soni, C D; Nagori, S A; Sarvaiya, K G

    2008-01-01

    The aim of present study was to prepare novel modified release press coated tablets of venlafaxine hydrochloride. Hydroxypropylmethylcellulose K4M and hydroxypropylmethylcellulose K100M were used as release modifier in core and coat, respectively. A 3(2) full factorial design was adopted in the optimization study. The drug to polymer ratio in core and coat were chosen as independent variables. The drug release in the first hour and drug release rate between 1 and 12 h were chosen as dependent variables. The tablets were characterized for dimension analysis, crushing strength, friability and in vitro drug release. A check point batch, containing 1:2.6 and 1:5.4 drug to polymer in core and coat respectively, was prepared. The tablets of check point batch were subjected to in vitro drug release in dissolution media with pH 5, 7.2 and distilled water. The kinetics of drug release was best explained by Korsmeyer and Peppas model (anomalous non-Fickian diffusion). The systematic formulation approach enabled us to develop modified release venlafaxine hydrochloride tablets.

  16. Effect of different polymers on release of ranolazine from extended release tablets

    OpenAIRE

    Murthy, T. E. G. K.; Bhukya Swapna

    2013-01-01

    An extended release tablet provides prolonged release of drug, maintains the desired concentration of drug in plasma and thereby reduce dosing frequency, improve patient compliance and reduce the dose-related side-effects. Ranolazine is indicated for the chronic treatment of angina in patients who have not achieved an adequate response with other anti-anginal agent. The present investigation was undertaken to design the extended release tablets of ranolazine employing different polymers as ma...

  17. Design and evaluation of nicorandil extended-release tablet

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    Ju-Young Kim

    2015-04-01

    Full Text Available The aim of this study was to design and evaluate extended-release formulations of a model drug, nicorandil, in order to achieve the desired steady-state plasma concentration of drug in vivo. Simulation was employed to estimate optimum dissolution and absorption rate of nicorandil. The dissolution test was employed using pH 1.2, 4.0, 6.8 buffer solution, or water, to measure the in vitro release behaviors of nicorandil formulations. A single dose (15 mg of each formulation was orally administered to four beagle dogs under fasted conditions, and the pharmacokinetic parameters were calculated. The in vitro/in vivo relationship of the extended-release formulation was confirmed using in vitro dissolution profiles and plasma concentrations of drug in beagle dogs. Nicorandil was released completely within 30 min from the immediate-release tablets and released for 24 h from the extended-release tablets. The nicorandil plasma concentration could be modified by adjusting the drug release rate from the extended-release formulation. The release rate of nicorandil was the rate-limiting step in the overall absorption of drug from the extended-release formulations. These results highlight the potential of a nicorandil extended-release formulation in the treatment of angina pectoris.

  18. FORMULATION AND DISSOLUTION STUDY OF DILTIAZEM HYDROCHLORIDE IMMEDIATE RELEASE TABLETS

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    BRAHMAIAH BONTHAGARALA

    2014-08-01

    Full Text Available Objective: The main aim and objective of the work is to formulate immediate release tablets using different direct compression vehicles (DCV’S in different ratios. Methods: In the present study, design of oral immediate release tablets of Diltiazem hydrochloride by direct compression technique was carried out. Results: The main motive is to compare the dissolution profile of these formulations and conclude the best formulation which release drug at a faster rate . To determine the best fit dissolution profile for the dosage forms. Diltiazem hydrochloride tablets were formulated by using microcrystalline cellulose (diluent, potato starch, acacia (binder and magnesium stearate (lubricant. The granules were compressed into tablets and were subjected to dissolution studies. The dissolution profile of the formulation F2 was found to have better dissolution rate compared to others. Conclusion: The Invitro dissolution studies of all the formulations were conducted and the results were obtained, it was concluded that formulation F2 was the best with fast release of drug compared to others.

  19. Formulation of Sustained-Release Matrix Tablets Using Cross ...

    African Journals Online (AJOL)

    Erah

    JSS College of Pharmacy, JSS University, Mysore, Karnataka-570015, India. Abstract. Purpose: To develop sustained release matrix tablets of diltiazem hydrochloride (DTZ) using ... channel blocker that is widely prescribed for ..... appearance of new peaks which were absent ... penetration of dissolution media into the.

  20. Effect of hydroxypropyl methylcellulose and hydrogenated castor oil on naproxen release from sustained-release tablets.

    Science.gov (United States)

    Amaral, M H; Lobo, J M; Ferreira, D C

    2001-04-09

    The effect of the concentration of hydrophilic (hydroxypropyl methylcellulose [HPMC]) and hydrophobic (hydrogenated castor oil [HCO]) products, fillers (lactose and dibasic calcium phosphate), and buffers (sodium bicarbonate, calcium carbonate, and sodium citrate) on naproxen release rate was studied. Matrix tablets were prepared by double compression, and in vitro dissolution tests were performed. The dissolution results showed that an increased amount of HPMC or hydrogenated castor oil resulted in reduced drug release. The inclusion of buffers in the HPMC matrix tablets enhanced naproxen release. For HCO tablets, only sodium bicarbonate enhanced naproxen release. The presence of lactose on HPMC matrix tablets did not show a significantly different result from that obtained with the formulation containing dibasic calcium phosphate as a filler. However, for the tablets containing HCO, the presence of lactose significantly enhanced the naproxen release rate. The matrix-forming materials in this study were suitable for use in sustained-release tablets containing naproxen. The drug release can be modulated by adding suitable amounts of diluents and buffers.

  1. 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.

  2. DEVELOPMENT OF SUSTAINED RELEASE TABLETS CONTAINING SOLID DISPERSIONS OF BACLOFEN

    Directory of Open Access Journals (Sweden)

    K. H. Janardhana

    2013-12-01

    Full Text Available Sustained release tablets containing solid dispersions granules of a poorly water soluble drug were prepared to investigate the controlled release of the drug. Baclofen was chosen because of its poor water solubility and short elimination half-life. Poloxamer 188 and PEG 6000 were used as solid dispersion carrier. Free flowing solid dispersion granules were prepared by adsorbing the melt of the drug and carriers onto the surface of an adsorbent, Carbopol 934P followed by direct compression with HPMC K4M and HPMC K100 to obtain an solid dispersion loaded sustained release tablets. FTIR studies confirmed that the compatibility of drug and carriers. Differential scanning calorimetry (DSC and X-ray diffraction (XRD revealed partially amorphous structures of the drug in solid dispersion granules. The solid dispersion granules dissolved completely within 30 min, which was much faster than that of pure drug baclofen. The sustained release of baclofen from the solid dispersion containing tablet was achieved for 2 h in gastric fluid (pH 1.2 and for up to 10 h in intestinal fluid (pH 6.8. A combination of solid dispersion techniques using adsorption and sustained release concepts is a promising approach to control the release rate of poorly water-soluble drugs.

  3. DEVELOPMENT OF SUSTAINED RELEASE TABLETS CONTAINING SOLID DISPERSIONS OF BACLOFEN

    Directory of Open Access Journals (Sweden)

    K. H. Janardhana

    2015-07-01

    Full Text Available Sustained release tablets containing solid dispersions granules of a poorly water soluble drug were prepared to investigate the controlled release of the drug. Baclofen was chosen because of its poor water solubility and short elimination half-life. Poloxamer 188 and PEG 6000 were used as solid dispersion carrier. Free flowing solid dispersion granules were prepared by adsorbing the melt of the drug and carriers onto the surface of an adsorbent, Carbopol 934P followed by direct compression with HPMC K4M and HPMC K100 to obtain an solid dispersion loaded sustained release tablets. FTIR studies confirmed that the compatibility of drug and carriers. Differential scanning calorimetry (DSC and X-ray diffraction (XRD revealed partially amorphous structures of the drug in solid dispersion granules. The solid dispersion granules dissolved completely within 30 min, which was much faster than that of pure drug baclofen. The sustained release of baclofen from the solid dispersion containing tablet was achieved for 2 h in gastric fluid (pH 1.2 and for up to 10 h in intestinal fluid (pH 6.8. A combination of solid dispersion techniques using adsorption and sustained release concepts is a promising approach to control the release rate of poorly water-soluble drugs.

  4. Formulation and Evaluation of Darifenacin Hydrobromide Extended Release Matrix Tablets

    Directory of Open Access Journals (Sweden)

    Syed Meraj Sultana

    2016-08-01

    Full Text Available Darifenacin hydrobromide is a highly selective muscarinic (M3 receptor blocker that has been widely used for the treatment of overactive bladder syndrome. The bioavailability of darifenacin hydrobromide is 15–19% due to extensive first pass metabolism. Hence oral administration of darifenacin hydrobromide as extended tablets is a possible solution to overcome this problem. So the aim of the study was to formulate and evaluate Darifenacin hydrobromide extended release matrix tablets using extended release polymers like HPMC K4M, HPMC K15M and HPMC K100M, Metalose 60 SH-50 and Xanthum gum in different concentrations. Formulated tablets were characterized for different parameters like hardness, thickness, weight variation, friability, % Cumulative drug release etc. Nine formulations (F1 – F9 were formulated using direct compression technique. From the results obtained, it was concluded that the optimized formulation containing HPMC K15 M and K100M (1:2 showed better release up to 24hrs.The dissolution profiles and kinetic studies indicate that the release of Darifenacin Hydrobromide can be effectively controlled by the use of hydrophilic matrix systems. Different kinetic models were applied to the optimized formulation and observed that formulation (F9 followed first order kinetic model and Non-Fickian diffusion (or Anomalous transport as mechanism of drug release.

  5. Gastroretentive Pulsatile Release Tablets of Lercanidipine HCl: Development, Statistical Optimization, and In Vitro and In Vivo Evaluation

    Directory of Open Access Journals (Sweden)

    Gagganapalli Santhoshi Reddy

    2014-01-01

    Full Text Available The present study was aimed at the development of gastroretentive floating pulsatile release tablets (FPRTs of lercanidipine HCl to enhance the bioavailability and treat early morning surge in blood pressure. Immediate release core tablets containing lercanidipine HCl were prepared and optimized core tablets were compression-coated using buoyant layer containing polyethylene oxide (PEO WSR coagulant, sodium bicarbonate, and directly compressible lactose. FPRTs were evaluated for various in vitro physicochemical parameters, drug-excipient compatibility, buoyancy, swelling, and release studies. The optimized FPRTs were tested in vivo in New Zealand white rabbits for buoyancy and pharmacokinetics. DoE optimization of data revealed FPRTs containing PEO (20% w/w with coat weight 480 mg were promising systems exhibiting good floating behavior and lag time in drug release. Abdominal X-ray imaging of rabbits after oral administration of the tablets, confirmed the floating behavior and lag time. A quadratic model was suggested for release at 7th and 12th h and a linear model was suggested for release lag time. The FPRT formulation improved pharmacokinetic parameters compared to immediate release tablet formulation in terms of extent of absorption in rabbits. As the formulation showed delay in drug release both in vitro and in vivo, nighttime administration could be beneficial to reduce the cardiovascular complications due to early morning surge in blood pressure.

  6. Formulation and Evaluation of Nateglinide Sustained Release Tablets

    Directory of Open Access Journals (Sweden)

    Sridevi Gowripattapu

    2016-01-01

    Full Text Available The objective of the present investigation was to design suitable sustained release tablet formulation of Nateglinide by using different polymers such as hydroxy propyl methyl cellulose K15M, xanthan gum, guar gum as release rate retarding polymers. The tablets were prepared by direct compression technique. Nateglinide is used as anti diabetic drug. The objective of the treatment is to achieve hypoglycemia, by using an ideal dosage regimen. The sustained release formulation provides extend duration of action in therapeutic range without reaching toxic levels as in the case of conventional dosage forms. The real formulation trails are carried from F1 to F9 in which Drug: Polymer ratio was set as 1:9 respectively. The prepared formulations F1 to F9 were evaluated for pre and post compression characteristics, along with the in vitro dissolution Studies. It was found that the release of drug from F1, F2, and F3 gave the better release than other formulations. In these three formulations F2 showing highest release following first order kinetics. From the Higuchi plot good correlation coefficient was observed showing diffusion mechanism. From the peppas plot it was observed that the release model was non fickian anomalous. The release rate was decreased as polymer concentration increased so it shows that increase in diffusion length of polymer decreases the release rate.

  7. SUSTAINED RELEASE ITOPRIDE HYDROCHLORIDE MATRIX TABLET

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    BHUPENDRA, PRAJAPATI, NIKLESH PATEL, HITESH

    2013-09-01

    Full Text Available Oral route gets the highest priority for thedelivery of the drug as well as better patient compliance incase of self delivery dosage formulation. The aim ofpresent investigation was undertaken with the objective offormulating sustain release formulation of Itopridehydrochloride for oral drug delivery. Itopride hydrochlorideis highly water soluble prokinetic drug.Hydroxypropylmethylcellulose K4M (lower viscositygrade and K100M (higher viscosity grade were used as amatrix forming agents to control the release of drug. HPMCK4M and HPMC K100M were used individually as well asin combination with different proportion in the preparationof the Sustained release formulation. 32 factorial designswere applied to the polymer concentration that affects thedrug release profile. Reduced equation for drug release at2hr,6hr,and10hrwere22 1 2 1 Q 37.644 5.41X 3.25X 2.017X ,26 1 2 1 Q 72.367 8.05X 4.4X 3.75X ,and10 1 1 2 90.844 5.8 2.633 2.8 2 Q X X X Xrespectively. Optimized batch F019 shows good tabletproperties like hardness(7-9kg/cm2, thickness(4.48mm,friability(0.024%,assay(99.3% and nearly similar drugrelease profile to the targeted reference drug release profileand it was indicated by similarity factor (f2=86.04.

  8. [Preparation and evaluation of press-coated aminophylline tablet using crystalline cellulose and polyethylene glycol in the outer shell for timed-release dosage forms].

    Science.gov (United States)

    Watanabe, Yoshiteru; Mukai, Baku; Kawamura, Ken-ichi; Ishikawa, Tatsuya; Namiki, Michihiro; Utoguchi, Naoki; Fujii, Makiko

    2002-02-01

    In an attempt to achieve chronopharmacotherapy for asthma, press-coated tablets (250 mg), which contained aminophylline in the core tablet in the form of low-substituted hydroxypropylcellulose (L-HPC) and coated with crystalline cellulose (PH-102) and polyethylene glycol (PEG) at various molecular weights and mixing ratios in the amounts of PH-102 and PEG as the outer shell (press-coating material), were prepared (chronopharmaceutics). Their applicability as timed-release (delayed-release) tablets with a lag time of disintegration and a subsequent rapid drug release phase was investigated. Various types of press-coated tablets were prepared using a tableting machine, and their aminophylline dissolution profiles were evaluated by the JP paddle method. Tablets with the timed-release characteristics could be prepared, and the lag time of disintegration was prolonged as the molecular weight and the amount of PEG, for example PEG 500,000, in the outer shell were increased. The lag time of disintegration could be controlled by the above-mentioned method, however, the pH of the medium had no effect on disintegration of the tablet and dissolution behavior of theophylline. The press-coated tablet (core tablet:aminophylline 50 mg, L-HPC and PEG 6000; outer shell:PH-102:PEG = 8:2 200 mg) with the timed-release characteristics was administered orally to rabbits for an in vivo test. Theophylline was first detected in plasma more than 2 h after administration; thus, this tablet showed a timed-release characteristics in the gastrointestinal tract. The time (tmax) required to reach the maximum plasma theophylline concentration (Cmax) observed after administration of the press-coated tablet was significantly (p 24) between the press-coated tablet and aminophylline solution. These results suggest that the press-coated aminophylline tablet (with the timed-release characteristic) offers a promising forms of theophylline chronotherapy for asthma.

  9. FORMULATION AND EVALUATION OF EXTENDED RELEASE TABLETS OF TRAMADOL HYDROCHLORIDE

    Directory of Open Access Journals (Sweden)

    Chilvalvar Sapnil

    2013-10-01

    Full Text Available The objective of this research work was to develop extended release tablets (Twice in a day of Tramadol Hydrochloride using different Hydrophilic polymers like HPMC K15M, HPMC K4M, Metalose 60SH50, Carbopol 971P, Sodium alginate, Xanthan gum by direct compression method. Various amounts of polymers was used in the twenty four proposed formulations (F1 to F24 for the study of release rate retardant effect at 10 %, 15 %, 20 %, 25 % of total weight of tablet matrix respectively. Then the tablets were evaluated in terms of their physical parameters (weight variation, hardness, friability and thickness, drug content and in-vitro release studies. All the formulations showed compliance with pharmacopoeial standards. The in-vitro dissolution study were conducted using USP dissolution apparatus type-II (paddle method in 900 ml 0.1 N HCl for first 2 h and remaining 10 h performed in 6.8 pH phosphate buffer at 100 rpm for a total period of 12 h. Based on the dissolution data comparison with innovator product, formulation F14 was found as the best formulation. The drug release of formulation F14 followed First Order kinetic model and the mechanism was found to be non-Fickian/anomalous according to Korsmeyer-Peppas equation.

  10. Erosion characteristics of an erodible tablet incorporated in a time-delayed capsule device.

    Science.gov (United States)

    McConville, Jason T; Ross, Alistair C; Florence, Alastair J; Stevens, Howard N E

    2005-01-01

    A time-delayed oral drug delivery device was investigated in which an erodible tablet (ET), sealing the mouth of an insoluble capsule, controlled the lag-time prior to drug release. The time-delayed capsule (TDC) lag-time may be altered by manipulation of the excipients used in the preparation of the ET. Erosion rates and drug release profiles from TDCs were investigated with four different excipient admixtures with lactose: calcium sulphate dihydrate (CSD), dicalcium phosphate (DCP), hydroxypropylmethyl cellulose (HPMC; Methocel K100LV grade) and silicified microcrystalline cellulose (SMCC; Prosolv 90 grade). Additionally, the compressibility of different insoluble coated capsules was tested at different moisture levels to determine their overall integrity and suitability for oral delivery. Erosion rates of CSD, DCP, and SMCC displayed a nonlinear relationship to their concentration, while HPMC indicated rapid first-order erosion followed by zero-order erosion, the onset of which was dependent on the HPMC concentration. Capsule integrity was confirmed to be most suitable for oral delivery when the insoluble ethyl cellulose coat was applied to a hard gelatin capsule using an organic spray coating process. T50% drug release times varied between 245 (+/-33.4) and 393 (+/-40.8) minutes for 8% and 20% DCP, respectively, T50% release times of 91 (+/-22.1) and 167 (+/-34.6) were observed for 8% and 20% CSD; both formulations showed incidence of premature drug release. The SMCC formulations showed high variability due to lamination effects. The HPMC formulations had T50% release times of 69 (+/-13.9), 213 (+/-25.4), and 325 (+/-30.3) minutes for 15%, 24%, and 30% HPMC concentrations respectively, with no premature drug release. In conclusion, HPMC showed the highest reproducibility for a range of time-delayed drug release from the assembled capsule formulation. The method of capsule coating was confirmed to be important by investigation of the overall capsule integrity at

  11. Effect of hydrophilic and hydrophobic polymers on release kinetics of metoprolol succinate extended release tablets

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    Ramani Gade

    2011-01-01

    Full Text Available The purpose of the present work is to design and evaluate extended release matrix tablets of metoprolol succinate to reduce the dosing frequency and to improve patient compliance. The matrix tablets were prepared by the combination of hydrophilic and hydrophobic polymers, using methocel 10000 Cps in combination with ethyl cellulose 7 Cps, Eudragit® RS100, Eudragit® S100, and Eudragit® L100.The tablets were prepared by direct compression technique. Prepared formulations were evaluated for various parameters like weight variation, thickness, hardness, friability, and % drug content. Tablets were subjected to in vitro drug release studies. The formulations containing methocel 10000 Cps, Eudragit® L100 showed good release retardation. All the prepared formulations showed first-order release kinetics with matrix diffusion mechanism of release. The formulation containing 52.06% w/w of methocel 10000 Cps, 8.75% Eudragit® L100 offered the required release rate according to USP Pharmacopoeial guidelines. The combination of hydrophilic and hydrophobic polymers can effectively control the drug release for freely water-soluble drugs in case of extended release formulations which are the upcoming dosage forms for patient compliance in all aspects.

  12. FORMULATION AND EVALUATION OF CANDESARTAN CILEXETIL IMMEDIATE RELEASE TABLETS

    Directory of Open Access Journals (Sweden)

    Jampani Neeharika

    2012-07-01

    Full Text Available Candesartan Cilexetil is an esterified prodrug of Candesartan, a non-peptide angiotensin II type-1(AT1 receptor antagonist used in the treatment of hypertension and congestive heart failure. Candesartan meets the requirement of high potency but it is poorly absorbed when administered orally. Therefore, the prodrug Candesartan Cilexetil is developed. It is soluble in methylene chloride, half life is 5.1 to 10.5hrs and bioavailability is 15%. It is marketed as conventional tablets. In this work, it is formulated as immediate release tablets by changing the concentration of ingredients. For many drug substances, conventional immediate-release formulations provide clinically effective therapy while maintaining the required balance of pharmacokinetic and pharmacodynamic profiles with in acceptable level of safety to the patient. The immediate release formulation of Candesartan Cilexetil is prepared by wet granulation method to provide rapid onset of action. In order to optimize the best formulation, ten different trials are developed. The main ingredients used in the formulation are lactose monohydrate, PEG, calcium CMC and MCC. Weight variation, thickness, friability, disintegration time, in-vitro release, pharmaceutical assay are studied as response variables. The formulation containing 38% of MCC is selected as an optimized product in which the different physical properties and in-vitro release profile showed best comparable results with innovator product.

  13. FORMULATION AND EVALUATION OF DICLOFENAC CONTROLLED RELEASE TABLETS EMPLOYING OLIBANUM RESIN

    Directory of Open Access Journals (Sweden)

    K.P.R. Chowdary and G. Rami Reddy *

    2012-04-01

    Full Text Available The objective of the study is to evaluate Olibanum resin, a natural resin polymer as matrix polymer for controlled release tablets and to design matrix tablets of diclofenac for controlled release. Matrix tablets of diclofenac were formulated employing Olibanum resin in different proportions of drug and polymer and the tablets were evaluated for drug release kinetics and mechanism .Two diluents namely lactose (water soluble and DCP (water insoluble were included in the formulations to assess their influence on drug release characteristics of olibanum resin matrix tablets. Matrix tablets were found t¬o be non- disint-egrating in water, acidic (pH 1.2 and alkaline (pH 7.4 fluids and were considered suitable for oral controlled release. Diclofenac release from the matrix tablets formulated was slow and spread over 24 h and depended on the concentration (% of olibanum resin in the matrix tablets and nature/type of diluent. As the concentration of olibanum resin in the matrix tablets was increased, drug release was decreased. Release was relatively faster with water soluble diluent lactose when compared to water insoluble diluent DCP at all concentrations of olibanum resin. Drug release from the tablets followed first order kinetics and followed non - Fickian (anomalous diffusion release mechanism. Good linear relationships were observed between percent polymer and release rate in each case. The results of the study thus indicated olibanum resin could be used as rate controlling matrix in design of controlled release tablets. Both water soluble and water insoluble diluents can be included in the olibanum resin matrix tablets without affecting its rate controlling efficiency. Matrix tablets formulated employing olibanum resin(DF2 are considered suitable for controlled release of diclofenac over 24 h (i.e. once-a-day administration.

  14. Press-coating of immediate release powders onto coated controlled release tablets with adhesives.

    Science.gov (United States)

    Waterman, Kenneth C; Fergione, Michael B

    2003-05-20

    A novel adhesive coating was developed that allows even small quantities of immediate-release (IR) powders to be press-coated onto controlled-release (CR), coated dosage forms without damaging the CR coating. The process was exemplified using a pseudoephedrine osmotic tablet (asymmetric membrane technology, AMT) where a powder weighing less than 25% of the core was pressed onto the osmotic tablet providing a final combination tablet with low friability. The dosage form with the adhesive plus the press-coated powder showed comparable sustained drug release rates to the untreated dosage form after an initial 2-h lag. The adhesive layer consisted of an approximately 100- microm coating of Eudragit RL, polyethylene glycol (PEG) and triethyl citrate (TEC) at a ratio of 5:3:1.2. This coating provides a practical balance between handleability before press-coating and good adhesion.

  15. Design and characterization of controlled release tablet of metoprolol

    Directory of Open Access Journals (Sweden)

    Gautam Singhvi

    2012-01-01

    Full Text Available Metoprolol succinate is a selective beta-adrenergic receptor blocker useful in treatment of hypertension, angina and heart failure. The purpose of the present work was to design and evaluate controlled release matrix type tablet of Metoprolo succinate using HPMC K15M and Eudragit (RLPO and RSPO as a matrix forming agents. Effect of various polymer alone and combinations were studied in pH 1.2 buffer using USP type II paddle at 50 rpm. HPMC was used to form firm gel with Eudragit polymer. Formulation with Equal proportion (1:1 of Eudragit RSPO and RLPO showed optimum drug release t50 =7 hrs and t100 =16 hrs indicate optimum permeability for drug release from matrix. The drug release mechanism was predominantly found to be Non-Fickian diffusion controlled.

  16. Evaluation of the tamper-resistant properties of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets.

    Science.gov (United States)

    Eisenhauer, Tiffani D; Matchett, Mike; Heasley, Ralph; Morton, Terri; Devarakonda, Krishna; Giuliani, Michael; Young, Jim L; Barrett, Thomas

    2016-01-01

    Abuse potential of extended-release (ER) opioid tablets increases if tampering causes rapid opioid release. To evaluate the susceptibility to tampering of biphasic immediate-release (IR)/ER oxycodone (OC)/acetaminophen (APAP) tablets compared with IR OC/APAP tablets. IR/ER OC/APAP and IR OC/APAP tablets were tested at room temperature and after heating, freezing and microwaving. Resistance to crushing was tested using manual and powered tools (e.g. spoons, mortar and pestle, blender, coffee grinder). Tampered tablets were tested for suitability for snorting, OC extraction in solvents and ease of drawing into a syringe. Dissolution of IR/ER OC/APAP in gastric fluid with and without ethanol was tested to determine the potential for facilitating precipitous release of opioid from the tablet. IR/ER OC/APAP tablets were more crush resistant than IR OC/APAP tablets. Heating, freezing and microwaving had no effect on crush resistance of IR/ER OC/APAP tablets. Although a mortar and pestle pulverized IR/ER OC/APAP tablets, upon contact with solvent, the powder formed a thick gel judged unsuitable for absorption through the nasal mucosa and could not be drawn into a syringe. In contrast, powder from crushed IR OC/APAP tablets dissolved readily, was judged suitable for snorting, and was easily drawn into a syringe. Dissolution of IR/ER OC/APAP tablets in gastric fluid was slowed by the addition of ethanol. IR/ER OC/APAP tablets are resistant to crushing and dissolution compared with IR OC/APAP tablets. IR/ER OC/APAP tablets may have less potential for abuse involving tampering compared with IR OC/APAP tablets.

  17. 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.

  18. Verapamil hydrochloride release characteristics from new copolymer zwitterionic matrix tablets.

    Science.gov (United States)

    Kostova, Bistra; Kamenska, Elena; Ivanov, Ivo; Momekov, George; Rachev, Dimitar; Georgiev, George

    2008-01-01

    The aim of this study was to synthesize stable copolymer (vinyl acetate-co-3-dimethyl[methacryloyloxyethyl] ammonium propane sulfinate) zwitterionic latex with different compositions for the first time by emulsifier-free emulsion copolymerization. Throughout the course of the study, a proposal was made for the explanation of the relationship between the "overshooting" phenomenon (a swelling kinetics with a maximum) and the specific self-association of the zwitterionic copolymers. The zwitterionic monomer unit mole fraction, pH, and ionic strength effects on this relationship, on the swelling kinetics of the zwitterionic copolymers, and on the sustained verapamil hydrochloride release from the model tablets were established by the study's authors.

  19. Design and evaluation of lornoxicam bilayered tablets for biphasic release

    Directory of Open Access Journals (Sweden)

    Songa Ambedkar Sunil

    2012-12-01

    Full Text Available The objective of the present investigation was to develop bilayered tablets of lornoxicam to achieve biphasic release pattern. A bilayered tablet, consisting of an immediate and controlled release layer, was prepared by direct compression technique. The controlled release effect was achieved by using various hydrophilic natural, semi synthetic and synthetic controlled release polymers such as xanthan gum, hydroxypropyl methylcellulose (HPMC and polyethylene oxide (PEO to modulate the release of the drug. The in vitro drug release profiles showed the biphasic release behavior in which the immediate release (IR layer containing the lornoxicam was released within 15 minutes, whereas the controlled release (CR layer controlled the drug release for up to 24 h. All the bilayered tablets formulated have followed the zero order release with non-Fickian diffusion controlled release mechanism after the initial burst release. FTIR studies revealed that there was no interaction between the drug and polymers used in the study. Statistical analysis (ANOVA showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p O objetivo do presente trabalho foi desenvolver comprimidos bicamada de lornoxicam para atingir padrão de liberação bifásica. Preparou-se, por compressão direta, comprimido bicamada, consistindo de uma camada de liberação imediata e uma de liberação controlada. A liberação controlada foi obtida pelo uso de vários polímeros naturais hidrofílicos, semi-sintéticos e sintéticos, tais como goma xantana, hidroxipropilmetil celulose (HPMC e óxido de polietileno (PEO para modular a liberação do fármaco. Os perfis de liberação in vitro mostraram comportamento bifásico em que a camada de liberação imediata (IR contendo lornoxicam foi liberada em 15 minutos, enquanto a camada de liberação controlada (CR liberou o fármaco em mais de 24 horas, Todos os comprimidos bicamada

  20. Effect of different polymers on release of ranolazine from extended release tablets

    Directory of Open Access Journals (Sweden)

    T. E. G. K. Murthy

    2013-01-01

    Full Text Available An extended release tablet provides prolonged release of drug, maintains the desired concentration of drug in plasma and thereby reduce dosing frequency, improve patient compliance and reduce the dose-related side-effects. Ranolazine is indicated for the chronic treatment of angina in patients who have not achieved an adequate response with other anti-anginal agent. The present investigation was undertaken to design the extended release tablets of ranolazine employing different polymers as matrix forming agents using direct compression technique. Formulated tablets were evaluated for weight variation, hardness, friability, drug content, swelling index and in vitro release studies. The drug release followed first order kinetics and controlled by both erosion and diffusion mechanism. It is concluded that the desired drug release pattern can be obtained from the formulation containing 9.8% w/w eudragit and 39.2% w/w metallose offered relatively much slow release of ranolazine compared with other formulations. The selected formulation showed a similarity factor 76 when comparing in vitro dissolution data of the commercial formulation ranozex 500.

  1. Pharmacokinetic Study on Lovastatin Sustained-release Tablet and Sustained-release Capsule in Begal Dogs

    Institute of Scientific and Technical Information of China (English)

    付琳; 代宗顺; 侯淑贤; 万元胜

    2004-01-01

    This study pharmacokinetically examined the lovastatin sustained-release tablet and sustained release capsule in Beagle dogs. An reversed-phase HPLC method was established for the determination of lovastatin in Beagle dog plasma. Pharmacokinetic findings were compared among three preparation(lovastatin sustained-release tablet, TP; sustained-release capsule, TJ and conventional capsule). Our results showed that the pharmacokinetic parameters in 6 dogs after single-dose oral administration of three perparations were calculated. Tmax , Cmax and MRT revealed significant difference (P<0.05). Relative bioavailability was 111. 5 ± 16. 9 % (TP) and 110.4% ± 9.6%(TJ). The pharmacokinetic parameters in the 6 dogs after multiple-dose oral administration of three perparations, Tmax Cmax MRT and DF had significant difference (P<0. 05); Cav, Cmin and AUC0-24 h displayed no significant difference (P>0.05). It is concluded that the lovastatin sustained-release tablet and sustained-release capsule are able to maintain a sustained-release for 24 h.

  2. Optimization of propranolol HCl release kinetics from press coated sustained release tablets.

    Science.gov (United States)

    Ali, Adel Ahmed; Ali, Ahmed Mahmoud

    2013-01-01

    Press-coated sustained release tablets offer a valuable, cheap and easy manufacture alternative to the highly expensive, multi-step manufacture and filling of coated beads. In this study, propranolol HCl press-coated tablets were prepared using hydroxylpropylmethylcellulose (HPMC) as tablet coating material together with carbopol 971P and compressol as release modifiers. The prepared formulations were optimized for zero-order release using artificial neural network program (INForm, Intelligensys Ltd, North Yorkshire, UK). Typical zero-order release kinetics with extended release profile for more than 12 h was obtained. The most important variables considered by the program in optimizing formulations were type and proportion of polymer mixture in the coat layer and distribution ratio of drug between core and coat. The key elements found were; incorporation of 31-38 % of the drug in the coat, fixing the amount of polymer in coat to be not less than 50 % of coat layer. Optimum zero-order release kinetics (linear regression r2 = 0.997 and Peppas model n value > 0.80) were obtained when 2.5-10 % carbopol and 25-42.5% compressol were incorporated into the 50 % HPMC coat layer.

  3. Formulation and Evaluation of sustained release matrix tablets of Glipizide

    Directory of Open Access Journals (Sweden)

    Shallu Sandhan*

    2013-12-01

    Full Text Available The aim of present investigation was to enhance the solubility of glipizide (BCS Class II. Glipizide is an oral antidiabetic agent with relatively short elimination half life. Inclusion complex of Glipizide with β-cyclodextrin was prepared by kneading method and evaluated for its in-vitro release. Phase solubility studies were performed according to method reported by Higuchi and Connors which was classified as AL type characterized by apparent 1:1 stability constant. The Glipizide & Beta Cyclodextrin found to be compatible which was observed from FTIR spectra of Glipizide β- CD Complex. The dissolution study of Glipizide β- CD complex shows significant increase in the drug release than pure drug. Matrix Glipizide β- CD complex tablet complex equivalent to 10 mg Glipizide were prepared by using Hydroxy propyl methyl cellulose (HPMC, Carboxy methyl cellulose sodium (NaCMC and Microcrytalline cellulose (MCC. The tablets were evaluated for various tests like hardness, friability, disintegration and in-vitro dissolution studies.

  4. 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

  5. Delayed-Release Oral Mesalamine 4.8 g/day (800 mg tablets Compared with 2.4 g/day (400 mg tablets for the Treatment of Mildly to Moderately Active Ulcerative Colitis: The ASCEND I Trial

    Directory of Open Access Journals (Sweden)

    Stephen B Hanauer

    2007-01-01

    Full Text Available BACKGROUND: Delayed-release oral mesalamine 2.4 g/day to 4.8 g/day has been shown to be effective in treating mildly to moderately active ulcerative colitis (UC, but it is unknown whether an initial dose of 4.8 g/day is more effective than 2.4 g/day in patients with mildly to moderately active UC and in the subgroup with moderate disease.

  6. Food effect on bioavailability of modified-release trimetazidine tablets.

    Science.gov (United States)

    Ozbay, Latif; Unal, Durisehvar Ozer; Erol, Dilek

    2012-10-01

    This study aimed to investigate a food effect on the bio-availability of modified-release (MR) trimetazidine tablets in 36 healthy volunteers. Trimetazidine, an anti-ischemic drug, protects the myocardial cell from the harmful effects of ischemia. The authors investigated the effect of being under a fasting or fed state at the time of drug intake on the bioavailability of trimetazidine 35-mg MR tablets in a randomized, open-label, crossover, 2-arm, 4-period, 2-sequence bioequivalence study design with a 14-day washout period. Plasma concentration of trimetazidine was assayed in timed samples with a validated high- performance liquid chromatography/mass selective detector that had a lower limit of quantification of 2.5 ng/mL. Test and reference formulations gave a mean trimetazidine C(max) of 63.26 ng/mL and 69.18 ng/mL for the fasting state and 64.19 ng/mL and 63.11 ng/mL for the fed state, respectively. The AUC(0-tlast) mean of trimetazidine was 726.31 ng·h/mL and 733.01 ng·h/mL for the fasting state and 706.40 ng·h/mL and 691.40 ng·h/mL for the fed state for test/reference formulations. There were no significant differences in pharmacokinetic parameters between the 2 formulations and the fasting/fed states. The authors showed that there is no food effect and no need for a 4-period study to evaluate the bioequivalence of trimetazidine MR tablets.

  7. Role of hydroxypropylmethylcellulose (HPMC 4000 in the protection of the polymorphs of Piroxicam extended release tablets

    Directory of Open Access Journals (Sweden)

    A. Merah

    2017-02-01

    The physico-chemical tests and the dissolution profiles of polymorphs and tablets showed that the metolose incorporated in the tablets at a rate equivalent to 5% could possibly act doubly; initially by protecting the piroxicam polymorphism transition (form II during compression, then modulating its in vitro release (extended release.

  8. Properties of gastroretentive sustained release tablets prepared by combination of melt/sublimation actions of L-menthol and penetration of molten polymers into tablets.

    Science.gov (United States)

    Fukuda, Mamoru; Goto, Akinori

    2011-01-01

    A novel floating sustained release tablet having a cavity in the center was developed by utilizing the physicochemical properties of L-menthol and the penetration of molten hydrophobic polymer into tablets. A dry-coated tablet containing famotidine as a model drug in outer layer was prepared with a L-menthol core by direct compression. The tablet was placed in an oven at 80°C to remove the L-menthol core from tablet. The resulting tablet was then immersed in the molten hydrophobic polymers at 90°C. The buoyancy and drug release properties of tablets were investigated using United States Pharmacopeia (USP) 32 Apparatus 2 (paddle 100 rpm) and 900 ml of 0.01 N HCl. The L-menthol core in tablets disappeared completely through pathways in the outer layer with no drug outflows when placed in an oven for 90 min, resulting in a formation of a hollow tablet. The hollow tablets floated on the dissolution media for a short time and the drug release was rapid due to the disintegration of tablet. When the hollow tablets were immersed in molten hydrophobic polymers for 1 min, the rapid drug release was drastically retarded due to a formation of wax matrices within the shell of tablets and the tablets floated on the media for at least 6 h. When Lubri wax® was used as a polymer, the tablets showed the slowest sustained release. On the other hand, faster sustained release properties were obtained by using glyceryl monostearate (GMS) due to its low hydrophobic nature. The results obtained in this study suggested that the drug release rate from floating tablets could be controlled by both the choice of hydrophobic polymer and the combined use of hydrophobic polymers.

  9. [Controlled release of prednisolone from suppository prepared using powder of pulverized tablet].

    Science.gov (United States)

    Tatsumi, Akitoshi; Oda, Shoko; Nakamoto, Tomoko; Muraoka, Reiko; Takahashi, Yoshiko; Tanaka, Kuniyoshi; Shikata, Toshiyuki; Tatsumi, Sumiyo; Tagawa, Noriko; Kobayashi, Yoshiharu; Hamaguchi, Tsuneo; Kadobayashi, Muneo

    2008-04-01

    Prednisolone suppositories have been used successfully for the treatment of ulcerative colitis in hospital settings. However, the raw material of prednisolone suppository, JP prednisolone powder (JP Powder), was recently removed from the market. Therefore we studied the effects of raw material and suppository base on the release of prednisolone suppository for the purpose of designing a new suppository with similar effects to those of suppository prepared using JP powder (old suppository). New suppositories consisting of the powder of pulverized tablet as raw material and Witepsol H-15 and Witepsol E-75 as suppository base were prepared according to the fusion method. Suppository release test was performed by reciprocating dialysis tube method with tapping (RDT method) and dialysis tubing method (DT method). Both RDT method and DT method were performed using a suppository dissolution apparatus (modified JP disintegration apparatus) and a JP15 paddle apparatus, respectively. The test fluid was 50 mM phosphate buffer solution (pH 7.4) maintained at 37+/-0.5 degrees C. The results of release test by RDT method were similar to those of DT method. Release rate of prednisolone from the new suppository was much faster than that of old suppository. The addition of Witepsol E-75 to new suppository base markedly delayed the release of prednisolone from the new suppository. Release rate of prednisolone from the new suppository, consisting of pulverized tablet and Witepsol H-15 and Witepsol E-75 (76:24), corresponded well with that of the old suppository. It was suggested that this suppository could be used as incoming preparation of suppository prepared using JP powder.

  10. Influence of cellulose derivatives and natural polymers on in vitro release kinetics of metoprolol succinate from extended release matrix tablets

    OpenAIRE

    Sunil, R.; Somagoni, Jagan M.; Panakanti, Pavan K.; Ega, Chandra M.; Yamsani, Madhusudan R.

    2011-01-01

    In the present investigation, extended release tablets of metoprolol succinate were developed using cellulose derivatives and natural gums as matrix formers and were evaluated for its extended release characteristics. The optimized formulation (F7) was obtained using cellulose derivatives in the ratio of 1:0.5:1drug, HPMC K 100M and Na CMC, respectively. Prepared tablets were subjected to all the Pharmacopeial quality tests and found to be in the limits. The in vitro release studies of prepar...

  11. ACECLOFENAC FLOATING TABLETS - A PROMISING SUSTAINED RELEASE DOSAGE FORM

    Directory of Open Access Journals (Sweden)

    Ambati Brahma reddy

    2011-06-01

    Full Text Available The purpose of the present study was to develop an optimized gastric floating drug delivery system (GFDDS containing Aceclofenac as a model drug by using various proportion of polymers such as HPMC E5M and Eudragit RS 100. This was employed to enhance the bioavailability and therapeutic efficacy of the drug. The sustained release formulations of aceclofenac using hydrophobic and hydrophilic polymers were prepared by direct compression method. Optimization of formulation was done by studying effect of drug to polymer ratio on drug release. FT- IR studies indicated absence of any interaction between aceclofenac, polymer (Eudragit RS 100, HPMCE5M and excipients. Five formulations were prepared and formulation A5 possessed good floating property with total floating time between 8-10 hours. The tablets were also evaluated for its hardness, friability and other In- vitro evaluation tests. All parameters complied with IP limits. Results of this study indicated that the combinations of hydrophilic polymers with hydrophobic polymers are suitable to optimize sustained release formulation of aceclofenac.

  12. Film coated tablets (ColoPulse technology) for targeted delivery in the lower intestinal tract: influence of the core composition on release characteristics.

    Science.gov (United States)

    Schellekens, Reinout C A; Baltink, Jan H; Woesthuis, Ellen M; Stellaard, Frans; Kosterink, Jos G W; Woerdenbag, Herman J; Frijlink, Henderik W

    2012-01-01

    The design of a film coating technology which allows a tablet to deliver the drug in the ileocolonic segment would offer new treatment possibilities. The objective is to develop a platform technology that is suitable for a broad range of drug compounds. We developed a coated tablet with a delayed, pulsatile release profile based on a pH-sensitive coating technology (ColoPulse). The production process was validated, and the effect of core composition on the in vitro release and water uptake investigated. The release profile of the standard tablet core composition, based on the use of cellulose as a filler, was independent of the coat thickness in a range of 9.0-13.2 mg/cm(2). The release profile of a coated tablet was strongly influenced when cellulose was partly replaced by the model substance glucose (loss of sigmoidal release), citric acid (stabilization), sodium bicarbonate (destabilization) or sodium benzoate (destabilization). The film coating takes up water when below the pH-threshold. However, this did not cause early disintegration of the coating. The ColoPulse technology is successfully applied on tablets. The in vitro release characteristics of the coated tablets are influenced by the composition of the core.

  13. Release kinetics of salbutamol sulphate from wax coated microcapsules and tableted microcapsules.

    Science.gov (United States)

    Raghuvanshi, R S; Tripathi, K P; Jayaswal, S B; Singh, J

    1992-01-01

    Microcapsules of salbutamol sulphate were prepared using beeswax and carnauba wax as coating materials. In vitro release kinetics were studied following the zero order, first order and Higuchi equations. Beeswax alone was not effective but beeswax and carnauba wax combinations were suitable in controlling the in vitro release of the drug. Microcapsules were compressed into tablets to get a controlled release oral dosage form. Release from tableted microcapsules was significantly more prolonged than the respective batches of the microcapsules. Best data fit with the highest correlation coefficient for the tableted microcapsules was obtained for first order.

  14. Preparation and scale up of extended-release tablets of bromopride

    Directory of Open Access Journals (Sweden)

    Guilherme Neves Ferreira

    2014-04-01

    Full Text Available Reproducibility of the tablet manufacturing process and control of its pharmaceutics properties depends on the optimization of formulation aspects and process parameters. Computer simulation such as Design of Experiments (DOE can be used to scale up the production of this formulation, in particular for obtaining sustained-release tablets. Bromopride formulations are marketed in the form of extended-release pellets, which makes the product more expensive and difficult to manufacture. The aim of this study was to formulate new bromopride sustained release formulations as tablets, and to develop mathematical models to standardize the scale up of this formulation, controlling weight and hardness of the tablets during manufacture according to the USP 34th edition. DOE studies were conducted using Minitab(tm software. Different excipient combinations were evaluated in order to produce bromopride sustained-release matrix tablets. In the scale-up study, data were collected and variations in tableting machine parameters were measured. Data were processed by Minitab(tm software, generating mathematical equations used for prediction of powder compaction behavior, according to the settings of the tableting machine suitable for scale-up purposes. Bromopride matrix tablets with appropriate characteristics for sustained release were developed. The scale-up of the formulation with the most suitable sustained release profile was established by using mathematical models, indicating that the formulation can be a substitute for the pellets currently marketed.

  15. Fabrication of controlled-release budesonide tablets via desktop (FDM) 3D printing.

    Science.gov (United States)

    Goyanes, Alvaro; Chang, Hanah; Sedough, Daniel; Hatton, Grace B; Wang, Jie; Buanz, Asma; Gaisford, Simon; Basit, Abdul W

    2015-12-30

    The aim of this work was to explore the feasibility of using fused deposition modelling (FDM) 3D printing (3DP) technology with hot melt extrusion (HME) and fluid bed coating to fabricate modified-release budesonide dosage forms. Budesonide was sucessfully loaded into polyvinyl alcohol filaments using HME. The filaments were engineered into capsule-shaped tablets (caplets) containing 9mg budesonide using a FDM 3D printer; the caplets were then overcoated with a layer of enteric polymer. The final printed formulation was tested in a dynamic dissolution bicarbonate buffer system, and two commercial budesonide products, Cortiment® (Uceris®) and Entocort®, were also investigated for comparison. Budesonide release from the Entocort® formulation was rapid in conditions of the upper small intestine while release from the Cortiment® product was more delayed and very slow. In contrast, the new 3D printed caplet formulation started to release in the mid-small intestine but release then continued in a sustained manner throughout the distal intestine and colon. This work has demonstrated the potential of combining FDM 3DP with established pharmaceutical processes, including HME and film coating, to fabricate modified release oral dosage forms.

  16. Release mechanisms behind polysaccharides-based famotidine controlled release matrix tablets.

    Science.gov (United States)

    Elmowafy, Enas M; Awad, Gehanne A S; Mansour, Samar; El-Shamy, Abd El-Hamid A

    2008-01-01

    Polysaccharides, which have been explored to possess gelling properties and a wide margin of safety, were used to formulate single-unit floating matrix tablets by a direct compression technique. This work has the aim to allow continuous slow release of famotidine above its site of absorption. The floating approach was achieved by the use of the low density polypropylene foam powder. Polysaccharides (kappa-carrageenan, gellan gum, xyloglucan, and pectin) and blends of polysaccharides (kappa-carrageenan and gellan gum) and cellulose ethers (hydroxypropylmethyl cellulose, hydroxypropylcellulose, sodium carboxymethyl cellulose) were tried to modulate the release characteristics. The prepared floating tablets were evaluated for their floating behavior, matrix integrity, swelling studies, in vitro drug release studies, and kinetic analysis of the release data. The differential scanning calorimetry and Fourier transform infrared spectroscopy studies revealed that changing the polymer matrix system by formulation of polymers blends resulted in formation of molecular interactions which may have implications on drug release characteristics. This was obvious from the retardation in drug release and change in its mechanistics.

  17. 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.

  18. A formulation approach for development of HPMC-based sustained release tablets for tolterodine tartrate with a low release variation

    DEFF Research Database (Denmark)

    Cao, Qing-Ri; Choi, Jae-Seung; Liu, Yan;

    2013-01-01

    Objective: The purpose of this study was to develop hydroxypropylmethylcellulose (HPMC)-based sustained release (SR) tablets for tolterodine tartrate with a low drug release variation. Methods: The SR tablets were prepared by formulating a combination of different grades of HPMC as the gelling...... of different grades of HPMC had remarkable effects on drug release from the SR tablets. Both the test and reference products had no significant difference in terms of comparative dissolution patterns in four different media (f(2) > 50). Furthermore, the dissolution method and rotation speed showed no effects...... on the drug release from the two products. The 90% confidence intervals of the AUC(0-36) and C(max) ratios for the test and reference products were within the acceptable bioequivalence intervals of log0.8-log1.25. Conclusions: A HPMC-based SR tablet for tolterodine tartrate with a low release variation...

  19. 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.

  20. Dissolution of Intact, Divided and Crushed Circadin Tablets: Prolonged vs. Immediate Release of Melatonin

    Directory of Open Access Journals (Sweden)

    Hui Ming Chua

    2016-01-01

    Full Text Available Circadin 2 mg prolonged-release tablet is the only licensed melatonin product available in the UK. Circadin is indicated for patients with primary insomnia aged 55 and over, but is more widely used “off-label” to treat sleep disorders especially in the paediatric population. Children and older people often have difficulty swallowing tablets and dividing the tablet is sometimes required to ease administration. The aim of this study was to measure the release profile of melatonin from Circadin tablets when divided or crushed, and compare this with release from intact tablets. Dissolution testing was also performed for unlicensed melatonin products for comparison. Dissolution tests were performed using the pharmacopoeial paddle apparatus, with melatonin release analyzed by high performance liquid chromatography. Melatonin content, hardness, friability, and disintegration of the products were also evaluated. The prolonged release of melatonin from Circadin tablets was unlike that of any other product tested. When divided into halves, Circadin preserved most of the prolonged-release characteristic (f2 = 58, whereas quarter-cut and crushed tablet had a more immediate melatonin release profile. Circadin is significantly less expensive and should be preferred to unlicensed medicines which are not pharmaceutically equivalent and offer less quality assurance.

  1. Preparation and pharmacokinetics study on gastro-floating sustained-release tablets of troxipide.

    Science.gov (United States)

    Gao, Yunyun; Gao, Yang; Yin, Fei; Wang, Mi; Wang, Zhenhong; Ye, Tiantian; Yang, Yonggang; Pan, W S; Yang, Xinggang

    2015-01-01

    The purpose of this research aimed at preparing gastro-floating sustained-release tablets of troxipide and a further study on in vitro release and in vivo bioavailability. Under the circumstances of direct powder compression, the floating tablets were successfully prepared with HPMC as main matrix material, Carbopol as assistant matrix material, octadecanol as floating agent and sodium bicarbonate as foaming agent to float by gas-forming. The floating time and accumulative release amount as evaluation indexes were utilized to perform pre-experiment screening and single-factor test, respectively, while central composite design response surface method was applied for formulation optimization, followed by in vivo pharmacokinetic study in beagles after oral administration for floating tablets and commercial tablets used as the control. The results indicated that the floating sustained-release tablets held a better capability for floating and drug release and more satisfactory pharmacokinetic parameters, such as a lower Cmax, a prolonged Tmax, but an equivalent bioavailability calculated by AUC0-24 compared to commercial tablets. So a conclusion was finally drawn that the floating sustained-release tablets possessing a good release property could be suitable for demands of design.

  2. Preparation of coated valproic acid and sodium valproate sustained-release matrix tablets

    Directory of Open Access Journals (Sweden)

    Phaechamud T

    2010-01-01

    Full Text Available The aim of this research was to investigate the technique for preparation of coated valproic acid and sodium valproate sustained-release matrix tablets. Different diluents were tested and selected as the effective absorbent for oily valproic acid. Effect of the amount of absorbent and hydroxypropylmethylcellulose on drug release from valproic acid-sodium valproate matrix tablets prepared with wet granulation technique was evaluated in pH change system. Colloidal silicon dioxide effectively adsorbed liquid valproic acid during wet granulation and granule preparation. The amounts of colloidal silicon dioxide and hydroxypropylmethylcellulose employed in tablet formulations affected drug release from the tablets. The drug release was prominently sustained for over 12 h using hydroxypropylmethylcellulose-based hydrophilic matrix system. The mechanism of drug release through the matrix polymer was a diffusion control. The drug release profile of the developed matrix tablet was similar to Depakine Chrono; , providing the values of similarity factor (f2 and difference factor (f1 of 85.56 and 2.37, respectively. Eudragit; L 30 D-55 was used as effective subcoating material for core matrix tablets before over coating with hydroxypropylmethylcellulose film with organic base solvent. Drug release profile of coated matrix tablet was almost similar to that of Depakine Chrono; .

  3. Coupling 3D printing with hot-melt extrusion to produce controlled-release tablets.

    Science.gov (United States)

    Zhang, Jiaxiang; Feng, Xin; Patil, Hemlata; Tiwari, Roshan V; Repka, Michael A

    2017-03-15

    The main objective of this work was to explore the potential of coupling fused deposition modeling in three-dimensional (3D) printing with hot-melt extrusion (HME) technology to facilitate additive manufacturing, in order to fabricate tablets with enhanced extended release properties. Acetaminophen was used as the model drug and different grades and ratios of polymers were used to formulate tablets. Three-point bending and hardness tests were performed to determine the mechanical properties of the filaments and tablets. 3D-printed tablets, directly compressed mill-extruded tablets, and tablets prepared from a physical mixture were evaluated for drug release rates using a USP-II dissolution apparatus. The surface and cross-sectional morphology of the 3D-printed tablets were assessed by scanning electron microscopy. Differential scanning calorimetry and thermogravimetric analysis were used to characterize the crystal states and thermal properties of materials, respectively. The 3D-printed tablets had smooth surfaces and tight structures; therefore, they showed better extended drug release rates than the directly compressed tablets did. Further, this study clearly demonstrated the feasibility of coupling HME with 3D printing technology, which allows for the formulation of drug delivery systems using different grades and ratios of pharmaceutical polymers. In addition, formulations can be made based on the personal needs of patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. IN-VITRO RELEASE CHARACTERIZATION OF KETOROLAC TROMETHAMINE LOADED MATRIX TABLETS

    Directory of Open Access Journals (Sweden)

    Sayed Koushik Ahamed, Sujan Banik and Mohammad Salim Hossain*

    2013-03-01

    Full Text Available ABSTRACT: The present investigation highlighted the formulation and release characterization of Ketorolac Tromethamine loaded matrix tablet. Various formulations of tablets were prepared by direct compression method along with Kollidon SR and Hydroxy Propyl Methyl Cellulose (HPMC as release retardant polymers. Each of the formulated tablets contains 50mg Ketorolac Tromethamine. The evaluation involved physical properties studies (weight variation, thickness, length, width, hardness, friability, and drug content of tablets and in vitro release kinetics assessment. The USP paddle method was operated at 50 rpm selected to perform the dissolution test and 900 ml phosphate buffer of pH 7.4 was used as dissolution medium. The drug release from each formulation was analyzed by using release kinetics theories. All formulations followed Higuchi release kinetics. When the release data was plotted into Korsemeyer-Peppas equation, then it was confirmed that F-1 to F-5 exhibited fickian type drug release whereas F-6 exhibited non-Fickian type drug release. The in-vitro release studies revealed that the formulation F-4 can be taken as an ideal or optimized formulation of sustained release tablets. Furthermore, the dissolution of the formulation-4 was performed in SLS (1%, 1.5%, and 2% medium, which was observed gradually decreasing release rate as concentration of SLS medium increased.

  5. Pharmacokinetic profile of a new controlled-release isosorbide-5-mononitrate 60 mg scored tablet (Monoket Multitab).

    Science.gov (United States)

    Stockis, Armel; De Bruyn, Steven; Deroubaix, Xavier; Jeanbaptiste, Bernard; Lebacq, Edouard; Nollevaux, Fabrice; Poli, Gianluigi; Acerbi, Daniela

    2002-01-01

    The influences of food, tablet splitting, and fractional dosing on the pharmacokinetics of a new controlled-release double-scored tablet containing 60 mg isosorbide-5-mononitrate (Monoket Multitab) were investigated in healthy male volunteers. Food interaction was evaluated after single dose administration under fasted conditions and after a standard high-fat breakfast. The effect of tablet splitting was assessed at steady-state, after 5 days of once daily dosing with the tablet taken intact or trisected. The influence of fractional dosing was assessed after 1 and 6 days of daily regimen of 40 mg in the morning (2/3 of a tablet) and 20 mg in the evening (1/3 of a tablet). The pharmacokinetics of isosorbide-5-mononitrate after taking the tablet intact or in three fragments were very similar with a mere 10% increase of maximum plasma concentration (C(max)) for the latter, while the time to peak (T(max)) decreased from 5 to 4 h and areas under the concentration vs. time curves (AUCs) were virtually unchanged. Morning trough concentration reached 53 and 46 ng/ml, respectively. Administration of the intact tablet after a high-fat breakfast increased C(max) by 18% and AUC by 21%, and slightly delayed T(max) from 5 to 6h. During fractional dosing, morning and evening C(max) reached 364 and 315 ng/ml on the first day, and 373 and 300 ng/ml on the 6th day, respectively. The ratio of AUC(0-24 h) on the last day to AUC(infinity) on the first day, was 82.1% (confidence limits 71.7-94.1%) possibly resulting from peripheral volume expansion. The release characteristics of Monoket Multitab are thus moderately influenced by concomitant intake of food and to a very minor extent by tablet breaking. Fractional dosing allows to achieve lower peak and higher morning trough levels, while total exposure is comparable to that during once daily dosing (AUC(0-24 h, s.s.) of 5.55+/-1.78 and 5.71+/-1.08 microg h/ml).

  6. Development of modified release 3D printed tablets (printlets) with pharmaceutical excipients using additive manufacturing.

    Science.gov (United States)

    Goyanes, Alvaro; Fina, Fabrizio; Martorana, Annalisa; Sedough, Daniel; Gaisford, Simon; Basit, Abdul W

    2017-07-15

    The aim of this study was to manufacture 3D printed tablets (printlets) from enteric polymers by single filament fused deposition modeling (FDM) 3D printing (3DP). Hot melt extrusion was used to generate paracetamol-loaded filaments from three different grades of the pharmaceutical excipient hypromellose acetate succinate (HPMCAS), grades LG, MG and HG. One-step 3DP was used to process these filaments into enteric printlets incorporating up to 50% drug loading with two different infill percentages (20 and 100%). X-ray Micro Computed Tomography (Micro-CT) analysis revealed that printlets with 20% infill had cavities in the core compared to 100% infill, and that the density of the 50% drug loading printlets was higher than the equivalent formulations loaded with 5% drug. In biorelevant bicarbonate dissolution media, drug release from the printlets was dependent on the polymer composition, drug loading and the internal structure of the formulations. All HPMCAS-based printlets showed delayed drug release properties, and in the intestinal conditions, drug release was faster from the printlets prepared with polymers with a lower pH-threshold: HPMCAS LG > HPMCAS MG > HPMCAS HG. These results confirm that FDM 3D printing makes it possible not only to manufacture delayed release printlets without the need for an outer enteric coating, but it is also feasible to adapt the release profile in response to the personal characteristics of the patient, realizing the full potential of additive manufacturing in the development of personalised dose medicines. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Generic sustained release tablets of trimetazidine hydrochloride: Preparation and in vitro–in vivo correlation studies

    Directory of Open Access Journals (Sweden)

    Longmei Wang

    2016-06-01

    Full Text Available The aim of the current work was to develop generic sustained-release tablets containing 35 mg trimetazidine dihydrochloride and to establish an in vitro–in vivo correlation that could predict the bioavailability. The marketed sustained release tablet (Vastarel MR used as reference, a sustained-release matrix tablet was prepared using hydroxypropyl methylcellulose (HPMC as matrix by wet granulation and the in vitro dissolution profiles of the self-made tablets were determined in four different dissolution media (0.1 M HCl, pH 4.5 PBS, pH 6.8 PBS and water. A higher similarity between prepared tablets and Vastarel MR was established, with similarity factor (f2 ranging from 60 to 75 in the four media. The in vivo pharmacokinetics was studied in six healthy beagles. Compared with Vastarel MR, the Cmax of self-made tablets was slightly decreased, while the Tmax and MRT0–t were slightly prolonged, but with no significant difference (P > 0.05. The average of relative bioavailability (F was 102.52% based on AUC0–t. For log-transformed AUC0–t and Cmax, the upper confidence limit on the appropriate criterion is <0, indicating these two formulations were population bioequivalent. The in vivo–in vitro correlation coefficient obtained from point-to-point analysis of self-made tablets was 0.9720. In conclusion, the prepared tablets were bioequivalent to the marketed tablets, according to both the in vitro release rate and extent of absorption, and a good in vivo–in vitro correlation was established for the self-made tablets that indicated in vitro dissolution tests could be used as a surrogate for bioavailability studies.

  8. Design and development of bilayer tablet for immediate and extended release of acarbose and metformin HCl

    Directory of Open Access Journals (Sweden)

    Meenakshi Joshi

    2014-01-01

    Full Text Available The present investigation studied a novel Bilayer tablet having extended release (ER system of metformin HCl (M.HCl with Eudragit RS 100 and RL 100 and immediate release (IR system of Acarbose with PVP K30 and PEG 6000 in different ratios using solvent evaporation technique. Solid dispersions (SDs were characterized by Fourier Transform-Infra Red spectroscopy, Diffrential Scanning Calorimetry, X-Ray Diffractometry and Scanning Electron Microscopy. Selected SD system was subjected to Bilayer tablet preparation by direct compression. Compressed tablets were evaluated for physical parameters, drug release and stability. SEM studies suggested the homogenous dispersion of the drug in polymers. FT-IR studies confirmed the formation of hydrogen bonding between the drug and polymer. XRD and DSC suggested the amorphous nature of the drug in SDs. All tablet formulations showed compliance with pharmacopoeial standards. In-vitro dissolution kinetics followed the Higuchi model via a non-fickian diffusion controlled release mechanism after the initial burst release. Stability studies conducted for optimized formulation did not show any change in the physical properties, drug content and drug release. Bilayer tablets showed an IR effect to provide the loading dose of the drug, followed by ER effect for 12 h, indicating a promising potential of the M.HCl and Acarbose Bilayer tablet as an alternative to the conventional dosage form.

  9. Mathematical Model-Based Accelerated Development of Extended-release Metformin Hydrochloride Tablet Formulation.

    Science.gov (United States)

    Chen, W; Desai, D; Good, D; Crison, J; Timmins, P; Paruchuri, S; Wang, J; Ha, K

    2016-08-01

    A computational fluid dynamic (CFD) model was developed to predict metformin release from a hydroxypropylmethylcellulose (HPMC) matrix-based extended-release formulation that took into consideration the physical and chemical properties of the drug substance, composition, as well as size and shape of the tablet. New high dose strength (1000 mg) tablet geometry was selected based on the surface area/volume (SA/V) approach advocated by Lapidus/Lordi/Reynold to obtain the desired equivalent metformin release kinetics. Maintaining a similar SA/V ratio across all extended-release metformin hydrochloride (Met XR) tablet strengths that had different geometries provided similar simulations of dissolution behavior. Experimental dissolution profiles of three lots of high-strength tablets agreed with the simulated release kinetics. Additionally, a pharmacokinetic absorption model was developed using GastroPlus™ software and known physicochemical, pharmacokinetic, and in vitro dissolution properties of metformin to predict the clinical exposure of the new high strength (1000 mg) tablet prior to conducting a human clinical bioequivalence study. In vitro metformin release kinetics were utilized in the absorption model to predict exposures in humans for new 1000-mg Met XR tablets, and the absorption model correctly projected equivalent in vivo exposure across all dose strengths. A clinical bioequivalence study was pursued based on the combined modeling results and demonstrated equivalent exposure as predicted by the simulations.

  10. Disulfiram-loaded immediate and extended release vaginal tablets for the localised treatment of cervical cancer.

    Science.gov (United States)

    Baffoe, Clara S; Nguyen, Nhi; Boyd, Peter; Wang, Weiguang; Morris, Mark; McConville, Christopher

    2015-02-01

    To develop and manufacture both immediate and sustained release vaginal tablets containing the anticancer drug disulfiram, which has the potential to be used as a non-invasive treatment for cervical cancer. Disulfiram-loaded vaginal tablets were manufactured at pilot scale using the direct compression method. These tablets were tested in accordance with the European Pharmacopeia testing of solid dosage form guidelines. They were also tested using a biorelevant dissolution method as well as a dual-chambered release model designed to better mimic the dynamic nature of the vaginal vault. We have developed both immediate and sustained release vaginal tablets, which when manufactured at pilot scale are within the limits set by the European Pharmacopeia for the testing of solid dosage forms. Furthermore, these tablets are capable of releasing disulfiram in vitro using the dual-chambered release model at levels 25,000 times and 35,000 times greater than its IC50 concentration for the HeLa cervical cancer cell line. The successful pilot manufacture and testing of both the immediate and sustained release disulfiram-loaded vaginal tablets warrant further investigation, using an in-vivo model, to assess their potential for use as a non-invasive treatment option for cervical cancer. © 2014 Royal Pharmaceutical Society.

  11. CONTROLLED-RELEASE OF PARACETAMOL FROM AMYLODEXTRIN TABLETS - IN-VITRO AND IN-VIVO RESULTS

    NARCIS (Netherlands)

    VANDERVEEN, J; EISSENS, AC; LERK, CF

    1994-01-01

    Amylodextrin is a suitable excipient for the design of solid controlled-release systems. The release of paracetamol from tablets containing 30% drug and 70% amylodextrin was studied in vitro and in vivo. In vitro dissolution profiles showed almost-constant drug release rates during 8 hr, when measur

  12. FORMULATION AND EVALUATION OF SUSTAINED RELEASE TABLET OF DILTIAZEM HYDROCHLORIDE BY MELT GRANULATION TECHNOLOGY

    Directory of Open Access Journals (Sweden)

    Birajdar Ganesh

    2013-07-01

    Full Text Available The objective behind present study was to formulate and evaluate sustained release tablet of Diltiazem hydrochloride by using different polymers by melt granulation technology and to study the effect of various concentrations of polymers on release rate from tablet. Tablets were prepared using bees wax, carnauba wax, paraffin wax as release ratardent polymers. The drug and excipient compatibility study was done by FTIR method using KBr pellet method. The granules prepared by melt granulation technique evaluated for characterization such as bulk density, tapped density, hausners ratio, angle of repose, cars index all granules shows good flow property. The tablet of Diltiazem HCL evaluated for characterization such as hardness, friability, weight variation and content uniformity all tablets shows sufficient hardness and friability shows that tablets are having sufficient strength. All results were satisfactory. The in vitro drug release studies for the prepared formulation were conducted for a period of 12 h using an EDT 08LX dissolution tester USP Type - II apparatus (rotating paddle set at 100 rpm and a temperature of 37 ± 0.5°C formulation was placed in the 900 ml of the medium. For first 2 h tablet was placed in 1.2 pH acidic medium which was replaced with 7.4 pH phosphate buffer for remaining 10 h. From the dissolution study and comparative graph it was concluded that increase in concentration of wax shows decrease in drug release from tablet. Batch F3 shows 99.84 % drug release at 12 h. In vitro release data of optimized formulations (Batch F3 was fitted to various kinetic models like zero order, first order, Higuchi, korsmeyer-peppas and pass Higuchi model as it has highest r2 value (0.955 among all models.

  13. Development of controlled release tablet by optimizing HPMC: consideration of theoretical release and RSM.

    Science.gov (United States)

    Pani, Nihar R; Nath, Lila K

    2014-04-15

    The objective of the study was to develop controlled release tablets of nateglinide, a meglitinide derivative anti-diabetic drug, considering theoretical release profile and response surface methodology (RSM). 3(2) factorial design was utilized to optimize concentration of hydroxylpropylmethylcellulose (HPMC) K15M and K100M to obtain the desired responses (drug release at one and six hours). Theoretical release profile of drug for controlled release formulation was calculated and considered as reference for the determination of similarity factor (f2) and desimilarity factor (f1). RSM, f2 and f1 were used to select the optimum formulation. Formulation containing HPMC K15M (5%) and HPMC K100M (15%) was found optimum with desired responses with f2=86.05 and drug release profile followed zero order kinetics. Excipients used were compatible with drug, confirmed initially through DSC and IST study. The optimization of experiments was validated and optimum formulation was passed the stability study. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Formulation and characterization of modified release tablets containing isoniazid using swellable polymers.

    Science.gov (United States)

    Akhtar, M F; Rabbani, M; Sharif, A; Akhtar, B; Saleem, A; Murtaza, G

    2011-01-01

    The aim of this work was to develop swellable modified release (MR) isoniazid tablets using different combinations of polyvinyl acetate (PVAc) and sodium-carboxymethylcellulose (Na-CMC). Granules were prepared by moist granulation technique and then compressed into tablets. In vitro release studies for 12 hr were carried out in dissolution media of varying pH i.e. pH 1.2, 4.5, 7.0 and 7.5. Tablets of all formulations were found to be of good physical quality with respect to appearance (width and thickness), content uniformity, hardness, weight variation and friability. In vitro release data showed that increasing total polymer content resulted in more retarding effect. Formulation with 35% polymer content exhibited zero order release profile and it released 35% of the drug in first hr, later on, controlled drug release was observed upto the 12(th) hour. Formulations with PVAc to Na-CMC ratio 20:80 exhibited zero order release pattern at levels of studied concentrations, which suggested that this combination can be used to formulate zero order release tablets of water soluble drugs like isoniazid. Korsmeyer-Peppas modeling of drug release showed that non-Fickian transport is the primary mechanism of isoniazid release from PVAc and Na-CMC based tablets. The value of mean dissolution time decreased with the increase in the release rate of drug clearly showing the retarding behavior of the swellable polymers. The application of a mixture of PVAc to Na-CMC in a specific ratio may be feasible to formulate zero order release tablets of water soluble drugs like isoniazid.

  15. In vitro release characteristics of matrix tablets: Study of Karaya gum and Guar gum as release modulators

    Directory of Open Access Journals (Sweden)

    Senapati M

    2006-01-01

    Full Text Available Matrix tablets of phenylpropanolamine were fabricated using karaya gum and guar gum, alone or in combination with other excipients. The tablets were evaluated for physical characteristics like hardness, weight variation, friability, swelling index and drug content. In vitro release of drug was performed in 0.1N HCl (pH 1.2 for 2 h and the rest of dissolution in phosphate buffer (pH 6.8. The effect of water-soluble (lactose and water-insoluble (dicalcium phosphate excipients on drug release was evaluated. All the physical characteristics of the fabricated tablets were within acceptable limits. The tablets with karaya gum exhibited greater swelling indices than those with guar gum. All the batches provided drug release over a period of 6 h. The level of matrix former in the tablets affects drug release. Incorporation of lactose or dicalcium phosphate influenced drug release, but at lower polymer levels only. A combination of karaya gum and guar gum exhibited more sustained release than individual gum.

  16. Formulation and evaluation of ranolazine extended release tablets: Influence of polymers

    Directory of Open Access Journals (Sweden)

    TEGK Murthy

    2011-01-01

    Full Text Available An extended release tablet provides prolonged periods of drug in plasma levels thereby reduce dosing frequency, improve patient compliance and reduce the dose-related side effects. Ranolazine is indicated for the chronic treatment of angina in patients who have not achieved an adequate response with other anti-anginal agents. The present investigation was undertaken to design extended release tablets of Ranolazine employing hypromellose phthalate grade HP-55, ethocel standard 7FP premium ethyl cellulose, Surelease E-7-19040, Klucel HF pharm and Natrosol Type 250 HHX as matrix forming agents using wet granulation method. Formulated tablets were evaluated for uniformity of weight, assay, water content, in vitro drug release studies and stability studies. The drug release followed first order kinetics with both erosion and diffusion as the release mechanism. It is concluded that the desired drug release pattern can be obtained by using natrosol type 250 HHX compared to other polymers. The similarity factor (f2 was calculated to select best formulation by comparing in vitro dissolution data of the commercial formulation Ranexa® . The formulated tablets fulfilled the compendia requirements. The formulated Ranolazine Extended release tablets were found to be stable.

  17. In vitro release kinetics and bioavailability of gastroretentive cinnarizine hydrochloride tablet.

    Science.gov (United States)

    Nagarwal, Ramesh C; Ridhurkar, Devendra N; Pandit, J K

    2010-03-01

    An oral sustained release dosage form of cinnarizine HCl (CNZ) based on gastric floating matrix tablets was studied. The release of CNZ from different floating matrix formulations containing four viscosity grades of hydroxypropyl methylcellulose, sodium alginate or polyethylene oxide, and gas-forming agent (sodium bicarbonate or calcium carbonate) was studied in simulated gastric fluid (pH 1.2). CNZ release data from the matrix tablets were analyzed kinetically using Higuchi, Peppas, Weibull, and Vergnaud models. From water uptake, matrix erosion studies, and drug release data, the overall release mechanism can be explained as a result of rapid hydration of polymer on the surface of the floating tablet and formation of a gel layer surrounding the matrix that controls water penetration into its center. On the basis of in vitro release data, batch HP1 (CNZ, HPMC-K100LV, SBC, LTS, and MgS) was subjected to bioavailability studies in rabbits and was compared with CNZ suspension. It was concluded that the greater bioavailability of HP1 was due to its longer retention in the gastric environment of the test animal. Batch no. HP1 of floating tablet in rabbits demonstrated that the floating tablet CNZ could be a 24-h sustained release formulation.

  18. Formulation and evaluation of once daily minocycline hydrochloride extended release matrix tablets

    Directory of Open Access Journals (Sweden)

    Keny R

    2009-01-01

    Full Text Available The present study was aimed to develop once daily extended release matrix tablets of minocycline hydrochloride, using hydroxypropylmethylcellulose either alone or in combination with ethyl cellulose as the matrix material in different proportions. The formulated tablets were also compared with a marketed product. The results of the dissolution study indicate that formulations FC-IV, FC-V and FC-VI showed maximum drug release upto 24 h, whereas the marketed product was found to extend the release only up to 14 h. Incase of formulations containing combination of hydroxypropylmethylcellulose and ethyl cellulose (FC-I to FC-IX, the release of the drug was found to be dependent on the relative proportions of hydroxypropylmethylcellulose and ethyl cellulose used in the tablet matrix. Mathematical treatment of the in vitro drug release data suggests that, all the formulations best fitted into first order release kinetics. Drug release from the matrix occurred by combination of two mechanisms, diffusion of drug from tablet matrix and erosion of tablet surface, which was reflected from Higuchi′s model and Erosion plot.

  19. Effect of polymers on in-vitro performance of eplerenone sustained release matrix tablets

    Directory of Open Access Journals (Sweden)

    Sunil Reddy

    2012-01-01

    Full Text Available Objectives: The intention of the present study was to design and assess oral sustained drug delivery systems for Eplerenone, using Cellulose and natural polymers as release modifiers in the form of matrix tablets. Material and methods: Matrix tablets containing cellulose polymers like HPMC K4M, HPMC K15M, NaCMC and natural polymers like Guar Gum, Xanthan Gum, and Karaya Gum were prepared by wet granulation technique using PVP K60 as a tablet binder. Results: The optimized formulation (F1 contains 1: 0.70 ratio (D: HPMC K4M and (F4 contains 1:1 ratio (D: Guar gum respectively. The in-vitro release kinetic studies of prepared matrix tablets with both the polymers were studied. The kinetic treatment illustrate that the optimized formulation (F1 and F4 followed zero order kinetics with release exponent (n 0.87. Drug content in the tablets and amount of drug released were estimated by reported HPLC method. The FT-IR and DSC studies did not show any interaction of drug with the excipients used in the formulation. Conclusion: The results clearly indicated that Eplerenone could be successfully prepared using an appropriate ratio of cellulose polymers like HPMC K4M, and natural gums like Guar gum in the form of matrix tablets

  20. Formulation and evaluation of sustained release matrix tablet of rabeprazole using wet granulation technique

    Directory of Open Access Journals (Sweden)

    Ruqaiyah Khan

    2014-01-01

    Full Text Available Introduction: Rabeprazole, a member of substituted benzimidazoles, inhibits the final step in gastric acid secretions. This drug claims to cause fastest acid separation (due to higher pKa, and more rapidly converts to the active species to aid gastric mucin synthesis. The most significant pharmacological action of Rabeprazole is dose dependent suppression of gastric acid secretion; without anticholinergic or H2-blocking action. It completely abolishes the hydrochloric acid secretion as it is powerful inhibitor of gastric acid. Rabeprazole is acid labile and hence commonly formulated as an enteric coated tablet. The absorption of rabeprazole occurs rapidly as soon as tablet leaves the stomach. Aim: In the present study an attempt was made to formulate and evaluate Rabeprazole sustained release matrix tablet using wet granulation technique incorporating various polymers like HPMC-E15, Carbopol934, and sodium carboxymethyl cellulose (CMC. Materials and Methods: The Formulated tablets were evaluated for different physicochemical properties like rheological properties, weight variation, thickness, hardness, % friability, in vitro release studies and drug content. Results: Studies revealed that all the physicochemical parameters comply with the official standards. The in vitro release studies exhibits the release up to 90%, over a prolonged period of time which confirms the extended release profile of formulation, having better bioavailability as well as decreased dosing frequency with reduced doses. Conclusion: The sustained release matrix tablets of rabiprazole shown better bioavailability, efficacy and potency, when compared with official standards.

  1. FABRICATION AND EVALUATION OF GLIPIZIDE ABELMOSCHUS ESCULENTUS FRUIT MUCILAGE POVIDONE CONTROLLED RELEASE MATRIX TABLETS

    Directory of Open Access Journals (Sweden)

    Hindustan Abdul Ahad

    2011-02-01

    Full Text Available The present investigation was aimed to prepare matrix type controlled release tablets of Glipizide with Abelmoschus esculentus fruit mucilage and Povidone. The polymers were studied for its functionality as a matrix forming property to sustain the Glipizide release from the dosage form. Physicochemical properties of dried powdered mucilage of Abelmoschus esculentus fruit mucilage and Povidone blend were studied. Various formulations of Glipizide Abelmoschus esculentus fruit mucilage and Povidone were prepared. The prepared tablets were found to have better pharmacopoeial parameters with low standard deviation values. The swelling behavior and release rate characteristics were studied. The in-vitro dissolution study proved that the dried Abelmoschus esculentus fruit mucilage and Povidone in combination can be used as a matrix forming polymers for making controlled release matrix tablets.

  2. DESIGN DEVELOPMENT AND EVALUATION OF MODIFIED RELEASE TABLET OF MONTELUKAST SODIUM USING ETHYL CELLULOSE AND TRAGACANTH

    OpenAIRE

    Patel Krunal M

    2011-01-01

    The purpose of this research was to prepare a modified release tablet of montelukast sodium. Montelukast sodium is Leukotriene antagonist which is rapidly absorbed after the oral administration. The drug was mixed with Ethyl Cellulose and Tragacanth as a dry binder and ethanol was used as solvent to perform the granulation in FBD by the bottom spray method. The granules obtain were mixed with the other ingredients and were compressed using 10 station tablet rotary press. The dissolution was c...

  3. Matrix forming excipients from natural origin for controlled release matrix type tablets

    OpenAIRE

    Hamman, Josias Hendrik; Jambwa, T.; Viljoen, A

    2011-01-01

    Since excipients from renewable sources are attractive due to their sustainable mass production, this study aimed at investigating the use of gel and whole leaf materials from Aloe vera and Aloe ferox to produce controlled release mini-matrix type tablets. The flow properties of the aloe materials were determined by means of different tests. Matrix type tablets manufactured from each aloe material individually and in combina- tion with other polymers were evaluated in terms of their physical ...

  4. Dual release and molecular mechanism of bilayered aceclofenac tablet using polymer mixture.

    Science.gov (United States)

    Van Nguyen, Hien; Nguyen, Van Hong; Lee, Beom-Jin

    2016-12-30

    The objectives of the present study were to develop a controlled-release bilayered tablet of aceclofenac (AFN) 200mg with dual release and to gain a mechanistic understanding of the enhanced sustained release capability achieved by utilizing a binary mixture of the sustained release materials. Different formulations of the sustained-release layer were formulated by employing hydroxypropyl methylcellulose (HPMC) and hydroxypropyl cellulose (HPC) as the major retarding polymers. The in vitro dissolution studies of AFN bilayered tablets were carried out in intestinal fluid (pH 6.8 buffer). The mechanism of the synergistic rate-retarding effect of the polymer mixture containing HPC and carbomer was elucidated by the rate of swelling and erosion in intestinal fluid and the molecular interactions in the polymer network. The optimized bilayered tablets had similar in vitro dissolution profiles to the marketed tablet Clanza(®)CR based on the similarity factor (f2) in combination with their satisfactory micromeritic, physicochemical properties, and stability profiles. Drug release from HPMC-based matrix was controlled by non-Fickian transport, while drug release from HPC-based matrix was solely governed by drug diffusion. The swelling and erosion data exhibited a dramatic increase of water uptake and a reduction of weight loss in the polymer mixture-loaded tablet. Fourier transform infrared (FTIR) spectra revealed strong hydrogen bonding between HPC and carbomer in the polymer mixture. Regarding spatial distribution of polymers in the polymer mixture-loaded tablet, carbomer was found to be the main component of the gel layer during the first 2h of the hydration process, which was responsible for retarding drug release at initial stage. This process was then followed by a gradual transition of HPC from the glassy core to the gel layer for further increasing gel strength. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. 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.

  6. Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage

    Directory of Open Access Journals (Sweden)

    M. Kaleemullah

    2017-07-01

    Full Text Available Currently, the use of natural gums and mucilage is of increasing importance in pharmaceutical formulations as valuable drug excipient. Natural plant-based materials are economic, free of side effects, biocompatible and biodegradable. Therefore, Ketoprofen matrix tablets were formulated by employing Hibiscus rosa-sinensis leaves mucilage as natural polymer and HPMC (K100M as a synthetic polymer to sustain the drug release from matrix system. Direct compression method was used to develop sustained released matrix tablets. The formulated matrix tablets were evaluated in terms of physical appearance, weight variation, thickness, diameter, hardness, friability and in vitro drug release. The difference between the natural and synthetic polymers was investigated concurrently. Matrix tablets developed from each formulation passed all standard physical evaluation tests. The dissolution studies of formulated tablets revealed sustained drug release up to 24 h compared to the reference drug Apo Keto® SR tablets. The dissolution data later were fitted into kinetic models such as zero order equation, first order equation, Higuchi equation, Hixson Crowell equation and Korsmeyer-Peppas equation to study the release of drugs from each formulation. The best formulations were selected based on the similarity factor (f2 value of 50% and more. Through the research, it is found that by increasing the polymers concentration, the rate of drug release decreased for both natural and synthetic polymers. The best formulation was found to be F3 which contained 40% Hibiscus rosa-sinensis mucilage polymer and showed comparable dissolution profile to the reference drug with f2 value of 78.03%. The release kinetics of this formulation has shown to follow non-Fickian type which involved both diffusion and erosion mechanism. Additionally, the statistical results indicated that there was no significant difference (p > 0.05 between the F3 and reference drug in terms of MDT and

  7. EFFECT OF FORMULATION VARIABLES ON THE RELEASE OF ACECLOFENAC FROM HPMC MATRIX TABLETS

    Directory of Open Access Journals (Sweden)

    S. R. Mettu

    2011-11-01

    Full Text Available The objective of this work was to study the effect of concentration and viscosity grade of HPMC, different diluents and inclusion of solid dispersions on the matrix tablets of aceclofenac. In present study, aceclofenac, a novel NSAID used for symptomatic treatment of pain and inflammation was formulated into matrix tablets with HPMC of two different viscosity grades (E50 LV and K15 M by direct compression method. Before compression the formulations were evaluated for angle of repose, % compressibility and Hausner’s ratio. Tablets were evaluated for hardness, friability, weight variation, uniformity of thickness and diameter, and drug content. All pre-compressional and post-compressional parameters were found within the official limits. In vitro drug release studies were conducted for a period of 8 hrs using USP paddle method (II at 37±0.5oC and at 75rpm speed in pH 7.2 phosphate buffer. Type of polymer and its concentration has influenced the drug release from matrix tablets. With increasing concentrations and increasing polymer viscosity the release rate decreased. Release rate increased with the addition of PEG and PVP. There was significant increase in drug release by inclusion of solid dispersions in the matrix tablets. It can be concluded that by incorporating water soluble excipients such as PEG and PVP and solid dispersions of drug with PVP into the matrix, drug release can be increased. Dissolution data was analysed by Power law expression, Mt / M¥ = ktn. Release of drug from the tablets varied on the basis of formulation and was found to be non-Fickian and case II transport with different formulations.

  8. Effect of polymers and excipients on the release kinetics, bioadhesion, and floatability of metronidazole tablet

    Directory of Open Access Journals (Sweden)

    Saahil Arora

    2011-01-01

    Full Text Available Stomach-specific floating tablet of metronidazole based on the buoyancy and bioadhesion concept was prepared with a purpose to retain the drug in stomach for longer duration and helps in releasing the drug in the antrum region of gastric mucosa, a safe heaven for Helicobacter pylori. This research work systematically studied the effects of various polymeric blends of bioadhesive polymers namely chitosan and carbopol 971P with low density polymer- methocel K100LV on the desired in vitro drug release profile in the stomach, buoyancy, swelling index, and mucoadhesion of tablet formulation. Chitosan and carbopol 971P concentration significantly influence the in vitro drug release and bioadhesion strength. An increase in buoyancy was observed with increase in Methocel K100LV concentration in the polymeric blend. The increase in buoyancy and drug release was obtained in the presence of microcrystalline cellulose, sodium bicarbonate, and sodium citrate. The optimum formulation provides desired high drug concentration (~35% during 1 hour and sustained release up to 12 hours, following the Higuchi model. The mechanism of release of metronidazole from the floating bioadhesive tablets was anomalous diffusion transport. The studies indicated successful formulation of gastroretentive compressed tablet with excellent controlled release, mucoadhesion, and hydrodynamic balance.

  9. A new approach for preparing a controlled release ketoprofen tablets by using beeswax.

    Science.gov (United States)

    Uner, Melike; Gönüllü, Umit; Yener, Gülgün; Altinkurt, Turan

    2005-01-01

    Solid lipid ketoprofen micropellets (SLKM) at different drug/beeswax ratios [(1:1) and (1:2)] were prepared by emulsion congealing technique and then compressed into tablets. Ketoprofen in solid state was incorporated into the melted beeswax at 90 degrees C and the mixture was emulsified in the hot aqueous Tween 80 solution by stirring at a constant rate. The SLKM were obtained by cooling the coarse emulsion down to room temperature and filtering. Drug entrapment efficiency and particle size analysis by laser diffractometry (LD) were determined, and existence of a drug-lipid interaction was investigated by differential scanning calorimetry (DSC) on the SLKM, before being compressed into the tablets by direct compression method. Finally, in vitro release studies were performed and the release kinetics of the waxy tablets were calculated. A commercial ketoprofen retard tablet (reference: Profenid Retard 200 mg) was also examined to compare the release properties. While the data obtained from DSC were indicating absence of drug-lipid interaction in the SLKM, it was determined that 28.62% (+/-2.08), 38.60% (+/-1.91) and 47.00% (+/-1.82) of ketoprofen was released from the tablets containing (1:2) and (1:1) SLKM and Profenid Retard 200 mg in pH 7.4 phosphate buffer solution after 8 h, respectively.

  10. Recent advances of starch-based excipients used in extended-release tablets: a review.

    Science.gov (United States)

    Hong, Yan; Liu, Guodong; Gu, Zhengbiao

    2016-01-01

    In recent years, polysaccharides, including starch and its derivatives, have been widely used in the pharmaceutical industry, including as diluents, fillers, binders, disintegrants and glidants. The use of native starch as excipient in extended-release tablets is limited due to its low compactibility and enzymatic degradability, leading to the formation of weakly structured tablets. To overcome these limitations and expand the application of starch as an excipient, researchers have modified starch by physical and chemical methods, as well as by enzymatic hydrolysis. Some starch derivatives, including retrograded starch, pregelatinized starch, carboxymethyl starch, starch acetate, cross-linked starch and grafted starch have recently been introduced as excipients in oral tablets to control drug release. In this review, applications of starch and its derivatives as extended release excipients are reviewed and future frontiers are described.

  11. Quantifying the release of lactose from polymer matrix tablets with an amperometric biosensor utilizing cellobiose dehydrogenase.

    Science.gov (United States)

    Knöös, Patrik; Schulz, Christopher; Piculell, Lennart; Ludwig, Roland; Gorton, Lo; Wahlgren, Marie

    2014-07-01

    The release of lactose (hydrophilic) from polymer tablets made with hydrophobically modified poly(acrylic acid) (HMPAA) have been studied and compared to the release of ibuprofen, a hydrophobic active substance. Lactose is one of the most used excipients for tablets, but lactose release has not been widely studied. One reason could be a lack of good analytical tools. A novel biosensor with cellobiose dehydrogenase (CDH) was used to detect the lactose release, which has a polydiallyldimethylammonium chloride (PDADMAC) layer that increases the response. A sample treatment using polyethylenimine (PEI) was developed to eliminate possible denaturants. The developed methodology provided a good approach to detect and quantify the released lactose. The release was studied with or without the presence of a model amphiphilic substance, sodium dodecyl sulphate (SDS), in the release medium. Ibuprofen showed very different release rates in the different media, which was attributed to hydrophobic interactions between the drug, the HMPAA and the SDS in the release medium. The release of hydrophilic lactose, which did not associate to any of the other components, was rapid and showed only minor differences. The new methodology provides a useful tool to further evaluate tablet formulations by a relatively simple set of experiments.

  12. Controlled release of metformin hydrochloride and repaglinide from sandwiched osmotic pump tablet.

    Science.gov (United States)

    Qin, Chao; He, Wei; Zhu, Chunli; Wu, Mengmeng; Jin, Zhu; Zhang, Qiang; Wang, Guangji; Yin, Lifang

    2014-05-15

    The marketed compound tablet of metformin hydrochloride (MH) and repaglinide (RG) exhibits perfect multidrug therapeutic effect of type 2 diabetes. However, due to the short half life of the drugs, the tablet has to be administered 2 to 3 times a day, causing inconvenience to patient and fluctuations of plasma concentration. Here, a sandwiched osmotic pump tablet was developed to deliver the two drugs simultaneously at zero-order rate, in which MH and RG were loaded in different layers separated by a push layer. The osmotic pump tablet was prepared by a combination of three tableting procedure and film coating method. The factors including type and amount of propellant, osmotic active agents, amount of porogenic agent, coating weight, orifice diameter were optimized. The pharmacokinetic study was performed in beagle dogs, and the drug concentration in plasma samples was assayed by HPLC-MS/MS method. Simultaneous, controlled release of MH and RG in the first 12 and 8h was achieved from the optimized formulation. A significantly decreased Cmax, prolonged Tmax and satisfactory bioavailability of the osmotic pump tablet were obtained, and a good in vivo-in vitro correlation of the two drugs was also established. In summary, the sandwiched osmotic pump tablet released the MH and RG simultaneously at zero-order rate, and exhibited significant sustained release effect in vivo and good in vivo-in vitro correlation. The designed controlled release system for MH and RG proposed a promising replacement for the marked compound product in the therapy of type 2 diabetes.

  13. 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.

  14. 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.

  15. In vitro aceclofenac release from IPN matrix tablets composed of chitosan-tamarind seed polysaccharide.

    Science.gov (United States)

    Jana, Sougata; Sen, Kalyan Kumar; Basu, Sanat Kumar

    2014-04-01

    This communication describes the formulation and in vitro evaluation of IPN matrix tablets of aceclofenac. IPN microparticles using chitosan and tamarind seed polysaccharide blend was prepared using glutaraldehyde as cross-linker. The drug entrapment efficiency and average particle size of these microparticles was found to be 91.97±1.30% and 498.12±38.67 μm, respectively. These IPN microparticles were characterized by scanning electron microscopy (SEM) and powder X-ray diffraction (P-XRD) study. These microparticles were compressed with tablet excipients through direct compression technique. These matrix tablets showed sustained aceclofenac release over 8 h. These matrix tablets might be helpful to minimize dosing frequency and reduction of various side effects during prolong period of treatment.

  16. Comparative bioequivalence studies of tramadol hydrochloride sustained-release 200 mg tablets

    OpenAIRE

    Suhas, Khandave; Satish ,Sawant; Santosh ,Joshi; Bansal,Yatish Kumar; Sonal Sushil Kadam,

    2010-01-01

    Suhas S Khandave1, Satish V Sawant1, Santosh S Joshi1, Yatish K Bansal2, Sonal S Kadam21Accutest Research Laboratories (I) Private Limited, Koparkhirne, Navi Mumbai, Maharashtra, India; 2Ipca Laboratories Limited, Kandivli Mumbai, Maharashtra, IndiaBackground: Tramadol hydrochloride is available as 50 mg immediate-release (IR) and 100 mg, 200 mg, and 300 mg sustained-release (SR) tablets. The recommended dose of tramadol is 50–100 mg IR tablets every 4–6 hours. The tramado...

  17. Evaluation of rate of swelling and erosion of verapamil (VRP) sustained-release matrix tablets.

    Science.gov (United States)

    Khamanga, Sandile M; Walker, Roderick B

    2006-01-01

    Tablets manufactured in-house were compared to a marketed sustained-release product of verapamil to investigate the rate of hydration, erosion, and drug-release mechanism by measuring the wet and subsequent dry weights of the products. Swelling and erosion rates depended on the polymer and granulating fluid used, which ultimately pointed to their permeability characteristics. Erosion rate of the marketed product was highest, which suggests that the gel layer that formed around these tablets was weak as opposed to the robust and resistant layers of test products. Anomalous and near zero-order transport mechanisms were dominant in tests and commercial product, respectively.

  18. EFFECT OF NATURAL AND SYNTHETIC POLYMER ON RELEASE OF KETOTIFEN FUMARATE MATRIX TABLETS: A SUSTAINED RELEASE DOSAGE FORM

    Directory of Open Access Journals (Sweden)

    Md. M. Rahman*, A. B. Ripon Khalipha , Md. A. K. Azad , MD. Z. Faruki , A. K. Chaurasiya and H. Hossain

    2013-04-01

    Full Text Available ABSTRACT: With the blend of Methocel K15, a synthetic polymer and xanthan gum, a natural polymer (3:1 was used in the formulation of matrix tablets to find out the effect of natural polymer in the sustained release dosage form. Direct compression process was applied for the preparation of Ketotifen fumarate tablets. The dissolution profiles were carried out by USP apparatus 2 (paddle at 50 rpm in 500 ml 0.1 N HCl and distilled water. For interpreting the results a one way analysis of variance (ANOVA was exploited. Statistically significant differences were found among the drug release profile from different matrices. At a higher polymeric content (60% of the total tablet weight, drug release from the combination of Methocel K15M and xanthan gum (3:1 was slower. On the contrary, at a lower polymeric level (30% of the total tablet weight; the rate of drug release was prominent. The best-fit release kinetics was accomplished with the Higuchi model followed by the zero-order plot, Korsmeyer and Hixson Crowell equations. One formulation showed drug release is more controlled. The data obtained proved that the formulations are useful for a sustained release of ketotifen fumarate. From these formulations corresponded more controlled of the drug release by the higher polymeric level of methocel K15M & xanthan gum and vice versa. The extended release of the model drug found from the higher proportion of methocel K15M and xanthan gum. As a result, the frequency of administration of such type of drug reduced.

  19. 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...

  20. 罗布麻定时脉冲片的制备及体外释药特性研究%Preparation and in vitro release characteristics of pulsed-release tablets of Apocynum venetum

    Institute of Scientific and Technical Information of China (English)

    杨华生; 谢富贵; 杨乐文; 罗永明

    2011-01-01

    Objective: Using Apocynum venetum as a model drug to prepare pulsed-release tablets based on diffusion, swelling, osmotic pressure mechanism and to evaluate the release characteristics.Method: The pulsatile release tablets were prepared by film coating methods using HPMC E5 and Eudragit.The effect of formulation on pulsatile release of A.venetum was investigated.Result: The pulsed-release tablet was prepared by a swelling layer coating which contains HPMC E5 and a controlled-release membrane containning Eudragit.The delayed release time of the tablets was (5.0 ± 0.5) h.Conclusion: The pulsatile release characteristics of A.venetum pulsatile release tablets were confirmed in vitro.%目的:以罗布麻为模型药物,研制基于扩散、溶胀、渗透压机制的定时脉冲片,并考察其体外释药特性.方法:通过体外释放度试验,考察片芯崩解剂种类与用量、渗透压活性物质种类与用量、包衣液的组成与厚度等处方因素对脉冲片体外释放的影响.结果:脉冲片由含有罗布麻干浸膏的片芯及外包2层衣膜构成,内层为溶胀层,由HPMC E5构成;外层为控释层,由Eudragit RS100,RL100的混合物构成.该制剂在体外释放时滞为(5±0.5)h.结论:罗布麻脉冲片在体外具有脉冲释放特性.

  1. Effect of molecular weight and glass transition on relaxation and release behaviour of poly(DL-lactic acid) tablets

    NARCIS (Netherlands)

    Steendam, R.; Van Steenbergen, M.J.; Hennink, W.E.; Frijlink, H.W.; Lerk, C.F.

    2001-01-01

    Different molecular weight grades of poly(DL-lactic acid) were applied as release controlling excipients in tablets for oral drug administration. The role of molecular weight and glass transition in the mechanism of water-induced volume expansion and drug release of PDLA tablets was investigated. Mo

  2. FORMULATION AND EVALUATION OF TIZANIDINE SUSTAINED RELEASE MATRIX TABLETS USING HYDROXY PROPYL METHY CELLULOSE

    Directory of Open Access Journals (Sweden)

    Ankita Srivastava et al

    2012-09-01

    Full Text Available Tizanidine is a muscle relaxant agent, with the half life of 2.5 hours and requires daily doses to maintain adequate plasma concentrations. The present study was undertaken to with an aim to formulation development and evaluation of Tizanidine hydrochloride sustained release tablets using hydrophilic polymer to sustain the action of Tizanidine. Different batches of Tizanidine hydrochloride were prepared based on preformulation studies using HPMC K100M HPMC K4M and HPMC K100 having different viscosities to calculate the sustained release properties. Tizanidine hydrochloride was analysed by using HPLC using wavelength 240 nm. Results of in-vitro study indicate that the trial formulation 5 having considerable sustaining property. From the discussion it is concluded that the trial formulation 5 had considerable in-vitro drug release. Trial formulation 5 can be taken as an ideal or optimized formulation of sustained release tablets for 12 hours release and it fulfils all the requirements for sustained.

  3. Preparation and evaluation of novel metronidazole sustained release and floating matrix tablets.

    Science.gov (United States)

    Asnaashari, Solmaz; Khoei, Nazaninossadat Seyed; Zarrintan, Mohammad Hosein; Adibkia, Khosro; Javadzadeh, Yousef

    2011-08-01

    In the present study, metronidazole was used for preparing floating dosage forms that are designed to retain in the stomach for a long time and have developed as a drug delivery system for better eradication of Helicobacter Pylori in peptic ulcer diseases. For this means, various formulations were designed using multi-factorial design. HPMC, psyllium and carbopol in different concentrations were used as floating agents, and sodium bicarbonate was added as a gas-forming agent. Hardness, friability, drug loading, floating ability and release profiles as well as kinetics of release were assessed. Formulations containing HPMC as filler showed prolonged lag times for buoyancy. Adding psyllium to these formulations had reduced relative lag times. Overall, selected formulations were able to float immediately and showed buoyancy for at least 8?h. Meanwhile, sustained profiles of drug release were also obtained. Kinetically, among the 10 assessed models, the release pattern of metronidazole from the tablets fitted best to Power law, Weibull and Higuchi models in respect overall to mean percentage error values of 3.8, 4.73 and 5.77, respectively, for calcium carbonate-based tablets and, 2.95, 6.39 and 3.9, respectively, for calcium silicate-based tablets. In general, these systems can float in the gastric condition and control the drug release from the tablets.

  4. Design of Controlled Release Non-erodible Polymeric Matrix Tablet Using Microwave Oven-assisted Sintering Technique.

    Science.gov (United States)

    Patel, Dm; Patel, Bk; Patel, Ha; Patel, Cn

    2011-07-01

    The objective of the present study was to evaluate the effect of sintering condition on matrix formation and subsequent drug release from polymer matrix tablet for controlled release. The present study highlights the use of a microwave oven for the sintering process in order to achieve more uniform heat distribution with reduction in time required for sintering. We could achieve effective sintering within 8 min which is very less compared to conventional hot air oven sintering. The tablets containing the drug (propranolol hydrochloride) and sintering polymer (eudragit S-100) were prepared and kept in a microwave oven at 540 watt, 720 watt and 900 watt power for different time periods for sintering. The sintered tablets were evaluated for various tablet characteristics including dissolution study. Tablets sintered at 900 watt power for 8 min gave better dissolution profile compared to others. We conclude that microwave oven sintering is better than conventional hot air oven sintering process in preparation of controlled release tablets.

  5. Evaluation of Calendula mucilage as a mucoadhesive and controlled release component in buccal tablets.

    Science.gov (United States)

    Sabale, V; Patel, V; Paranjape, A

    2014-01-01

    Mucoadhesive drug delivery systems were developed to sustain drug delivery via various mucus membranes for either local or systemic delivery of poorly absorbed drugs such as peptides and proteins as well as drugs that are subjected to high first-pass metabolism. The present study was undertaken to use isolated Calendula mucilage as a mucoadhesive agent and to formulate controlled release buccoadhesive tablets with an intention to avoid hepatic first-pass metabolism as well as to enhance residence time of drug in the buccal cavity. The mucilage was isolated from the Calendula petals by aqueous extraction method and characterized for various physiochemical parameters as well as for its adhesive properties. By using direct compression technique, tablets were prepared containing dried mucilage and chlorpheniramine maleate (CPM) as a model drug. Three batches of tablets were prepared and evaluated containing three mucoadhesive components namely Methocel K4M, Carbopol 974P and isolated Calendula mucilage in 16.66%, 33.33 % and 50 % (1:2:3 ratio) resulting in 9 different formulations. FTIR studies between mucilage and CPM suggested the absence of a chemical interaction between CPM and Calendula mucilage. The results of the study showed that the isolated mucilage had good physicochemical and morphological characteristics and tablets conformed to the pharmacopoeial specifications. Also in vitro release studies showed controlled action of drug with increasing the concentration of the isolated Calendula mucilage as a mucoadhesive agent in the formulations. Permeability studies indicated that permeability behavior was not statistically different (P>0.05) by changing the mucoadhesive component. The formulated mucoadhesive tablets for buccal administration containing 75 mg Calendula mucilage showed controlled drug release. Thus, mucoadhesive natural Calendula mucilage based buccal tablets for controlled release were successfully formulated.

  6. Matrix formation in sustained release tablets: possible mechanism of dose dumping.

    Science.gov (United States)

    Krajacic, Aleksandra; Tucker, Ian G

    2003-01-30

    Conditions under which poly(ethyl acrylate, methyl methacrylate) 2:1 (poly(EA-MMA), Eudragit NE) forms a stable matrix were investigated in tablets with diclofenac sodium (DS) as an active substance. DS was granulated with the aqueous polymer dispersion. Granules and/or tablets were cured under various temperature and humidity conditions. A six position rotating disk (200 rpm) apparatus was used for the release studies conducted in 37 degrees C acid then phosphate buffer (0.4 M) pH 6.8 or buffer only as the dissolution media. Morphological characteristics of the tablet surface were observed under SEM. Changes in tablet structure upon curing were evaluated through changes in tablet mechanical characteristics. Modulus of rupture, Young's modulus, AUC, AUC(max), where AUC=AUC(max), were determined by the three-point bending test. Some poorly cured tablets dose-dumped when placed directly into buffer but not if first placed in acid and then buffer. A higher content of polymer in the matrix, led to formation of a stronger polymer network upon higher curing temperature and/or longer curing duration, whereas relative humidity had a minor effect.

  7. Formulation and evaluation of controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum

    Directory of Open Access Journals (Sweden)

    Gurpreet Arora

    2011-01-01

    Full Text Available The aim of study was to prepare controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum as natural polymer. Tablets were formulated by direct compression technology employing the natural polymer in different concentrations (5, 10, 15 and 20% w/w. The prepared batches were evaluated for drug assay, diameter, thickness, hardness and tensile strength, swelling index, mucoadhesive strength (using texture analyzer and subjected to in vitro drug release studies. Real-time stability studies were also conducted on prepared batches. In vitro drug release data were fitted in various release kinetic models for studying the mechanism of drug release. Tensile strength was found to increase from 0.808 ± 0.098 to 1.527 ± 0.10 mN/cm 2 and mucoadhesive strength increased from 13.673 ± 1.542 to 40.378 ± 2.345 N, with an increase in the polymer concentration from 5 to 20% (A1 to A4. Swelling index was reported to increase with both increase in the concentration of gum and the time duration. The in vitro drug release decreased from 97.76 to 83.4% (A1 to A4 with the increase in polymer concentration. The drug release from the matrix tablets was found to follow zero-order and Higuchi models, indicating the matrix-forming potential of natural polymer. The value of n was found to be between 0.5221 and 0.8992, indicating the involvement of more than one drug release mechanism from the formulation and possibly the combination of both diffusion and erosion. These research findings clearly indicate the potential of S. plebeian gum to be used as binder, release retardant and mucoadhesive natural material in tablet formulations.

  8. Influence of Different Polymer Types on the Overall Release Mechanism in Hydrophilic Matrix Tablets

    Directory of Open Access Journals (Sweden)

    Bengt Wittgren

    2009-07-01

    Full Text Available The effect of three different types of polymer chain structures on the polymer release from hydrophilic matrix tablets was investigated by comparing a synthetic semi-crystalline linear polymer (PEO, a branched amorphous polysaccharide (dextran and an amorphous substituted cellulose derivative (HPMC. The polymer release rates for tablets containing mixtures of high and low molecular weight grades in different ratios were determined by using a modified USP II method and a SEC-RI chromatography system. The results showed that independent of polymer type: (i plots of the release versus time had similar shapes, (ii the release of long and short polymer chains was equal and no fractionation occurred during the release and (iii the release rate could be related to the average intrinsic viscosity of the polymer mixtures. This confirms the hypothesis that the release rate can be related to a constant viscosity on the surface of the hydrophilic matrix tablet and that it is valid for all the investigated polymers.

  9. Influence of ethanol on swelling and release behaviors of Carbopol(®)-based tablets.

    Science.gov (United States)

    Rahim, Safwan Abdel; Al-Ghazawi, Mutasim; Al-Zoubi, Nizar

    2013-01-01

    The aim of this work was to investigate the effect of ethanol on the in vitro swelling and release behaviors of Carbopol(®)-based tablets. The swelling behavior of drug-free compacts and the release of model drugs (metformin HCl, caffeine and theophylline) from matrix tablets were evaluated in acidic and buffered media with 0, 20 and 40% (v/v) ethanol. Release data were analyzed by fitting to Higuchi and Peppas models and calculation of similarity factor (f2). ANOVA tests were performed to determine significant factors on swelling and release. It was found that ethanol affects swelling and erosion of drug-free Carbopol(®) compacts, and the effect was highly dependent on medium pH. For matrix tablets, no dose dumping due to ethanol was manifested. The release rate and mechanism, however, were significantly affected by ethanol concentration as indicated by ANOVA applied to the constant, KH, from Higuchi model and the exponent, n, from Peppas model, respectively. The effect of ethanol on release was further confirmed by similarity factor results, which indicated that ethanol led to different release profiles (f2 < 50) in seven of eight cases for matrices containing metformin HCl and in three of eight cases for matrices containing caffeine and theophylline.

  10. A pharmacokinetic comparison of the modified release capsule and a plain tablet formulation of mebeverine.

    Science.gov (United States)

    Winsemius, A; Meuwsen, I M; Boon, C; van der Laan, A; Brekle, A; de Vries, M

    2002-11-01

    This study was conducted to compare the pharmacokinetic properties of the modified release 200 mg capsule of mebeverine and the plain 135 mg tablet of mebeverine after single and multiple doses in 12 healthy subjects in a randomised, crossover design. Single doses were given on days 1 and 7 and multiple doses (200 mg b.i.d. for the capsule and 135 mg t.i.d. for the tablet) on days 2-6 of the study. The 200 mg modified release capsule of mebeverine has extended release properties, as indicated by a lower Cmax, a later tmax and a longer elimination half-life than the plain tablet, while the bioavailability is optimal. No significant accumulation occurs after multiple doses of either formulation. The twice-daily dosage regimen of the 200 mg modified release capsule is a good alternative to the three times daily dosage regimen of the 135 mg plain tablet, because the reduced daily intake is likely to benefit patient compliance.

  11. The effect of hydrophilic and hydrophobic polymers on release profiles of diclofenac sodium from matrix tablets

    Directory of Open Access Journals (Sweden)

    Md Imamul Islam

    2013-01-01

    Conclusion: The present study demonstrated that Diclofenac could be successfully prepared using an appropriate amount of Methocel K15 MCR® and CA in the form of matrix tablets with similar dissolution profile of patent product Voltaren SR® . The type of polymers used was found to induce a profound effect on release rate and mechanism.

  12. IDENTIFICATION OF PHARMACEUTICAL EXCIPIENT BEHAVIOR OF CHICKPEA (CICER ARIETINUM) STARCH IN GLICLAZIDE IMMEDIATE RELEASE TABLETS.

    Science.gov (United States)

    Meka, Venkata Srikanth; Yee, Phung; Sheshala, Ravi

    2016-01-01

    In the past few years, there are number of researchers carrying out their research on the excipients derived from polysaccharides and some of these researches show that natural excipients are comparable and can serve as an alternative to the synthetic excipients. Hence, the objectives of this research are to characterize the naturally sourced chickpea starch powder and to study the pharmaceutical excipient behavior of chickpea starch in gliclazide immediate release (IR) tablets. In this research, the binding properties of chickpea starch were compared to that of povidone, whereas the disintegrant properties of chickpea starch were compared to those of crospovidone, croscarmellose sodium and sodium starch glycolate. Flow property of chickpea starch was assessed with the measurement of bulk density, tapped density, compressibility index and angle of repose. Calibration curve for gliclazide in phosphate buffer pH 7.4 was developed. Gliclazide IR tablets were then produced with direct compression method. Physicochemical characteristics of the tablets, including thickness, tablet weight uniformity, hardness, disintegration time and friability were evaluated. Then, in vitro dissolution studies were performed by following United States Pharmacopeia (USP) dissolution method. The dissolution results were analyzed and compared with t30, t50, dissolution efficiency (DE). Lastly, drug-excipient compatibility studies, including Fourier transform infrared (FTIR) spectroscopic analysis and differential scanning calorimetric (DSC) analysis were carried out. Fair flow property was observed in the chickpea starch powder. Furthermore, the tablets produced passed all the tests in physicochemical characteristics evaluation except hardness and disintegration test. Additionally, in vitro dissolution studies show that chickpea starch acted as a disintegrant instead of a binder in gliclazide IR tablets and its disintegrant properties were comparable to those of crospovidone, croscarmellose

  13. Physicochemical properties of harpagoside and its in vitro release from Harpagophytum procumbens extract tablets.

    Science.gov (United States)

    Chrubasik, S; Sporer, F; Dillmann-Marschner, R; Friedmann, A; Wink, M

    2000-01-01

    The objective of this investigation was to characterize the active-component harpagoside of Harpagophytum extract from a physico-chemical perspective and to determine its in-vitro release from tablets according to DAB 1996. It was found that both pure harpagoside and harpagoside in Harpagophytum extract have an octanol-water distribution coefficient of approximately 4 which is neither dependent on temperature nor on pH. The mean harpagoside content in Harpagophytum tablets of Batch 9102 was 16.4 mg (S.D. 0.2; S.E. 0.03). Related to a tablet weight of 365 mg (100%), this corresponds to a haragoside content of 4.5% (S.D. 0.049; S.E. 0.006). On average the tablets disintegrate after 18 +/- 3 minutes (mean +/- SD). The tablets taken from Batch 9102 released the active component harpagoside well, with a t50 of 13.5 min, a t90 of 23 min and a t95 of 25 min in relation to 16.5 mg of harpagoside per dose. Harpagoside content decreased by about 10% in artificial gastric fluid within a period of 3 hours and remained stable in artificial intestinal fluid for a period of 6 hours.

  14. A novel electrostatic dry powder coating process for pharmaceutical dosage forms: immediate release coatings for tablets.

    Science.gov (United States)

    Qiao, Mingxi; Zhang, Liqiang; Ma, Yingliang; Zhu, Jesse; Chow, Kwok

    2010-10-01

    An electrostatic dry powder coating process for pharmaceutical solid dosage forms was developed for the first time by electrostatic dry powder coating in a pan coater system. Two immediate release coating compositions with Opadry® AMB and Eudragit® EPO were successfully applied using this process. A liquid plasticizer was sprayed onto the surface of the tablet cores to increase the conductivity of tablet cores to enhance particle deposition, electrical resistivity reduced from greater than 1×10(13)Ωm to less than 1×10(9)Ωm, and to lower the glass transition temperature (T(g)) of the coating polymer for film forming in the pan coater. The application of liquid plasticizer was followed by spraying charged coating particles using an electrostatic charging gun to enhance the uniform deposition on tablet surface. The coating particles were coalesced into a thin film by curing at an acceptable processing temperature as formation was confirmed by SEM micrographs. The results also show that the optimized dry powder coating process produces tablets with smooth surface, good coating uniformity and release profile that are comparable to that of the tablet cores. The data also suggest that this novel electrostatic dry powder coating technique is an alternative to aqueous- or solvent-based coating process for pharmaceutical products. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

  15. The Preparation of Salbutamol Sulfate Controlled Release TabletsCoated with Cellulose Acetate Aqueous Dispersion

    Institute of Scientific and Technical Information of China (English)

    ZhangFengyu; WuTao; PanWeisan; ChenJimin; ZhangRuhua

    2001-01-01

    In this study, emulsion-solvent evaporation method was applied to prepare the cellulose acetate(CA) aqueous dispersion. Upon the analyzing of the character of the aqueous dispersion, a controlled releaseformulation of salbutamol sulfate coated with cellulose acetate aqueous dispersion was prepared through orthogonalexperiment design. The factors that control the drug release character of the tablets were investigated. The drugrelease mechanism of the formulation was also studied. The experimental results indicated that CA aqueousdispersion had excellent film-forming ability under the effect of plasticizer. The drug release profile of the controlledrelease tablets coated with CA aqueous dispersion exhibited zero-order release character and the drug release rate wasmodulated by the osmotic pressure of the dissolution medium.

  16. In Vitro – In Vivo Evaluation of Sustained – Release Lithium Carbonate Matrix Tablets: Influence of Hydrophilic Matrix Materials

    Directory of Open Access Journals (Sweden)

    J Emami

    2004-04-01

    Full Text Available Background: Conventional Lithium carbonate (LC tablets produce rapid and relatively high peak blood levels resulting in adverse effects. These drawbacks can be overcome by designing a suitable sustained or controlled-release LC preparation. Methods: Sustained-release matrix tablets were therefore developed using different types and ratios of polymers including carbomer (CP, Na carboxymethylcellulose (Na CMC and hydroxypropylmethylcellulose (HPMC, to assess the release profiles and in vivo performance of the formulations. The tablets were prepared by either direct compression (DC or wet granulation (WG. In the DC method, 69% (450 mg LC, 5, 10 or 15% CP or Na CMC (of total tablet weight, lactose and /or Avicel (to maintain constant tablet weight were mixed and directly compressed. In the WG method, 450 mg LC and 10, 20, or 30% HPMC were granulated with Eudragit S100 solution, dried, and then compressed to formulate the tablets. In vitro and in vivo, newly formulated sustained-release LC tablets were compared with sustained-release commercial tablets (Eskalith and Priadel. In vivo studies were conducted in nine healthy subjects in a cross-over design, with a 3x3 Latin square sequence, and pharmacokinetic parameters were estimated using classical methods. Results: The matrix tablets containing 15% CP exhibited suitable release kinetics and uniform absorption characteristics comparable to that of Eskalith. In vivo, this formulation produced a smooth and extended absorption phase very much similar to that of Eskalith with the identical elimination half-life and extent of absorption. Conclusion: The matrix tablets containing 15% CP reduces the incidence of side effects often associated with high serum concentration of Lithium and blood level variations. Direct correlation between the dissolution profiles and the relative bioavailability of the formulations could be observed. Keywords: Lithium carbonate, Matrix tablets, Sustained-release, In vitro

  17. Formulation and evaluation of bilayer tablet for bimodal release of venlafaxine hydrochloride

    OpenAIRE

    2015-01-01

    The aim of the present research was to develop a bilayer tablet of venlafaxine hydrochloride for bimodal drug release. In the present investigation authors have tried to explore fenugreek mucilage (FNM) for bioadhesive sustained release layer. The attempt has been made to combine FNM with well studied bioadhesive polymers like hydroxy propyl methyl cellulose (HPMC), Carbopol, and Xanthan Gum. The formulations were evaluated for swelling Index, ex vivo bioadhesion, water uptake studies, in vit...

  18. Design and development of bilayer tablet for immediate and extended release of acarbose and metformin HCl

    OpenAIRE

    Meenakshi Joshi; Ruchi Tiwari; Gaurav Tiwari

    2014-01-01

    The present investigation studied a novel Bilayer tablet having extended release (ER) system of metformin HCl (M.HCl) with Eudragit RS 100 and RL 100 and immediate release (IR) system of Acarbose with PVP K30 and PEG 6000 in different ratios using solvent evaporation technique. Solid dispersions (SDs) were characterized by Fourier Transform-Infra Red spectroscopy, Diffrential Scanning Calorimetry, X-Ray Diffractometry and Scanning Electron Microscopy. Selected SD system was subjected to Bilay...

  19. On the Correlation of Effective Terahertz Refractive Index and Average Surface Roughness of Pharmaceutical Tablets

    Science.gov (United States)

    Chakraborty, Mousumi; Bawuah, Prince; Tan, Nicholas; Ervasti, Tuomas; Pääkkönen, Pertti; Zeitler, J. Axel; Ketolainen, Jarkko; Peiponen, Kai-Erik

    2016-08-01

    In this paper, we have studied terahertz (THz) pulse time delay of porous pharmaceutical microcrystalline compacts and also pharmaceutical tablets that contain indomethacin (painkiller) as an active pharmaceutical ingredient (API) and microcrystalline cellulose as the matrix of the tablet. The porosity of a pharmaceutical tablet is important because it affects the release of drug substance. In addition, surface roughness of the tablet has much importance regarding dissolution of the tablet and hence the rate of drug release. Here, we show, using a training set of tablets containing API and with a priori known tablet's quality parameters, that the effective refractive index (obtained from THz time delay data) of such porous tablets correlates with the average surface roughness of a tablet. Hence, THz pulse time delay measurement in the transmission mode provides information on both porosity and the average surface roughness of a compact. This is demonstrated for two different sets of pharmaceutical tablets having different porosity and average surface roughness values.

  20. Development and evaluation of controlled-release buccoadhesive verapamil hydrochloride tablets

    Directory of Open Access Journals (Sweden)

    Emami J.

    2008-05-01

    Full Text Available Background and purpose of the study: Verapamil hydrochloride is a calcium channel blocker which is used in the control of supraventricular arrhythmia, hypertension and myocardial infraction. There are considerable inter-individual variations in serum concencentration of verpamil due to variation in the extent of hepatic metabolism. In this study controlled-release buccoadhesive tablets of verapamil hydrochloride (VPH were prepared in order to achieve constant plasma concentrations, to improve the bioavailability by the avoidance of hepatic first-pass metabolism, and to prevent frequent administration. Materials and methods: Tablets containing fixed amount of VPH were prepared by direct compression method using polymers like carbomer (CP, hydroxypropylmethyl cellulose (HPMC and sodium carboxymethyl cellulose (NaCMC in various combination and ratios and evaluated for thickness, weight variation, hardness, drug content uniformity, swelling, mucoadhesive strength, drug release and possible interaction between ingredients. Results: All tablets were acceptable with regard to thickness, weight variation, hardness, and drug content. The maximum bioadhesive strength was observed in tablets formulated with a combination of CP-NaCMC followed by CP-HPMC and NaCMC-HPMC.  Decreasing the content of CP in CP-HPMC tablets or NaCMC in CP-NaCMC or NaCMC-HPMC systems resulted in decrease in detachment forces. Lower release rates were observed by lowering the content of CP in CP-HPMC containing formulations or NaCMC in tablets which contained CP-NaCMC or NaCMC-HPMC. The release behavior was non-Fickian controlled by a combination of diffusion and chain relaxation mechanisms and best fitted zero-order kinetics. Conclusion: The buccoadhesive VPH tablets containing 53% CP and 13.3% HPMC showed suitable release kinetics (n = 0.78, K0 zero order release = 4.11 mg/h, MDT = 5.66 h and adhesive properties and did not show any interaction between polymers and drug based on

  1. DESIGN DEVELOPMENT AND EVALUATION OF MODIFIED RELEASE TABLET OF MONTELUKAST SODIUM USING ETHYL CELLULOSE AND TRAGACANTH

    Directory of Open Access Journals (Sweden)

    Patel Krunal M

    2011-01-01

    Full Text Available The purpose of this research was to prepare a modified release tablet of montelukast sodium. Montelukast sodium is Leukotriene antagonist which is rapidly absorbed after the oral administration. The drug was mixed with Ethyl Cellulose and Tragacanth as a dry binder and ethanol was used as solvent to perform the granulation in FBD by the bottom spray method. The granules obtain were mixed with the other ingredients and were compressed using 10 station tablet rotary press. The dissolution was carried out using USP paddle apparatus.

  2. Core-in-cup tablet design of metoprolol succinate and its evaluation for controlled release.

    Science.gov (United States)

    Nagaraju, Ravouru; Meera, Durgumahanthi Sai; Kaza, Rajesh; Arvind, Vakati Venkata; Venkateswarlu, Vobalaboina

    2009-12-01

    The core-in-cup matrix tablets of Metoprolol succinate were prepared by wet granulation technique. Of all the investigated formulations, the optimized formulation of MS-09 followed zero-order kinetics of drug release. Trail on MS-09 was formulated using 7.5% hydrogenated castor-oil (HCO) and 4% of hydroxyl propyl methylcellulose (HPMC K15M) with an objective to achieve a linear release profile for 24 h. There is no initial burst release, with 16.17% of drug released during the first hour and release was extended up to 24 hrs. Study of drug release kinetics was performed by application of dissolution data to various kinetic equations like zero-order; first order, Higuchi and Korsmeyer-Peppas, from R(2) value (0.9975) it was concluded that the drug release followed zero order kinetics with both erosion and diffusion as the release mechanisms.

  3. Examples of NIR based real time release in tablet manufacturing.

    NARCIS (Netherlands)

    Skibsted, E.; Westerhuis, J.A.; Smilde, A.K.; Witte, D.T.

    2007-01-01

    Real time release (RTR) of products is a new paradigm in the pharmaceutical industry. An RTR system assures that when the last manufacturing step is passed all the final release criteria are met. Various types of models can be used within the RTR framework. For each RTR system, the monitoring capabi

  4. Preparation of fenofibrate immediate-release tablets involving wet grinding for improved bioavailability.

    Science.gov (United States)

    Zhang, Lili; Chai, Guihong; Zeng, Xueping; He, Haibing; Xu, Hui; Tang, Xing

    2010-09-01

    The purpose of this study was to investigate the dissolution and oral bioavailability of an immediate-release tablet involving wet grinding of a poorly water-soluble drug, fenofibrate. The milled suspension was prepared using a Basket Dispersing Mill in the presence of a hydrophilic polymer solution and then granulated with common excipients, and compressed into an immediate-release tablet with blank microcrystalline cellulose granules. Compared with unmilled tablets (56% within 30 minutes), the dissolution of wet-milled tablets (about 98% in 30 minutes) was markedly enhanced. No significant decrease in the dissolution rate (96% in 30 minutes) of the wet-milled tablet was observed after 3 months under 40 degrees C and 75% relative humidity storage. In addition, the oral bioavailability of the wet-milled tablets (test) and Lipanthyl supra-bioavailability tablets (reference) was determined in beagle dogs after a single dose (160 mg fenofibrate) in a randomized crossover, own-control study. The results suggested that both the area under the plasma concentration-time curve (AUC((0-t)) = 46.83 +/- 11.09 microg/mL h) and the mean peak concentration of the test (C(max) = 4.63 +/- 1.71 microg/mL) were higher than the reference (AUC((0-t)) = 35.12 +/- 10.97 microg/mL h, C(max) = 2.11 +/- 0.08 microg/mL). The relative bioavailability of the wet-milled tablet was approximately 1.3-fold higher. Furthermore, the apparent rate of absorption of fenofibrate from the wet-milled tablet (T(max) = 2.63 hours) was faster than that from Lipanthyl (T(max) = 3.75 hours). These results indicated that the dissolution and the bioavailability of fenofibrate were significantly enhanced by wet-grinding process. So, this shows that wet grinding is a powerful technique to improve the bioavailability for poorly water-soluble drugs, especially for Biopharmaceutics Classification System Class II compounds.

  5. Design and In-vitro Evaluation of Sustained Release Floating Tablets of Metformin HCl Based on Effervescence and Swelling

    OpenAIRE

    Senjoti, Faria Gias; Mahmood, Syed; Jaffri, Juliana Md; Mandal, Uttam Kumar

    2016-01-01

    An oral sustained-release floating tablet formulation of metformin HCl was designed and developed. Effervescence and swelling properties were attributed on the developed tablets by sodium bicarbonate and HPMC-PEO polymer combination, respectively. Tablet composition was optimized by response surface methodology (RSM). Seventeen (17) trial formulations were analyzed according to Box-Behnken design of experiment where polymer content of HPMC and PEO at 1: 4 ratio (A), amount of sodium bi-carbon...

  6. Sustained-release of caffeine from a polymeric tablet matrix: An in vitro and pharmacokinetic study

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Donna [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore); Zhao Bin [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore); Moochhala, Shabbir [Defence Medical and Environmental Research Institute, DSO National Laboratories (Kent Ridge), 27 Medical Drive, 12-00, Singapore 117597 (Singapore)]. E-mail: mshabbir@dso.org.sg; Yang Yiyan [Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, 04-01, The Nanos, Singapore 138669 (Singapore)

    2006-07-25

    Caffeine is utilized as a stimulant to impart a desired level of alertness during certain working hours. Usually, a single dose of caffeine induces 2-3 h of alertness coupled with side effects whereas a longer effect of 8-12 h is very useful for both daily life and military action. Thus, there is a need to deliver the stimulant continuously to an individual at one time to impart an increased level of alertness for the period stated after administration. This study aimed to design a polymeric microparticle system for sustained delivery of caffeine using a polymeric matrix. Poly(ethylene oxide) (PEO) was used as the erodible matrix material and the caffeine polymeric tablets were fabricated by compression using a Graseby Specac hydraulic press. In vitro release profiles as well as the pharmacokinetics studies data were obtained. Caffeine tablets fabricated using various polymers showed a high initial burst release type profile as compared to the caffeine-PEO-tablet. The PK studies showed sustained delivery of caffeine resulted in two expected phenomena: a reduction in the initial high rate of caffeine release (burst release) as well as a reduction in the change in caffeine concentration in the systemic circulation. A simple two-component system for sustained-release caffeine formulation therefore has been achieved.

  7. Formulation and evaluation of modified-release effervescent floating tablets of ofloxacin

    Directory of Open Access Journals (Sweden)

    Sarat Chandra Prasad Malisetty

    2013-01-01

    Full Text Available Aims: Ofloxacin is used as anti-microbial agent. Due to its high solubility in gastric pH, a floating drug delivery system was selected to improve the bioavailability and therapeutic efficacy of the drug. Settings and Design: The purpose of the study was to prepare and evaluate effervescent floating tablets of ofloxacin to prolong its gastric residence and increase bioavailability. Materials and Methods: Drug, semi-synthetic and natural polymers, such as HPMC K4M, Guar gum, Xanthan gum and Chitosan, were used. Sodium bicarbonate and citric acid were used as gas-generating agents and tablet compression was done by direct compression. The prepared tablets were characterized and were evaluated for in vitro floating behavior, swelling index, in vitro drug release studies and release kinetics. Results: Formulation F6 containing xanthan gum and chitosan in a 1:1 ratio attained sustained release for 12 h and drug release observed was about 76.7%. Swelling index was in the range 62.17 ± 1.49% to 194.02 ± 1.05%. Floating lag time was observed in the range 4.11-6.26 min. Conclusion: The in vitro results showed better drug release conditions, supported by follow-up in vivo studies, suggesting that this formulation is advantageous over the current marketed formulation, through increased gastric residence and bioavailability.

  8. 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.

  9. 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.

  10. 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).

  11. Formulation and evaluation of floating tablets of niacin for sustained release

    Directory of Open Access Journals (Sweden)

    Haripriya Puthoori

    2012-01-01

    Full Text Available Niacin or nicotinic acid (NA is used in the treatment of hyperlipidemia. NA immediate release formulation shows undesirable effects like flushing of the face and neck parts. In the present study, NA floating sustained release dosage form was developed to prolong the drug release, to retain the drug delivery system above the site of absorption for the desired period of time, and to reduce the drug release rate compared to conventional formulations in order to minimize the side effects. The preformulation parameters such as flow properties and drug-excipient compatibility studies were performed. The drug excipient compatibility studies were performed using the FTIR study and the results showed that all the polymers used in the study are compatible with the pure drug. The floating sustained release tablets of niacin were prepared by the wet granulation method and the granules were evaluated for various micromeritic properties like bulk density, tapped density, Carr′s Index, Hausner′s ratio, and angle of repose. The tablets were evaluated for post-compressional parameters like average weight, thickness, hardness, friability, swelling index, floating lag time and total floating time, and in vitro drug release studies. All the formulations showed total floating time >20 hr. The concentration of the effervescent agent and the concentration and type of polymer showed an effect on the floating behavior and drug release. The formulation containing 13% sodium bicarbonate, HPMC (33% and Eudragit RS PO (4% showed required drug release up to 20 hr.

  12. Formulation and optimization of sustained release tablets of venlafaxine resinates using response surface methodology

    Directory of Open Access Journals (Sweden)

    Madgulkar Ashwini

    2009-01-01

    Full Text Available The aim of the current study was to design sustained release matrix tablets of venlafaxine hydrochloride using ion exchange resin with the incorporation of hydrophilic and hydrophobic polymer combinations. Venlafaxine HCl was loaded onto Indion 244 by batch method and then resinate were wet granulated with ethyl cellulose and blended with hydroxypropylmethylcellulose and compressed. A central composite design for 2 factors at 3 levels each was employed to systematically optimize drug release profile at 2 h and at 18 h. Hydroxypropylmethylcellulose and ethylcellulose were taken as the independent variables. Response surface plots and contour plots were drawn, and optimum formulations were selected by feasibility and grid searches. Resinate shows inadequate sustained release profile. Compressed matrices exhibited the anomalous release mechanism, as the value of release rate exponent (n varied between 08109 and 08719, resulting in regulated and complete release until 20 h. Validation of optimization study, performed using five confirmatory runs, indicated very high degree of prognostic ability of response surface methodology, with mean percentage error as 1.152±1.88%. Regulated drug release study indicates that the hydrophilic and hydrophobic matrix tablets of venlafaxine resinate prepared using hydroxypropylmethylcellulose and ethylcellulose, can successfully be employed as a once-a-day oral controlled release drug delivery system.

  13. 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.

  14. 3D printing of modified-release aminosalicylate (4-ASA and 5-ASA) tablets.

    Science.gov (United States)

    Goyanes, Alvaro; Buanz, Asma B M; Hatton, Grace B; Gaisford, Simon; Basit, Abdul W

    2015-01-01

    The aim of this study was to explore the potential of fused-deposition 3-dimensional printing (FDM 3DP) to produce modified-release drug loaded tablets. Two aminosalicylate isomers used in the treatment of inflammatory bowel disease (IBD), 5-aminosalicylic acid (5-ASA, mesalazine) and 4-aminosalicylic acid (4-ASA), were selected as model drugs. Commercially produced polyvinyl alcohol (PVA) filaments were loaded with the drugs in an ethanolic drug solution. A final drug-loading of 0.06% w/w and 0.25% w/w was achieved for the 5-ASA and 4-ASA strands, respectively. 10.5mm diameter tablets of both PVA/4-ASA and PVA/5-ASA were subsequently printed using an FDM 3D printer, and varying the weight and densities of the printed tablets was achieved by selecting the infill percentage in the printer software. The tablets were mechanically strong, and the FDM 3D printing was shown to be an effective process for the manufacture of the drug, 5-ASA. Significant thermal degradation of the active 4-ASA (50%) occurred during printing, however, indicating that the method may not be appropriate for drugs when printing at high temperatures exceeding those of the degradation point. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) of the formulated blends confirmed these findings while highlighting the potential of thermal analytical techniques to anticipate drug degradation issues in the 3D printing process. The results of the dissolution tests conducted in modified Hank's bicarbonate buffer showed that release profiles for both drugs were dependent on both the drug itself and on the infill percentage of the tablet. Our work here demonstrates the potential role of FDM 3DP as an efficient and low-cost alternative method of manufacturing individually tailored oral drug dosage, and also for production of modified-release formulations.

  15. FORMULATION DEVELOPMENT AND IN-VITRO EVALUATION OF SUSTAINED RELEASE MATRIX TABLETS OF SALBUTAMOL SULPHATE

    Directory of Open Access Journals (Sweden)

    AMITAVA GHOSH KOUSHIK SEN GUPTA

    2013-09-01

    Full Text Available ABSTRACT: The objective of the present study was to develop salbutamol sulphate matrix tablets, sustained release dosage form, for the treatment of Chronic Obstructive Pulmonary Disease (COPD. Simultaneous equations were formed to calculate the concentration values of Salbutamol sulphate and drug compatibility study was performed through Infrared spectroscopy. The matrix tablets were prepared by wet granulation method using two hydrophobic polymers such as Ethyl cellulose and Acrycoat S-100 in varying ratios. The granules exhibited satisfactory rheological demeanor. All the seven tablet formulations showed acceptable pharmacotechnical properties and complied with the in-house specifications for tested parameters. The results of formulation F-4 (Ethyl cellulose and Acrycoat in 2:1 ratio could extend the release of Salbutamol sulphate up to 12 hr and was found comparable to marketed sustained release products. Model fitting analysis (Zero order, Higuchi and Korsmeyer-Peppas model for all the formulations were performed and it was seen that all the formulations predominantly follow the Higuchi model. While comparing with the ‘n’ values of all the formulations of Korsmeyer-Peppas model, Fickian/Diffusion controlled release was observed in case of F-4 and F-5, whereas for the other formulations non-Fickian transport was observed.

  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. Formulation And Evaluation Of Bilayer Tablet for Bimodal Release of Venlafaxine Hydrochloride

    Directory of Open Access Journals (Sweden)

    Munira eMomin

    2015-07-01

    Full Text Available The aim of the present research was to develop a bilayer tablet of venlafexine hydrochloride for bimodal drug release. In the present investigation authors have tried to explore Fenugreek Mucilage (FNM for bioadhesive sustained release layer. The attempt has been made to combine FNM with well studied bioahesive polymers like Hydroxy Propyl Methyl Cellulose, Carbopol and Xanthan Gum. The formulations were evaluated for swelling Index, ex-vivo bioadhesion, water uptake studies, in-vitro drug release and dissolution kinetics was studied. Substantial bioadhesion force (2.4±0.023 gms and tablet adhesion retention time (24±2 hrs was observed with FNM and HPMC combination at 80:20 ratio. The dissolution kinetics followed the Higuchi model (R2 =0.9913 via a non-Fickian diffusion controlled release mechanism after the initial burst. The 32 full factorial design was employed in the present study. The type of polymers used in combination with FNM (X1 and percent polymer replaced with FNM (X2 were taken as independent formulations variables. The selected responses, bioadhesion force (0.11-0.25±0.023gm, amount of drug released in 10 h, Y10 (78.20–95.78±1.24 % and bioadhesive strength, (19-24±2hrs presented good correlation with the selected independent variables. Statistical analysis (ANOVA of the optimized bilayer formulations showed no significant difference in the cumulative amount of drug release after 15 min, but significant difference (p < 0.05 in the amount of drug released after 1 hr till 12 h from optimized formulations was observed. The natural mucilage like FNM could be successfully incorporated into tablet with only 20% replacement with HPMC and it showed good bioadhesiveness and sustained drug release.

  18. FORMULATION, OPTIMIZATION AND EVALUATION OF BILAYERED TABLETS OF AMLODIPINE BESILATE AS IMMEDIATE RELEASE AND METOPROLOL SUCCINATE AS SUSTAINED RELEASE

    OpenAIRE

    Arup Ratan Deb; Vivek Keshri; Padmakana Malakar

    2013-01-01

    The purpose of the study was to develop a bilayer tablet of Amlodipine besilate (IR) and Metoprolol succinate (SR) having different release pattern, which is indicated for the management of hypertension. The study was planned in three stages. In the first stage six batches (A1, A2, A3, A4, A5 and A6) of immediate release tables of Amlodipine besilate was prepared by direct compression method using sodium starch glycolate and pre-gelatinised starch as super disintegrant. In the second stage, s...

  19. Design and in vivo evaluation of oxycodone once-a-day controlled-release tablets

    Directory of Open Access Journals (Sweden)

    Kim JY

    2015-01-01

    Full Text Available Ju-Young Kim,1,* Sung-Hoon Lee,2,3,* Chun-Woong Park,4 Yun-Seok Rhee,5 Dong-Wook Kim,6 Junsang Park,3 Moonseok Lee,3 Jeong-Woong Seo,2 Eun-Seok Park2 1College of Pharmacy, Woosuk University, Wanju-gun, Republic of Korea; 2School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea; 3GL Pharmtech, Seongnam, Republic of Korea; 4College of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea; 5College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Republic of Korea; 6Department of Pharmaceutical Engineering, Cheongju University, Cheongju, Republic of Korea *These authors contributed equally to this work Abstract: The aim of present study was to design oxycodone once-a-day controlled-release (CR tablets and to perform in vitro/in vivo characterizations. Release profiles to achieve desired plasma concentration versus time curves were established by using simulation software and reported pharmacokinetic parameters of the drug. Hydroxypropyl methylcellulose (HPMC 100,000 mPa·s was used as a release modifier because the polymer was found to be resistant to changes in conditions of the release study, including rotation speed of paddle and ion strength. The burst release of the drug from the CR tablets could be suppressed by applying an additional HPMC layer as a physical barrier. Finally, the oxycodone once-a-day tablet was comprised of two layers, an inert HPMC layer and a CR layer containing drug and HPMC. Commercial products, either 10 mg bis in die (bid [twice a day] or once-a-day CR tablets (20 mg were administered to healthy volunteers, and calculated pharmacokinetic parameters indicated bioequivalence of the two different treatments. The findings of the present study emphasize the potential of oxycodone once-a-day CR tablets for improved patient compliance, safety, and efficacy, which could help researchers to develop new CR dosage forms of oxycodone. Keywords

  20. 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.

  1. HPLC Method for the Determination of Tamsulosin Hydrochloride in Sustained Release Tablets

    Institute of Scientific and Technical Information of China (English)

    齐美玲; 王鹏; 耿颖姝; 顾峻岭

    2003-01-01

    The development and validation of an isocratic high performance liquid chromatographic method is described for the determination of tamsulosin hydrochloride in sustained release tablets. The determination was performed on a Diamonsil BDS C18 column with a mobile phase consisting of a mixture of acetonitrile, methanol and 0.5% phosphoric acid solution (20∶30∶50,V/V/V) at a flow rate of 1.0 mL/min. UV detection was made at 274 nm. The linear range for tamsulosin hydrochloride was 0.81-8.10 μg/mL. The mean recovery was 99.8% (SR=0.7%, n=9), and the precision was found to be 0.45% (n=9). The proposed method can be used for routine analysis of tamsulosin hydrochloride in sustained release tablets.

  2. In Vitro-In Vivo Correlation Evaluation of Generic Alfuzosin Modified Release Tablets

    OpenAIRE

    2012-01-01

    Alfuzosin, a selective alpha-1a antagonistis is the most recently approved AARAS, with limited cardiac toxicity and exclusively used for lower urinary tract syndromes (LUTS). In order to reduce pill burden and better patient compliance modified release (MR) formulations have been developed. Alfuzosin MR tablet was developed by the use of hot-melt granulation techniques using mono- and diglycerides as rate controlling membranes to minimize health care cost and uses of costly excipients. The ot...

  3. Bioequivalence of Sandoz methylphenidate osmotic-controlled release tablet with Concerta® (Janssen-Cilag)

    OpenAIRE

    Schapperer, Elisabeth; Daumann, Heike; Lamouche, Stéphane; Thyroff-Friesinger, Ursula; Viel, François; Weitschies, Werner

    2015-01-01

    The aim was to assess the bioequivalence of Sandoz methylphenidate osmotic-controlled release (OCR) tablets (Sandoz [Methylphenidate[ MPH OCR) with Concerta®, a methylphenidate formulation indicated for the treatment of attention deficit/hyperactivity disorder (ADHD). Four open-label, randomized, single-dose, two-way crossover bioequivalence studies were conducted in healthy subjects: three fasting studies with 54-, 36- and 18-mg doses of methylphenidate, and one fed study with the 54-mg dose...

  4. WATER HYACINTH: A POSSIBLE ALTERNATIVE RATE RETARDING NATURAL POLYMER USED IN SUSTAINED RELEASE TABLET DESIGN

    Directory of Open Access Journals (Sweden)

    Sabera eKhatun

    2014-06-01

    Full Text Available In recent years natural polymers have been widely used, because of their effectiveness and availability over synthetic polymers. In this present investigation matrix tablets of Metformin hydrochloride were formulated using Water hyacinth powder and its rate retardant activity was studied. Tablets were prepared using wet granulation method with 8% starch as granulating agent and 5%, 10%, 15%, 20%, 25% and 30% of Water hyacinth powder to the drug. In preformulation study, angle of repose, Carr’s Index and Hausner ratio were calculated. Fourier Transform Infrared Spectroscopy (FTIR, Differential Scanning Calorimetry (DSC and Scanning Electron Microscopy (SEM studies were performed and no interactions were found between drug and excipients. Weight variation, friability, hardness, thickness, diameter, and in vitro release study were performed with the prepared matrix tablets. Dissolution studies were conducted using USP type II apparatus at a speed of 100 rpm at 37oC ± 0.5 temperature, for 8 hours. All the formulations comply with both BP and USP requirements, but among all the formulations F-1 (5% of Water hyacinth was the best fitted formula. The drug release patterns were explained in different kinetic models such as Zero order, First order, Higuchi, Hixson Crowell and Korsmeyer-Peppas equations. The current investigation implies that Water hyacinth has the potential to be used as a rate-retarding agent in sustained release drug formulations.

  5. HPLC determination and pharmacokinetics of sustained-release bupropion tablets in dogs.

    Science.gov (United States)

    Zhang, Dandan; Yuan, Bo; Qiao, Mingxi; Li, Famei

    2003-09-19

    The pharmacokinetics and bioequivalency of a newly developed sustained-release bupropion tablet was studied in six dogs after single oral administration and compared with a regular tablet (RT) in randomized two-period crossover design. A sensitive and rapid HPLC method was developed and validated for the quantitative determination of bupropion in dog plasma. The compound and the internal standard (I.S.) (hydroxyethylfludiazepam) were extracted from the plasma samples by liquid-liquid extraction. The extracts were analyzed by a reversed-phase HPLC with 50 mmol/l phosphate buffer (pH 5.5)-methanol (45:55, v/v) as the eluent. The assay was specific for bupropion. The calibration curves were linear in the range between 1 and 750 ng/ml. The validated lower limit of quantification was 1 ng/ml. The overall precision (expressed as R.S.D.) of quality controls were within 15%. The method was successfully applied to the bioequivalency study of bupropion in the two formulations. The Cmax of sustained-release tablet (ST) was significantly lower than that of the RT and the Tmax was significantly longer than that of the RT (P<0.05). The relative bioavailability of the ST was (99.1+/-1.51)%, the results of ANOVA and two one sided tests indicated that the new ST exhibited good sustained release properties and was bioequivalent to the RT.

  6. Effect of polysulfonate resins and direct compression fillers on multiple-unit sustained-release dextromethorphan resinate tablets.

    Science.gov (United States)

    Pongjanyakul, Thaned; Priprem, Aroonsri; Chitropas, Padungkwan; Puttipipatkhachorn, Satit

    2005-09-30

    The purpose of this work was to investigate the effect of different polysulfonate resins and direct compression fillers on physical properties of multiple-unit sustained-release dextromethorphan (DMP) tablets. DMP resinates were formed by a complexation of DMP and strong cation exchange resins, Dowex 50 W and Amberlite IRP69. The tablets consisted of the DMP resinates and direct compression fillers, such as microcrystalline cellulose (MCC), dicalcium phosphate dihydrate (DCP), and spray-dried rice starch (SDRS). Physical properties of tablets, such as hardness, disintegration time, and in vitro release, were investigated. A good performance of the tablets was obtained when MCC or SDRS was used. The use of rod-like and plate-like particles of Amberlite IRP69 caused a statistical decrease in tablet hardness, whereas good tablet hardness was obtained when spherical particle of Dowex 50 W was used. The plastic deformation of the fillers, such as MCC and SDRS, caused a little change in the release of DMP. A higher release rate constant was found in the tablets containing DCP and Dowex 50 W, indicating the fracture of the resinates under compression, which was attributable to the fragmentation of DCP. However, the release of DMP from the tablets using Amberlite IRP69 was not significantly changed because of the higher degree of cross-linking of the resinates, which exhibited more resistance to deformation under compression. In conclusion, the properties of polysulfonate resin, such as particle shape and degree of cross-linking, and the deformation under compaction of fillers affect the physical properties and the drug release of the resinate tablets.

  7. Controlled release from triple layer, donut-shaped tablets with enteric polymers.

    Science.gov (United States)

    Kim, Cherng-ju

    2005-10-22

    The purpose of this research was to evaluate triple layer, donut-shaped tablets (TLDSTs) for extended release dosage forms. TLDSTs were prepared by layering 3 powders sequentially after pressing them with a punch. The core tablet consisted of enteric polymers, mainly hydroxypropyl methylcellulose acetate succinate, and the bottom and top layers were made of a water-insoluble polymer, ethyl cellulose. Drug release kinetics were dependent on the pH of the dissolution medium and the drug properties, such as solubility, salt forms of weak acid and weak base drugs, and drug loading. At a 10% drug loading level, all drugs, regardless of their type or solubility, yielded the same release profiles within an acceptable level of experimental error. As drug loading increased from 10% to 30%, the drug release rate of neutral drugs increased for all except sulfathiazole, which retained the same kinetics as at 10% loading. HCl salts of weak base drugs had much slower release rates than did those of neutral drugs (eg, theophylline) as drug loading increased. The release of labetalol HCl retarded as drug loading increased from 10% to 30%. On the other hand, Na salts of weak acid drugs had much higher release rates than did those of neutral drugs (eg, theophylline). Drug release kinetics were governed by the ionization/erosion process with slight drug diffusion, observing no perfect straight line. A mathematical expression for drug release kinetics (erosion-controlled system) of TLDSTs is presented. In summary, a TLDST is a good design to obtain zero-order or nearly zero-order release kinetics for a wide range of drug solubilities.

  8. Drug release-modulating mechanism of hydrophilic hydroxypropylmethylcellulose matrix tablets: distribution of atoms and carrier and texture analysis.

    Science.gov (United States)

    Park, Jun-Bom; Lim, Jisung; Kang, Chin-Yang; Lee, Beom-Jin

    2013-12-01

    Although release profiles of drug from hydrophilic matrices have been well recognized, the visual distribution of hydroxypropylmethylcellulose (HPMC) and atoms inside of internal structures of hydrophilic HPMC matrices has not been characterized. In this paper, drug release mechanism from HPMC matrix tablet was investigated based on the release behaviors of HPMC, physical properties of gelled HPMC tablet and atomic distributions of formulation components using diverse instruments. A matrix tablet consisting of hydroxypropyl methylcellulose (HPMC 6, 4,000 and 100,000 mPa·s), chlorpheniramine maleate (CPM) as a model and fumed silicon dioxide (Aerosil(®) 200) was prepared via direct compression. The distribution of atoms and HPMC imaging were characterized using scanning electron microscope (SEM)/ energy-dispersive X-ray spectroscopy (EDX), and near-infrared (NIR) analysis, respectively as a function of time. A texture analyzer was also used to characterize the thickness and maintenance of gel layer of HPMC matrix tablet. The HPMC matrix tablets showed Higuchi release kinetics with no lag time against the square root of time. High viscosity grades of HPMC gave retarded release rate because of the greater swelling and gel thickness as characterized by texture analyzer. According to the NIR imaging, low-viscosity-grade HPMC (6 mPa·s) quickly leached out onto the surface of the tablet, while the high-viscosity-grade HPMC (4000 mPa·s) formed much thicker gel layer around the tablet and maintained longer via slow erosion, resulting in retarded drug release. The atomic distribution of the drug (chlorine, carbon, oxygen), HPMC (carbon, oxygen) and silicon dioxide (silica, oxygen) and NIR imaging of HPMC corresponded with the dissolution behaviors of drug as a function of time. The use of imaging and texture analyses could be applicable to explain the release- modulating mechanism of hydrophilic HPMC matrix tablets.

  9. FORMULATION AND EVALUATION OF EXTENDED RELEASE MATRIX TABLETS OF TRIMETAZIDINE DIHYDROCHLORIDE

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    Mogili Dinesh

    2013-01-01

    Full Text Available Oral ingestion has long been the most convenient and commonly employed route of drug delivery. Indeed, for Extended release systems, the oral route of administration has by far received the most attention with respect to research on physiological and drug constraints as well as design and testing of products. The primary objective of the extended release (Matrix drug delivery system is to ensure safety and to improve efficacy of drug as well as patient compliance. The present invention provides a novel sustained release composition comprising Trimetazidine Dihydrochloride. The objective of the present study was to formulate and evaluate once daily extended release matrix tablets of Trimetazidine Dihydrochloride using hydrophilic polymers Hydroxypropylmethylcellulose, Polyox, and natural polymer Xanthan gum. Trimetazidine has a half life 6 hrs and usual oral dosage regimen 0.5 mg and 60 mg daily. To reduce the frequency of administration and to improve patient compliance, a once-daily extended release formulation of Trimetazidine is desirable. The most commonly used method of modulating the drug release is to include it in a matrix system. Hydrophilic polymer matrix systems were widely used in oral controlled drug delivery because they make it easier to achieve a desirable drug-release profile, they are cost effective and they have broad US Food and Drug Administration acceptance. Hence, in present work, an attempt has been made to develop once daily sustained release matrix tablets of Trimetazidine using putative hydrophilic matrix materials. The drug release for extended duration using a hydrophilic matrix system is restricted because of rapid diffusion of dissolved drug through the hydrophilic gel network.

  10. Effect of formulation composition on the properties of controlled release tablets prepared by roller compaction.

    Science.gov (United States)

    Hariharan, Madhusudan; Wowchuk, Christina; Nkansah, Paul; Gupta, Vishal K

    2004-07-01

    This study discusses the effect of formulation composition on the physical characteristics and drug release behavior of controlled-release formulations made by roller compaction. The authors used mixture experimental design to study the effect of formulation components using diclofenac sodium as the model drug substance and varying relative amounts of microcrystalline cellulose (Avicel), hydroxypropyl methylcellulose (HPMC), and glyceryl behenate (Compritol). Dissolution studies revealed very little variability in drug release. The t70 values for the 13 formulations were found to vary between 260 and 550 min. A reduced cubic model was found to best fit the t70 data and gave an adjusted r-square of 0.9406. Each of the linear terms, the interaction terms between Compritol and Avicel and between all three of the tested factors were found to be significant. The longest release times were observed for formulations having higher concentrations of HPMC or Compritol. Tablets with higher concentrations of Avicel showed reduced ability to retard the release of the drug from the tablet matrix. Crushing strength showed systematic dependence on the formulation factors and could be modeled using a reduced quadratic model. The crushing strength values were highest at high concentrations of Avicel, while tablets with a high level of Compritol showed the lowest values. A predicted optimum formulation was derived by a numerical, multiresponse optimization technique. The validity of the model for predicting physical attributes of the product was also verified by experiment. The observed responses from the calculated optimum formulation were in very close agreement with values predicted by the model. The utility of a mixture experimental design for selecting formulation components of a roller compacted product was demonstrated. These simple statistical tools can allow a formulator to rationally select levels of various components in a formulation, improve the quality of products, and

  11. FORMULATION AND EVALUATION OF SUSTAINED RELEASE LIQUISOLID TABLETS OF METOPROLOL SUCCINATE

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    Jarag Ravindra Jagannath

    2013-03-01

    Full Text Available Liquisolid technique is the novel concept of drug delivery via the oral route. This technique is applied to poorly water soluble, water insoluble or liphophilic drugs. According to the new formulation method of liquisolid compacts, liquid medications such as solutions or suspensions of water insoluble drugs in suitable non-volatile vehicles can be converted into acceptably flowing and compressible powders by blending with selected powder excipients. The present research endeavor is directed towards the development of liquisolid compact for the production of sustained release tablet of water-soluble Metoprolol succinate. Liquisolid compacts were prepared by using Tween 80 as the liquid vehicle or non-volatile solvent, Avicel PH 102 as absorbing carrier and Aerosil 200 as adsorbing coating material. The prepare dliquisolid systems were evaluated for their micromeretic properties and possible drug-excipients interactions. P-XRD analysis confirmed that no change in crystallinity of Metoprolol succinate Liquisolid compacts. The DSC and IR spectra analysis study ruled out no any significant interaction between the drug and excipients used in preparation of Metoprolol succinate Liquisolid compacts. The tableting properties were falling within acceptable limits. The in vitro dissolution study confirmed reduction in drug release from Liquisolid compacts compared to conventional matrix tablet, in-vivo study was carried out to check the plasma drug concentration. Tween 80 has plasticizer effect by which it can reduce the glass transition temperature of polymer and impart flexibility in sustaining the release of drug from liquisolid matrices. The results showed that wet granulation had a remarkable impact on the release rate of Metoprolol succinate from liquisolid compacts, reducing the release rate of drug from liquisolid compacts.

  12. Influence of Selected Natural Polymers on In-vitro Release of Colon Targeted Mebeverine HCl Matrix Tablet

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    Dharmarajsinh Chauhan

    2012-06-01

    Full Text Available The objective of the present study was to develop and evaluate colon specific matrices of mebeverine HCl using various polysaccharides like guar gum, Locust bean gum and xanthan gum by direct compression method. The matrix tablets were evaluated for their physico-chemical properties, swelling study, in-vitro release study and stability studies. The prepared tablets were found to be uniform with respect to thickness (5.53 to 6.03 mm and hardness (5.7 to 6.9 kg/cm2. The friability (0.41 to 0.95 % and weight variation (1.04-1.66% of different batch of tablets were found within prescribed limits. Drug content (96.01 to 99.89 % was found uniform within the batches of different tablets. Swelling studies indicated that, matrix tablets prepared with XG (X4 swelled more as compared to those prepared using GG and LBG. Release profiles indicated that, increase in the polymer concentration has drastically retarded the release of Mebeverine Hcl. The optimized tablets prepared using GG (G4, LG (L4 & XG (X4 showed controlled release over periods of 24 hrs, whereas the marketed product controlled the drug release over a period of 12 hrs. The mechanism of drug release was Non-Fickian diffusion controlled first order kinetics for optimized matrix tablets of GG (G4 and LBG (L4 where as for XG (X4 it followed Highuchi model. The developed matrix tablets can be viewed as a better approach in the colonic delivery of Mebeverine HCl.

  13. Formulation optimization of hydrodynamically balanced oral controlled release bioadhesive tablets of tramadol hydrochloride.

    Science.gov (United States)

    Singh, Bhupinder; Rani, Ashu; Babita; Ahuja, Naveen; Kapil, Rishi

    2010-01-01

    The directly compressible floating-bioadhesive tablets of tramadol were formulated using varying amounts Carbopol 971P (CP) and hydroxy-propylmethyl cellulose (HPMC), along with other requisite excipients. In vitro drug release profile, floatational characteristics and ex vivo bioadhesive strength using texture analyzer were determined, and systematically optimized using a 3(2) central composite design (CCD). The studies indicated successful formulation of gastroretentive compressed matrices with excellent controlled release, mucoadhesion and hydrodynamic balance. Comparison of the dissolution profiles of the optimized formulation, with optimal composition of CP:HPMC :: 80.0:125.0, with that of the marketed controlled release formulation other indicated analogy of drug release performance with each other. Validation of optimization study using eight confirmatory experimental runs indicated very high degree of prognostic ability of CCD with mean  SEM of â0.06%  0.37. Further, the study successfully unravels the effect of the polymers on the selected response variables.

  14. Formulation and evaluation of sustained release matrix tablets of pioglitazone hydrochloride using processed Aloe vera mucilage as release modifier

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    Manoj Choudhary

    2015-01-01

    Full Text Available Background: Natural gums and mucilage which hydrates and swells on contact with aqueous media are used as additives in the formulation of hydrophilic drug delivery system. Aim: The purpose of this study was to develop a new monolithic matrix system for complete delivery of Pioglitazone hydrochloride (HCl, in a zero-order manner over an extended time period using processed Aloe vera gel mucilage (PAG as a release modifier. Materials and Methods: The matrices were prepared by dry blending of selected ratios of polymer and ingredients using direct compression technique. Physicochemical properties of dried powdered mucilage of A. vera were studied. Various formulations of pioglitazone HCl and A. vera mucilage were prepared using different drug: Polymer ratios viz., 1:1, 1:2, 1:3, 1:4, 1:5 for PAG by direct compression technique. Results: The formulated matrix tablets were found to have better uniformity of weight and drug content with low statistical deviation. The swelling behavior and in vitro release rate characteristics were also studied. Conclusion: The study proved that the dried A. vera mucilage can be used as a matrix forming material for controlled release of Pioglitazone HCl matrix tablets.

  15. IVIVR in oral absorption for fenofibrate immediate release tablets using dissolution and dissolution permeation methods.

    Science.gov (United States)

    Buch, P; Holm, P; Thomassen, J Q; Scherer, D; Kataoka, M; Yamashita, S; Langguth, P

    2010-10-01

    In a previous study it has been demonstrated that a dissolution/permeation (D/P) system can discriminate between different immediate release fenofibrate formulations. The fractions permeated were correlated with fenofibrate's in vivo exposure in rats following p.o. administration. In the present study more detailed investigations are presented using data from six fenofibrate tablets tested in vivo in humans. In these pharmacokinetic studies no significant differences between formulations in AUC but in Cmax were found. Differences between the Cmax values were not explained by the dissolution characteristics of the tablets but were rationalized on the basis of micellar entrapment and diminished mobility of the active ingredient by surfactants in the formulations. This was demonstrated by a permeation system using dialysis membranes. Thus a permeation step in addition to dissolution measurement may significantly improve the establishment of an IVIV relationship.

  16. Effect of binders on the release rates of direct molded verapamil tablets using twin-screw extruder in melt granulation.

    Science.gov (United States)

    Tan, David Cheng Thiam; Chin, William Wei Lim; Tan, En Hui; Hong, Shiqi; Gu, Wei; Gokhale, Rajeev

    2014-03-10

    Conventional manufacturing of pharmaceutical tablets often involves single processes such as blending, granulation, milling and direct compression. A process that minimizes and incorporates all these in a single continuous step is desirable. The concept of omitting milling step followed by direct-molding of tablets utilizing a twin-screw extruder in a melt granulation process using thermoplastic binders was explored. The objective of this study was to investigate the effect of combining hydrophilic binder (HPMC K4M, PEO 1M), and hydrophobic binder (Compritol® ATO 888, Precirol® ATO 5) on the release profiles of direct-molded tablets and direct-compressed tablets from milled extrudates using a quality-by-design approach. It was identified that hydrophilic binder type and process significantly affects (p=0.005) the release profiles of verapamil. Moreover, two-way interaction analysis demonstrated that the combination of process with type of hydrophilic polymer (p=0.028) and the type of hydrophilic polymer with polymer ratio (p=0.033) significantly affected the release profiles. The formulation release kinetics correlated to Higuchi release model and the mechanism correlated to a non-Fickian release mechanism. The results of the present study indicated that direct-molded tablets with different release profiles can be manufactured without milling process and through a continuous melt granulation using twin-screw extruder with appropriate thermoplastic binder ratio.

  17. CONTROLLED RELEASE FORMULATION DEVELOPMENT AND EVALUATION OF FELODIPINE MATRIX TABLETS BY USING HYDROPHOBIC POLYMERS

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    S. Kiran Kumar*, T. Ramarao, D.B.R.N. Bikshapathi and K.N. Jayaveera

    2013-01-01

    Full Text Available Felodipine is a long-acting 1, 4-dihydropyridine calcium channel blocker, used to control hypertension by selective action on peripheral resistance. The conventional felodipine tablet gives a rather high peak and comparatively low trough levels, due to rapid absorption and distribution. More sustained plasma concentrations might thus produce a more even effect on blood pressure. The main aim of the study was to improve dissolution rate of the dosage form in a controlled manner over extended period of 24 hrs. Matrix tablets were prepared by direct compression method,using hydrophobic polymers like Glyceryl monostearate and Carnauba wax. The prepared formulations were evaluated for hardness, thickness, weight variation, friability and in-vitro dissolution studies. Among all the formulations F8 was selected as optimized formulation based on the evaluation parameters and in-vitro release profile of 100% drug release for 24 hrs. The FTIR and DSC results of optimized formulation showed no drug-excipient interaction. For optimized formulation(F8, the drug release mechanism was explored and explained by zero-order (r2=0.984, first-order (r2=0.947, Higuchi (r2=0.967 and Korsmayer-peppas (r2=0.982 & n=0.855 equations, which explained the drug release follows zero-order and is fit for Higuchi equation & mechanism was anomalous diffusion i.e diffusion and erosion.

  18. Formulation and evaluation of controlled release floating matrix tablets of Stavudine

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    Suryadevara Vidyadhara

    2012-01-01

    Full Text Available The purpose of this research was to prepare and evaluate floating drug delivery systems of Stavudine. Floating matrix tablets of Stavudine were developed to prolong gastric residence time and increase its bioavailability. Rapid gastrointestinal transit could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy of the administered dose. The matrix tablets were prepared by direct compression technique, using polymers such as hydroxylpropylmethyl cellulose (HPMC K15M, karaya gum and other standard excipients. Sodium bicarbonate was incorporated as a gas-generating agent. The effect of different concentrations of polymers on drug release profile and floating properties were investigated. Comparable release profiles between the commercial product and the designed system were obtained. The matrix formulations were evaluated for physical parameters, drug release by in vitro dissolution studies and in vitro buoyancy studies. Surface characteristics, drug-excipient interactions and crystal morphology of optimized formulations were evaluated by SEM analysis and DSC studies.

  19. Formulation Development and Stability Studies of Norfloxacin Extended-Release Matrix Tablets

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    Paulo Renato Oliveira

    2013-01-01

    Full Text Available The aim of this research was to develop a new hydrophilic matrix system containing norfloxacin (NFX. Extended-release tablets are usually intended for once-a-day administration with benefits to the patient and lower discontinuation of the therapy. Formulations were developed with hydroxypropylmethylcellulose or poly(ethylene oxide as hydrophilic polymers, with different molecular weights (MWs and concentrations (20 and 30%. The tablets were found to be stable (6 months at 40±2°C and 75±5% relative humidity, and the film-coating process is recommended to avoid NFX photodegradation. The dissolution profiles demonstrated an extended-release of NFX for all developed formulations. Dissolution curves analyzed using the Korsmeyer exponential equation showed that drug release was controlled by both drug diffusion and polymer relaxation or erosion mechanisms. A more erosion controlled system was obtained for the formulations containing lower MW and amount of polymer. With the increase in both MW and amount of polymer in the formulation, the gel layer became stronger, and the dissolution was more drug-diffusion dependent. Formulations containing intermediate MW polymers or high concentration (30% of low MW polymers demonstrated a combination of extended and complete in vitro drug release. This way, these formulations could provide an increased bioavailability in vivo.

  20. Formulation Development and Stability Studies of Norfloxacin Extended-Release Matrix Tablets

    Science.gov (United States)

    Oliveira, Paulo Renato; Klein, Lilian; Sangoi, Maximiliano da Silva; Bernardi, Larissa Sakis; Silva, Marcos Antônio Segatto

    2013-01-01

    The aim of this research was to develop a new hydrophilic matrix system containing norfloxacin (NFX). Extended-release tablets are usually intended for once-a-day administration with benefits to the patient and lower discontinuation of the therapy. Formulations were developed with hydroxypropylmethylcellulose or poly(ethylene oxide) as hydrophilic polymers, with different molecular weights (MWs) and concentrations (20 and 30%). The tablets were found to be stable (6 months at 40 ± 2°C and 75 ± 5% relative humidity), and the film-coating process is recommended to avoid NFX photodegradation. The dissolution profiles demonstrated an extended-release of NFX for all developed formulations. Dissolution curves analyzed using the Korsmeyer exponential equation showed that drug release was controlled by both drug diffusion and polymer relaxation or erosion mechanisms. A more erosion controlled system was obtained for the formulations containing lower MW and amount of polymer. With the increase in both MW and amount of polymer in the formulation, the gel layer became stronger, and the dissolution was more drug-diffusion dependent. Formulations containing intermediate MW polymers or high concentration (30%) of low MW polymers demonstrated a combination of extended and complete in vitro drug release. This way, these formulations could provide an increased bioavailability in vivo. PMID:24083235

  1. Fabrication of extended-release patient-tailored prednisolone tablets via fused deposition modelling (FDM) 3D printing.

    Science.gov (United States)

    Skowyra, Justyna; Pietrzak, Katarzyna; Alhnan, Mohamed A

    2015-02-20

    Rapid and reliable tailoring of the dose of controlled release tablets to suit an individual patient is a major challenge for personalized medicine. The aim of this work was to investigate the feasibility of using a fused deposition modelling (FDM) based 3D printer to fabricate extended release tablet using prednisolone loaded poly(vinyl alcohol) (PVA) filaments and to control its dose. Prednisolone was loaded into a PVA-based (1.75 mm) filament at approximately 1.9% w/w via incubation in a saturated methanolic solution of prednisolone. The physical form of the drug was assessed using differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). Dose accuracy and in vitro drug release patterns were assessed using HPLC and pH change flow-through dissolution test. Prednisolone loaded PVA filament demonstrated an ability to be fabricated into regular ellipse-shaped solid tablets using the FDM-based 3D printer. It was possible to control the mass of printed tablet through manipulating the volume of the design (R(2) = 0.9983). On printing tablets with target drug contents of 2, 3, 4, 5, 7.5 and 10mg, a good correlation between target and achieved dose was obtained (R(2) = 0.9904) with a dose accuracy range of 88.7-107%. Thermal analysis and XRPD indicated that the majority of prednisolone existed in amorphous form within the tablets. In vitro drug release from 3D printed tablets was extended up to 24h. FDM based 3D printing is a promising method to produce and control the dose of extended release tablets, providing a highly adjustable, affordable, minimally sized, digitally controlled platform for producing patient-tailored medicines. Copyright © 2015. Published by Elsevier B.V.

  2. Studies on applicability of press-coated tablets using hydroxypropylcellulose (HPC) in the outer shell for timed-release preparations.

    Science.gov (United States)

    Fukui, E; Uemura, K; Kobayashi, M

    2000-08-10

    Press-coated tablets, containing diltiazem hydrochloride (DIL) in the core tablet and coated with hydroxypropylcellulose (HPC) as the outer shell, were examined for applicability as timed-release tablets with a predetermined lag time and subsequent rapid drug release phase. Various types of press-coated tablets were prepared using a rotary tabletting machine and their DIL dissolution behavior was evaluated by the JP paddle method. The results indicated that tablets with the timed-release function could be prepared, and that the lag times were prolonged as the viscosity of HPC and the amount of the outer shell were increased. The lag times could be controlled widely by the above method, however, the compression load had little effect. Two different kinds of timed-release press-coated tablets that showed lag times of 3 and 6 h in the in vitro test (denoted PCT(L3) and PCT(L6), respectively) were administered to beagle dogs. DIL was first detected in the plasma more than 3 h after administration, and both tablets showed timed-release. The lag times showed a good agreement between the in vivo and in vitro tests in PCT(L3). However, the in vivo lag times were about 4 h in PCT(L6) and were much shorter than the in vitro lag time. The dissolution test was performed at different paddle rotation speeds, and good agreement was obtained between the in vivo and in vitro lag times at 150 rpm. This suggested that the effects of gastrointestinal peristalsis and contraction should also be taken into consideration for the further development of drug delivery systems.

  3. A Lower Temperature FDM 3D Printing for the Manufacture of Patient-Specific Immediate Release Tablets.

    Science.gov (United States)

    Okwuosa, Tochukwu C; Stefaniak, Dominika; Arafat, Basel; Isreb, Abdullah; Wan, Ka-Wai; Alhnan, Mohamed A

    2016-11-01

    The fabrication of ready-to-use immediate release tablets via 3D printing provides a powerful tool to on-demand individualization of dosage form. This work aims to adapt a widely used pharmaceutical grade polymer, polyvinylpyrrolidone (PVP), for instant on-demand production of immediate release tablets via FDM 3D printing. Dipyridamole or theophylline loaded filaments were produced via processing a physical mixture of API (10%) and PVP in the presence of plasticizer through hot-melt extrusion (HME). Computer software was utilized to design a caplet-shaped tablet. The surface morphology of the printed tablet was assessed using scanning electron microscopy (SEM). The physical form of the drugs and its integrity following an FDM 3D printing were assessed using x-ray powder diffractometry (XRPD), thermal analysis and HPLC. In vitro drug release studies for all 3D printed tablets were conducted in a USP II dissolution apparatus. Bridging 3D printing process with HME in the presence of a thermostable filler, talc, enabled the fabrication of immediate release tablets at temperatures as low as 110°C. The integrity of two model drugs was maintained following HME and FDM 3D printing. XRPD indicated that a portion of the loaded theophylline remained crystalline in the tablet. The fabricated tablets demonstrated excellent mechanical properties, acceptable in-batch variability and an immediate in vitro release pattern. Combining the advantages of PVP as an impeding polymer with FDM 3D printing at low temperatures, this approach holds a potential in expanding the spectrum of drugs that could be used in FDM 3D printing for on demand manufacturing of individualised dosage forms.

  4. Design and In-vitro Evaluation of Sustained Release Floating Tablets of Metformin HCl Based on Effervescence and Swelling.

    Science.gov (United States)

    Senjoti, Faria Gias; Mahmood, Syed; Jaffri, Juliana Md; Mandal, Uttam Kumar

    2016-01-01

    An oral sustained-release floating tablet formulation of metformin HCl was designed and developed. Effervescence and swelling properties were attributed on the developed tablets by sodium bicarbonate and HPMC-PEO polymer combination, respectively. Tablet composition was optimized by response surface methodology (RSM). Seventeen (17) trial formulations were analyzed according to Box-Behnken design of experiment where polymer content of HPMC and PEO at 1: 4 ratio (A), amount of sodium bi-carbonate (B), and amount of SSG (C) were adopted as independent variables. Floating lag time in sec (Y1), cumulative percent drug released at 1 h (Y2) and 12 h (Y3) were chosen as response variables. Tablets from the optimized formulation were also stored at accelerated stability condition (40°C and 75% RH) for 3 months to assess their stability profile. RSM could efficiently optimize the tablet composition with excellent prediction ability. In-vitro drug release until 12 h, floating lag time, and duration of floating were dependent on the amount of three selected independent variables. Optimized tablets remained floating for more than 24 h with a floating lag time of less than 4 min. Based on best fitting method, optimized formulation was found to follow Korsmeyer-Peppas release kinetic. Accelerated stability study revealed that optimized formulation was stable for three months without any major changes in assay, dissolution profile, floating lag time and other physical properties.

  5. Sustained release coating of tablets with Eudragit(®) RS/RL using a novel electrostatic dry powder coating process.

    Science.gov (United States)

    Qiao, Mingxi; Luo, Yanfeng; Zhang, Liqiang; Ma, Yingliang; Stephenson, Tyler Shawn; Zhu, Jesse

    2010-10-31

    The objectives of this study were to develop an electrostatic dry powder coating process for sustained coating tablets with Eudragit(®) RS/RL and to investigate the effects of various factors and operating conditions on the coating process and drug release profile. A liquid plasticizer (triethyl citrate) was sprayed onto the surface of the tablets followed by spraying coating powder by an electrostatic spray gun. The powder coated tablets were cured at elevated temperature for a film formation. Liquid plasticizer played important roles in lowering down the glass transition temperature (T(g)) of the coating polymer and increasing the surface electrical conduction of tablet cores. Electrostatic assisted coating deposition was confirmed by the fact that higher coating level was obtained with electrical charging than the ones without it. The micrographs of scanning electron microscopy (SEM) of coated tablets showed that the film formation mainly occurred during the curing step. Higher curing temperature and longer curing time help enhance the film formation. The in vitro drug release profiles indicated that curing time, temperature, coating level and ratio of Eudragit(®) RS/RL were the main factors affecting the sustained release profile. The electrostatic dry powder coating process has been demonstrated to be an alternative for tablet sustained release coating with Eudragit(®) RS and RL.

  6. Preparation and In-Vitro Evaluation of Sustained Release Matrix Diclofenac Sodium Tablets Using HPMC KM 100 and Gums

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    Zafar Iqbal, Raza Khan, Fazli Nasir, Jamshaid Ali Khan, Lateef Ahmad, Abad Khan, Yaser Shah

    2010-12-01

    Full Text Available Objectives: The impact of hydroxypropylmethyl cellulose(HPMC K 100M alone and in combination with the guar gum,xanthan gum and gum tragacanth on the release of the diclofenac sodium matrix tablets were evaluated.Materials and Methods: The granules were prepared using wet granulation method and compressed into tablets using different ratio of drug and gum ratio. The physical properties of the tablets were within acceptable pharmacopeial limits.The release profiles of the matrix tablets were evaluated in vitro,using USP dissolution apparatus II (paddle method.Results: The formulations containing HPMC K 100M drug ratio1:1.3 and 1:1.6 and formulations containing HPMC, gum and drug with different ratio also sustained the release of diclofenac sodium for 12 hours. The mechanism of drug release from the matrix tablets was studied using Zero order, First order, Higuchi and Korsmeyer’s models using regression coefficient method. The stability of the selected formulations was evaluated at 40˚C and 70% RH for 6 months.Conclusions: HPMC K100M alone and in combination with natural gums as the retarding material retarded the release upto 12 hours and showed little deviation from the theoretical release pattern.

  7. Development and evaluation of modified release wax matrix tablet dosage form for tramadol hydrochloride

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    Paresh Ramesh Mahaparale

    2015-01-01

    Full Text Available The objective of this study was to develop modified release dosage forms of tramadol hydrochloride using wax matrix system by melt granulation method. The effect of various waxes, concentration of waxes, effect of excipients on the release profile of drug from wax matrix system was studied. Release retardant effect was observed in the order of hydrogenated vegetable oil (HVO > compritol >precirol. This may be due to more lipophilicity imparted by HVO than any other waxy substances. It was also observed that as ratio of drug: Wax was increased, it sustained release of drug for more time. This may be due to proper embedment/entrapment of drug in sufficient wax matrix system. In case of excipients, release retardant effect was found in order of dicalcium phosphate (DCP > microcrystalline cellulose (MCC > lactose. DCP is insoluble which helps in release retardation of drug. MCC is hydrophilic swellable polymer which showed release of drug by swelling. Lactose is soluble excipient which get dissolved and formed channels for entry of dissolution medium and release of drug occurred by erosion mechanism. Wax matrix tablets were found to be stable.

  8. FORMULATION AND EVALUATION OF METOPROLOL SUCCINATE CONTROLLED RELEASE TABLETS USING NATURAL AND SYNTHETIC POLYMER

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    A. Sathyaraj

    2012-01-01

    Full Text Available The objective of the present study to develop controlled release tablets of Metoprolol succinate using Natural polymer, guar gum and synthetic polymer, carbopol as a rate controlling polymers.. It was also desired to study the effect of polymer concentration. Metoprolol succinate, β1- selective adrenergic receptor- blocking agent used in the management of hypertension, angina pectoris, cardiac arrthymias, myocardial infarction, heart failure, hyperthyroidism and in the prophylactic treatment of migraine. The half-life of drug is relatively short approximately 4-6 hrs and in normal course of therapy drug administration is required every 4-6 hrs, thus warrants the use of controlled release formulation for prolong action and to improve patient compliance. In the present investigation Natural polymer, guar gum and synthetic polymer, carbopol have been selected as matrix forming materials for the drug. The formulations are made by employing the conventional wet granulation method, to achieve prolonged release of medicaments.

  9. Serum posaconazole levels among haematological cancer patients taking extended release tablets is affected by body weight and diarrhoea: single centre retrospective analysis.

    Science.gov (United States)

    Miceli, Marisa H; Perissinotti, Anthony J; Kauffman, Carol A; Couriel, Daniel R

    2015-07-01

    The posaconazole extended release tablet formulation was developed to improve bioavailability relative to the oral suspension. Therapeutic drug monitoring has been used to optimise posaconazole dosing to achieve a target trough level ≥0.7 μg ml(-1). We retrospectively evaluated 28 patients with haematological malignancies who received posaconazole tablets for antifungal prophylaxis. Posaconazole serum trough levels were obtained 5 days after initiation of therapy. Mean trough level was 1.19 ± 0.63 μg ml(-1), and 71% achieved a trough level ≥0.7 μg ml(-1). Diarrhoea was associated with lower mean trough levels (0.65 ± 0.08 μg ml(-1) vs. 1.31 ± 0.13 μg ml(-1)), P = 0.002. Mean trough levels were lower in patients ≥90 kg (0.74 ± 0.09 μg ml(-1)) vs. Posaconazole delayed release tablets attain appropriate trough levels in most patients, but patients with a higher weight and those experiencing diarrhoea are more likely to have lower levels.

  10. Identification of critical formulation and processing variables for metoprolol tartrate extended-release (ER) matrix tablets.

    Science.gov (United States)

    Rekhi, G S; Nellore, R V; Hussain, A S; Tillman, L G; Malinowski, H J; Augsburger, L L

    1999-06-02

    The objective of this study, was to examine the influence of critical formulation and processing variables as described in the AAPS/FDA Workshop II report on scale-up of oral extended-release dosage forms, using a hydrophilic polymer hydroxypropyl methylcellulose (Methocel K100LV). A face-centered central composite design (26 runs+3 center points) was selected and the variables studied were: filler ratio (lactose:dicalcium phosphate (50:50)), polymer level (15/32.5/50%), magnesium stearate level (1/1.5/2%), lubricant blend time (2/6/10 min) and compression force (400/600/800 kg). Granulations (1.5 kg, 3000 units) were manufactured using a fluid-bed process, lubricated and tablets (100 mg metoprolol tartrate) were compressed on an instrumented Manesty D3B rotary tablet press. Dissolution tests were performed using USP apparatus 2, at 50 rpm in 900 ml phosphate buffer (pH 6.8). Responses studied included percent drug released at Q1 (1 h), Q4, Q6, Q12. Analysis of variance indicated that change in polymer level was the most significant factor affecting drug release. Increase in dicalcium phosphate level and compression force were found to affect the percent released at the later dissolution time points. Some interaction effects between the variables studied were also found to be statistically significant. The drug release mechanism was predominantly found to be Fickian diffusion controlled (n=0.46-0.59). Response surface plots and regression models were developed which adequately described the experimental space. Three formulations having slow-, medium- and fast-releasing dissolution profiles were identified for a future bioavailability/bioequivalency study. The results of this study provided the framework for further work involving both in vivo studies and scale-up.

  11. Evaluation of Prosopis africana Seed Gum as an Extended Release Polymer for Tablet Formulation.

    Science.gov (United States)

    Nadaf, Sameer; Nnamani, Petra; Jadhav, Namdeo

    2015-06-01

    In the present work, an attempt has been made to screen Prosopis africana seed gum (PG), anionic polymer for extended release tablet formulation. Different categories of drugs (charge basis) like diclofenac sodium (DS), chlorpheniramine maleate (CPM), and ibuprofen (IB) were compacted with PG and compared with different polymers (charge basis) like xanthan gum (XG), hydroxypropyl methyl cellulose (HPMC-K100M), and chitosan (CP). For each drug, 12 batches of tablets were prepared by wet granulation technique, and granules were evaluated for flow properties, compressibility, and compactibility by Heckel and Leuenberger analysis, swelling index, in vitro dissolution studies, etc. It has been observed that granules of all batches showed acceptable flowability. According to Heckel and Leuenberger analysis, granules of PG-containing compacts showed similar and satisfactory compressibility and compactibility compared to granules of other polymers. PG showed significant swelling (P < 0.05) compared to HPMC, and better than CP and XG. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) study showed no interaction between drugs and polymers. From all PG-containing compacts of aforesaid drugs, drug release was sustained for 12 h following anomalous transport. Especially, polyelectrolyte complex formation retarded the release of oppositely charged drug (CPM-PG). However, extended release was noted in both anionic (DS) and nonionic (IB) drugs, maybe due to swollen gel. All compacts were found to be stable for 3-month period during stability study. This concludes that swelling and release retardation of PG has close resemblance to HPMC, so it can be used as extended release polymer for all types of drugs.

  12. Extended release matrix tablets of Stavudine: Formulation and in vitro evaluation

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    Saravanakumar M

    2010-01-01

    Full Text Available During the past two decades, there has been a steady increase in both the number of antiretroviral medications and the number of possible regimens available to manage human immunodeficiency virus (HIV and acquired immune deficiency syndrome (AIDS. But still, regimen fails due to some reasons such as toxicity, adverse effects, and consequent difficulties with patient adherence. Stavudine is the Food and Drug Administration approved drug for clinical use for the treatment of HIV infection, AIDS, and AIDS related conditions, either alone or in combination with other antiviral agents. The side effects of Stavudine are dose dependent and a reduction of the total administered dose reduces the severity of the toxicity. To reduce the frequency of administration and to improve patient compliance, a once daily sustained release formulation of Stavudine is desirable. Hence, in the present work, an attempt has been made to develop once daily sustained release matrix tablets of Stavudine using putative hydrophilic matrix materials such as hydroxyl propyl methyl cellulose (HPMC K4M and Carbopol 974P. The prepared extended release tablets were then evaluated for various physical tests like diameter, thickness, weight variation, hardness, friability, and drug content uniformity. The results of all these tests were found to be satisfactory. Formulation F9 extended the drug release till the end of 24 hours and showed higher r values for zero order plot, indicating that drug release followed zero order kinetics. This finding reveals that above a particular concentration, HPMC K4M and Carbopol 974P are capable of providing almost zero order drug release.

  13. Use of hydrophilic and hydrophobic polymers for the development of controlled release tizanidine matrix tablets

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    Tariq Ali

    2014-12-01

    Full Text Available The aim of the present study was to develop tizanidine controlled release matrix. Formulations were designed using central composite method with the help of design expert version 7.0 software. Avicel pH 101 in the range of 14-50% was used as a filler, while HPMC K4M and K100M in the range of 25-55%, Ethylcellulose 10 ST and 10FP in the range of 15 - 45% and Kollidon SR in the range of 25-60% were used as controlled release agents in designing different formulations. Various physical parameters including powder flow for blends and weight variation, thickness, hardness, friability, disintegration time and in-vitro release were tested for tablets. Assay of tablets were also performed as specified in USP 35 NF 32. Physical parameters of both powder blend and compressed tablets such as compressibility index, angle of repose, weight variation, thickness, hardness, friability, disintegration time and assay were evaluated and found to be satisfactory for formulations K4M2, K4M3, K4M9, K100M2, K100M3, K100M9, E10FP2, E10FP9, KSR2, KSR3 & KSR9. In vitro dissolution study was conducted in 900 ml of 0.1N HCl, phosphate buffer pH 4.5 and 6.8 medium using USP Apparatus II. In vitro release profiles indicated that formulations prepared with Ethocel 10 standard were unable to control the release of drug while formulations K4M2, K100M9, E10FP2 & KSR2 having polymer content ranging from 40-55% showed a controlled drug release pattern in the above mentioned medium. Zero-order drug release kinetics was observed for formulations K4M2, K100M9, E10FP2 & KSR2. Similarity test (f2 results for K4M2, E10FP2 & KSR2 were found to be comparable with reference formulation K100M9. Response Surface plots were also prepared for evaluating the effect of independent variable on the responses. Stability study was performed as per ICH guidelines and the calculated shelf life was 24-30 months for formulation K4M2, K100M9 and E10FP2.

  14. PREPARATION, CHARACTERIZATION AND PHARMACEUTICAL APPLICATION OF LINEAR DEXTRINS .4. DRUG-RELEASE FROM CAPSULES AND TABLETS CONTAINING AMYLODEXTRIN

    NARCIS (Netherlands)

    WIERIK, GHPT; EISSENS, AC; LERK, CF

    1993-01-01

    Linear dextrin (amylodextrin) and its soluble fraction were investigated for their suitability to enhance diazepam release from capsules and tablets. Drug release was analyzed in the USP XXI paddle apparatus and performed in phosphate buffer pH 6.8, with and without alpha-amylase, and in 0.1 N HCl s

  15. Evaluation of chitosan–anionic polymers based tablets for extended-release of highly water-soluble drugs

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    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.

  16. Evaluation of in vitro release rate and in vivo absorption characteristics of four metoprolol tartrate immediate-release tablet formulations.

    Science.gov (United States)

    Rekhi, G S; Eddington, N D; Fossler, M J; Schwartz, P; Lesko, L J; Augsburger, L L

    1997-02-01

    The purpose of this investigation was to examine the impact of formulation and process changes on dissolution and bioavailability/bioequivalency of metoprolol tartrate tablets manufactured using a high-shear granulation process. A half-factorial (2(4-1), Res IV) design was undertaken to study the selected formulation and processing variables during scale-up. Levels and ranges for excipients and processing changes studied represented level 2 or greater changes as indicated by the SUPAC-IR Guidance. Blend and tableting properties were evaluated. Changes in sodium starch glycolate and magnesium stearate levels, and the order of addition microcrystalline cellulose (intra- vs. extragranular) were significant only in affecting percent drug released (Q) in 5, 10, and 15 min. Statistical analysis of data showed no significant curvature. No interaction effects were found to be statistically significant. To examine the impact of formulation and processing variables on in vivo absorption, three batches were selected for a bioavailability study based on their dissolution profiles. Subjects received four metoprolol treatments (Lopressor, slow-, medium-, and fast-dissolving formulations) separated by 1 week according to a randomized crossover design. After an overnight fast, subjects were administered one tablet (100 mg), blood samples were collected over 24 hr and plasma samples were analyzed. The formulations were found to be bioequivalent with respect to the log Cmax and log AUC0-infinity. The results of this study suggest that: (i) bioavailability/bioequivalency studies may not be necessary for metoprolol tartrate and perhaps other class 1 drugs after level 2 type changes and (ii) in vitro dissolution tests may be used to show bioequivalence of metoprolol formulations with processing or formulation changes within the specified level 2 ranges for the equipment examined.

  17. Kinetic Modelling of Drug Release from Pentoxifylline Matrix Tablets based on Hydrophilic, Lipophilic and Inert Polymers

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    Mircia Eleonora

    2015-12-01

    Full Text Available Pentoxifylline is a xanthine derivative used in the treatment of peripheral vascular disease, which because of its pharmacokinetic and pharmacologic profile is an ideal candidate for the development of extended release formulations. The aim of this study is to present a kinetic analysis of the pentoxifylline release from different extended release tablets formulations, using mechanistic and empirical kinetic models. A number of 28 formulations were prepared and analysed; the analysed formulations differed in the nature of the matrix forming polymers (hydrophilic, lipophilic, inert and in their concentrations. Measurements were conducted in comparison with the reference product Trental 400 mg (Aventis Pharma. The conditions for the dissolution study were according to official regulations of USP 36: apparatus no. 2, dissolution medium water, volume of dissolution medium is 1,000 mL, rotation speed is 50 rpm, spectrophotometric assay at 274 nm. Six mathematical models, five mechanistic (0 orders, 1st-order release, Higuchi, Hopfenberg, Hixson-Crowell and one empirical (Peppas, were fitted to pentoxifylline dissolution profile from each pharmaceutical formulation. The representative model describing the kinetics of pentoxifylline release was the 1st-order release, and its characteristic parameters were calculated and analysed.

  18. Continuous twin screw melt granulation of glyceryl behenate: Development of controlled release tramadol hydrochloride tablets for improved safety.

    Science.gov (United States)

    Keen, Justin M; Foley, Connor J; Hughey, Justin R; Bennett, Ryan C; Jannin, Vincent; Rosiaux, Yvonne; Marchaud, Delphine; McGinity, James W

    2015-06-20

    Interest in granulation processes using twin screw extrusion machines is rapidly growing. The primary objectives of this study were to develop a continuous granulation process for direct production of granules using this technique with glyceryl behenate as a binder, evaluate the properties of the resulting granules and develop controlled release tablets containing tramadol HCl. In addition, the granulation mechanism was probed and the polymorphic form of the lipid and drug release rate were evaluated on stability. Granules were prepared using a Leistritz NANO16 twin screw extruder operated without a constricting die. The solid state of the granules were characterized by differential scanning calorimetry and X-ray diffraction. Formulated tablets were studied in 0.1N HCl containing 0-40% ethanol to investigate propensity for alcohol induced dose dumping. The extrusion barrel temperature profile and feed rate were determined to be the primary factors influencing the particle size distribution. Granules were formed by a combination immersion/distribution mechanism, did not require subsequent milling, and were observed to contain desirable polymorphic forms of glyceryl behenate. Drug release from tablets was complete and controlled over 16 h and the tablets were determined to be resistant to alcohol induced dose dumping. The drug release rate from the tablets was found to be stable at 40°C and 75% relative humidity for the duration of a 3 month study.

  19. Floating matrix tablets based on low density foam powder: effects of formulation and processing parameters on drug release.

    Science.gov (United States)

    Streubel, A; Siepmann, J; Bodmeier, R

    2003-01-01

    The aim of this study was to develop and physicochemically characterize single unit, floating controlled drug delivery systems consisting of (i). polypropylene foam powder, (ii). matrix-forming polymer(s), (iii). drug, and (iv). filler (optional). The highly porous foam powder provided low density and, thus, excellent in vitro floating behavior of the tablets. All foam powder-containing tablets remained floating for at least 8 h in 0.1 N HCl at 37 degrees C. Different types of matrix-forming polymers were studied: hydroxypropyl methylcellulose (HPMC), polyacrylates, sodium alginate, corn starch, carrageenan, gum guar and gum arabic. The tablets eroded upon contact with the release medium, and the relative importance of drug diffusion, polymer swelling and tablet erosion for the resulting release patterns varied significantly with the type of matrix former. The release rate could effectively be modified by varying the "matrix-forming polymer/foam powder" ratio, the initial drug loading, the tablet geometry (radius and height), the type of matrix-forming polymer, the use of polymer blends and the addition of water-soluble or water-insoluble fillers (such as lactose or microcrystalline cellulose). The floating behavior of the low density drug delivery systems could successfully be combined with accurate control of the drug release patterns.

  20. Formulation and evaluation of rifampicin sustained release tablets using juice of Citrus limetta as bio-retardant

    Directory of Open Access Journals (Sweden)

    K Pawan Gaur

    2012-01-01

    Full Text Available The advantages of biopolymers over synthetic polymers are low cost, natural origin, free from side effects, biocompatible, bio-acceptable, environmental friendly processing, local availability, better patient tolerance as well as public acceptance. Sustained release tablets containing rifampicin was prepared by adding 100 mg polymer and 50 mg Drug and Granules. Same procedure was followed with 3% and 5% of polymer for preparation of sustained release tablets. Additional Tablets of 100 mg, 200 mg and 400 mg were prepared using 5% of the polymer. The results indicated that the selected biopolymer had a good release retardant property thus it can be concluded that the selected biopolymer can be utilized as low cost natural biocompatible and biodegradable agent.

  1. Development of trilayered mucoadhesive tablet of itraconazole with zero-order release

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    Madgulkar Ashwini

    2008-01-01

    Full Text Available Itraconazole is practically insoluble in water; large interindividual and intraindividual variations of its oral bioavailability are reported. A mucoadhesive drug delivery system is useful to prolong the retention time of a dosage form in the stomach, thereby improving the oral bioavailability of the drug. Solid dispersion of itraconazole with Eudragit E100 was prepared by spray-drying method to improve dissolution. Trilayered mucoadhesive tablet was prepared, with inner core containing solid dispersion of the drug and with carbopol and HPMC sandwiched between two layers of hydrophilic mucoadhesive polymer mixture of carbopol and Hydroxypropyl methyl cellulose (HPMC. Amounts of Carbopol 934P (CP and Methocel K4M (HPMC were varied in the outer coat around the solid dispersion. The drug-release pattern for all the formulation combinations was found to be nonfickian, approaching zero-order kinetics. Suitable combination of two polymers provided adequate bioadhesive strength and sustained-release profile with zero-order kinetics.

  2. [Tablet splitting].

    Science.gov (United States)

    Quinzler, R; Haefeli, W E

    2006-06-01

    The splitting of scored tablets provides many advantages. One benefit is to achieve dose flexibility to account for the huge interindividual differences in dose requirements for instance in paediatric and geriatric patients, which are often not covered by the available strengths in the market. Moreover, large-sized tablets can easier be swallowed if broken before swallowing and medication costs can often be reduced by splitting brands with higher strength. But not all tablets, mostly unscored tablets, are suitable for splitting. Splitting of extended release formulations can result in an overdose by uncontrolled release of the active component and degradation of the compound can occur if an enteric coating is destroyed by the splitting process. Whether tablets are suitable for splitting depends on the properties of the active component (e.g. light sensitivity), the galenics, the shape of the tablet, and the shape of the scoreline. Moreover, not all patients are informed, able, or willing to split tablets and the majority of the elderly population is not capable to break tablets. When split tablets are prescribed it is therefore important to view the shape of the tablet, to assess the patients ability and willingness to break tablets, to properly inform the patient about the appropriate way of splitting, and if necessary to suggest (and instruct) the use of a tablet splitting device.

  3. Design and evaluation of an extended-release matrix tablet formulation; the combination of hypromellose acetate succinate and hydroxypropylcellulose

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    Sachiko Fukui

    2017-03-01

    Full Text Available The purpose of this study was to develop an extended-release (ER matrix tablet that shows robust dissolution properties able to account for the variability of pH and mechanical stress in the GI tract using a combination of enteric polymer and hydrophilic polymer. Hypromellose acetate succinate (HPMCAS and hydroxypropylcellulose (HPC were selected as ER polymers for the ER matrix tablet (HPMCAS/HPC ER matrix tablet. Oxycodone hydrochloride was employed as a model drug. Dissolution properties of the HPMCAS/HPC ER matrix tablets were evaluated and were not affected by the pH of the test medium or paddle rotating speed. In a USP apparatus 3 (bio-relevant dissolution method, dissolution profiles of the HPMCAS/HPC ER matrix tablets containing oxycodone hydrochloride were similar to that of the reference product (OxyContin. Moreover, in vivo performance after oral administration of the HPMCAS/HPC ER matrix tablets to humans was simulated by GastroPlus based on dissolution profiles from the USP apparatus 3. The plasma concentration-time profile simulated was similar to that of the reference product. These results suggest that the combination of HPMCAS and HPC shows a robust dissolution profile against pH and paddle rotating speed and indicates the appropriate extended-release profile in humans.

  4. Comparative bioequivalence studies of tramadol hydrochloride sustained-release 200 mg tablets

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    Suhas S Khandave

    2010-11-01

    Full Text Available Suhas S Khandave1, Satish V Sawant1, Santosh S Joshi1, Yatish K Bansal2, Sonal S Kadam21Accutest Research Laboratories (I Private Limited, Koparkhirne, Navi Mumbai, Maharashtra, India; 2Ipca Laboratories Limited, Kandivli Mumbai, Maharashtra, IndiaBackground: Tramadol hydrochloride is available as 50 mg immediate-release (IR and 100 mg, 200 mg, and 300 mg sustained-release (SR tablets. The recommended dose of tramadol is 50–100 mg IR tablets every 4–6 hours. The tramadol SR 200 mg tablet is a better therapeutic option, with a reduced frequency of dosing, and improved patient compliance and quality of life. The present study evaluated the bioequivalence of a generic tramadol SR 200 mg tablet.Methods: A comparative in vitro dissolution study was performed on the test and reference products, followed by two separate single-dose bioequivalence studies under fasting and fed conditions and one multiple-dose bioequivalence study under fasting conditions. These bioequivalence studies were conducted in healthy human subjects using an open-label, randomized, two-treatment, two-period, two-sequence, crossover design. The oral administration of the test and reference products was done on day 1 for both the single-dose studies and on days 1–5 for the multiple-dose study in each study period as per the randomization code. Serial blood samples were collected at predefined time points in all the studies. Analysis of plasma concentrations of tramadol and O-desmethyltramadol (the M1 metabolite was done by a validated liquid chromatography-mass spectrometry analytical method. The standard acceptance criterion of bioequivalence was applied on log-transformed pharmacokinetic parameters for tramadol and its M1 metabolite.Results: The ratios for geometric least-square means and 90% confidence intervals were within the acceptance range of 80%–125% for log-transformed primary pharmacokinetic parameters for tramadol and its M1 metabolite in all the three studies

  5. A fixed-dose combination tablet of gemigliptin and metformin sustained release has comparable pharmacodynamic, pharmacokinetic, and tolerability profiles to separate tablets in healthy subjects

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    Park SI

    2015-02-01

    Full Text Available Sang-In Park,1,* Howard Lee,1,2,* Jaeseong Oh,1 Kyoung Soo Lim,3 In-Jin Jang,1 Jeong-Ae Kim,4 Jong Hyuk Jung,4 Kyung-Sang Yu1 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 2Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Clinical Trials Center, Seoul National University Hospital, Seoul, 3Department of Clinical Pharmacology and Therapeutics, CHA University School of Medicine and CHA Bundang Medical Center, Seongnam, 4LG Life Sciences, Ltd, Seoul, Republic of Korea *These authors contributed equally to this work Background: In type 2 diabetes mellitus, fixed-dose combination (FDC can provide the complementary benefits of correction of multiple pathophysiologic defects such as dysfunctions in glycemic or metabolic control while improving compliance compared with separate tablets taken together. The objective of the study reported here was to compare the pharmacodynamic (PD, pharmacokinetic (PK, and tolerability profiles of gemigliptin and extended-release metformin (metformin XR between FDC and separate tablets.Methods: A randomized, open-label, single-dose, two-way, two-period, crossover study was conducted in 28 healthy male volunteers. Two FDC tablets of gemigliptin/metformin 25/500 mg or separate tablets of gemigliptin (50 mg ×1 and metformin XR (500 mg ×2 were orally administered in each period. Serial blood samples were collected up to 48 hours post-dose to determine dipeptidyl peptidase 4 (DPP-4 activity using spectrophotometric assay and concentrations of gemigliptin and metformin using tandem mass spectrometry. Geometric mean ratios (GMRs of FDC to separate tablet formulations and their 90% confidence intervals (CIs were calculated to compare the PD and PK parameters between the two formulations. Tolerability was assessed throughout the study.Results: The plasma DPP-4 activity

  6. Development and evaluation of natural gum-based extended release matrix tablets of two model drugs of different water solubilities by direct compression.

    Science.gov (United States)

    Ofori-Kwakye, Kwabena; Mfoafo, Kwadwo Amanor; Kipo, Samuel Lugrie; Kuntworbe, Noble; Boakye-Gyasi, Mariam El

    2016-01-01

    The study was aimed at developing extended release matrix tablets of poorly water-soluble diclofenac sodium and highly water-soluble metformin hydrochloride by direct compression using cashew gum, xanthan gum and hydroxypropylmethylcellulose (HPMC) as release retardants. The suitability of light grade cashew gum as a direct compression excipient was studied using the SeDeM Diagram Expert System. Thirteen tablet formulations of diclofenac sodium (∼100 mg) and metformin hydrochloride (∼200 mg) were prepared with varying amounts of cashew gum, xanthan gum and HPMC by direct compression. The flow properties of blended powders and the uniformity of weight, crushing strength, friability, swelling index and drug content of compressed tablets were determined. In vitro drug release studies of the matrix tablets were conducted in phosphate buffer (diclofenac: pH 7.4; metformin: pH 6.8) and the kinetics of drug release was determined by fitting the release data to five kinetic models. Cashew gum was found to be suitable for direct compression, having a good compressibility index (ICG) value of 5.173. The diclofenac and metformin matrix tablets produced generally possessed fairly good physical properties. Tablet swelling and drug release in aqueous medium were dependent on the type and amount of release retarding polymer and the solubility of drug used. Extended release of diclofenac (∼24 h) and metformin (∼8-12 h) from the matrix tablets in aqueous medium was achieved using various blends of the polymers. Drug release from diclofenac tablets fitted zero order, first order or Higuchi model while release from metformin tablets followed Higuchi or Hixson-Crowell model. The mechanism of release of the two drugs was mostly through Fickian diffusion and anomalous non-Fickian diffusion. The study has demonstrated the potential of blended hydrophilic polymers in the design and optimization of extended release matrix tablets for soluble and poorly soluble drugs by direct

  7. Preparation and optimization of sustained release matrix tablets of metoprolol succinate and taro gum using response surface methodology

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    M. Soumya

    2014-01-01

    Full Text Available In the present study, an effort was made to formulate and evaluate matrix tablets of tarogum utilizing metaprolol succinate as the model drug. 3 2 full optimization procedure was adopted where two factors are studied at three levels. The amount of taro gum (X1 and polyvinylpyrrolidone (PVP K30 (X2 were selected as independent variables. The time required for 90% of drug release was selected as the dependent variable. Tablets were prepared by direct compression and were evaluated for various post compression parameters such as tablet hardness, friability, weight variation, drug content and in vitro dissolution. The results were found to be within the acceptable limits. The release exponent (n lies between 0.416 and 0.584 indicating drug release from the matrix tablets may be fickian or non-fickian (anomalous depending upon the concentration of natural polymer. T90 was 10.70, 11.20, 12.05, 12.66 h for B6, B7, B8 and B9 batches respectively showing overriding potential of taro gum, but still the effect of PVP K 30 is noteworthy. PVP K 30 has an indirect effect on all the factors by increasing tensile strength and making the tablet firm and intact.

  8. Synthesis and Characterization of Sodium Alginate Conjugate and Study of Effect of Conjugation on Drug Release from Matrix Tablet.

    Science.gov (United States)

    Satheeshababu, B K; Mohamed, I

    2015-01-01

    The aim of the present research work to study the effect of conjugation of the polymer on drug release from the matrix tablets. Sodium alginate L-cysteine conjugate was achieved by covalent attachment of thiol group of L-cysteine with the primary amino group of sodium alginate through the amide bonds formed by primary amino groups of the sodium alginate and the carboxylic acid group of L-cysteine. The synthesised sodium alginate L-cysteine conjugate was characterised by determining of charring point, Fourier transmission-infrared and differential scanning calorimetric analysis. To study the effect of conjugation on drug release pattern, the matrix tablets were prepared using various proportions of sodium alginate and sodium alginate L-cysteine conjugate along with atorvastatin calcium as model drug. The wet granulation technique was adopted and prepared matrix tablets were evaluated for various physical parameters. The in vitro drug release study results suggested that tablet formulated in combination of sodium alginate and sodium alginate L-cysteine conjugate S4 showed 100% after 8 h drug release whereas formulated with only sodium alginate S0 released 40% in 8 h.

  9. Quaternary polymethacrylate-sodium alginate films: effect of alginate block structures and use for sustained release tablets.

    Science.gov (United States)

    Pongjanyakul, Thaned; Khuathan, Natnicha

    2016-01-01

    The objectives in this study were to characterize quaternary polymethacrylate-sodium alginate (QPM-SA) films prepared using high G block or high M block SA (GSA or MSA, respectively), and to investigate the effects of QPM-SA ratios, film-coating levels and SA block structures on propranolol HCl (PPN) released from coated tablets. The results demonstrated that GSA and MSA shared a similar interaction mechanism with QPM. The QPM-GSA films had higher puncture strength than the QPM-MSA films in dry and wet states, whereas the % elongations were not different. The drug permeability of the QPM-GSA films was lower than that of the QPM-MSA films in both acidic and neutral media, but higher water uptake of the QPM-GSA films was found at neutral pH. Moreover, the QPM-MSA-coated tablets had a greater PPN release rate than the QPM-GSA-coated tablets, and drug release was dependent on the film-coating levels. In addition, the QPM-SA films at a ratio of 4:0.5 produced a stronger film and could sustain PPN release. These results indicate that the QPM-GSA films had greater film strength and lower drug permeability than the QPM-MSA films. Additionally, the QPM-SA films have a strong potential for use in sustained-release tablets.

  10. Poly(DL-lactic acid) as a direct compression excipient in controlled release tablets - Part I. Compaction behaviour and release characteristics of poly(DL-lactic acid) matrix tablets

    NARCIS (Netherlands)

    Steendam, R; Lerk, CF

    1998-01-01

    High-molecular weight poly(DL-lactic acid) (PDLA, M-v 85000) was applied as a direct compression excipient in controlled release tablets. PDLA powders with good flowing properties were obtained by milling pre-cooled PDLA granules. Apparent yield pressure values ranged from 44 to 71 MPa for tablettin

  11. Hydroxypropylcellulose controlled release tablet matrix prepared by wet granulation: effect of powder properties and polymer composition

    Directory of Open Access Journals (Sweden)

    Antonio Zenon Antunes Teixeira

    2009-02-01

    Full Text Available The aim of this study was to attain 100% drug release of caffeine after 24 h from hydroxypropylcellulose (HPC tablet matrices and to investigate the effect of co-excipient. Physical properties of the powders were evaluated and suggested for a wet granulation process. The tablet containing caffeine was formulated by different weight ratios of hydrophilic polymers. The results of polymer evaluation confirmed that the increase of HPC level with the same drug content significantly decreased the rate of drug release. The presence of co-polymer excipients carboxymethylcellulose (CMC and polyvinylpyrrolidone (PVP in the tablet matrix was also investigated. The release rate was also controlled by low levels of CMC (O objetivo deste estudo é desenvolver a liberação 100% da droga cafeína em 24 horas em comprimidos matrizes e investigar o uso de hidroxipropilcelulose (HPC mais os efeitos de co-excipiente. As propriedades físicas dos pós foram avaliadas assim como seu uso no processo de granulação úmida. O comprimido contendo a cafeína foi formulado por diferentes relações de peso dos polímeros hidrofílicos. Os resultados da avaliação do polímero confirmaram que o aumento do nível de HPC com o mesmo índice da droga diminuiu significativamente a taxa de liberação da droga. A presença do co-polímero excipiente carboximetilcelulose (CMC e do polivinilpirrolidona (PVP na matriz do comprimido foi também investigado. A taxa de liberação foi controlada principalmente por baixos níveis de CMC (< 10% enquanto PVP não mostrou efeito diferente considerável. A melhor taxa de liberação de cafeína 100% em 24 horas foi obtida quando 10% da lactose monoidrato foi adicionado na formulação.

  12. Gum Ghatti--a pharmaceutical excipient: development, evaluation and optimization of sustained release mucoadhesive matrix tablets of domperidone.

    Science.gov (United States)

    Gurpreetarora; Malik, Karan; Rana, Vikas; Singh, Inderbir

    2012-01-01

    The objective of this study was to extend the GI residence time of the dosage form and to control the release of domperidone using directly compressible sustained release mucoadhesive matrix (SRMM) tablets. A 2-factor centre composite design (CCD) was employed to study the influence of independent variables like gum ghatti (GG) (X1) and hydroxylpropylmethyl cellulose K 15M (HPMC K 15M) (X2) on dependent variable like mucoadhesive strength, tensile strength, release exponent (n), t50 (time for 50% drug release), rel(10 h) (release after 10 h) and rel(18 h) (release after 18 h). Tablets were prepared by direct compression technology and evaluated for tablet parametric test (drug assay, diameter, thickness, hardness and tensile strength), mucoadhesive strength (using texture analyzer) and in vitro drug release studies. The tensile strength and mucoadhesive strength were found to be increased from 0.665 +/- 0.1 to 1.591 +/- 0.1 MN/cm2 (Z1 to Z9) and 10.789 +/- 0.985 to 50.924 +/- 1.150 N (Z1 to Z9), respectively. The release kinetics follows first order and Hixson Crowell equation indicating drug release following combination of diffusion and erosion. The n varies between 0.834 and 1.273, indicating release mechanism shifts from non fickian (anomalous release) to super case II, which depict that drug follows multiple drug release mechanism. The t50 time was found to increase from 5 +/- 0.12 to 11.4 +/- 0.14 h (Z1 to Z9) and release after 10 and 18 h decreases with increasing concentration of both polymers concluding with release controlling potential of polymers. The accelerated stability studies were performed on optimized formulation as per ICH guideline and the result showed that there was no significant change in tensile strength, mucoadhesive strength and drug assay.

  13. Aqueous coating dispersion (pseudolatex) of zein improves formulation of sustained-release tablets containing very water-soluble drug.

    Science.gov (United States)

    Li, X N; Guo, H X; Heinamaki, J

    2010-05-01

    Zein is an alcohol soluble protein of corn origin that exhibits hydrophobic properties. Pseudolatexes are colloidal dispersions containing spherical solid or semisolid particles less than 1 microm in diameter and can be prepared from any existing thermoplastic water-insoluble polymer. The novel plasticized film-coating pseudolatex of zein was studied in formulation of sustained-release tablets containing very water-soluble drug. Film formation of plasticized aqueous dispersion was compared with film forming properties of plasticized organic solvent system (ethanol) of zein. The water vapor permeability (WVP), water uptake and erosion, and moisture sorption were evaluated with free films. The tablets containing metoprolol tartrate as a model drug were used in pan-coating experiments. Aqueous film coatings plasticized with PEG 400 exhibited very low water uptake. No significant difference in WVP, moisture sorption and erosion were found between aqueous films and organic solvent-based films of zein plasticized with PEG 400. The atomic force microscopy (AFM) images on microstructure of films showed that colloidal particle size of zein in the aqueous films was smaller than that observed in the solvent-based films. In addition, the aqueous-based films were more compact and smoother than the respective solvent-based films. The aqueous zein-coated tablets containing very water-soluble drug (metoprolol tartrate) exhibited clear sustained-release dissolution profiles in vitro, while the respective solvent-based film-coated tablets showed much faster drug release. Furthermore, aqueous zein-coated tablets had lower water absorption at high humidity conditions. In conclusion, the plasticized aqueous dispersion (pseudolatex) of zein can be used for moisture resistant film coating of sustained-release tablets containing very water-soluble drug.

  14. Film-coated matrix mini-tablets for the extended release of a water-soluble drug.

    Science.gov (United States)

    Mohamed, Faiezah A A; Roberts, Matthew; Seton, Linda; Ford, James L; Levina, Marina; Rajabi-Siahboomi, Ali R

    2015-04-01

    Extended release (ER) of water-soluble drugs from hydroxypropylmethylcellulose (HPMC) matrix mini-tablets (mini-matrices) is difficult to achieve due to the large surface area to volume ratio of the mini matrices. Therefore, the aims of this study were to control the release of a water-soluble drug (theophylline) from mini-matrices by applying ER ethylcellulose film coating (Surelease®), and to assess the effects of Surelease®:pore former (Opadry®) ratio and coating load on release rates. Mini-matrices containing 40%w/w HPMC K100M CR were coated with 100:0, 85:15, 80:20, 75:25 or 70:30 Surelease®:Opadry® to different coating weight gains (6-20%). Non-matrix mini-tablets were also produced and coated with 80:20 Surelease®:Opadry® to different coating weight gains. At low coating weight gains, nonmatrix mini-tablets released the entire drug within 0.5 h, while at high coating weight gains only a very small amount (<5%) of drug was released after 12 h. The gel formation of HPMC prevented disintegration of mini-matrices at low coating weight gains but contributed to rupture of the film even at high coating weight gains. As a result, drug release from mini-matrices was slower than that from nonmatrix mini-tablets at low coating weight gains, yet faster at high coating weight gains. An increase in the lag time of drug release from mini-matrices was observed as the concentration of Opadry® reduced or the coating weight gain increased. This study has demonstrated the possibility of extending the release of a water-soluble drug from HPMC mini-matrices by applying ER film coating with appropriate levels of pore former and coating weight gains to tailor the release rate.

  15. 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

  16. Bioequivalence of Sandoz methylphenidate osmotic-controlled release tablet with Concerta® (Janssen-Cilag).

    Science.gov (United States)

    Schapperer, Elisabeth; Daumann, Heike; Lamouche, Stéphane; Thyroff-Friesinger, Ursula; Viel, François; Weitschies, Werner

    2015-02-01

    The aim was to assess the bioequivalence of Sandoz methylphenidate osmotic-controlled release (OCR) tablets (Sandoz [Methylphenidate[ MPH OCR) with Concerta®, a methylphenidate formulation indicated for the treatment of attention deficit/hyperactivity disorder (ADHD). Four open-label, randomized, single-dose, two-way crossover bioequivalence studies were conducted in healthy subjects: three fasting studies with 54-, 36- and 18-mg doses of methylphenidate, and one fed study with the 54-mg dose. The d- and l-threo-methylphenidate plasma levels were quantified using liquid chromatographic methods with tandem mass spectrometry (LC MS/MS). Bioequivalence of the formulations was accepted if the 90% geometric confidence intervals of the ratio of least-squares means of Sandoz MPH OCR to Concerta® of ln-transformed area under the curve (AUC0-t ) and C max were within the acceptance range of 80-125%. All studies met the bioequivalence criteria, and 90% geometric confidence intervals for AUC0-t and C max were within the predefined range. All plasma concentration time curves for Sandoz MPH OCR under fasting conditions showed a biphasic profile comparable with Concerta®, confirmed by bioequivalence of the partial metrics AUC0-2h, AUC2-24 h, C max(0-2 h) and C max(2-24 h). Both products were well tolerated and no relevant differences in the safety profiles were observed. It was concluded that Sandoz MPH OCR is bioequivalent to Concerta® in terms of rate and extent of absorption when administered as a single dose of one extended-release tablet of 54, 36, or 18 mg under fasting conditions and at a dose of 54 mg under fed conditions.

  17. A stable fixed-dose combination tablet of pseudoephedrine and KOB extracts for the extended release.

    Science.gov (United States)

    Hwang, C-J; Park, M-H; Jung, H-W; Park, Y-K; Kim, Y-H; Kang, J-S; Cho, C-W

    2013-11-01

    Allergic rhinitis (AR) is characterized by inflammation of the nasal mucosa with hypersensitivity resulting from seasonal or perennial responses to specific environmental allergens and by symptoms like nasal rubbing, sneezing, rhinorrhea, lacrimation, nasal congestion and obstruction, and less frequently cough. KOB extracts, which is a polyherbal medicine consisting of 5 different herbs (Atractylodes macrocephala, Astragalus membranaceus, Saposhnikovia divaricata, Ostericum koreanum and Scutellaria baicalensis) had commonly been used for the treatment of various allergic diseases showed an anti-allergic effect by modulating mast cell-mediated allergic responses in allergic rhinitis, recently. On the other hand, pseudoephedrine is a sympathomimetic amine commonly used to relieve congestion in patients with allergic rhinitis and common colds. Considering the KOB's therapeutic mechanism, the combination with pseudoephedrine would be suitable for allergic rhinitis. This study is to obtain an effective extended release formulation using pseudoephedrine and KOB extracts to reduce side effects of drug due to repeated dosing and improve the compliance of patients for treatment of rhinitis and nasal decongestion. So, the fixed-dose combination tablet of pseudoephedrine and KOB extracts was prepared by direct compression and characterized by drug content, flowing characteristics and dissolution test. The drug content of baicalin of KOB extracts was within the range of 95-105% except for T1 formulation. The hardness and friability values of all formulations ranged from 9 to 13 kp and less than 1%, respectively. Taken together, T4 or T8 could be a stable fixed-dose combination tablet for extended release of pseudoephedrine and KOB extracts for nasal rhinitis.

  18. Monolithic LC method applied to fesoterodine fumarate low dose extended-release tablets: Dissolution and release kinetics

    Directory of Open Access Journals (Sweden)

    Maximiliano S. Sangoi

    2015-04-01

    Full Text Available A dissolution test for fesoterodine low dose extended-release tablets using liquid chromatographic (LC method equipped with a C18 monolithic column was developed and validated. LC system was operated isocratically at controlled temperature (40 °C using a mobile phase of acetonitrile:methanol:0.03 M ammonium acetate (pH 3.8 (30:15:55, v/v/v, run at a flow rate of 1.5 mL/min and detected at 208 nm. The best dissolution conditions for this formulation were achieved using a USP apparatus 2 (paddle at 100 rpm and 900 mL of phosphate buffer at pH 6.8 as the dissolution medium. Validation parameters such as the specificity, linearity, accuracy, precision, and robustness were evaluated according to international guidelines, giving results within the acceptable range. The kinetic parameters of drug release were also investigated using model-dependent methods and the dissolution profiles were best described by the Higuchi model. The validated dissolution test can be applied for quality control of this formulation.

  19. Monolithic LC method applied to fesoterodine fumarate low dose extended-release tablets:Dissolution and release kinetics

    Institute of Scientific and Technical Information of China (English)

    Maximiliano S. Sangoi; Vítor Todeschini; Martin Steppe

    2015-01-01

    A dissolution test for fesoterodine low dose extended-release tablets using liquid chromato-graphic (LC) method equipped with a C18 monolithic column was developed and validated. LC system was operated isocratically at controlled temperature (40 1C) using a mobile phase of acetonitrile:methanol:0.03 M ammonium acetate (pH 3.8) (30:15:55, v/v/v), run at a flow rate of 1.5 mL/min and detected at 208 nm. The best dissolution conditions for this formulation were achieved using a USP apparatus 2 (paddle) at 100 rpm and 900 mL of phosphate buffer at pH 6.8 as the dissolution medium. Validation parameters such as the specificity, linearity, accuracy, precision, and robustness were evaluated according to international guidelines, giving results within the acceptable range. The kinetic parameters of drug release were also investigated using model-dependent methods and the dissolution profiles were best described by the Higuchi model. The validated dissolution test can be applied for quality control of this formulation.

  20. Influence of β - cyclodextrin complexation on lovastatin release from osmotic pump tablets (OPT

    Directory of Open Access Journals (Sweden)

    Mehramizi A.

    2007-05-01

    Full Text Available An extended-release osmotic dosage form was designed and the effect of β-cyclodextrin (BCD inclusion complexation on the solubility of lovastatin in aqueous media was investigated. The lovastatin BCD solid systems were prepared by kneading method. The elementary osmotic pumps (EOPs were prepared with lovastatin BCD complex with cellulose acetate (CA and polyethylene glycol as plasticizer. The effect of the BCD molar ratio on enhancement of lovastatin dissolution rate and the influences of various parameters (e.g. drug –BCD ratio, molecular weight and amount of PVP, coating weight gain on drug release profiles were investigated. The solubility and dissolution rates of lovastatin were significantly increased by using inclusion complexation. It was found that PVP K90 was a suitable hydrophilic polymer with thickening effect and had profoundly positive effect on drug release. The present results confirmed that dissolution rate of lovastatin BCD were greatly enhanced and this system has suitable solubility behavior in EOP tablet formulations.

  1. Development and Evaluation of Sustained Release Tablet of Betahistine Hydrochloride Using Ion Exchange Resin Tulsion T344

    OpenAIRE

    Wagh, Vijay D.; Pawar, Nilesh

    2012-01-01

    An attempt was made to sustain the release of Betahistine hydrochloride by complexation technique using strong cation-exchange resin, Tulsion T344. The drug loading onto ion-exchange resin was optimized for mixing time, activation, effect of pH, swelling time, ratio of drug : resin, and temperature. The resinate was evaluated for micromeritic properties and characterized using XRPD and IR. For resinate sustained release tablets were formulated using hydoxypropyl methylcellulose K100M. The tab...

  2. In-vitro/in-vivo correlation of pulsatile drug release from press-coated tablet formulations: a pharmacoscintigraphic study in the beagle dog.

    Science.gov (United States)

    Ghimire, Manish; McInnes, Fiona J; Watson, David G; Mullen, Alexander B; Stevens, Howard N E

    2007-09-01

    The aim of the current study was to investigate the in-vitro and in-vivo performance of a press-coated tablet (PCT) intended for time delayed drug release, consisting of a rapidly disintegrating theophylline core tablet, press-coated with barrier granules containing glyceryl behenate (GB) and low-substituted hydroxypropylcellulose (L-HPC). The PCTs showed pulsatile release with a lag time dependent upon the GB and L-HPC composition of the barrier layer. In-vivo gamma-scintigraphic studies were carried out for PCTs containing GB:L-HPC at 65:35 w/w and 75:25 w/w in the barrier layer in four beagle dogs, in either the fed or fasted state. The in-vivo lag time in both the fed and fasted states did not differ significantly (p>0.05) from the in-vitro lag time. Additionally, no significant difference (p<0.05) between in-vivo fed and fasted disintegration times was observed, demonstrating that in-vivo performance of the PCT was not influenced by the presence or absence of food in the gastrointestinal tract. A distinct lag time was obtained prior to the appearance of drug in plasma and correlated (R2=0.98) with disintegration time observed from scintigraphic images. However, following disintegration, no difference in pharmacokinetic parameters (AUC(0-6 dis), K(el), Cmax) was observed. The current study highlighted the potential use of these formulations for chronopharmaceutical drug delivery.

  3. High-amylose sodium carboxymethyl starch matrices: development and characterization of tramadol hydrochloride sustained-release tablets for oral administration.

    Science.gov (United States)

    Nabais, Teresa; Leclair, Grégoire

    2014-01-01

    Substituted amylose (SA) polymers were produced from high-amylose corn starch by etherification of its hydroxyl groups with chloroacetate. Amorphous high-amylose sodium carboxymethyl starch (HASCA), the resulting SA polymer, was spray-dried to obtain an excipient (SD HASCA) with optimal binding and sustained-release (SR) properties. Tablets containing different percentages of SD HASCA and tramadol hydrochloride were produced by direct compression and evaluated for dissolution. Once-daily and twice-daily SD HASCA tablets containing two common dosages of tramadol hydrochloride (100 mg and 200 mg), a freely water-soluble drug, were successfully developed. These SR formulations presented high crushing forces, which facilitate further tablet processing and handling. When exposed to both a pH gradient simulating the pH variations through the gastrointestinal tract and a 40% ethanol medium, a very rigid gel formed progressively at the surface of the tablets providing controlled drug-release properties. These properties indicated that SD HASCA was a promising and robust excipient for oral, sustained drug-release, which may possibly minimize the likelihood of dose dumping and consequent adverse effects, even in the case of coadministration with alcohol.

  4. Interaction between fed and gastric media (ensure Plus) and different hypromellose based caffeine controlled release tablets; comparison and mechanistic study of caffeine release in fed and fasted media versus water using USP dissolution apparatus 3

    DEFF Research Database (Denmark)

    Franek, Frans; Holm, Per; Larsen, Frank

    2014-01-01

    The aim of the study was to investigate caffeine release in fed and fasted state media from three controlled release matrix tablets containing different HPMC viscosity grades. The biorelevant in vitro dissolution methods utilize the USP 3 dissolution apparatus and biorelevant media to simulate fed...... and fasted gastro-intestinal dissolution conditions. The effect of tablet reciprocation rate (dip speed) in dissolution media (10 and 15 dips per minute) and media (water, fed and fasted) on caffeine release rate from – and erosion rate of – 100, 4000 and 15,000 mPa s HPMC viscosity tablets was investigated....... Using fasted media instead of water slightly decreases caffeine release from 100 and 4000 mPa s HPMC viscosity tablets as well as erosion rates, while 15,000 mPa s tablets remain unaffected. Fed compared to fasted media decreases caffeine release rate, and the food effect is greater for the 100 mPa s...

  5. Formulation and evaluation of a sustained-release tablets of metformin hydrochloride using hydrophilic synthetic and hydrophobic natural polymers

    Directory of Open Access Journals (Sweden)

    K J Wadher

    2011-01-01

    Full Text Available Metformin hydrochloride has relatively short plasma half-life, low absolute bioavailability. The need for the administration two to three times a day when larger doses are required can decrease patient compliance. Sustained release formulation that would maintain plasma level for 8-12 h might be sufficient for daily dosing of metformin. Sustained release products are needed for metformin to prolong its duration of action and to improve patient compliances. The overall objective of this study was to develop an oral sustained release metformin hydrochloride tablet by using hydrophilic Eudragit RSPO alone or its combination with hydrophobic natural polymers Gum copal and gum damar as rate controlling factor. The tablets were prepared by wet granulation method. The in vitro dissolution study was carried out using USP 22 apparatus I, paddle method and the data was analysed using zero order, first order, Higuchi, Korsmeyer and Hixson-Crowell equations. The drug release study revealed that Eudragit RSPO alone was unable to sustain the drug release. Combining Eudragit with gum Copal and gum Damar sustained the drug release for more than 12 h. Kinetic modeling of in vitro dissolution profiles revealed the drug release mechanism ranges from diffusion controlled or Fickian transport to anomalous type or non-Fickian transport. Fitting the in vitro drug release data to Korsmeyer equation indicated that diffusion along with erosion could be the mechanism of drug release.

  6. STUDYING THE IMPACT OF FORMULATION AND PROCESSING PARAMETERS ON THE RELEASE CHARACTERISTICS FROM HYDROXYPROPYL METHYLCELLULOSE MATRIX TABLETS OF DICLOFENAC.

    Science.gov (United States)

    Elzayat, Ehab M; Abdel-Rahman, Ali A; Ahmed, Sayed M; Alanazi, Fars K; Habib, Walid A; Sakr, Adel

    2016-01-01

    Hydrophilic matrices, especially HPMC based, are widely used to provide sustained delivery where drug release occurs mainly by diffusion. A 3(2) full factorial design was used to develop and evaluate HPMC matrix tablet for sustained delivery of diclofenac. The influences of polymer concentration/viscosity, diluent type/ratio, drug load/solubility, compression force and pH change on drug release were investigated. Ten tablet formulations were prepared using wet granulation. HPMC K15M (10-30% w/w) was used as the polymer forming matrix. The release kinetics, compatibility studies, lot reproducibility and effect on storage were discussed. Increasing polymer concentration and compression force showed antagonistic effect on release rate. Mannitol tends to increase release rate more than lactose. Reversing diluent ratio between lactose and MCC did not affect drug release. Changing pH resulted in burst release whereas drug solubility is pH independent. F1 showed similar release to Voltaren SR and followed Higuchi model. Drug and polymer were compatible to each other. The formulation is stable at long and intermediate conditions with a significant increase in release rate at accelerated conditions due to water uptake and polymer swelling. The developed formulation was successful for a sustained delivery of diclofenac.

  7. Formulation and evaluation of a sustained-release tablets of metformin hydrochloride using hydrophilic synthetic and hydrophobic natural polymers.

    Science.gov (United States)

    Wadher, K J; Kakde, R B; Umekar, M J

    2011-03-01

    Metformin hydrochloride has relatively short plasma half-life, low absolute bioavailability. The need for the administration two to three times a day when larger doses are required can decrease patient compliance. Sustained release formulation that would maintain plasma level for 8-12 h might be sufficient for daily dosing of metformin. Sustained release products are needed for metformin to prolong its duration of action and to improve patient compliances. The overall objective of this study was to develop an oral sustained release metformin hydrochloride tablet by using hydrophilic Eudragit RSPO alone or its combination with hydrophobic natural polymers Gum copal and gum damar as rate controlling factor. The tablets were prepared by wet granulation method. The in vitro dissolution study was carried out using USP 22 apparatus I, paddle method and the data was analysed using zero order, first order, Higuchi, Korsmeyer and Hixson-Crowell equations. The drug release study revealed that Eudragit RSPO alone was unable to sustain the drug release. Combining Eudragit with gum Copal and gum Damar sustained the drug release for more than 12 h. Kinetic modeling of in vitro dissolution profiles revealed the drug release mechanism ranges from diffusion controlled or Fickian transport to anomalous type or non-Fickian transport. Fitting the in vitro drug release data to Korsmeyer equation indicated that diffusion along with erosion could be the mechanism of drug release.

  8. Formulation and evaluation of press coated tablets of salbutamol sulphate for time controlled release

    Directory of Open Access Journals (Sweden)

    M D Wasimul Hasan

    2014-01-01

    Full Text Available The objective of the present study was to formulate and evaluate a press coated pulsatile drug delivery system of salbutamol sulphate in order to attain a time controlled release for treatment of nocturnal asthma. The core was prepared by direct compression, while press coating technique was used in coating the outer layer there by preparing a press coated tablet. The immediate release core formulations comprised of salbutamol sulphate and disintegrants like crospovidone, croscarmellose sodium and sodium starch glycolate in different ratios with the drug. The outer coat formulations were prepared using a hydrophilic (HPMC and hydrophobic (EC polymer of similar viscosity. The polymers were reviewed individually for their influence on lag time further obtaining the lag time using polymer combinations were assessed by employing central composite design. All the preliminary trials were evaluated for various post compression parameters along with the dissolution study that was performed using USP paddle method at 50 rpm in 0.1 N HCl and phosphate buffer pH 6.8. The formulation containing 300 mg of EC N50 and 75-100 mg of HPMC E50 may be regarded as the minimum quantity required in outer press coat so as to attain a predetermined lag time of 6 h.

  9. A dual strategy to improve psychotic patients’ compliance using sustained release quetiapine oral disintegrating tablets

    Directory of Open Access Journals (Sweden)

    Refaat Ahmed

    2016-12-01

    Full Text Available Quetiapine (QT is a short acting atypical antipsychotic drug effective in schizophrenia and bipolar disorder. This study aims at designing a novel dosage form of sustained release taste-masked QT orally disintegrating tablets (ODTs based on solid lipid micro-pellets (SLMPs. QT SLMPs were prepared using the hot melt extrusion technique and utilizing three lipid carriers: Compritol, Precirol and white beeswax either alone or in mixtures. They showed sustained QT release and a taste masking effect. The selected QT SLMP was further blended with an aqueous solution containing polyvinylpyrollidone (2.5 %, croscarmellose sodium (2 % and mannitol (50 %; it was then lyophilized into ODT in a mass ratio of 1:2, respectively. ODTs containing QT SLMPs showed: average wetting time (40.92 s, average oral disintegration time (21.49 s, average hardness (16.85 N and also imparted suitable viscosity to suspend pellets during the lyophilization process. In conclusion, lyophilization is a promising technique for the formulation of multiparticulate systems into ODTs.

  10. Development and optimization of press coated tablets of release engineered valsartan for pulsatile delivery.

    Science.gov (United States)

    Shah, Sunny; Patel, Romik; Soniwala, Moinuddin; Chavda, Jayant

    2015-01-01

    The present work is aimed to develop and optimize pulsatile delivery during dissolution of an improved formulation of valsartan to coordinate the drug release with circadian rhythm. Preliminary studies suggested that β cyclodextrin could improve the solubility of valsartan and showed AL type solubility curve. A 1:1 stoichiometric ratio of valsartan to β cyclodextrin was revealed from phase solubility studies and Job's plot. The prepared complex showed significantly better dissolution efficiency (p press-coated tablets of valsartan β cyclodextrin complex were subsequently prepared and application of the Plackett-Burman screening design revealed that HPMC K4M and EC showed significant effect on lag time. A 3(2) full factorial design was used to measure the response of HPMC K4M and EC on lag time and time taken for 90% drug release (T90). The optimized batch prepared according to the levels obtained from the desirability function had a lag time of 6 h and consisted of HPMC K4M:ethylcellulose in a 1:1.5 ratio with 180 mg of coating and revealed a close agreement between observed and predicted value (R(2 )= 0.9694).

  11. Development of Maltodextrin-Based Immediate-Release Tablets Using an Integrated Twin-Screw Hot-Melt Extrusion and Injection-Molding Continuous Manufacturing Process.

    Science.gov (United States)

    Puri, Vibha; Brancazio, Dave; Desai, Parind M; Jensen, Keith D; Chun, Jung-Hoon; Myerson, Allan S; Trout, Bernhardt L

    2017-07-04

    The combination of hot-melt extrusion and injection molding (HME-IM) is a promising process technology for continuous manufacturing of tablets. However, there has been limited research on its application to formulate crystalline drug-containing immediate-release tablets. Furthermore, studies that have applied the HME-IM process to molded tablets have used a noncontinuous 2-step approach. The present study develops maltodextrin (MDX)-based extrusion-molded immediate-release tablets for a crystalline drug (griseofulvin) using an integrated twin-screw HME-IM continuous process. At 10% w/w drug loading, MDX was selected as the tablet matrix former based on a preliminary screen. Furthermore, liquid and solid polyols were evaluated for melt processing of MDX and for impact on tablet performance. Smooth-surfaced tablets, comprising crystalline griseofulvin solid suspension in the amorphous MDX-xylitol matrix, were produced by a continuous process on a twin-screw extruder coupled to a horizontally opening IM machine. Real-time HME process profiles were used to develop automated HME-IM cycles. Formulation adjustments overcame process challenges and improved tablet strength. The developed MDX tablets exhibited adequate strength and a fast-dissolving matrix (85% drug release in 20 min), and maintained performance on accelerated stability conditions. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  12. Biopharmaceutical constants for carbamazepine immediate release tablets in simplifying bioequivalence studies

    Directory of Open Access Journals (Sweden)

    Nanayakkara Mangala

    2006-01-01

    Full Text Available Current study was undertaken in order to determine model biopharmaceutical constants for carbamazepine immediate release tablets (200 mg from documented data of plasma concentration vs time curves. The constants and the proposed methodology simplify bioequivalence determinations to blood sampling restricted only to two time points. Twelve volunteer drug plasma concentration (Cp determinations from a crossover design bioequivalence study were fitted into equations containing two rate processes. The optimized rate constants were used to generate the Cp vs time curves (generated curves. Generated curves were then differentiated (dCp/dt to obtain the first derivative curve for each volunteer from which times for highest rate of absorption (TAmaxn and highest rate of elimination (TEmaxn were determined. The corresponding highest rate of absorption and the highest rate of elimination for each individual were then obtained from the generated curve and named as Amaxn and Emaxn. Individual Amaxn and Emaxn values were then averaged to obtain the mean Amax and Emax. Out of the 24 determinations, a total of 13 Amaxn and 20 Emaxn values fell within ±20% of the overall mean. Final Amax and Emax values ware arrived at by averaging each set of individual 13 values and 20 values respectively. From these two mean coordinates, the corresponding constants, plasma drug concentration at the point of highest rate of absorption (CpAmax and corresponding time TAmax, as well as the plasma drug concentration at the point of highest rate of elimination (CpEmax and the corresponding time TEmax, were determined.

  13. Oral controlled release drug delivery system and Characterization of oral tablets; A review

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    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. Dissolution of tablet-in-tablet formulations studied with ATR-FTIR spectroscopic imaging.

    Science.gov (United States)

    Wray, Patrick S; Clarke, Graham S; Kazarian, Sergei G

    2013-03-12

    This work uses ATR-FTIR spectroscopic imaging to study the dissolution of delayed release and pH resistant compressed coating pharmaceutical tablets. Tablets with an inner core and outer shell were constructed using a custom designed compaction cell. The core of the delayed release tablets consisted of hydroxypropyl methylcellulose (HPMC) and caffeine. The shell consisted of microcrystalline cellulose (MCC) and glucose. The core of the pH resistant formulations was an ibuprofen and PEG melt and the shell was constructed from HPMC and a basic buffer. UV/vis spectroscopy was used to monitor the lag-time of drug release and visible optical video imaging was used as a complementary imaging technique with a larger field of view. Two delayed release mechanisms were established. For tablets with soluble shell sections, lag-time was dependent upon rapid shell dissolution. For tablets with less soluble shells, the lag-time was controlled by the rate of dissolution medium ingress through the shell and the subsequent expansion of the wet HPMC core. The pH resistant formulations prevented crystallization of the ibuprofen in the core during dissolution despite an acidic dissolution medium. FTIR imaging produced important information about the physical and chemical processes occurring at the interface between tablet sections during dissolution.

  15. FORMULATION AND EVALUATION OF EFFERVESCENT GASTRO-RETENTIVE FLOATING TABLETS FOR CONTROLLED RELEASE OF AN ANTI-ULCER COMPOUND

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    Aleksandar Aleksovski

    2013-02-01

    Full Text Available Effervescent floating gastro-retentive matrix tablets present novel and promising approach towards targeted and controlled drug delivery in the stomach and in the upper part of the small intestine. This kind of dosage form could be obtained by combining in a suitable ratio effervescent compounds and hydrophilic/hydrophobic polymer/s. The aim of our investigation was to develop controlled release effervescent matrix tablet which will float over the gastric media for longer than 8 hours and will release the active compound in a continuous manner over 8 hours period. We used ranitidine HCl as a model drug which has narrow absorption window in the upper small intestine, and is a good candidate for this type of dosage forms. We employed sodium bicarbonate and citric acid as effervescent compounds and two different types of hydroxypropyl methylcellulose (HPMC K4M and HPMC K15M as a controlled release hydrophilic polymer. Three batches of tablets were produced (one containing HPMC K4M, other containing HPMC K15M, and the third containing 1:1 mixture of these two polymers and every batch was compressed with two different forces 5.5 kN and 4.7 kN, so completely six probes of tablets were made. All six probes complied the pharmacopoeial requirements concerning mass uniformity, content, friability and hardness. All six probes tended to float fast to the surface of the medium and tend to hydrate and swell fast enough which actions provided controlled release of the compound over period of 8 hours. No significant differences in the dissolution profiles of all six probes were noticed during the investigation.

  16. Formulation and evaluation of self-emulsifying orlistat tablet to enhance drug release and in vivo performance: factorial design approach.

    Science.gov (United States)

    Gade, Mukund Maruti; Hurkadale, Pramod Jayadevappa

    2016-06-01

    The purpose of the present research work was to formulate, evaluate, and optimize self-emulsifying orlistat tablet to enhance drug release followed by in vivo antiobesity activity in Wistar rats. Initially, the solubility of orlistat was determined in different natural oils, surfactant, and co-surfactants. Self-emulsifying drug delivery system (SEDDS) was prepared by using castor oil, Tween 80, and Capryol PGMC as components. Liquid SEDDS evaluated for globule size and emulsification time. A 3(2) full factorial design was utilized for the optimization purpose. Formulation variables such as quantity of oil (X1) and ratio of surfactant to co-surfactant (X2) were investigated for their effect on globule size and emulsification time. Optimized formulation with minimum globule size was freeze-dried which further compressed into the tablet. Finally, optimized formulation evaluated for the in vitro drug release study followed by weight losing potential in Wistar rats. Globule size and emulsification time for the optimized formulation were found to be 96.4 ± 8.5 nm and 26 ± 4 s, respectively. Fourier transform infra red spectroscopy (FTIR) studies indicated that there was no interaction between drug and excipients. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) study revealed that there was the conversion of crystalline orlistat to the amorphous form. Orlistat release from the self-emulsifying tablet formulation was faster with higher weight reduction potential in Wistar rats than the marketed formulation. Increased in vitro drug release with considerable in vivo weight loss by self-emulsifying tablet suggests that the SEDDS could serve as potential formulation strategy for orlistat.

  17. Effect of thermal and chemical modifications on the mechanical and release properties of paracetamol tablet formulations containing corn, cassava and sweet potato starches as filler-binders

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    Mariam Vbamiunomhene Lawal

    2015-07-01

    Conclusions: Modification of the experimental starches improved the mechanical and release properties of directly compressed paracetamol tablet formulations. Thus, they can be developed for use as pharmaceutical excipients in specific formulations.

  18. Formulation development, optimization and study on drug release kinetics of Eudragit® L100-HPMC E15 LV mixed film-coated colon-targeted Mesalamine tablets

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    A Maria John Newton

    2012-01-01

    Full Text Available The study was designed to evaluate the in vitro dissolution characteristics of pH-sensitive polymer - HPMC E 15 LV-coated tablets - in various simulated fluids (pH range 1.2, 6, 7.2. The Mesalamine tablets were fabricated by mixing the drug with microcrystalline cellulose and other ingredients. The fabricated Mesalamine tablets were coated with Eudragit L100 polymer and HPMC E 15 LV. The fluctuation in colonic pH conditions during inflammatory bowel disease and the nature of less fluid content in the colon may limit the expected drug release in the colon. Addition of HPMC E 15 LV may control this problem by hydrophilic nature and excellent film-forming characteristics like ductility and elasticity. The different batches of Mesalamine tablets (FM1-FM5 were coated with increasing concentration of Eudragit L100 and HPMC E 15 LV. The coating was given up to 8% TWG(Total weight gain of the uncoated tablet. Drug release studies were conducted in different pH conditions in the presence of rat ceaecal contents. The different buffer conditions were chosen to mimic the pH changes in the terminal part of the ileum as well as in the colon. The drug release profile was analyzed for colon-targeting performance in vitro. The release profile of the tablets indicates that the drug release was retarded in the tablet by film coating. The addition of HPMC E 15 LV ensures the channels for allowing colonic fluids to penetrate into the core and subsequent drug release at the target site. The kinetics of the drug release also evaluated the release pattern that was best fitted with Higuchian release. The results of the mechanism of release revealed that drug release was found to be a complex one with diffusion, erosion and swelling.

  19. Effect of thermal and chemical modifications on the mechanical and release properties of paracetamol tablet formulations containing corn, cassava and sweet potato starches as filler-binders

    Institute of Scientific and Technical Information of China (English)

    Mariam; Vbamiunomhene; Lawal; Michael; Ayodele; Odeniyi; Oludele; Adelanwa; Itiola

    2015-01-01

    Objective: To investigate the effects of acetylation and pregelatinization of cassava and sweet potato starches on the mechanical and release properties of directly compressed paracetamol tablet formulations in comparison with official corn starch.Methods: The native starches were modified by acetylation and pregelatinization. The tablets were assessed using friability(Fr), crushing strength(Cs), disintegration time(Dt) and dissolution parameters. Results: Starch acetylation produced paracetamol tablets that were stronger and had the best balance of mechanical and disintegration properties, while pregelatinization produced tablets that were more friable but had a better overall strength in relation to disintegration than formulations made from natural starches. Correlations mainly existed between Dt and the dissolution parameters t80, t2 and k1 in the formulations. Conclusions: Modification of the experimental starches improved the mechanical and release properties of directly compressed paracetamol tablet formulations. Thus, they can be developed for use as pharmaceutical excipients in specific formulations.

  20. Effect of thermal and chemical modiifcations on the mechanical and release properties of paracetamol tablet formulations containing corn, cassava and sweet potato starches as ifller-binders

    Institute of Scientific and Technical Information of China (English)

    Mariam Vbamiunomhene Lawal; Michael Ayodele Odeniyi; Oludele Adelanwa Itiola

    2015-01-01

    Objective:To investigate the effects of acetylation and pregelatinization of cassava and sweet potato starches on the mechanical and release properties of directly compressed paracetamol tablet formulations in comparison with official corn starch. Methods: The native starches were modified by acetylation and pregelatinization. The tablets were assessed using friability (Fr), crushing strength (Cs), disintegration time (Dt) and dissolution parameters. Results: Starch acetylation produced paracetamol tablets that were stronger and had the best balance of mechanical and disintegration properties, while pregelatinization produced tablets that were more friable but had a better overall strength in relation to disintegration than formulations made from natural starches. Correlations mainly existed between Dt and the dissolution parameters t80, t2 and k1 in the formulations. Conclusions:Modification of the experimental starches improved the mechanical and release properties of directly compressed paracetamol tablet formulations. Thus, they can be developed for use as pharmaceutical excipients in specific formulations.

  1. AN IN-VITRO STUDY FOR MUCOADHESION AND CONTROL RELEASE PROPERTIES OF GUAR GUM AND CHITOSAN IN ITRACONAZOLE MUCOADHESIVE TABLETS

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    A. A. Shaikh*, Y. D. Pawar and S. T. Kumbhar

    2012-05-01

    Full Text Available This study describes the effect of Guar gum and chitosan on formulation of mucoadhesive drug delivery system of itraconazole. Mucoadhesive strength, Drug content, Hardness, Friability, Weight variation, Moisture content and accelerated stability studies were performed to study the effect of polymers on prepared mucoadhesive tablets. Results of the present study clarified the potential of guar gum and chitosan in mucoadhesion and control release of itraconazole tablets. Both polymers i.e. Chitosan and guar gum were helpful for controlling the drug release in better way when used in proper combinations. When result of mucoadhesion was checked guar gum gives more mucoadhesive strength to the prepared tablets as compared to chitosan. Accelerated stability studies were performed on prepared formulations, results indicates that the formulations were stable that mince excipients used in the formulations were stable and are not causing major changes in drug release pattern after a period of 6 months. From above mentioned work it can be concluded that combination of Chitosan and guar gum is better and effective approach to have controlled mucoadhesive drug delivery system of Itraconazole.

  2. Effect Of Ether Derivative Cellulose Polymers On Hydration, Erosion And Release Kinetics Of Diclofenac Sodium Matrix Tablets

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    Muhammad Akhlaq*1,2, Gul Majid Khan1 , Abdul Wahab1, Waqas Rabbani1, Abid Hussain1, Asif Nawaz1, & Alam Zeb1

    2011-09-01

    Full Text Available Objectives: The work aims to investigate the effect ofhydrophilic and hydrophobic polymers swelling and erosionon the release behaviour of DCL-Na from controlled matrixtablets prepared by direct compression and wet-granulationtechniques.Materials and Methods: Powder preformulation studies wereconducted. Tablets were prepared by direct compressiontechnique and their physicochemical properties wereevaluated. Drug-polymer interaction was analyzed by FTIRspectroscopy. The in-vitro drug release study was conductedusing phosphte buffer pH 7.4 as dissolution medium anddifferent kinetic parameters were applied.Results and Discussion: F-1 and F-5 containing ethycelluloseprepared by direct compression and wet granulationtechniques released 94 % and 84 % drug after 24hrs, while F-2and F-6 containing hydroxypropylmethylcellulose polymerprepared by direct compression and wet granulation released98.46 % and 91.25 % drug after within 24 hrs respectively.Ethylcellulose and hydroxypropylmethylcellulose based matrixtablets showed the best anomalous drug release behaviour,with the release exponents “ n ” ranging from 0.685 to 0.809.Conclusion: It has been concluded that ethylcellulose etherderivative polymer is used to prepare oral controlled releasematrix tablet of diclofenac sodium. Fickian drug diffusion,polymer hydration and erosion mechanisms occurredsimultaneously and were considered as the main drug releasecontrolling factors.

  3. FORMULATION AND IN VITRO EVALUATION OF ARAUCARIA BIDWILLI GUM-BASED SUSTAIN RELEASE MATRIX TABLETS OF DICLOFENAE SODIUM

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    J. ASHOK KUMAR, M.RAJESH, S.MYTHIESH KUMAR,T. GIRIRAJ KULKARNI, V.GOPAL

    2013-10-01

    Full Text Available A gel forming Polysaccharide gum obtained form the bark of Araucaria bidwilli was employed as a matrix sustained release tablet formulation of Diclofenac sodium (a non steroidal anti inflammatory agent. The effect of Araucaria bidwilli gum (Natural and Synthetic polymer Hydroxypropyl methyl cellulose (HPMC K4 M on the release of Diclofenac sodium was studied. The FT-IR spectroscopic studies of drug, gum and mixture indicated no chemical interaction. Six formulations were prepared by wet granulation method containing Araucaria bidwilli gum powder concentration 10% 20% & 30% w\\w and 10% 20% &30% w\\w of HPMC K4 M with sufficient volume of granulating agent Polyvinyl pyrrolene (PVP K 30, Avicel pH101 as diluents, Magnesium stearate and Aerosil is used lubricant and glidant respectively.This study was carried out to find out the difference between synthetic and natural gum and whether synthetic gum can be replaced by natural gums. Physical and technological studies of granules and tablets were compliance with Pharmacopoial standards.The drug release increased with Araucaria bidwilli gum when compared to synthetics polymer concentration .The value of release exponent were found to be almost straight line and regression coefficient value between 0.938 and 0.998.This implies that the release mechanism is diffusion. Formulation F3 ( contained 30% w\\w Araucaria bidwilli gum met the desired requirements for a sustained release dosage form.

  4. Development and evaluation of natural gum-based extended release matrix tablets of two model drugs of different water solubilities by direct compression

    OpenAIRE

    Ofori-Kwakye, Kwabena; Mfoafo, Kwadwo Amanor; Kipo, Samuel Lugrie; Kuntworbe, Noble; Boakye-Gyasi, Mariam EL

    2015-01-01

    The study was aimed at developing extended release matrix tablets of poorly water-soluble diclofenac sodium and highly water-soluble metformin hydrochloride by direct compression using cashew gum, xanthan gum and hydroxypropylmethylcellulose (HPMC) as release retardants. The suitability of light grade cashew gum as a direct compression excipient was studied using the SeDeM Diagram Expert System. Thirteen tablet formulations of diclofenac sodium (∼100 mg) and metformin hydrochloride (∼200 mg) ...

  5. Kozeny-Carman permeability relationship with disintegration process predicted from early dissolution profiles of immediate release tablets.

    Science.gov (United States)

    Kumari, Parveen; Rathi, Pooja; Kumar, Virender; Lal, Jatin; Kaur, Harmeet; Singh, Jasbir

    2017-07-01

    This study was oriented toward the disintegration profiling of the diclofenac sodium (DS) immediate-release (IR) tablets and development of its relationship with medium permeability kperm based on Kozeny-Carman equation. Batches (L1-L9) of DS IR tablets with different porosities and specific surface area were prepared at different compression forces and evaluated for porosity, in vitro dissolution and particle-size analysis of the disintegrated mass. The kperm was calculated from porosities and specific surface area, and disintegration profiles were predicted from the dissolution profiles of IR tablets by stripping/residual method. The disintegration profiles were subjected to exponential regression to find out the respective disintegration equations and rate constants kd. Batches L1 and L2 showed the fastest disintegration rates as evident from their bi-exponential equations while the rest of the batches L3-L9 exhibited the first order or mono-exponential disintegration kinetics. The 95% confidence interval (CI95%) revealed significant differences between kd values of different batches except L4 and L6. Similar results were also spotted for dissolution profiles of IR tablets by similarity (f2) test. The final relationship between kd and kperm was found to be hyperbolic, signifying the initial effect of kperm on the disintegration rate. The results showed that disintegration profiling is possible because a relationship exists between kd and kperm. The later being relatable with porosity and specific surface area can be determined by nondestructive tests.

  6. A unified multicomponent stress-diffusion model of drug release from non-biodegradable polymeric matrix tablets.

    Science.gov (United States)

    Salehi, Ali; Zhao, Jin; Cabelka, Tim D; Larson, Ronald G

    2016-02-28

    We propose a new transport model of drug release from hydrophilic polymeric matrices, based on Stefan-Maxwell flux laws for multicomponent transport. Polymer stress is incorporated in the total mixing free energy, which contributes directly to the diffusion driving force while leading to time-dependent boundary conditions at the tablet interface. Given that hydrated matrix tablets are dense multicomponent systems, extended Stefan-Maxwell (ESM) flux laws are adopted to ensure consistency with the Onsager reciprocity principle and the Gibbs-Duhem thermodynamic constraint. The ESM flux law for any given component takes into account the friction exerted by all other species and is invariant with respect to reference velocity, thus satisfying Galilean translational invariance. Our model demonstrates that penetrant-induced plasticization of polymer chains partially or even entirely offsets the steady decline of chemical potential gradients at the tablet-medium interface that drive drug release. Utilizing a Flory-Huggins thermodynamic model, a modified form of the upper convected Maxwell constitutive equation for polymer stress and a Fujita-type dependence of mutual diffusivities on composition, depending on parameters, Fickian, anomalous or case II drug transport arises naturally from the model, which are characterized by quasi-power-law release profiles with exponents ranging from 0.5 to 1, respectively. A necessary requirement for non-Fickian release in our model is that the matrix stress relaxation time is comparable to the time scale for water diffusion. Mutual diffusivities and their composition dependence are the most decisive factors in controlling drug release characteristics in our model. Regression of the experimental polymer dissolution and drug release profiles in a system of Theophylline/cellulose (K15M) demonstrate that API-water mutual diffusivity in the presence of excipient cannot generally be taken as a constant.

  7. [Preparation of peroral delayed-action drug forms using biological polymers as the base. 4. Preparation of erosion tablets with a base of starch hydrolysis products].

    Science.gov (United States)

    Mank, R; Kala, H; Lorenz, A

    1989-09-01

    The preparation and investigation of erosonic tablets using a modified starch product are described. Codeine phosphate and pholedrine sulfate served as model drugs. The pharmaceutical investigations showed, that this product is a good auxiliary substance for the direct compression. When in contact with water, the tablets form a gel. This gel determines the drug release. In in vitro investigations a degradation of the starch product by enzymes was detected. Especially the amount of the release values obtained were analyzed by the equation of Noyes-Whitney.

  8. Properties and mechanisms of drug release from matrix tablets containing poly(ethylene oxide) and poly(acrylic acid) as release retardants.

    Science.gov (United States)

    Zhang, Feng; Meng, Fan; Lubach, Joseph; Koleng, Joseph; Watson, N A

    2016-08-01

    The interactions between poly(ethylene oxide) (PEO) and poly(acrylic acid) (PAA) in aqueous medium at pH 6.8 were investigated in the current study. We have also studied the effect of interpolymer interactions and various formulation variables, including the molecular weight of PEO, the ratio between PEO and PAA, the crystallinity of PEO, and the presence of an acidifying agent, on the release of theophylline from matrix tablets containing both PEO and PAA as release retardants. At pH 6.8, the synergy in solution viscosity between PEO and PAA as the result of ion-dipole interaction was observed in this study. The release of theophylline from the matrix tablets containing physical mixtures of PEO and PAA was found to be a function of dissolution medium pH because of the pH-dependent interactions between these two polymers. Because of the formation of water insoluble interpolymer complex between PEO and PAA in aqueous medium at pH below 4.0, the release of theophylline was independent of PEO molecular weight and was controlled by Fickian diffusion mechanism in 0.01N hydrochloric acid solution. In comparison, the drug release was a function of PEO molecular weight and followed the anomalous transport mechanism in phosphate buffer pH 6.8. The presence of PAA exerted opposite effects on the release of theophylline in phosphate buffer pH 6.8. In one aspect, theophylline release was accelerated because the erosion of PAA was much faster than that of PEO at pH6.8. On the opposite aspect, theophylline release was slowed down because of the formation of insoluble complex inside the gel layer as the result of the acidic microenvironment induced by PAA, and the increase in the viscosity of the gel layer as the result of the synergy between PEO and PAA. These two opposite effects offset each other. As a result, the release of theophylline remained statistically the same even when 75% PEO in the formulation was replaced with PAA. In phosphate buffer pH 6.8, the release of

  9. Release Characteristics of 4-Phenylazoaniline From Alginate Microparticles and Matrix Tablets%海藻酸微球及骨架片中苯基偶氮苯的释放特性

    Institute of Scientific and Technical Information of China (English)

    涂家生; Sam Bolla; John Barr; Jelmer Miedema; Xiaoling Li; Bhaskara Jiasti

    2003-01-01

    AIM:To investigate the release characteristics of insoluble drug from alginate macroparticles and matrix tablets.METHOD:Alginate microparticles were manufactured by spray-coagulation method. 4-phenylazoaniline (PAA) was selected as a insoluble model drug. PAA was loaded into alginate microparticles by adsorption method. Matrix tablets composed of PAA loaded alginate microparticles, HPMC (K4M), pectin were directly compressed. The release experiments of PAA from alginate microparticles and matrix tablets were conducted in different medium. To elucidate the release mechanism, swelling experiments were conducted, the erosion front, diffusion front and swelling front of tablets were measured.RESULT:The release of PAA from the microparticles was found to depend upon the release medium and incomplete \\%in vitro\\% release in deionized water was observed. Delayed release of PAA from both microparticles and matrix tablets in simulated gastrointestinal (GI) fluid were observed. Pectinase could increase the release rate of PAA from the matrix tablets. Both release data and swelling data indicated that the release of PAA from matrix tablets was controlled by swelling process.CONCLUSION: Alginate microparticles could be useful in delayed release of insoluble drugs.%目的:研究海藻酸微球及由海藻酸微球、果胶、HPMC组成的骨架片中苯基偶氮苯的释放特性.方法:海藻酸微球通过喷雾-凝聚法制得,苯基偶氮苯 (PAA)作为疏水性模型药物通过吸附法被微球载运.制备了由海藻酸微球、果胶、HPMC组成的骨架片.测定了海藻酸微球及骨架片中苯基偶氮苯的释放.为进一步探讨药物释放机制,进行了骨架片的溶胀实验.结果:微球中PAA的释放依赖于释放介质,其中在水中释放不完全,在人工胃肠液中呈延缓到肠内释放的特性.在骨架片中也观察在人工胃肠液中的延缓释放行为.果胶酶有一定的加速骨架片释放的的作用.释放度和溶胀

  10. Design and in vitro/in vivo evaluation of sustained-release floating tablets of itopride hydrochloride

    Directory of Open Access Journals (Sweden)

    Ahmed SM

    2016-12-01

    Full Text Available Sayed M Ahmed,1 Adel Ahmed Ali,2 Ahmed MA Ali,2,3 Omiya A Hassan2,4 1Department of Industrial Pharmacy, Faculty of Pharmacy, Assiut University, Assiut, 2Department of Pharmaceutics, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt; 3Department of Pharmaceutics, Faculty of Pharmacy, Taif University, Taif, Kingdom of Saudi Arabia; 4Department of Pharmaceutics, Faculty of Pharmacy, Deraya University, El-Minia Gadida, Egypt Purpose: The aim of the present study was to improve the bioavailability of itopride (ITO and sustain its action by formulating as a floating dosage form. Materials and methods: Sustained-release floating tablets of ITO hydrochloride (HCl were prepared by direct compression using different hydrocolloid polymers such as hydroxypropyl methylcellulose and ethylcellulose and/or methacrylic acid polymers Eudragit RSPM and Carbopol 934P. The floating property was achieved using an effervescent mixture of sodium bicarbonate and anhydrous citric acid (1:1 mol/mol. Hardness, friability, content uniformity, and dissolution rate of the prepared floating tablets were evaluated. The formulation F10 composed of 28.5% Eudragit RSPM, 3% NaHCO3, and 7% citric acid provided sustained drug release. Results: In vitro results showed sustained release of F10 where the drug release percentage was 96.51%±1.75% after 24 hours (P=0.031.The pharmacokinetic results indicated that the area under the curve (AUC0–∞ of the prepared sustained-release floating tablets at infinity achieved 93.69 µg·h/mL compared to 49.89 µg·h/mL for the reference formulation (Ganaton® and the relative bioavailability of the sustained-release formulation F10 increased to 187.80% (P=0.022. Conclusion: The prepared floating tablets of ITO HCl (F10 could be a promising drug delivery system with sustained-release action and enhanced drug bioavailability. Keywords: itopride HCl, oral drug delivery, stability study, bioavailability

  11. Development of a multiparticulate system containing enteric-release mini-tablets of omeprazole

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    Volnei Jose Tondo Filho

    2014-09-01

    Full Text Available The main aim of this study was to develop a multiparticulate system containing mini-tablets of omeprazole formulated with an enteric polymer with pH-dependent solubility. Pre-formulation studies showed good flow and compaction capacity, leading to the production ofhigh quality mini-tablets. The mini-tablets were coated in a fluidized bed with hydroxypropylmethylcellulose /Eudragit(r L30D55 and packed into hard gelatin capsules. The dissolution profile showed gastro-resistance and zero-order kinetics. The dissolution profile for the formulation containing lactose as the diluent and coated with 12% (tablet weight gain of polymer was similar to that ofthe reference drug.

  12. Application of acid-treated yeast cell wall (AYC) as a pharmaceutical additive. II: effects of curing on the medicine release from AYC-coated tablets.

    Science.gov (United States)

    Yuasa, H; Kaneshige, J; Ozeki, T; Kasai, T; Eguchi, T; Ishiwaki, N

    2000-11-19

    Acid-treated yeast cell wall (AYC) was newly prepared by acidifying brewers' yeast cell wall. Core tablets containing 3% of acetaminophen (AAP) were coated with the AYC aqueous dispersion containing 5% (w/v) of AYC and 0.35% (w/v) of glycerol. The curing of AYC-coated tablets was performed at various curing periods of time and temperatures. The effects of curing on AAP release from AYC-coated tablets, the weight and thickness of the coated layer of AYC and the water sorption into the AYC-coated tablets were studied. The tensile strength and pore size distribution of the AYC cast film were measured. In the case of 60, 80, or 100 degrees C curing, AAP release from AYC-coated tablets showed a sigmoidal release profile with an initial lag time. The duration of the lag time increased with the increasing curing time and temperature, though the release rate after the lag time hardly changed. At 120 degrees C curing, the release rate after the lag time decreased with the increasing curing time and a sustained release was observed. The weight and thickness of the AYC-coated layer and the water sorption rate into AYC-coated tablets decreased with the increasing curing time and temperature. The tensile strength of the AYC cast film increased with increasing the curing temperature, particularly at 120 degrees C curing. It is considered that the water was evaporated from the AYC-coated layer and the adhesion force between AYC particles increased during curing, making the structure of the AYC-coated layer densely firm. The changes in the duration of lag time and the release rate may be due to changes in the structure of the AYC-coated layer caused by curing. These results show that it is feasible to control the lag time and the release rate of AAP from AYC-coated tablets by varying the curing time and temperature.

  13. Regulating Drug Release Behavior and Kinetics from Matrix Tablets Based on Fine Particle-Sized Ethyl Cellulose Ether Derivatives: An In Vitro and In Vivo Evaluation

    Directory of Open Access Journals (Sweden)

    Kifayat Ullah Shah

    2012-01-01

    Full Text Available The design and fabrication of sustained/controlled release dosage forms, employing new excipients capable of extending/controlling the release of drugs from the dosage forms over prolonged periods, has worked well in achieving optimally enhanced therapeutic levels of the drugs. In this sense, the objective of this study was to investigate the suitability of selected cellulose ether derivatives for use in direct compression (DC and as efficient drug release controlling agents. Controlled release matrix tablets of ciprofloxacin were prepared at different drug-to-polymer (D : P ratios by direct compression using a fine particle sized ethylcellulose ether derivative (ETHOCEL Standard Premium 7FP as rate controlling polymer. The tablets obtained were evaluated for various physico-chemical characteristics and in-vitro drug release studies were conducted in phosphate buffer (pH 7.4 using PharmaTest dissolution apparatus at constant temperature of 37∘C±0.1. Similarity factor 2 was employed to the release profiles of test formulations and were compared with marketed ciprofloxacin conventional tablets. Drug release mechanism and the kinetics involved were investigated by fitting the release profile data to various kinetic models. It was found that with increasing the proportion of ethylcellulose ether derivative in the matrix, the drug release was significantly extended up to 24 hours. The tablets exhibited zero order or nearly zero order drug transport mechanism. In vivo drug release performance of the developed controlled release tablets and reference conventional tablets containing ciprofloxacin were determined in rabbit serum according to randomized two-way crossover study design using High Performance Liquid Chromatography. Several bioavailability parameters of both the test tablets and conventional tablets including max, max and AUC0- were compared which showed an optimized max and max (<0.05. A good correlation was obtained between in vitro

  14. Regulating drug release behavior and kinetics from matrix tablets based on fine particle-sized ethyl cellulose ether derivatives: an in vitro and in vivo evaluation.

    Science.gov (United States)

    Shah, Kifayat Ullah; Khan, Gul Majid

    2012-01-01

    The design and fabrication of sustained/controlled release dosage forms, employing new excipients capable of extending/controlling the release of drugs from the dosage forms over prolonged periods, has worked well in achieving optimally enhanced therapeutic levels of the drugs. In this sense, the objective of this study was to investigate the suitability of selected cellulose ether derivatives for use in direct compression (DC) and as efficient drug release controlling agents. Controlled release matrix tablets of ciprofloxacin were prepared at different drug-to-polymer (D : P) ratios by direct compression using a fine particle sized ethylcellulose ether derivative (ETHOCEL Standard Premium 7FP) as rate controlling polymer. The tablets obtained were evaluated for various physico-chemical characteristics and in-vitro drug release studies were conducted in phosphate buffer (pH 7.4) using PharmaTest dissolution apparatus at constant temperature of 37 °C ± 0.1. Similarity factor f(2) was employed to the release profiles of test formulations and were compared with marketed ciprofloxacin conventional tablets. Drug release mechanism and the kinetics involved were investigated by fitting the release profile data to various kinetic models. It was found that with increasing the proportion of ethylcellulose ether derivative in the matrix, the drug release was significantly extended up to 24 hours. The tablets exhibited zero order or nearly zero order drug transport mechanism. In vivo drug release performance of the developed controlled release tablets and reference conventional tablets containing ciprofloxacin were determined in rabbit serum according to randomized two-way crossover study design using High Performance Liquid Chromatography. Several bioavailability parameters of both the test tablets and conventional tablets including C(max⁡), T(max⁡) and AUC(0-t) were compared which showed an optimized C(max⁡) and T(max⁡) (P < 0.05). A good correlation was obtained

  15. Dalfampridine extended release tablets: 1 year of postmarketing safety experience in the US

    Directory of Open Access Journals (Sweden)

    Jara M

    2013-03-01

    Full Text Available Michele Jara,1 Graham Barker,2 Herbert R Henney 3rd1 1Acorda Therapeutics, Inc, Ardsley, NY, USA; 2Biogen Idec, Inc, Maidenhead, Berkshire, UK Background: Dalfampridine extended release tablets (dalfampridine-ER; prolonged-, modified, or sustained-release fampridine in some countries were approved in the US to improve walking in patients with multiple sclerosis, as demonstrated by improvement in walking speed. Postmarketing safety experience is available from exposure of approximately 46,000 patients in the US from product approval through March 2011. Objective: To provide a descriptive analysis of all spontaneously reported postmarketing adverse events (AEs for dalfampridine-ER since product launch. Methods: AE data were extracted from the safety database from product launch through March 31, 2011; AEs were classified using the Medical Dictionary for Regulatory Activities. Seizure cases were reviewed for patient demographics, time to event from treatment onset, and presence of additional risk factors. Results: The most frequently reported postmarketing AEs were similar to those reported during clinical development: dizziness, insomnia, balance disorder, headache, nausea, urinary tract infection, asthenia, and back pain (all included in US product labeling. New clinically significant findings are related to lack of efficacy and inappropriate dosing. Of the approximately 46,000 patients exposed, 85 seizures were reported (~5.4/1000 patient-years, of which 82 were reported or confirmed by a health care practitioner (~5.2/1000 patient-years. Beyond the intrinsic multiple sclerosis-related seizure risk, more than half of the 85 cases (62% had an additional potential risk factor for seizure including a previous history of convulsions, renal impairment, incorrect dosing, or use of concurrent medications with a labeled seizure risk. Duration of treatment prior to the seizure ranged from one dose to 365 days; 26/85 (31% patients suffered a seizure

  16. Formulation and development of pH-independent/dependent sustained release matrix tablets of ondansetron HCl by a continuous twin-screw melt granulation process.

    Science.gov (United States)

    Patil, Hemlata; Tiwari, Roshan V; Upadhye, Sampada B; Vladyka, Ronald S; Repka, Michael A

    2015-12-30

    The objective of the present study was to develop pH-independent/dependent sustained release (SR) tablets of ondansetron HCl dihydrate (OND), a selective 5-HT3 receptor antagonist that is used for prevention of nausea and vomiting caused by chemotherapy, radiotherapy and postoperative treatment. The challenge with the OND API is its pH-dependent solubility and relatively short elimination half-life. Therefore, investigations were made to solve these problems in the current study. Formulations were prepared using stearic acid as a binding agent via a melt granulation process in a twin-screw extruder. The micro-environmental pH of the tablet was manipulated by the addition of fumaric acid to enhance the solubility and release of OND from the tablet. The in vitro release study demonstrated sustained release for 24h with 90% of drug release in formulations using stearic acid in combination with ethyl cellulose, whereas 100% drug release in 8h for stearic acid-hydroxypropylcellulose matrices. The formulation release kinetics was correlated to the Higuchi diffusion model and a non-Fickian drug release mechanism. The results of the present study demonstrated for the first time the pH dependent release from hydrophilic-lipid matrices as well as pH independent release from hydrophobic-lipid matrices for OND SR tablets manufactured by means of a continuous melt granulation technique utilizing a twin-screw extruder.

  17. Factorial study on influence of gas generating agent and diluent on drug release kinetics of clopidogrel bisulfate floating tablets

    Directory of Open Access Journals (Sweden)

    K R Koteswara Rao

    2013-01-01

    Full Text Available The purpose of present work was to formulate and characterize a floating drug delivery system for Clopidogrel bisulphate to improve bioavailability and to minimize the side-effects of the drug such as gastric bleeding and drug resistance development. Clopidogrel floating tablets were prepared by direct compression technique by the use of xanthan gum at different concentrations (20%, 25% and 30% w/w. Sodium bicarbonate (15% w/w and microcrystalline cellulose (MCC (30% w/w were used as gas generating agent and diluent respectively. The effects of sodium bicarbonate and MCC on the drug release kinetics and floating properties were investigated. A 2 2 factorial design was applied systematically to optimized formulation. The percentage amount of sodium bicarbonate (X 1 and percentage amount of MCC (X 2 were selected as independent variables. The drug release rate constant (K and time required for 85% drug dissolution (T85 was selected as dependent variables. Factorial design revealed that the percentage amount of sodium bicarbonate and MCC had insignificant effect on drug release kinetics (K, T85 within the chosen levels and a high level of sodium bicarbonate (X 1 and the low level of MCC (X 2 favor the preparation of clopidogrel floating tablets. All the Clopidogrel floating formulations followed first order kinetics, Higuchi drug release kinetics with diffusion as the dominant mechanism of drug release. As per Korsmeyer-Peppas equation, the release exponent "n" ranged 0.455-0.654 indicating that drug release from all the formulations was by non-fickian diffusion mechanism.

  18. Design and Comparative Evaluation of In-vitro Drug Release, Pharmacokinetics and Gamma Scintigraphic Analysis of Controlled Release Tablets Using Novel pH Sensitive Starch and Modified Starch- acrylate Graft Copolymer Matrices

    Science.gov (United States)

    Kumar, Pankaj; Ganure, Ashok Laxmanrao; Subudhi, Bharat Bhushan; Shukla, Shubhanjali

    2015-01-01

    The present investigation deals with the development of controlled release tablets of salbutamol sulphate using graft copolymers (St-g-PMMA and Ast-g-PMMA) of starch and acetylated starch. Drug excipient compatibility was spectroscopically analyzed via FT-IR, which confirmed no interaction between drug and other excipients. Formulations were evaluated for physical characteristics like hardness, friability, weight variations, drug release and drug content analysis which satisfies all the pharmacopoeial requirement of tablet dosage form. Release rate of a model drug from formulated matrix tablets were studied at two different pH namely 1.2 and 6.8, spectrophotometrically. Drug release from the tablets of graft copolymer matrices is profoundly pH-dependent and showed a reduced release rate under acidic conditions as compared to the alkaline conditions. Study of release mechanism by Korsmeyer’s model with n values between 0.61-0.67, proved that release was governed by both diffusion and erosion. In comparison to starch and acetylated starch matrix formulations, pharmacokinetic parameters of graft copolymers matrix formulations showed a significant decrease in Cmax with an increase in tmax, indicating the effect of dosage form would last for longer duration. The gastro intestinal transit behavior of the formulation was determined by gamma scintigraphy, using 99mTc as a marker in healthy rabbits. The amount of radioactive tracer released from the labelled tablets was minimal when the tablets were in the stomach, whereas it increased as tablets reached to intestine. Thus, in-vitro and in-vivo drug release studies of starch-acrylate graft copolymers proved their controlled release behavior with preferential delivery into alkaline pH environment. PMID:26330856

  19. 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

  20. Research Article. Kinetics and Mechanism of Drug Release from Loratadine Orodispersible Tablets Developed without Lactose

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    Ciurba Adriana

    2017-03-01

    Full Text Available Objective: The aim of this study is to develop lactose-free orodispersible tablets with loratadine for patients with lactose intolerance. Materials and methods: Seven compositions (F1-F7 of 10 mg loratadine were prepared in form of orally disintegrating tablets, by direct compression, using croscarmellose sodium and pre-gelatinized starch in various concentrations as superdisintegrants, diluted with microcrystalline cellulose and combined with mannitol and maltodextrin as binder agents. The tablets had been studied in terms of their pharmacotechnical characteristics, by determining: the weight uniformity of the tablets, their friability, breaking strength and disintegration time, drug content and the dissolution profile of loratadine. The statistical analyses were performed with GraphPad Prism Software Inc. As dependent variables, both the hardness of the tablets and their disintegration ability differ between batches due to their compositional differences (as independent variables. DDSolver were used for modeling the kinetic of the dissolution processes by fitting the dissolution profiles with time-dependent equations (Zero-order, First-order, Higuchi, Korsmeyer-Peppas, Peppas-Sahlin. Results: All proposed formulas shows rapid disintegration, in less than 15 seconds, and the dissolution loratadine spans a period of about 10 minutes. Akaike index as well as R2 adjusted parameter have demonstrated that the studied dissolution profiles are the best fitted by Zero-order kinetic. Conclusion: In conclusion, association of croscarmellose sodium (7.5% with pre-gelatinized starch (6% as superdisintegrants and mannitol as the binder agent (35%, positively influences the dissolution properties of loratadine from orally fast dispersible tablets.

  1. Development and characterisation of sustained release solid dispersion oral tablets containing the poorly water soluble drug disulfiram.

    Science.gov (United States)

    Shergill, Mandip; Patel, Mina; Khan, Siraj; Bashir, Ayesha; McConville, Christopher

    2016-01-30

    Administration of drugs via the oral route is the most common and preferred route due to its ease of administration, cost-effectiveness and flexibility in design. However, if the drug being administered has limited aqueous solubility it can result in poor bioavailability. Furthermore, the low pH of the stomach as well as enzymatic activity can result in drugs delivered via the oral route being rapidly metabolised and degraded. Here we demonstrate the development and characterisation of sustained release solid dispersion oral tablets, containing the poorly water-soluble drug disulfiram (DSF). The tablets, which are manufactured from two different polymers (Kolliphor(®) P 188 and P 237) specifically designed for the manufacture of solid dispersions and two different polymers (Kollidon(®) SR and HPMC) specifically designed to provide sustained release, can enhance the solubility of DSF, sustain its release, while protecting it from degradation in simulated gastric fluid (SGF). The paper demonstrates that when using the hot melt method at 80°C the DSF loading capacity of the Kolliphor(®) P 188 and P 237 polymers is approximately 43 and 46% respectively, with the DSF completely in an amorphous state. The addition of 80% Kollidon(®) SR to the formulation completely protected the DSF in SGF for up to 70 min with 16% degradation after 120 min, while 75% degradation occurred after 120 min with the addition of 80% HPMC. The release rate of DSF can be manipulated by both the loading and type of sustained release polymer used, with HPMC providing for a much faster release rate compared to Kollidon(®) SR.

  2. Synthesis and Characterization of Sodium Alginate Conjugate and Study of Effect of Conjugation on Drug Release from Matrix Tablet

    OpenAIRE

    Satheeshababu, B. K.; Mohamed, I.

    2015-01-01

    The aim of the present research work to study the effect of conjugation of the polymer on drug release from the matrix tablets. Sodium alginate L-cysteine conjugate was achieved by covalent attachment of thiol group of L-cysteine with the primary amino group of sodium alginate through the amide bonds formed by primary amino groups of the sodium alginate and the carboxylic acid group of L-cysteine. The synthesised sodium alginate L-cysteine conjugate was characterised by determining of charrin...

  3. 21 CFR 520.2260c - Sulfamethazine sustained-release tablets.

    Science.gov (United States)

    2010-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520... grams (1 tablet) per 45 pounds of body weight as a single dose. (2) Indications for use. In calves for... Escherichia coli; and calf diptheria caused by Fusobacterium necrophorum. (3) Limitations. If there is...

  4. Novel gastroretentive sustained-release tablet of tacrolimus based on self-microemulsifying mixture:in vitro evaluation and in vivo bioavailability test

    Institute of Scientific and Technical Information of China (English)

    Yan-ping WANG; Yong GAN; Xin-xin ZHANG

    2011-01-01

    Aim:To develop a novel gastroretentive drug delivery system based on a self-microemulsifying (SME) lipid mixture for improving the oral absorption of the immunosuppressant tacrolimus.Methods:Liquid SME mixture,composed of Cremophor RH40 and monocaprylin glycerate,was blended with polyethylene oxide,chitosan,polyvinylpyrrolidone and mannitol,and then transformed into tablets via granulation,with ethanol as the wetting agent.The tablets were characterized in respect of swelling,bioadhesive and SME properties.In vitro dissolution was conducted using an HCl buffer at pH 1.2.Oral bioavailability of the tablets was examined in fasted beagle dogs.Results:The tablet could expand to 13.5 mm in diameter and 15 mm in thickness during the initial 20 min of contact with the HClbuffer at pH 1.2.The bioadhesive strength was as high as 0.98±0.06 N/cm2.The SME gastroretentive sustained-release tablets preserved the SME capability of the liquid SME formations under transmission electron microscope.The drug-release curve was fit to the zero-order release model,which was helpful in reducing fluctuations in blood concentration.Compared with the commercially available capsules of tacrolimus,the relative bioavailability of the SME gastroretentive sustained-release tablets was 553.4%±353.8%.Conclusion:SME gastroretentive sustained-release tablets can enhance the oral bioavailability of tacrolimus with poor solubility and a narrow absorption window.

  5. Adaptation of pharmaceutical excipients to FDM 3D printing for the fabrication of patient-tailored immediate release tablets.

    Science.gov (United States)

    Sadia, Muzna; Sośnicka, Agata; Arafat, Basel; Isreb, Abdullah; Ahmed, Waqar; Kelarakis, Antonios; Alhnan, Mohamed A

    2016-11-20

    This work aims to employ fused deposition modelling 3D printing to fabricate immediate release pharmaceutical tablets with several model drugs. It investigates the addition of non-melting filler to methacrylic matrix to facilitate FDM 3D printing and explore the impact of (i) the nature of filler, (ii) compatibility with the gears of the 3D printer and iii) polymer: filler ratio on the 3D printing process. Amongst the investigated fillers in this work, directly compressible lactose, spray-dried lactose and microcrystalline cellulose showed a level of degradation at 135°C whilst talc and TCP allowed consistent flow of the filament and a successful 3D printing of the tablet. A specially developed universal filament based on pharmaceutically approved methacrylic polymer (Eudragit EPO) and thermally stable filler, TCP (tribasic calcium phosphate) was optimised. Four model drugs with different physicochemical properties were included into ready-to-use mechanically stable tablets with immediate release properties. Following the two thermal processes (hot melt extrusion (HME) and fused deposition modelling (FDM) 3D printing), drug contents were 94.22%, 88.53%, 96.51% and 93.04% for 5-ASA, captopril, theophylline and prednisolone respectively. XRPD indicated that a fraction of 5-ASA, theophylline and prednisolone remained crystalline whilst captopril was in amorphous form. By combining the advantages of thermally stable pharmaceutically approved polymers and fillers, this unique approach provides a low cost production method for on demand manufacturing of individualised dosage forms. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. 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.

  7. Gastrointestinal pH and Transit Time Profiling in Healthy Volunteers Using the IntelliCap System Confirms Ileo-Colonic Release of ColoPulse Tablets.

    Directory of Open Access Journals (Sweden)

    Jacoba M Maurer

    Full Text Available ColoPulse tablets are an innovative development in the field of oral dosage forms characterized by a distal ileum and colon-specific release. Previous studies in humans showed release in the ileo-colonic region, but the relationship between gastrointestinal pH and release was not experimentally proven in vivo. This information will complete the in vivo release-profile of ColoPulse tablets.Release from ColoPulse tablets was studied in 16 healthy volunteers using the dual label isotope strategy. To determine gastrointestinal pH profiles and transit times the IntelliCap system was used. A ColoPulse tablet containing 13C-urea and an uncoated, immediate release tablet containing 15N2-urea were taken simultaneously followed by a standardized breakfast after three hours. Five minutes after intake of the tablets the IntelliCap capsule was swallowed and pH was measured until excretion in the feces. Breath and urine samples were collected for isotope analysis.Full analysis could be performed in 12 subjects. Median bioavailability of 13C -urea was 82% (95% CI 74-94%, range 61-114%. The median lag time (5% release of 13C was 5:42 h (95% CI 5:18-6:18 h, range 2:36-6:36 h, There was no statistically significant difference between lag time based on isotope signal and colon arrival time (CAT based on pH (median 5:42 vs 5:31 h p = 0.903. In all subjects an intestinal pH value of 7.0 was reached before release of 13C from the ColoPulse tablet occurred.From the combined data from the IntelliCap system and the 13C -isotope signal it can be concluded that release from a ColoPulse tablet in vivo is not related to transit times but occurs in the ileo-colonic region after pH 7.0 is reached. This supports our earlier findings and confirms that the ColoPulse system is a promising delivery system for targeting the distal ileum and colon.ISRCTN Registry 18301880.

  8. Gender differences in pharmacokinetics of a combination tablet of niacin extended-release/simvastatin in healthy Chinese volunteers.

    Science.gov (United States)

    Wang, Xiao-lin; Liu, Man; Yang, Man; Zhang, Ya-nan; Zhang, Dan; Zhang, Li-na; Han, Jing; Liu, Hui-chen

    2014-12-01

    The gender differences in pharmacokinetics of a combination tablet of niacin extended-release/simvastatin were evaluated in healthy Chinese volunteers. Thirty-six healthy male and female volunteers were enrolled in the study receiving a single oral dose of niacin extended-release/simvastatin 1,000/20 mg. The results indicated that the systemic exposure of simvastatin hydroxy acid and the total urine excretion of niacin were significantly higher for females compared with those for males, and the T max of niacin in plasma was significantly shorter for males than that for females. There were no significant differences in the systemic exposure of simvastatin, niacin, and NUA in plasma between males and females.

  9. 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.

  10. Sustained-release liquisolid compact tablets containing artemether–lumefantrine as alternate-day regimen for malaria treatment to improve patient compliance

    Science.gov (United States)

    Nnamani, Petra Obioma; Ugwu, Agatha Adaora; Ibezim, Emmanuel Chinedu; Kenechukwu, Franklin Chimaobi; Akpa, Paul Achile; Ogbonna, John-Dike Nwabueze; Obitte, Nicholas Chinedu; Odo, Amelia Ngozi; Windbergs, Maike; Lehr, Claus-Michael; Attama, Anthony Amaechi

    2016-01-01

    The present study aimed to develop low-dose liquisolid tablets of two antimalarial drugs artemether–lumefantrine (AL) from a nanostructured lipid carrier (NLC) of lumefantrine (LUM) and estimate the potential of AL as an oral delivery system in malariogenic Wistar mice. LUM-NLCs were prepared by hot homogenization using Precirol® ATO 5/Transcutol® HP and tallow fat/Transcutol® HP optimized systems containing 3:1 ratios of the lipids, respectively, as the matrices. LUM-NLC characteristics, including morphology, particle size, zeta potential, encapsulation efficiency, yield, pH-dependent stability, and interaction studies, were investigated. Optimized LUM-NLCs were mixed with artemether powder and other dry ingredients and the resultant powder evaluated for micromeritics. Subsequent AL liquisolid tablets were tested for in vitro drug release and in vivo antiplasmodial activity in mice infected with Plasmodium berghei berghei (NK 65). Results showed that optimized LUM-NLC were stable, spherical, polydispersed but nanometric. Percentage yield and encapsulation efficiency were ~92% and 93% for Precirol® ATO 5/Transcutol® HP batch, then 81% and 95% for tallow fat/Transcutol® HP batch while LUM was amorphous in NLC matrix. In vitro AL release from liquisolid compacts revealed initial burst release and subsequent sustained release. Liquisolid tablet compacts formulated with Precirol® ATO 5/Transcutol® HP-AL4 achieved higher LUM release in simulated intestinal fluid (84.32%) than tallow fat/Transcutol® HP-BL3 (77.9%). Non-Fickian (anomalous) diffusion and super case II transport were the predominant mechanisms of drug release. Equal parasitemia reduction was observed for both batches of tablet compacts (~92%), superior to the reduction obtained with commercial antimalarial formulations: Coartem® tablets (86%) and chloroquine phosphate tablets (66%). No significant difference (Poral administration to improve patient compliance, which is currently not obtainable

  11. Sustained-release liquisolid compact tablets containing artemether-lumefantrine as alternate-day regimen for malaria treatment to improve patient compliance.

    Science.gov (United States)

    Nnamani, Petra Obioma; Ugwu, Agatha Adaora; Ibezim, Emmanuel Chinedu; Kenechukwu, Franklin Chimaobi; Akpa, Paul Achile; Ogbonna, John-Dike Nwabueze; Obitte, Nicholas Chinedu; Odo, Amelia Ngozi; Windbergs, Maike; Lehr, Claus-Michael; Attama, Anthony Amaechi

    The present study aimed to develop low-dose liquisolid tablets of two antimalarial drugs artemether-lumefantrine (AL) from a nanostructured lipid carrier (NLC) of lumefantrine (LUM) and estimate the potential of AL as an oral delivery system in malariogenic Wistar mice. LUM-NLCs were prepared by hot homogenization using Precirol(®) ATO 5/Transcutol(®) HP and tallow fat/Transcutol(®) HP optimized systems containing 3:1 ratios of the lipids, respectively, as the matrices. LUM-NLC characteristics, including morphology, particle size, zeta potential, encapsulation efficiency, yield, pH-dependent stability, and interaction studies, were investigated. Optimized LUM-NLCs were mixed with artemether powder and other dry ingredients and the resultant powder evaluated for micromeritics. Subsequent AL liquisolid tablets were tested for in vitro drug release and in vivo antiplasmodial activity in mice infected with Plasmodium berghei berghei (NK 65). Results showed that optimized LUM-NLC were stable, spherical, polydispersed but nanometric. Percentage yield and encapsulation efficiency were ~92% and 93% for Precirol(®) ATO 5/Transcutol(®) HP batch, then 81% and 95% for tallow fat/Transcutol(®) HP batch while LUM was amorphous in NLC matrix. In vitro AL release from liquisolid compacts revealed initial burst release and subsequent sustained release. Liquisolid tablet compacts formulated with Precirol(®) ATO 5/Transcutol(®) HP-AL4 achieved higher LUM release in simulated intestinal fluid (84.32%) than tallow fat/Transcutol(®) HP-BL3 (77.9%). Non-Fickian (anomalous) diffusion and super case II transport were the predominant mechanisms of drug release. Equal parasitemia reduction was observed for both batches of tablet compacts (~92%), superior to the reduction obtained with commercial antimalarial formulations: Coartem(®) tablets (86%) and chloroquine phosphate tablets (66%). No significant difference (Poral administration to improve patient compliance, which is

  12. Formulation and the in-vitro and biopharmaceutical evaluation of sustained release tablet of verapamil HCL using precirol ATO 5 through melt granulation technique

    Directory of Open Access Journals (Sweden)

    Bhagwat Durgacharan

    2009-01-01

    Full Text Available Sustained release tablet of Verapamil hydrochloride (VPH was prepared by using Precirol ATO 5 (PREC by direct compression of matrices prepared by using the melt granulation technique. The effect of different concentrations of PREC on the in-vitro drug release of VPH was studied by comparing it with the marketed formulation and percent release given in USP for VPH extended release tablets. Effect of release enhancers such as microcrystalline cellulose (MCC and lactose on in-vitro drug release was also studied. Biopharmaceutical evaluation of the satisfactory formulation was also performed in order to estimate the maximum concentration of drug in plasma (C max , time required to reach maximum concentration (t max , elimination rate constant (k, elimination rate constant (t 1/2 , area under curve (AUC (0-t and AUC (02a, apparent volume of distribution (V d and mean residence time. The results showed that PREC can be utilized as the matrix forming agent to sustain the release of VPH. The results of biopharmaceutical evaluation showed that the rate of absorption appeared to be more sustained, resulting in a more uniform plasma concentration profile of VPH. More bioavailability was noted with the sustained release formulation even though the drug has substantial first pass metabolism. The results indicated that it is possible to make once-a-day sustained-release tablet of VPH by using the melt granulation technique.

  13. Near-infrared spectroscopic analysis of the breaking force of extended-release matrix tablets prepared by roller-compaction: influence of plasticizer levels and sintering temperature.

    Science.gov (United States)

    Dave, Vivek S; Fahmy, Raafat M; Hoag, Stephen W

    2015-06-01

    The aim of this study was to investigate the feasibility of near-infrared (NIR) spectroscopy for the determination of the influence of sintering temperature and plasticizer levels on the breaking force of extended-release matrix tablets prepared via roller-compaction. Six formulations using theophylline as a model drug, Eudragit® RL PO or Eudragit® RS PO as a matrix former and three levels of TEC (triethyl citrate) as a plasticizer were prepared. The powder blend was roller compacted using a fixed roll-gap of 1.5 mm, feed screw speed to roller speed ratio of 5:1 and roll pressure of 4 MPa. The granules, after removing fines, were compacted into tablets on a Stokes B2 rotary tablet press at a compression force of 7 kN. The tablets were thermally treated at different temperatures (Room Temperature, 50, 75 and 100 °C) for 5 h. These tablets were scanned in reflectance mode in the wavelength range of 400-2500 nm and were evaluated for breaking force. Tablet breaking force significantly increased with increasing plasticizer levels and with increases in the sintering temperature. An increase in tablet hardness produced an upward shift (increase in absorbance) in the NIR spectra. The principle component analysis (PCA) of the spectra was able to distinguish samples with different plasticizer levels and sintering temperatures. In addition, a 9-factor partial least squares (PLS) regression model for tablets containing Eudragit® RL PO had an r(2) of 0.9797, a standard error of calibration of 0.6255 and a standard error of cross validation (SECV) of 0.7594. Similar analysis of tablets containing Eudragit® RS PO showed an r(2) of 0.9831, a standard error of calibration of 0.9711 and an SECV of 1.192.

  14. 石杉碱甲双层缓释片的研制及体外释药研究%Preparation of Huperzine A Double - layer Sustained Release Tablets and Their in Vitro Release Charac-teristics

    Institute of Scientific and Technical Information of China (English)

    周红祖; 刘湘丹; 余惠雯

    2009-01-01

    目的:研制石杉碱甲双层缓释片并考察其体外释药特征.方法:缓释层以HPMC K4M为缓释骨架材料,乳糖为稀释剂;速释层以淀粉-碳酸钙为稀释剂,羧甲基淀粉钠为崩解剂,压制双层片,高效液相色谱法检测释放度.结果:制备的石杉碱甲双层片速释层在1~2 min崩解,呈粉末状,符合要求;缓释层的释药曲线用Higuehi方程拟合,可维持12 h释药.结论:该处方下研制的石杉碱甲双层缓释片可达到既速效又长效的目的.%OBJECTIVE: To study the preparation of Huperzine- A double- layer sustained release tablets and their in vitro release characteristics. METHODS: With HPMC K4M as matrix and lactose as diluting agent for the sustained release layer, and with starch - calcium carbonate as diluting agent and sodium carboxymethyl starch as disintegrating agent for the fast release layer to prepare the double- layer tablets by compression, with the release rate of the compressed tablets deter-mined by HPLC. RESULTS: The fast release layer of the prepared Huperzine- A double- layer tablets disintegrated within 1~2 min and appeared as fine powder, meeting the requirement; the release curve of the sustained release layer of the tablets was in line with Higuchi equation and maintained a sustained release of 12 hours. CONCLUSION: The prepared Huperzine-A double - layer tables achieved the goal of both immediate release and sustained release.

  15. Ionotropic Cross-linked Carbo-protein Micro Matrix System: An Approach for Improvement of Drug Release, Compaction and Tableting behavior of Losartan Potassium.

    Science.gov (United States)

    Khandai, Madhusmruti; Chakraborty, Santanu; Ghosh, Ashoke Kumar

    2015-01-01

    The aim of the present research work is to develop carbo-protein polymeric complex based sustain release microspheres of losartan potassium and investigate the ability of this dosage form to improve the flowability, compressibility and tableting properties of losartan potassium. The influence of silk sericin, alginate and its blend on various physicochemical parameters and in vitro drug release pattern were studied to optimize the concentration of polymeric blend required for 12 h. sustain release. Optimized batch was subjected to different flowability, compressibility and tableting properties studies to observe the effects of carbo-protein microspheres on flow properties. Results indicated that the concentration of sericin was found to be the main influential factor for prolonged drug release. Different micromeritic studies revealed that the poor flowability and compressibility properties of pure losartan potassium were significantly improved by this algino-sericin microspheric dosage form. Research findings also revealed that plasticity, die filling behavior and tableting properties of the pure drug were significantly improved by this microsphere formulation. So these prospective results concluded that carbo-protein polymeric microspheres helps to sustain the drug release for prolong hours as well as improve the flowability, compressibility and tableting properties of losartan potassium.

  16. 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

  17. 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.

  18. Quality by Design approach to understand the physicochemical phenomena involved in controlled release of captopril SR matrix tablets.

    Science.gov (United States)

    Saurí, J; Millán, D; Suñé-Negre, J M; Colom, H; Ticó, J R; Miñarro, M; Pérez-Lozano, P; García-Montoya, E

    2014-12-30

    The aim of this study is to obtain swelling controlled release matrix tablets of captopril using the Quality by Design methodology (ICH Q8) and to know the transport mechanisms involved in captopril release. To obtain the area of knowledge, the design of experiments studying the effect of two components (HPMC K15M and ethylcellulose) at different levels has been applied, with the captopril dissolution profile as the product's most important critical quality attribute (CQA). Different dissolution profiles have been obtained with the design of experiments performed, which is a key factor in the development of controlled release matrix tablets. Kinetic analysis according to the equations of Higuchi and Korsmeyer-Peppas demonstrates that the release mechanism is a mechanism of erosion when the whole percentage of the polymer is ethylcellulose, and a diffusion mechanism when the whole percentage of the polymer is HPMC K15M. The physico-chemical characteristics of the gel layer determine the release rate of captopril. The thickness of the gel layer, the porosity which is formed in the matrix upon contact with water, pore size, the swelling rate, the erosion rate of the matrix, and the physico-chemical characteristics of captopril, are factors related to the kinetic equations described and that allow us to predict the release mechanism of captopril. A new relationship of the kinetic equations governing the in vitro behavior with the physical characteristics of the gel layer of the different formulations has been established. This study shows that the size of water-filled pores and the degree of crosslinking between the chains of HPMC K15M of the matrix are related to the exponent n of the Korsmeyer-Peppas equation and the type of transport of the captopril from within the matrix to the dissolution medium, that is, if the transport is only through water-filled pores, or if a combination of diffusion occurs through water-filled pores with a transport through continuous

  19. 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.

  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. Study on dissolution in vitro of Zhike Pingchuan sustained-release tablets%止咳平喘缓释片体外释放度的研究

    Institute of Scientific and Technical Information of China (English)

    李晓燕; 冯中; 霍务贞; 李苑新; 王博; 朱盛山

    2009-01-01

    Objective:To establish a method to evaluate the in vitro release of Zhike Pingchuan sustained-release tablets.Method:The ephedrine,pseudoephedrine,scopolamine were chosen as marker components components,and the chromatographic conditions were chosen according to the separation of baseline and theoretical plate number for determining the marker in vitro release of Zhike Pingchuan sustained-release tablets;through the dissolution curves of the three active components,the release behavior was judged as well-balanced release or not.Result:Compared with conventional tablets,the Zhike Pingchuan sustained-release tablets had a well-balanced behavior in 10 h.Conclusion:The maker components of Zhike Pingchuan sustained-release tablets and two chromato-graphic conditions,which were used to determine the dissolution of the sustained-release table's,could be chosen as evaluation meth-ods for the in vitro release of Zhike Pingchuan sustained-release tablets.%目的:建立止咳平喘缓释片体外均衡释放的评价方法.方法:以麻黄碱、伪麻黄碱、东莨菪碱为指标成分,以色谱基线分离和理论塔板数考察选择止咳平喘缓释片体外释放度评价测定色谱条件;以3个指标成分的释放度曲线条件评价缓释片是否均衡释放.结果:与止咳平喘普通片相比,止咳平喘缓释片3个指标成分在10 h内成均衡释放.结论:止咳平喘缓释片释放度测定选择的3个指标成分和2个色谱条件可作为建立该缓释片均衡释放度评价方法的基础.

  2. Effect of gel formation on the dissolution behavior of clarithromycin tablets.

    Science.gov (United States)

    Inukai, Koki; Takiyama, Kei; Noguchi, Shuji; Iwao, Yasunori; Itai, Shigeru

    2017-04-15

    Clarithromycin (CAM) is a macrolide antibiotic that is widely used at clinical sites. We found that release of CAM is suppressed when tablets of CAM were exposed to an external solvent containing carboxylate buffers such as citrate. The suppressed release of CAM can be attributed to the formation of gels on the tablet surfaces, which inhibits penetration of the solvent into the tablet and thus disintegration of the tablets. Delayed disintegration of the tablets was also observed for commercial tablets. This suggests that taking CAM and carboxylates at the same time might be avoided. The crystal structure of CAM citrate reveals that molecular chains of CAM are cross-linked by hydrogen bond between citrate groups in the crystal. The crystal structure indicates that cross-linked CAM chains of the three-dimensional mesh structure might also be formed in high concentration CAM solutions in the presence of carboxylates, resulting in gel formation.

  3. [The enantioselective pharmacokinetic study of desvenlafaxine sustained release tablet in Chinese healthy male volunteers after oral administration].

    Science.gov (United States)

    Chen, Yin-xia; Du, Jiang-bo; Zhang, Yi-fan; Chen, Xiao-yan; Zhong, Da-fang

    2015-04-01

    A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine (DVS) enantiomers in human plasma was developed and applied to a pharmacokinetic study on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard (IS). Chromatographic separation was performed on the Astec Chirobiotic V chiral column (150 mm x 4.6 mm, 5 μm). The assay was linear over the concentration range of 0.500-150 ng x mL(-1) for both enantiomers (r2 > 0.99). The method was successfully applied to a stereoselective pharmacokinetic study of 100 mg desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under fasting conditions. The results showed that the pharmacokinetic parameters were similar to both enantiomers in Chinese healthy volunteers. The AUC(0-t), and C(max) of the two enantiomers were about 1.5 times higher than those of blacks and whites reported in the literature.

  4. Formulation Development and Evaluation of Drug Release Kinetics from Colon-Targeted Ibuprofen Tablets Based on Eudragit RL 100-Chitosan Interpolyelectrolyte Complexes.

    Science.gov (United States)

    Ofokansi, Kenneth Chibuzor; Kenechukwu, Franklin Chimaobi

    2013-01-01

    Colon-targeted drug delivery systems (CTDDSs) could be useful for local treatment of inflammatory bowel diseases (IBDs). In this study, various interpolyelectrolyte complexes (IPECs), formed between Eudragit RL100 (EL) and chitosan (CS), by nonstoichiometric method, and tablets based on the IPECs, prepared by wet granulation, were evaluated as potential oral CTDDSs for ibuprofen (IBF). Results obtained showed that the tablets conformed to compendial requirements for acceptance and that CS and EL formed IPECs that showed pH-dependent swelling properties and prolonged the in vitro release of IBF from the tablets in the following descending order: 3 : 2 > 2 : 3 > 1 : 1 ratios of CS and EL. An electrostatic interaction between the carbonyl (-CO-) group of EL and amino (-NH3 (+)) group of CS of the tablets formulated with the IPECs was capable of preventing drug release in the stomach and small intestine and helped in delivering the drug to the colon. Kinetic analysis of drug release profiles showed that the systems predominantly released IBF in a zero-order manner. IPECs based on CS and EL could be exploited successfully for colon-targeted delivery of IBF in the treatment of IBDs.

  5. Characterisation of a novel, multifunctional, co-processed excipient and its effect on release profile of paracetamol from tablets prepared by direct compression

    Institute of Scientific and Technical Information of China (English)

    Eraga; Sylvester; Okhuelegbe; Arhewoh; Matthew; Ikhuoria; Uhumwangho; Michael; Uwumagbe; Iwuagwu; Magnus; Amara

    2015-01-01

    Objective: To characterise a novel multifunctional pharmaceutical excipient and investigate its ef ect on paracetamol release from tablets prepared by direct compression.Methods: The excipient was prepared by co-processing gelatinized maize starch with sodium carboxymethyl cellulose and microcrystalline cellulose in a ratio of 2:1:1, dried and pulverized into powder. The excipient formulated was characterized using Fourier transform infrared spectroscopy and dif erential scanning calorimetry. The excipient was used to prepare batches of tablets by direct compression with drug-excipient ratios of 1:1, 1:2, 1:3 and 1:4. Parameters evaluated on tablets include crushing strength, friability and in vitro dissolution studies. Results: Differential scanning calorimetry analysis revealed a crystalline excipient while Fourier transform infrared spectroscopy showed no interaction between the excipient and paracetamol. Tablets from all the batches gave average crushing strength values between 3.47 and 4.88 kp. The 1:1 and 1:2 tablet batches were comparable to each other while 1:3 and 1:4 were also comparable to one another in their dissolution proi les. The dissolution parameters of the 1:4 batch was faster with- m∞(90.5%), t50%(3.5 min), t70%(11.6 min) while that of ratio 1:1 was the least with- m∞(48.6%), m5min(23.8%). Their release kinetics followed a KorsmeyerPeppas model with a super case-II transport mechanism.Conclusions: The drug-excipient ratios of 1:3 and 1:4 gave pharmaceutically acceptable tablets that met the British Pharmacopoeia specii cations. The t50% value of the 1:4 batch of tablets may i nd its usefulness in formulating drugs for which a fast onset of action is desired.

  6. Characterisation of a novel, multifunctional, co-processed excipient and its effect on release profile of paracetamol from tablets prepared by direct compression

    Institute of Scientific and Technical Information of China (English)

    Eraga Sylvester Okhuelegbe; Arhewoh Matthew Ikhuoria; Uhumwangho Michael Uwumagbe; Iwuagwu Magnus Amara

    2015-01-01

    To characterise a novel multifunctional pharmaceutical excipient and investigate its effect on paracetamol release from tablets prepared by direct compression. Methods: The excipient was prepared by co-processing gelatinized maize starch with sodium carboxymethyl cellulose and microcrystalline cellulose in a ratio of 2:1:1, dried and pulverized into powder. The excipient formulated was characterized using Fourier transform infrared spectroscopy and differential scanning calorimetry. The excipient was used to prepare batches of tablets by direct compression with drug-excipient ratios of 1:1, 1:2, 1:3 and 1:4. Parameters evaluated on tablets include crushing strength, friability and in vitro dissolution studies. Results: Differential scanning calorimetry analysis revealed a crystalline excipient while Fourier transform infrared spectroscopy showed no interaction between the excipient and paracetamol. Tablets from all the batches gave average crushing strength values between 3.47 and 4.88 kp. The 1:1 and 1:2 tablet batches were comparable to each other while 1:3 and 1:4 were also comparable to one another in their dissolution profiles. The dissolution parameters of the 1:4 batch was faster with - m∞(90.5%), t50% (3.5 min), t70% (11.6 min) while that of ratio 1:1 was the least with - m∞ (48.6%), m5min (23.8%). Their release kinetics followed a Korsmeyer-Peppas model with a super case-II transport mechanism. Conclusions: The drug-excipient ratios of 1:3 and 1:4 gave pharmaceutically acceptable tablets that met the British Pharmacopoeia specifications. The t50% value of the 1:4 batch of tablets may find its usefulness in formulating drugs for which a fast onset of action is desired.

  7. Clinical application of OxyContin hydrochloride controlled release tablets in treatment of pain suffered from advanced cancer

    Institute of Scientific and Technical Information of China (English)

    Wenwu Wang; Xuenong OuYang; Zongyang Yu; Zhangshu Chen

    2012-01-01

    Objective: The aim of this study was to evaluate the efficacy and adverse reactions of OxyContin hydrochloride controlled release tablets in the treatment of moderate or severe pain in patients with terminal cancer and to observe any improvement on the cancer patients' quality of life. Methods: Sixty-eight patients with moderate or severe cancer pain were treated with OxyContin hydrochloride controlled release tablets. The initial dose was 5 mg/12h, or 1/2 that of the standard morphine regimen. During the course of treatment, the dosage was adjusted according to the patients' condition until the pain completely disappeared or nearly did so. Each patient received a treatment for at least 15 days. At the same time, adverse reactions, the quality of life and scores for the intensity of pain were observed and recorded [1]. Results: The final titrated dosage of OxyContin was as follows: the patients in 30 cases (44.1%) received a dosage of ≤ 30 mg/d, those in 16 cases (23.5%) received a dosage of 31 to 60 mg/d, those in 18 cases (26.5%) received a dosage of 61 to 120 mg/d and those in 4 cases (5.9%) received a dosage of ≥ 120 mg/d. The overall rate of relief from pain was 95.6%, among which the rates of excellent, effective and moderate relief were respectively 39.7%, 48.5% and 7.4%. OxyContin had mild adverse reactions and patients' quality of life was markedly improved. Conclusion: OxyContin is effective in treatment of moderate and severe cancer pain. The adverse reactions of OxyContin are mild, and the drug can significantly improve the quality of life of patients with cancer pain.

  8. FORMULATION OF FLOATING TABLETS OF MEFENAMIC ACID WITH DIFFERENT GRADES OF HYDROXY PROPYL METHYL CELLULOSE POLYMER AND STUDYING THE RELEASE PROFILES

    Directory of Open Access Journals (Sweden)

    Ramanathan.G, Kavitha.K

    2010-09-01

    Full Text Available Hydrodynamically balanced system (HBS or Floating tablets has gained importance in recent days to improve absorption of drugs especially those that are absorbed from stomach and small intestine. In the present study, an attempt was made to fabricate and evaluate an HBS dosage form of Mefenamic Acid tablet The different viscosity grades of Hydroxypropylmethyl cellulose polymer like HPMC K100, HPMC K4M, HPMC KV600, HPMC K50 was incorpated as hydrophilic swellable polymers for preparing matrix-floating tablets. Sodium bicarbonate was incorporated as a gas-generating agent. The prepared floating tablets were evaluated for the physical parameters like thickness, hardness, friability, drug content, floating lag time, floating time and Invitro dissolution studies. The mechanism of drug release was anomalous type and depends upon the viscosity of polymers, which was mainly concluded as the major controlling factor for the drug release. The results showed that the formulation containing Drug: Hpmc kv600 in the ratio of 1:0.5 is suitable for the formulation of gastroretentive floating tablets of mefenamic acid

  9. 美乐托宁缓释片在不同介质中的释放试验%Study on the release of melatonin sustained release tablets in different mediums

    Institute of Scientific and Technical Information of China (English)

    杨大龙; 杨意波; 卢定强; 谢浩; 严相平

    2012-01-01

    OBJECTIVE To prepare melatonin sustained release tablets. Melatonin sustained release lahlets were used as reference preparation, which have been licensed overseas. And the release behavior similarity was investigated between reference preparation tablets and self-prepared preparation in release mediums with different pH, the in vitro drug release mechanism also was investgated. METHODS The release tests were carried out with rotating basket, HPLC method was used to determine the release of melatonin sustained release tablets, the f2 similarity factor was used to evaluate the similarity of release curves. RESULTS In different release mediums, the release curves of melatonin sustained release tablets from self-prepared preparation compared with reference preparation, similar factor(f2) are all more than 50; In vitro drug release of melatonin sustained release tablets was consistent with first-class equation, Higuchi equation and Peppas equation in 4 kinds of medium. CONCLUSION The release behavior of self-prepared preparation and reference preparation were similar in release mediums with differ ent pH, the release mechanism was diffusion drug release.%目的:制备美乐托宁缓释片,以国外上市制剂美乐托宁缓释片为参比制剂,考察自研制剂和参比制剂在不同pH释放介质中体外释放行为的相似性及体外释药机制.方法:采用释放度测定法转篮法的装置进行体外释放实验,用HPLC法测定释放度,采用f2相似因子对2种制剂释放曲线的相似度进行评价,并进行释放行为模型的拟合.结果:在不同pH的释放介质中,自制制剂释放度曲线与参比制剂比较,f2相似因子均大于50;美乐托宁缓释片在4种释放介质中体外释药拟合模型更接近一级方程、Higuchi方程和Peppas方程.结论:参比制剂与自制制剂在不同pH释放介质中的体外释放一致,释放机制为扩散释药.

  10. Assessment of Alcohol-Induced Dose Dumping with a Hydrocodone Bitartrate Extended-Release Tablet Formulated with CIMA® Abuse Deterrence Technology

    OpenAIRE

    Darwish, Mona; Bond, Mary; Yang, Ronghua; Tracewell, William; Robertson, Philmore

    2015-01-01

    Background Greater drug content requirements for extended-release (ER) opioids necessitate greater protection against dose dumping. Hydrocodone ER employs the CIMA® Abuse-Deterrence Technology platform, which provides resistance against rapid release of the active moiety when the tablet is manipulated or taken with alcohol. Objective Assess effects of alcohol on hydrocodone ER pharmacokinetics. Study Design Open-label, crossover (January 25–April 30, 2010). Setting Single center. Participants...

  11. Development and Optimization of Gastro-Retentive Controlled-Release Tablet of Calcium-Disodium Edentate and its In Vivo Gamma Scintigraphic Evaluation.

    Science.gov (United States)

    Kumar, Neeraj; Soni, Sandeep; Singh, Thakuri; Kumar, Amit; Ahmad, Farhan Jalees; Bhatnagar, Aseem; Mittal, Gaurav

    2015-12-01

    Medical management of heavy metal toxicity, including radioactive ones, is a cause for concern because of their increased use in energy production, healthcare, and mining. Though chelating agents like EDTA and DTPA in parenteral form are available, no suitable oral formulation is there that can trap ingested heavy metal toxicants in the stomach itself, preventing their systemic absorption. The objective of the present study was to develop and optimize gastro-retentive controlled-release tablets of calcium-disodium edentate (Ca-Na2EDTA). Gastro-retentive tablet of Ca-Na2EDTA was prepared by direct compression method. Thirteen tablet formulations were designed using HPMC-K4M, sodium chloride, and carbopol-934 along with effervescing agents sodium bicarbonate and citric acid. Tablet swelling ability, in vitro buoyancy, and drug dissolution studies were conducted in 0.1 N HCl at 37 ± 0.5°C. Ca-Na2EDTA was radiolabeled with technetium-99m for scintigraphy-based in vivo evaluation. Formula F8 (Ca-Na2EDTA 200 mg, carbopol 100 mg, avicel 55 mg, citric acid 30 mg, NaHCO3 70 mg, NaCl 100 mg, and HPMC 95 mg) was found to be optimum in terms of excellent floating properties and sustained drug release. F8 fitted best for Korsmeyer-Peppas equation with an R (2) value of 0.993. Gamma scintigraphy in humans showed mean gastric retention period of 6 h. Stability studies carried out in accordance with ICH guidelines and analyzed at time intervals of 0, 1, 2, 4, and 6 months have indicated insignificant difference in tablet hardness, drug content, total floating duration, or matrix integrity of the optimized formulation. Gastro-retentive, controlled-release tablet of Ca-Na2EDTA was successfully developed using effervescent technique as a potential oral antidote for neutralizing ingested heavy metal toxicity.

  12. In vitro-in vivo relationships of several "immediate" release tablets containing a low permeability drug.

    Science.gov (United States)

    Polli, J E

    1997-01-01

    The objective of this work was to gain insight into the biopharmaceutical performance of four different but bioequivalent ranitidine hydrochloride tablet formulations. This analysis employed a recently described method1 to relate in vitro and in vivo data and aimed to facilitate an understanding of oral drug product performance. For each ranitidine formulation, dissolution was performed using the USP procedure. A four-way, single dose bioequivalence study (n = 14) was performed. The fraction of the total amount of dose absorbed at each plasma sample time was determined by the Wagner-Nelson method. Equation 1 (see below) was fitted to the in vitro vs. in vivo data. For all four formulations, this analysis suggests absorption was permeation-rate limited, where ranitidine exhibited a low permeation rate constant of 0.01/min.

  13. THE EFFECTS OF TIME-RELEASED GARLIC POWDER TABLETS ON ACUTE RESPIRATORY DISEASES IN CHILDREN

    Directory of Open Access Journals (Sweden)

    IGOR SOBENIN

    2011-11-01

    Full Text Available In spite of commonly spread positive opinion about the antibacterial and antiviral properties of garlic, very few and fragmented data exist on the benefits of garlic and garlic-based preparations in the prevention of acute respiratory diseases (ARD. This study was performed to elucidate the effect of timereleased garlic powder tablets (Allicor in prevention of ARD in children. At the first stage, in open-labeled 5-months study it has been shown that ARD morbidity was reduced by 2.4-fold in 172 Allicor-treated (600 mg daily schoolchildren aged 7-16 as compared to 468 controls. At the second stage, the effects of Allicor (300 mg daily on ARD morbidity were investigated in the double-blinded placebo-controlled randomized 5-months comparative study in 42 children aged 10-12 in comparison with 41 placebo-treated children and 73 benzimidazole-treated children. Allicor treatment reduced ARD morbidity by 2.4-fold as compared to placebo, and by 1.7-fold as compared to benzimidazole. Health index in Allicor-treated group was 1.5-fold higher as compared either to placebo- or benzimidazole-treated children. The results of this study have demonstrated that garlic powder tablets Allicor are effective in non-specific prevention of acute respiratory infections in children and possess no side effects. Additionally, the commonly used ARD prevention withbenzimidazole turned to be entirely ineffective in placebocontrolled study, so the development of new useful and safe efficient drugs like garlic-based preparations is of ultimate importance.

  14. 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.

  15. Hybrid polymeric matrices for oral modified release of Desvenlafaxine succinate tablets.

    Science.gov (United States)

    Samy, Wael; Elnoby, Ayman; El-Gowelli, Hanan M; Elgindy, Nazik

    2017-07-01

    Purpose: Desvenlafaxine succinate (DSV) is a water soluble anti-depressant drug, which is rapidly absorbed after oral administration exaggerating its side effects. The current work aimed to prepare controllable release DSV matrix to reduce DSV side effects related to its initial burst. Methods: Fifteen DSV matrix formulations were prepared using different polymers, polymer/drug ratios and matrix excipients and characterized using Differential Scanning Calorimetry (DSC), infrared (IR) spectroscopy, water uptake and in vitro DSV release. The release kinetics were calculated to determine the drug release mechanism. Ex-vivo DSV absorption via rat intestinal mucosal cells and the calculation of the apparent permeability coefficient (Papp) were performed using everted sac technique. Results: Maltodextrin was the best matrix excipient (F7 and F10) showing acceptable decrease in the initial burst compared to the innovator. The addition of negatively charged polymers sodium carboxy methyl cellulose (SCMC) or sodium alginate resulted in an interaction that was proved by DSC and IR findings. This interaction slowed DSV release. F10 showed an excellent absorption of more than 80% of DSV after 4 h and the highest similarity factor with the innovator (84.7). Conclusion: A controllable release pattern of DSV was achieved using Methocel, Maltodextrin and SCMC. The obtained results could be used as a platform to control the release of cationic water soluble drugs that suffer from side effects associated with their initial burst after oral administration.

  16. Hybrid polymeric matrices for oral modified release of Desvenlafaxine succinate tablets

    Directory of Open Access Journals (Sweden)

    Wael Samy

    2017-07-01

    Full Text Available Purpose: Desvenlafaxine succinate (DSV is a water soluble anti-depressant drug, which is rapidly absorbed after oral administration exaggerating its side effects. The current work aimed to prepare controllable release DSV matrix to reduce DSV side effects related to its initial burst. Methods: Fifteen DSV matrix formulations were prepared using different polymers, polymer/drug ratios and matrix excipients and characterized using Differential Scanning Calorimetry (DSC, infrared (IR spectroscopy, water uptake and in vitro DSV release. The release kinetics were calculated to determine the drug release mechanism. Ex-vivo DSV absorption via rat intestinal mucosal cells and the calculation of the apparent permeability coefficient (Papp were performed using everted sac technique. Results: Maltodextrin was the best matrix excipient (F7 and F10 showing acceptable decrease in the initial burst compared to the innovator. The addition of negatively charged polymers sodium carboxy methyl cellulose (SCMC or sodium alginate resulted in an interaction that was proved by DSC and IR findings. This interaction slowed DSV release. F10 showed an excellent absorption of more than 80% of DSV after 4 h and the highest similarity factor with the innovator (84.7. Conclusion: A controllable release pattern of DSV was achieved using Methocel, Maltodextrin and SCMC. The obtained results could be used as a platform to control the release of cationic water soluble drugs that suffer from side effects associated with their initial burst after oral administration.

  17. Sustained release tablet of theophylline by hot melt wax coating technology

    OpenAIRE

    Padsalgi Amol; Bidkar Sanjay; Jadhav Vijay; Sheladiya Deepak

    2008-01-01

    Coating is one of the effective method used for sustaining the release of dosage form. There are various hydrophilic and hydrophilic polymers which are use to sustain the drug release. Waxes are one of the material which can be use to coat the drug in order to control the release. Coating with waxes can be achieved by dissolving it in suitable solvent or by hot melt wax coating. Hot melt coating technique defined as the application of fine layer of coating material in molten state over the su...

  18. 熔融制粒法制备盐酸二甲双胍缓释片%Preparation of Metformin Hydrochloride Sustained-release Tablets By Melt Granulation

    Institute of Scientific and Technical Information of China (English)

    许谙; 孙丹青

    2013-01-01

    OBJECTIVE To prepare metformin hydrochloride sustained-release tablets and to study its release characterization in vitro and the factors affecting drug release.METHODS Metformin hydrochloride sustained-release tablets were prepared with glycery behenate as matrix material,microcrystalline cellulose as pore-forming agent by melt granulation.The impacts of releasing transmitter,contents of glycery behenate and microcrystalline cellulose,and preparation process factors on the drug release in vitro of the tablets were studied.RESULTS The contents of glycery behenate and microcrystalline cellulose were critical factors affecting drug release rate.The tablets had a remarkable sustained-release property,the drug release profile in vitro followed zero order or Higuchi kinetics.CONCLUSION Using glycery behenate as the wax matrix material,combining with other filers,a sustained release tablet of once daily administration is prepared by melt granulation.%目的 制备盐酸二甲双胍缓释片,并考察其释药行为及影响因素.方法 以山嵛酸甘油酯为骨架材料,微晶纤维素为致孔剂,采用熔融制粒技术制备盐酸二甲双胍缓释片,并考察不同释放介质,山嵛酸甘油酯、微晶纤维素的不同用量以及制备工艺参数等对该缓释片体外释放的影响.结果 山嵛酸甘油酯和微晶纤维素的用量为药物释放的主要影响因素,制备的缓释片具有明显的缓释特征,体外释药过程符合零级动力学模型.结论 采用山嵛酸甘油酯作为蜡质骨架材料,结合其他辅料,采用熔融制粒技术可制备日服1次的盐酸二甲双胍缓释片.

  19. Controlled-release effervescent floating matrix tablets of ciprofloxacin hydrochloride: development, optimization and in vitro-in vivo evaluation in healthy human volunteers.

    Science.gov (United States)

    Tadros, Mina Ibrahim

    2010-02-01

    Ciprofloxacin hydrochloride has a short elimination half-life, a narrow absorption window and is mainly absorbed in proximal areas of GIT. The purpose of this study was to develop a gastroretentive controlled-release drug delivery system with swelling, floating, and adhesive properties. Ten tablet formulations were designed using hydroxypropylmethylcellulose (HPMC K15M) and/or sodium alginate (Na alginate) as release-retarding polymer(s) and sodium bicarbonate (NaHCO(3)) or calcium carbonate (CaCO(3)) as a gas former. Swelling ability, floating behaviour, adhesion period and drug release studies were conducted in 0.1 N HCl (pH 1.2) at 37+/-0.5 degrees C. The tablets showed acceptable physicochemical properties. Drug release profiles of all formulae followed non-Fickian diffusion. Statistical analyses of data revealed that tablets containing HPMC K15M (21.42%, w/w), Na alginate (7.14%, w/w) and NaHCO(3) (20%, w/w) (formula F7) or CaCO(3) (20%, w/w) (formula F10) were promising systems exhibiting excellent floating properties, extended adhesion periods and sustained drug release characteristics. Both formulae were stored at 40 degrees C/75% RH for 3months according to ICH guidelines. Formula F10 showed better physical stability. Abdominal X-ray imaging of formula F10, loaded with barium sulfate, in six healthy volunteers revealed a mean gastric retention period of 5.50+/-0.77h.

  20. 盐酸帕罗西汀缓释片的研制%Preparation of Paroxetine Hydrochloride Sustained-Release Tablets

    Institute of Scientific and Technical Information of China (English)

    胡献跃; 郑一美

    2016-01-01

    目的:制备盐酸帕罗西汀缓释片。方法通过以不同黏度的羟丙基甲基纤维素( HPMC )为阻滞剂,比较试制缓释片与SEROXAT对照片的体外释放曲线,采用 f2相似因子法评价两者溶出曲线的相似度,并对释放行为进行机制拟合。结果确定以HPMC E50和K4M按1:1配比为阻滞剂,制备成的缓释片与上市样品的体外释放曲线基本一致,f2值为77.25,试制片与对照片的体外释放均符合Korsmeyer-reppas方程。结论该处方工艺简单,体外释放与上市对照药高度拟合。%Objective To prepare the Paroxetine Hydrochloride Sustained-Release Tablets. Methods The HPMC of different specifica-tions was used as the blocking agent, the release characteristics of the self-made and SEROXAT reference tablets were compared in vitro, f2 was used to evaluate the similarity of the two dissolution curves, and the mechanism of the release behavior was fitted. Results The sustained-release tablets were made using HPMC E50 and K4M ( 1:1 ) as blocker, and the in vitro release behaviors were basi-cally the same with the reference tablets, the f2 was 77. 25. Both the release curve fitted the Korsmeyer-reppas equation. Conclusion The preparation method of Paroxetine Hydrochloride Sustained-Release Tablets is simple, and its dissolution behavior is highly similar to the reference tablets in the market.

  1. Predicting absorption and pharmacokinetic profile of carbamazepine from controlled-release tablet formulation in humans using rabbit model

    Directory of Open Access Journals (Sweden)

    Homšek Irena

    2011-01-01

    Full Text Available Controlled-release (CR pharmaceutical formulations offer several advantages over the conventional, immediate release dosage forms of the same drug, including reduced dosing frequency, decreased incidence and/or intensity of adverse effects, greater selectivity of pharmacological activity, reduced drug plasma fluctuation, and better compliance. After a drug product has been registered, and is already on market, minor changes in formulation might be needed. At the same time, the product has to remain effective and safe for patients that could be confirmed via plasma drug concentrations and pharmacokinetic characteristics. It is challenging to predict human absorption and pharmacokinetic characteristics of a drug based on the in vitro dissolution test and the animal pharmacokinetic data. Therefore, the objective of this study was to establish correlation of the pharmacokinetic parameters of carbamazepine (CBZ CR tablet formulation between the rabbit and the human model, and to establish in vitro in vivo correlation (IVIVC based on the predicted fractions of absorbed CBZ. Although differences in mean plasma concentration profiles were notified, the data concerning the predicted fraction of drug absorbed were almost superimposable. Accordingly, it can be concluded that rabbits may be representative as an in vivo model for predicting the pharmacokinetics of the CR formulation of CBZ in humans.

  2. Effects of coformers on phase transformation and release profiles of carbamazepine cocrystals in hydroxypropyl methylcellulose based matrix tablets.

    Science.gov (United States)

    Qiu, Shi; Li, Mingzhong

    2015-02-01

    The aim of this study was to investigate the effects of coformers on phase transformation and release profiles of carbamazepine (CBZ) cocrystals in hydroxypropyl methylcellulose (HPMC) based matrix tablets. It has been found that selection of different coformers of saccharin (SAC) and cinnamic acid (CIN) can affect the stability of CBZ cocrystals in solution, resulting in significant differences in the apparent solubility of CBZ. The dissolution advantage of CBZ-SAC cocrystals can only be shown for a short period during dissolution because of the fast conversion to its dihydrate form (DH). HPMC can partially inhibit the crystallisation of CBZ DH during dissolution of CBZ-SAC cocrystal. However, the increased viscosity of HPMC dissolution medium reduced the dissolution rate of CBZ-SAC cocrystals. Therefore the CBZ-SAC cocrystal formulation did not show any significant advantage in CBZ release rate. In contrast the improved CBZ dissolution rate of CBZ-CIN cocrystal can be realised in both solution and formulation due to its high stability. In conclusion, exploring and understanding the mechanisms of the phase transformation of pharmaceutical cocrystals in aqueous medium for selection of lead cocrystals is the key for success of product development.

  3. Quality-by-design III: application of near-infrared spectroscopy to monitor roller compaction in-process and product quality attributes of immediate release tablets.

    Science.gov (United States)

    Kona, Ravikanth; Fahmy, Raafat M; Claycamp, Gregg; Polli, James E; Martinez, Marilyn; Hoag, Stephen W

    2015-02-01

    The objective of this study is to use near-infrared spectroscopy (NIRS) coupled with multivariate chemometric models to monitor granule and tablet quality attributes in the formulation development and manufacturing of ciprofloxacin hydrochloride (CIP) immediate release tablets. Critical roller compaction process parameters, compression force (CFt), and formulation variables identified from our earlier studies were evaluated in more detail. Multivariate principal component analysis (PCA) and partial least square (PLS) models were developed during the development stage and used as a control tool to predict the quality of granules and tablets. Validated models were used to monitor and control batches manufactured at different sites to assess their robustness to change. The results showed that roll pressure (RP) and CFt played a critical role in the quality of the granules and the finished product within the range tested. Replacing binder source did not statistically influence the quality attributes of the granules and tablets. However, lubricant type has significantly impacted the granule size. Blend uniformity, crushing force, disintegration time during the manufacturing was predicted using validated PLS regression models with acceptable standard error of prediction (SEP) values, whereas the models resulted in higher SEP for batches obtained from different manufacturing site. From this study, we were able to identify critical factors which could impact the quality attributes of the CIP IR tablets. In summary, we demonstrated the ability of near-infrared spectroscopy coupled with chemometrics as a powerful tool to monitor critical quality attributes (CQA) identified during formulation development.

  4. Comparative pharmacokinetics of two modified-release oral morphine formulations (Reliadol® and Kapanol®) and an immediate-release morphine tablet (Morfin 'DAK') in healthy volunteers

    DEFF Research Database (Denmark)

    Bochner, F.; Somogyi, A.A.; Danz, C.

    1999-01-01

    , its metabolites morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G), after ingestion of Reliadol® (2 x 30 mg capsules) compared with Kapanolo (3 x 20 mg) [Glaxo Wellcome Australia Ltd] and an immediate-release morphine tablet (Morfin 'DAK', 30 mg; Nycomed Denmark A/S). Design and Setting...

  5. Compression and evaluation of extended release matrix pellets prepared by the extrusion/spheronization process into disintegrating tablets

    Directory of Open Access Journals (Sweden)

    Raveendra Pai

    2012-03-01

    Full Text Available In this study, a novel approach for compression of matrix pellets into disintegrating tablets has been studied in an attempt to overcome the issues pertaining to rupture of polymer coat during compression of reservoir-type pellets. Extended release matrix pellets were prepared by the extrusion/spheronization technique using commercially available aqueous dispersions of ethyl cellulose, acrylic polymers and sodium alginate at 10%, 20% and 30%w/w levels. Sertraline hydrochloride was used as the model drug and an in vitro release profile of 12 h was targeted. Tablets containing matrix pellets were prepared by the direct compression process. Acceptance Value, a pharmacopeial test, was applied to study the uniformity of drug distribution. Effect of compression force (2-6 kN, extrusion screen aperture size, diluent blend composition and pellet percentage on drug release and acceptance value were studied. As polymer is uniformly distributed within each pellet, the drug release pattern from uncompressed pellets was comparable to compressed tablets. Surface morphological changes due to calcium chloride treatment were observed using Scanning electron microscopy. The pellet segregated from the surface of the tablet was found to be flattened in the direction of applied compression force with minor deformities. In conclusion, matrix pellets can constitute an alternative approach to reservoir-type pellets in obtaining disintegrating tablets for extended delivery of drugs.Nesse trabalho, estudou-se nova abordagem para a compressão de matrizes de péletes em comprimidos desintegrantes, com o intuito de resolver os problemas relativos à ruptura do polímero de revestimento durante a compressão dos péletes do tipo reservatório. Matrizes de péletes de liberação estendida foram preparadas pela técnica de extrusão/esferonização, utilizando dispersões aquosas comercialmente disponíveis de etil celulose, polímeros acrílicos e alginato de sódio a 10

  6. Pharmacokinetics and effect of food after oral administration of prolonged-release tablets of ropinirole hydrochloride in Japanese patients with Parkinson's disease.

    Science.gov (United States)

    Hattori, N; Hasegawa, K; Sakamoto, T

    2012-10-01

    Ropinirole hydrochloride, a dopamine receptor agonist with a non-ergot alkaloid structure, is highly selective for the dopamine D(2) /D(3) receptors. This study was conducted to evaluate the steady-state pharmacokinetics, safety and efficacy after repeated oral administration of prolonged-release tablets of ropinirole hydrochloride in the absence of L-dopa preparations in Japanese patients with Parkinson's disease (PD). This was a multicenter, open-label, uncontrolled study. The total duration of participation in the study ranged from 56 to 63 weeks. In the study, the plasma concentrations of ropinirole, its major metabolite SK&F104557 (N-depropyl ropinirole) and another metabolite SK&F89124 (ropinirole hydroxylated at the seventh position of the indole ring) were assessed. Safety based on adverse events, haematology, biochemistry, urinalysis and electrocardiography (ECG) (standard 12-lead ECG) were evaluated, and vital signs (blood pressure/pulse rate) were measured. Efficacy based on the Japanese version of Unified Parkinson's Disease Rating Scale (UPDRS) Parts III (motor) and II [activities of daily living (ADL)] as well as tolerability was evaluated. After repeated oral administration of prolonged-release tablets of ropinirole hydrochloride in Japanese patients with PD, ropinirole, SK&F104557 and low levels of SK&F89124 were detected in plasma. The trough concentrations of ropinirole and the two metabolites increased in proportion to the dose when ropinirole hydrochloride prolonged-release tablets were administered at doses ranging from 2 to 16 mg/day. The plasma exposure to ropinirole and its two metabolites after intake of normal diet was comparable to that in the fasting state. The most common adverse events (10% or more) were somnolence, nausea, constipation, hallucination and nasopharyngitis. Most adverse events were mild or moderate in severity, and with no death. During the treatment period, serious adverse events were reported in five patients. Efficacy

  7. Investigating the effect of processing parameters on pharmaceutical tablet disintegration using a real-time particle imaging approach.

    Science.gov (United States)

    Rajkumar, Arthi D; Reynolds, Gavin K; Wilson, David; Wren, Stephen; Hounslow, Michael J; Salman, Agba D

    2016-09-01

    tablet porosity by monitoring the tablet area and particle release. It was found that when 20 and 50bar roller compaction pressure was used the USP analysis showed almost identical disintegration times for the consequent tablets. With the flow cell method a greater tablet swelling was observed for the lower pressure followed by steady tablet erosion. Additionally, more particles were released during disintegration due to the smaller granule size distribution within the tablet. When a higher tableting pressure was applied the tablet exhibited a delay in the time taken to reach the maximum swelling area, and slower tablet erosion and particle release were also observed, largely due to the tablet being much denser causing slower water uptake. This was in agreement with the USP analysis data. Overall it was confirmed by using both the standard USP analysis and flow cell method that the tablet porosity affects the tablet disintegration, whereby a more porous tablet disintegrates more slowly. But a more in-depth understanding was obtained using the flow cell method as it was determined that tablets will swell to varying degrees and release particles at different rates depending on the roller compaction and tableting pressure used.

  8. Design and Comparative Evaluation of In-vitro Drug Release, Pharmacokinetics and Gamma Scintigraphic Analysis of Controlled Release Tablets Using Novel pH Sensitive Starch and Modified Starch- acrylate Graft Copolymer Matrices

    OpenAIRE

    Kumar, Pankaj; Ganure, Ashok Laxmanrao; Subudhi, Bharat Bhushan; Shukla, Shubhanjali

    2015-01-01

    The present investigation deals with the development of controlled release tablets of salbutamol sulphate using graft copolymers (St-g-PMMA and Ast-g-PMMA) of starch and acetylated starch. Drug excipient compatibility was spectroscopically analyzed via FT-IR, which confirmed no interaction between drug and other excipients. Formulations were evaluated for physical characteristics like hardness, friability, weight variations, drug release and drug content analysis which satisfies all the pharm...

  9. Preparation and in vitro Drug Release of Betahistine Dihydrochloride Sustained-release Matrix Tablets%盐酸倍他司汀缓释骨架片的制备及体外释药特性研究

    Institute of Scientific and Technical Information of China (English)

    李凯; 陈鹰; 柴俊; 熊运; 熊姣

    2014-01-01

    目的::制备盐酸倍他司汀缓释骨架片。方法:采用亲水性高分子材料HPMC为骨架,制备盐酸倍他司汀缓释片,并用单因素试验考察其释药特征。正交试验优化处方工艺。结果:以60% HPMC K15M为骨架材料,磷酸氢钙为填充剂,用10%PVP的90%乙醇溶液为黏合剂,湿法制粒压片为最佳工艺,片重为500 mg。药物体外释放接近Higuchi模型,能实现药物12 h内缓慢释放。结论:本品制备工艺简便,具有缓解特性。%Objective: To prepare betahistine dihydrochloride sustained-release matrix tablets. Methods: The tablets were pre-pared with water soluble HPMC matrix, and the release behaviors were investigated by single factor study. The formula and preparation procedures were optimized by orthogonal design. Results:The optimal technology was as follows:using 60% HPMC K15M as the ma-trix material, calcium hydrogen phosphate as the filler, 10% PVP in 90% alcohol as the bonding agent;wet granulation compression technique was used to prepare the tablets with the tablet weight of 500mg. The in vitro drug release fits a Higuchi equation and the drug can be sustained-released within 12 h. Conclusion:The preparation technology is simple and the tablets have sustainol release behav-ior.

  10. Pharmacokinetic and bioequivalence studies of immediate release diclofenac potassium tablets (50mg) in healthy volunteers.

    Science.gov (United States)

    Ali, Huma; Shoaib, Muhammad Harris; Zafar, Farya; Hanif, Muhammad; Bushra, Rabia; Naz, Asia; Khursheed, Raheela

    2016-09-01

    This study was conducted with the aim to determine the pharmacokinetic and bioequivalence of diclofenac potassium 50 mg test (F4) tablet formulation with reference product (Caflam). Present study was single dose, randomized, two phase cross over design, conducted in 12 healthy Pakistani volunteers and planned in accordance with FDA guidelines. In this study a simple, selective, sensitive and reproducible HPLC procedure was developed and validated for the estimation of diclofenac potassium in plasma. The process was validated in the range of 50 - 0.05 µg.mL-1 and used in bioequivalence trial of two products. Multiple blood samples were collected at various time points (0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12 and 14 hr after treating volunteers with test (F4) and marketed reference brand. Plasma separation and deproteination were carried out with acetonitrile; samples (20µL) were injected using the validated HPLC method. Various pharmacokinetic parameters (compartmental and noncompartmental) were estimated using KineticaTM 4.4.1 (Thermo Electron Corp. USA). Bioequivalence among the products was established by calculating the 90% CI with log and non log transformed data for Cmaxcalc, Tmaxcalc, AUC0-∞, AUCtot and AUClast using two way ANOVA and Schirmann's Two one sided t- test. No significant difference was found between log and non-log data. The 90% confidence interval values using log transformed data for AUC0-∞ (0.997-1.024), AUCtot (1.004-1.031), AUClast (0.997 -1.024), Cmaxcalc (0.994-1.007) and Tmaxcalc (0.996-1.013) for the trial and reference products were found within the FDA acceptable limits of 0.8-1.25. Results were further verified by the Schirmann's one-sided t test. Results showed the bioequivalence of test and reference formulations. Both the products were well tolerated.

  11. Physicochemical properties and mechanism of drug release from ethyl cellulose matrix tablets prepared by direct compression and hot-melt extrusion.

    Science.gov (United States)

    Crowley, Michael M; Schroeder, Britta; Fredersdorf, Anke; Obara, Sakae; Talarico, Mark; Kucera, Shawn; McGinity, James W

    2004-01-28

    The objective of this research project was to determine the physicochemical properties and investigate the drug release mechanism from ethyl cellulose (EC) matrix tablets prepared by either direct compression or hot-melt extrusion (HME) of binary mixtures of water soluble drug (guaifenesin) and the polymer. Ethyl cellulose was separated into "fine" or "coarse" particle size fractions corresponding to 325-80 and 80-30 mesh particles, respectively. Tablets containing 30% guaifenesin were prepared at 10, 30, or 50 kN compaction forces and extruded at processing temperatures of 80-90 and 90-110 degrees C. The drug dissolution and release kinetics were determined and the tablet pore characteristics, tortuosity, thermal properties and surface morphologies were studied using helium pycnometry, mercury porosimetry, differential scanning calorimetry and scanning electron microscopy. The tortuosity was measured directly by a novel technique that allows for the calculation of diffusion coefficients in three experiments. The Higuchi diffusion model, Percolation Theory and Polymer Free Volume Theory were applied to the dissolution data to explain the release properties of drug from the matrix systems. The release rate was shown to be dependent on the ethyl cellulose particle size, compaction force and extrusion temperature.

  12. 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.

  13. Presence of Tablet Remnants of Nevirapine Extended-Release in Stools and Its Impact on Virological Outcome in HIV-1-Infected Patients: A Prospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Yi-Chieh Lee

    Full Text Available Nevirapine extended-release (NVP-XR taken once daily remains an effective antiretroviral agent for patients infected with HIV-1 strains that do not harbor resistance mutations. Presence of tablet remnants of NVP XR in stools was reported in 1.19% and 3.05% of subjects in two clinical trials. However, the prevalence may have been underestimated because the information was retrospectively collected in the studies.Between April and December 2014, we prospectively inquired about the frequency of noticing tablet remnants of NVP XR in stools in HIV-1-infected patients who switched to antiretroviral regimens containing NVP XR plus 2 nucleos(tide reverse-transcriptase inhibitors. Patients were invited to participate in therapeutic drug monitoring of plasma concentrations of NVP 12 or 24 hours after taking the previous dose (C12 and C24, respectively of NVP XR using high-performance liquid chromatography. The information on clinical characteristics, including plasma HIV RNA load and CD4 lymphocyte count, at baseline and during follow-up was recorded.During the 9-month study period, 272 patients switched to NVP XR-based regimens and 60 (22.1% noticed tablet remnants of NVP XR in stools, in whom 54.2% reported noticing the tablet remnants at least once weekly. Compared with patients who did not notice tablet remnants, those who noticed tablet remnants had a higher mean CD4 lymphocyte count (629 vs 495 cells/mm3, P = 0.0002 and a similar mean plasma HIV RNA load (1.57 vs 1.61 log10 copies/mL, P = 0.76 on switch. At about 12 and 24 weeks after switch, patients who noticed tablet remnants continued to have a similar mean plasma HIV RNA load (1.39 vs 1.43 log10 copies/mL, P = 0.43; and 1.30 vs 1.37 log10 copies/mL, P = 0.26, respectively, but had a lower median NVP C12 (3640 vs 4730 ng/mL, P = 0.06, and a similar median NVP C24 (3220 vs 3330 ng/ml, P = 0.95 when compared with those who did not notice tablet remnants.The presence of tablet remnants of NVP XR in

  14. Preparation and in vitro release of ginkgo biloba extract sustained-release tablets%银杏提取物缓释片的制备及其体外释放度的研究

    Institute of Scientific and Technical Information of China (English)

    崔启华; 朱云峰; 崔京浩

    2009-01-01

    目的:制备银杏提取物缓释片并考察其体外释放度.方法:以溶胀性材料羧甲基纤维素钠和羟丙甲基纤维素为骨架材料,直接粉末压片制备银杏提取物缓释片.根据单因素试验中各因素对银杏提取物体外释放度影响结果,进行正交设计,优化处方和工艺,以f_2相似因子法评价释放的差异.结果:羟丙甲基纤维素与羧甲基纤维素钠的用量比、羟丙甲基纤维素的黏度、不同的稀释剂均对药物释放有一定的影响,而缓释片的硬度、片重等对药物的释放没有显著的影响.结论:以羟丙甲基纤维素和羧甲基纤维素钠为骨架材料,制得持续释药12 h的银杏提取物缓释片.%Objective:To prepare ginkgo biloba extract (GBE) sustained-release tablets and observe its in vitro release profile.Method:GBE sustained-release tablets were prepared by direct compression method using sodium carboxymethylcellulose (CMC-Na) and hydroxypropyl methylcellulose HPMC) as matrix excipients.Based on the result of single-factor selecting experiment,the formulations and preparation process were optimized through orthogonal design,and release difference of tablets was evaluated with similarity factor (f_2).Result:The ratio of HPMC and CMC-Na,the viscosity of HPMC and the different types of the diluents had pronounced effect on the release of GBE sustained release tablets,ahhough the hardness and weight difference of tablets did not show notable influences.Conclusion:GBE sustained-release tablets that prepared by using the mixture of HPMC and CMC-Na display constant release profile in 12 h.

  15. Effect of release of hydroxypropylmethyl cellulose on single and bilayer sustained-release matrix tablets%羟丙基甲基纤维素对单层及双层缓释骨架制剂体外释放的影响

    Institute of Scientific and Technical Information of China (English)

    杨亚鹏; 汪梦圆; 常俊标; 郭旻彤

    2013-01-01

    Objective:To study the influence of HPMC as hydrophilic matrix materials and controlled-layer components on the drug release of sustained-release matrix tablets and bilayer tablets. Methods: Diltiazem hydrochloride was chosen as the water-soluble model drug to prepare different kinds of matrix tablets and double layer tablets with different formulations, and evaluate how the levels and grades of HPMC affect the drug release in sustained-release tablets and bilayer tablets. Results: HPMC with high viscosity and the amount of 20% -40% could delay the drug release to certain degree, but it was difficult to further slow down the drug release up to 24 h, especially for a water soluble drug. Combining HPMC with 5% -20% of CMC-Na was proven to be an effective way to achieve the 24 h release profile with the water soluble drug. HPMC was also investigated as a component in the double layer tablet as base layer. Drug release was complicated compared with EC as the base layer in the double layer tablet due to the great swelling ability of HPMC. HPMC' s larger swilling let it form a big cap to retard the drug release, which could significantly affect the drug release with a large ratio of the base layer to the drug layer; furthermore increasing the quality of 10% -40% of the base layer and the proportion of HPMC could reduce the initial burst release. Conclusion: The grade/level of HPMC and combinations with other matrix materials had a big impact on the drug release. HPMC could be used in the base layer of the double tablet to alternate the drug release profile, and reduce the initial burst release of the double-layer matrix tablet, and potentially change the drug mechanism.%目的:考察羟丙基甲基纤维素(hydroxypropylmethyl cellulose,HPMC)作为亲水凝胶材料和调控层材料对骨架型缓释制剂体外释放的影响.方法:以盐酸地尔硫卓为水溶性模型药物,HPMC为亲水凝胶材料,分别制备盐酸地尔硫卓缓释片和具

  16. In vitro release testing of matrices based on starch-methyl methacrylate copolymers: effect of tablet crushing force, dissolution medium pH and stirring rate.

    Science.gov (United States)

    Ferrero, C; Jiménez-Castellanos, M R

    2014-01-30

    Direct-compressed matrix tablets were obtained from a variety of potato starch-methyl methacrylate copolymers(1) as sustained-release agents, using anhydrous theophylline as a model drug. The aim of this work was to investigate the influence of the copolymer type, the tablet crushing force and dissolution variables such as the pH of the dissolution medium and the agitation intensity on the in vitro drug release behaviour of such matrices. Commercial sustained-release theophylline products (Theo-Dur(®) 100mg, Theolair(®) 175 mg) were used as standards. Test formulations were compacted into tablets at three different crushing force ranges (70-80, 90-100 and 110-120 N) to examine the effect of this factor on the porous network and drug release kinetics. In vitro release experiments were conducted in a pH-changing medium (1.2-7.5) with basket rotation speeds in the range 25-100 r.p.m. to simulate the physiological conditions of the gastrointestinal tract. The release rate of theophylline was practically not affected by pH in the case of Theo-Dur(®) and HSMMA matrices. In contrast, Theolair(®) and CSMMA tablets demonstrated a biphasic drug release pattern, which appeared to be sensitive to the pH of the dissolution medium. An increase in the crushing force of the copolymer matrices was accompanied by a reduction of the matrix porosity, although the porous network depends markedly on the type of copolymer, having a strong influence on the drug release kinetics. Mathematical modelling of release data shows a Fickian diffusion or anomalous transport mechanism. Based on the similarity factor f2, FD-HSMMA, OD-CSMMA and FD-CSMMA at 90-100 N were selected for agitation studies. In general, all formulations showed an agitation speed-dependent release, with Theo-Dur(®) and FD-CSMMA matrices being the less susceptible to this factor. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. [Development of glipizide push-pull osmotic pump controlled release tablets by using expert system and artificial neural network].

    Science.gov (United States)

    Zhang, Zhi-Hong; Wang, Yue; Wu, Wen-Fang; Zhao, Xi; Sun, Xiao-Cui; Wang, Huan-Qing

    2012-12-01

    The purpose of this study is to develop glipizide push-pull osmotic pump (PPOP) tablets by using a formulation design expert system and an artificial neural network (ANN). Firstly, the expert system for the formulation design of osmotic pump of poor water-soluble drug was employed to design the formulation of glipizide PPOP, taking the dissolution test results of Glucotrol XL as the goal. Then glipizide PPOP was prepared according to the designed formulations and the in vitro dissolution was carried out. And in vivo evaluation was carried out between the samples which were similar to Glucotrol XL and the Glucotrol XL in Beagle dogs. The range of the factors of formulation and procedure, which could influence the drug release, was optimized using artificial neural network. Finally, the design space was found. It was found that the target formulation which was similar to Glucotrol XL in dissolution test could be obtained in a short period by using the expert system. The samples which were similar to Glucotrol XL were bio-equivalent to the Glucotrol XL in Beagle dogs. The design space of the key parameter coating weight gain was 9.5%-12.0%. It could be concluded that a well controlled product of glipizide PPOP was developed since the dissolution test standard of our product was more strict than that of Glucotrol XL.

  18. Characterization of physicochemical properties of hydroxypropyl methylcellulose (HPMC) type 2208 and their influence on prolonged drug release from matrix tablets.

    Science.gov (United States)

    Devjak Novak, S; Šporar, E; Baumgartner, S; Vrečer, F

    2012-07-01

    The key physicochemical properties of functional excipients should be identified, and the influence of their variability on the properties of the final dosage form should be evaluated during the development phase. Excipients produced by different manufacturers and/or by different manufacturing processes should have comparable properties. Hydroxypropyl methylcellulose (HPMC) with a high molecular weight is a functional excipient often used in solid matrix systems with prolonged release of active pharmaceutical ingredients (API). This study investigates whether HPMC manufactured by two manufacturers using different chemical procedures differs in particle-size distribution, particle shape, particle morphology, chemical composition, and dissolution of diclofenac sodium as a model drug. NIR spectroscopy was introduced and calibration models were developed to detect physical differences among HPMC batches from two different origins. The physical differences between HPMC samples were additionally confirmed with scanning electron microscopy (SEM), gas chromatography (GC) measurements, and dissolution testing of hydrophilic matrix tablets. Our results prove that, even if HPMC polymers manufactured from two different sources comply with the pharmacopeial specification, they significantly differ in physicochemical properties and thus influence the properties of the formulated dosage forms.

  19. Biowaiver Eligibility of a Lower Strength Ramipril/Hydrochlorothiazide Immediate Release Tablets Using a New Validated HPLC Analytical Method.

    Science.gov (United States)

    Zaid, A N; Ghanem, M; Maqboul, L; Zaid, H; Mahasne, A

    2016-10-01

    Bioequivalence studies are expensive, time consuming and invasive to humans. Accordingly, an alternative in vitro study (biowaivers) has been introduced for drugs which belong to BCS class I and III and for other strengths of already approved higher drug strength. The main objective of this study was to prove the biowaiver eligibility of a lower strength Ramipril/Hydrochlorothiazide (2.5/12.5 mg) tablets. Visual and pharmacopoeial quality tests were performed on the higher and lower generic and on the reference listed drug to determine whether they are pharmaceutically equivalent. All products were investigated using the biowaiver criteria. Dissolution profiles were conducted at pH values 1.2, 4.5 and 6.8. Difference factor (f1) and similarity factor (f2) were calculated. The tested products were successfully complied with pharmacopeial requirements. f1 was below 15 and f2 was above 50 in all dissolution conditions. Precisely, Ramipril showed release higher than 85% within 15 min. f1 and f2 for Hydrochlorothiazide were 8 and 61 respectively at the recommended discriminative pH media.These results suggest that the current biowaiver criteria could be a sufficient guarantee of bioequivalence of the lower strength of Ramizide assuming that the product is manufactured at the same site and contains same quality and grade of excipients and in a proportional amounts.

  20. Preparation of Sinomenine Hydrochloride Sustained Release Tablet and determination of the release rate%盐酸青藤碱缓释片的制备及其释放度测定

    Institute of Scientific and Technical Information of China (English)

    洪怡; 刘亚杰; 胡建峰

    2012-01-01

    Objective To prepare the Sinomenine Hydrochloride Sustained Release Tablet. Methods The prescription was selected by orthogonal design and the investigation index was the effect of EC, MCC and lactose to the release rate. The release rate and the release behavior were studied. Results The release rate of sustained release tablet fitted the first release eqution and the release rate for 12 h was more than 75%. Conclusion The prescription is reasonable, the technology is simple and the release effect is good.%目的 制备盐酸青藤碱缓释片.方法 采用正交设计法,考察乙基纤维素、微晶纤维素、乳糖对缓释片溶出度的影响,进行处方筛选,对最佳处方进行溶出度测定及释放行为的拟合.结果 缓释片的释放行为符合一级释放方程,12 h释放度大于75%.结论 该缓释片处方合理,工艺简单,缓释效果好.

  1. RP-HPLC法测定格列吡嗪缓释片的释放度%RP-HPLC determination of drug release of glipizide sustained release tablets

    Institute of Scientific and Technical Information of China (English)

    屠思远; 蒋海松; 朱德志; 王建明

    2012-01-01

    建立了高效液相色谱法测定格列吡嗪缓释片的释放度.采用反相高效液相色谱法.固定相为ODS C18色谱柱(5μm,4.6 mm×250 mm)以0.1 mol/L磷酸二氢钠溶液(用2 mol/L氢氧化钠溶液调节pH值至(6.00±0.05)-甲醇(55:45)为流动相,流速为1.0 mL/min.柱温室温.检测波长为225nm.采用溶出度测定法第三法装置,以0.5%十二烷基硫酸钠溶液250 mL作为释放介质,转速为50r/min,依法操作,经2、6、10 h取样测定.当格列吡嗪在释放介质中在1.019 ~ 26.49μg/mL质量浓度范围内,峰面积与质量浓度呈良好的线性关系(r =0.999 9).证明方法结果准确,不受制剂中辅料的干扰,适用于格列吡嗪缓释片的释放度测定.%This paper established an RP - HPLC method for the determination of the drug release of glipizide sustained release tablets. The RP - HPLC was on a ODS C18 column (5 μm, 4. 6 mm × 250 mm) at room temperature, using the mobile phase of methanol - buffer solution(0. 1 mol/L sodium dihydrogen phosphate, adjusted to pH (6. 00 ±0. 05) with 2 mol/L sodium hydroxide) (55∶45) , at a flow rate of 1. 0 mL/min and the detection wavelength of 225 nm. Glipizide was detected by the apparatus Ⅲ of dissolution, using as the medium 250 mL of 0. 5% lauryl sodium sulfate solution, at 50 r/min. 5 mL sample of the medium in turn at 2, 6 and 10 h to determine following the above method. The calibration curve was linear in the range of 1. 019 ~ 26. 49 μg/mL. The method was accurate for the drug release determination of glipizide sustained release tablets. The analysis was out of interference of excipients.

  2. 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.

  3. Pharmacokinetics of melatonin sustained release tablets and common tablets in Beagle dogs%美乐托宁缓释片与普通片在Beagle犬体内药代动力学及检测方法

    Institute of Scientific and Technical Information of China (English)

    杨大龙; 狄斌; 林荣锦; 尤淋君

    2011-01-01

    Objective: To compare the in vivo pharmacokinetic parameters of melatonin sustained release tablets and common tablets in Beagle dogs. Methods: Three-way crossover design was used. Six Beagle dogs orally took 6 mg melatonin sustained release tablets, melatonin common tablets, or foreign sustained release tablets. Then, plasma concentration was determined by a LC-MS-MS method and calculated. Results: Pharmacokinetic parameters of the 3 preparations were as follows; Cmax (8. 929 ± 5. 220) , (29. 653 ± 14. 503 ) and (8. 196 ± 4.723) ng·mL-1; Tmax, (1. 140 ±0.608), (0.250 ±0.051) and (1.083 ±0.492) h; t1/2, (1.723 ±1.080), (0.946 ±0.548) and (1.105 ±0.308) h; MRT, (1. 834 ±0.651), (0.784 ±0.637) and (1. 617 ±0.296) h; AUC0-12, (13.832 ±6.967), (12.272 ±5.623) and (14. 190 ±7.003) ng·mL-1·h; AUC0_∞ , (13.873 ± 6.941), (12.308 ±5.556) and (14. 216 ±7. 004) ng·mL-1·h. Conclusion: Compared with the common tablets , the sustained release tablets show slower absorption, longer peak time, lower peak concentration, and longer duration. The 3 formulations are bioequivalent.%目的:比较美乐托宁缓释片与普通片在Beagle犬体内的药动学参数.方法:6条Beagle犬三交叉单剂量口服美乐托宁缓释片、普通片和国外缓释片6 mg后,采用LC-MS-MS法测定血浆药物浓度,计算各制剂的药动学参数.结果:上述3种制剂在Beagle犬血浆中的Cmax分别为(8.929±5.220),(29.653±14.503)和(8.196±4.723 )ng· mL-1,Tmax分别为(1.140±0.608),(0.250±0.051)和(1.083±0.492)h,t1/2分别为(1.723±1.080),(0.946±0.548)和(1.105±0.308)h,MRT分别为(1.834±0.651),(0.784±0.637)和(1.617±0.296)h,AUC0-12分别为(13.832±6.967),(12.272±5.623)和(14.190±7.003) ng·mL-1·h,AUC0~∞分别为(13.873±6.941),(12.308±5,556)和(14.216±7.004) ng.mL -·h.结论:与普通片比较,缓释片吸收较慢,药物达峰时间更长,峰浓度更低,维持时间更长.3种制剂具有生物等效性.

  4. 琥珀酸美托洛尔缓释片体外释药特性评价%Evaluation of In Vitro Release of Metoprolol Succinate Sustained-release Tablets

    Institute of Scientific and Technical Information of China (English)

    董萱; 陆步实; 周立新; 孙磊

    2012-01-01

    以进口的琥珀酸美托洛尔缓释片为参比制剂,采用f2相似因子法评价自研制剂和参比制剂在不同pH值的释放介质中体外释放行为的相似性,结果显示f2值均大于50,两种制剂体外释放行为相似.运用药物释放动力学模型拟合琥珀酸美托洛尔的释放过程,释放动力学特征以Higuchi模型拟合较好,根据Peppas方程,其释放机制是药物扩散和骨架溶蚀的共同作用.%Metoprolol succinate sustained-release tablets were used as reference preparation, which have been imported from overseas. The release behavior similarity was investigated between the reference and self-prepared tablets in release mediums at different pH. Similar factors (f2) were used to evaluate the similarity of release curves. The values of f2 were all more than 50. The release behaviors were similar. Appling the release kinetic models to the tablets at different release mediums, the release of metoprolol succinate was basically in conformity with the Higuchi model. According to the Peppas equation, the release of metoprolol succinate was affected by drug diffusion and matrix erosion.

  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. Effect of HPMC - E15 LV premium polymer on release profile and compression characteristics of chitosan/ pectin colon targeted mesalamine matrix tablets and in vitro study on effect of pH impact on the drug release profile.

    Science.gov (United States)

    Newton, A M J; Lakshmanan, Prabakaran

    2014-04-01

    The study was designed to investigate the in vitro dissolution profile and compression characteristics of colon targeted matrix tablets prepared with HPMC E15 LV in combination with pectin and Chitosan. The matrix tablets were subjected to two dissolution models in various simulated fluids such as pH 1.2, 6, 6.8, 7.2, 5.5. The fluctuations in colonic pH conditions during IBD (inflammatory bowel disease) and the nature of less fluid content in the colon may limit the expected drug release in the polysaccharide-based matrices when used alone. The Hydrophilic hydroxyl propyl methylcellulose ether premium polymer (HPMC E15 LV) of low viscosity grade was used in the formulation design, which made an excellent modification in physical and compression characteristics of the granules. The release studies indicated that the prepared matrices could control the drug release until the dosage form reaches the colon and the addition HPMC E15 LV showed the desirable changes in the dissolution profile by its hydrophilic nature since the colon is known for its less fluid content. The hydrophilic HPMC E15 LV allowed the colonic fluids to enter into the matrix and confirmed the drug release at the target site from a poorly water soluble polymer such as Chitosan and also from water soluble Pectin. The dramatic changes occurred in the drug release profile and physicochemical characteristics of the Pectin, Chitosan matrix tablets when a premium polymer HPMC E15 LV added in the formulation design in the optimized concentration. Various drug release mechanisms used for the examination of drug release characteristics. Drug release followed the combined mechanism of diffusion, erosion, swelling and polymer entanglement. In recent decade, IBD attracts many patents in novel treatment methods by using novel drug delivery systems.

  8. Single-Dose Pharmacokinetic Study of Tramadol Extended-Release Tablets in Children and Adolescents.

    Science.gov (United States)

    Vandenbossche, Joris; Van Peer, Achiel; Richards, Henry

    2016-09-01

    Combined analyses from 2 open-label, phase-1 studies-the pharmacokinetic profile of tramadol and its metabolite (M1) following a single oral dose of tramadol extended release (ER) (25 to 100 mg) in children (7 to 11 years old; study 1: n = 37) and adolescents (12 to 17 years old; study 2: n = 38) with painful conditions-were historically compared with that of healthy adults following similar dosing. The dose-normalized area under the curve (DN AUC0-24h ) and maximum concentration (DN Cmax ) of tramadol and of M1 in children and in adolescents were lower than those in adults (children vs adults: tramadol, DN AUC0-24h 82.19%; DN Cmax 80.38%, P = .0031; M1, DN AUC0-24h 51.19%, DN Cmax 52.68%, P < .0001; adolescents vs adults: tramadol, DN AUC0-24h 89.56%, DN Cmax 84.01%; M1, DN AUC0-24h 85.28%, DN Cmax 83.03%, P = .0004). The arithmetic mean terminal elimination t1/2 of tramadol in children and adolescents was comparable to that in adults (children 8.4 hours; adolescents 8.5 hours; adults 7.9 hours). The most frequently reported (≥5% of participants) treatment-emergent adverse events in children included headache, upper abdominal pain and constipation, and in adolescents were headache, nausea, dizziness, and stomach discomfort. Multiple factors may have contributed to these observations, including a higher proportion of children (56%) who may have a lower activity of CYP2D6, resulting in reduced clearance of tramadol.

  9. Efficacy and Safety of a Chewable Methylphenidate Extended-Release Tablet in Children with Attention-Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Wigal, Sharon B; Childress, Ann; Berry, Sally A; Belden, Heidi; Walters, Faith; Chappell, Phillip; Sherman, Nancy; Orazem, John; Palumbo, Donna

    2017-05-30

    This phase 3, laboratory classroom study assessed the efficacy and safety of methylphenidate hydrochloride extended-release chewable tablets (MPH ERCT) compared with placebo in children with attention-deficit/hyperactivity disorder (ADHD). Following a 6-week, open-label, dose-optimization period, children 6-12 years of age (n = 90) with ADHD were randomly assigned to double-blind MPH ERCT at the final optimized dose (20-60 mg/day) or placebo. After 1 week of double-blind treatment, efficacy was assessed predose and 0.75, 2, 4, 8, 10, 12, and 13 hours postdose in a laboratory classroom setting. The primary efficacy measure was the average of postdose Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale-Combined scores, analyzed using a mixed-model, repeated-measures analysis. Secondary efficacy measures included Permanent Product Measure of Performance (PERMP) total number of problems attempted and total number of problems correct. Safety assessments included adverse event (AE) monitoring and the Columbia-Suicide Severity Rating Scale (C-SSRS). MPH ERCT treatment statistically significantly reduced the average of all postdose SKAMP-Combined scores versus placebo (least-squares mean difference [95% confidence interval], -7.0 [-10.9, -3.1]; p 1 subject receiving MPH ERCT in the double-blind period (placebo: URTI, contusion, wound, and initial insomnia). No suicidal ideation or behavior was reported on the C-SSRS at baseline or at any postbaseline assessment. MPH ERCT 20-60 mg significantly improved ADHD symptoms compared with placebo at 2 hours postdose through at least 8 hours postdose. MPH ERCT was generally safe and well tolerated, with a safety profile consistent with other MPH ER formulations. ClinicalTrials.gov Identifier: NCT01654250. www.clinicaltrials.gov/ct2/show/NCT01654250 .

  10. Implementation of quality by design approach in manufacturing process optimization of dry granulated, immediate release, coated tablets - a case study.

    Science.gov (United States)

    Teżyk, Michał; Jakubowska, Emilia; Milanowski, Bartłomiej; Lulek, Janina

    2017-10-01

    The aim of this study was to optimize the process of tablets compression and identification of film-coating critical process parameters (CPPs) affecting critical quality attributes (CQAs) using quality by design (QbD) approach. Design of experiment (DOE) and regression methods were employed to investigate hardness, disintegration time, and thickness of uncoated tablets depending on slugging and tableting compression force (CPPs). Plackett-Burman experimental design was applied to identify critical coating process parameters among selected ones that is: drying and preheating time, atomization air pressure, spray rate, air volume, inlet air temperature, and drum pressure that may influence the hardness and disintegration time of coated tablets. As a result of the research, design space was established to facilitate an in-depth understanding of existing relationship between CPPs and CQAs of intermediate product (uncoated tablets). Screening revealed that spray rate and inlet air temperature are two most important factors that affect the hardness of coated tablets. Simultaneously, none of the tested coating factors have influence on disintegration time. The observation was confirmed by conducting film coating of pilot size batches.

  11. Abuse Potential with Oral Route of Administration of a Hydrocodone Extended-Release Tablet Formulated with Abuse-Deterrence Technology in Nondependent, Recreational Opioid Users

    Science.gov (United States)

    Darwish, Mona; Ma, Yuju; Tracewell, William; Robertson, Philmore; Webster, Lynn R.

    2017-01-01

    Objective. To compare the oral abuse potential of hydrocodone extended-release (ER) tablet developed with CIMA® Abuse-Deterrence Technology with that of hydrocodone immediate release (IR). Design. Randomized, double-blind, placebo-controlled, crossover study. Setting and Patients. One study site in the United States; adult nondependent, recreational opioid users. Methods. After confirming their ability to tolerate and discriminate hydrocodone IR 45 mg from placebo, eligible participants were randomized to receive each of the following oral treatments once: finely crushed placebo, hydrocodone IR 45-mg powder, intact hydrocodone ER 45-mg tablet, and finely crushed hydrocodone ER 45-mg tablet. Primary pharmacodynamic measure was “at the moment” drug liking. Secondary measures included overall drug liking, drug effects (e.g., balance, positive, negative, sedative), pupillometry, pharmacokinetics, and safety. Results. Mean maximum effect (Emax) for “at the moment” drug liking was significantly lower for intact (53.9) and finely crushed hydrocodone ER (66.9) vs. hydrocodone IR (85.2; P < 0.001). Drug liking for intact hydrocodone ER was comparable to placebo (Emax: 53.9 vs. 53.2). Secondary measures were consistent with these results, indicating that positive, negative, and sedative drug effects were diminished with intact and crushed hydrocodone ER tablet vs. hydrocodone IR. The 72-hour plasma concentration-time profile for each treatment mimicked its respective “at the moment” drug-liking-over-time profile. Incidence of adverse events was lower with intact hydrocodone ER (53%) vs. hydrocodone IR (79%) and finely crushed hydrocodone ER (73%). Conclusions. The oral abuse potential of hydrocodone ER (intact and finely crushed) was significantly lower than hydrocodone IR in healthy, nondependent, recreational opioid users. Hydrocodone ER was generally well tolerated. PMID:27330154

  12. Non-destructive Determination of Disintegration Time and Dissolution in Immediate Release Tablets by Terahertz Transmission Measurements.

    Science.gov (United States)

    Markl, Daniel; Sauerwein, Johanna; Goodwin, Daniel J; van den Ban, Sander; Zeitler, J Axel

    2017-05-01

    The aim of this study was to establish the suitability of terahertz (THz) transmission measurements to accurately measure and predict the critical quality attributes of disintegration time and the amount of active pharmaceutical ingredient (API) dissolved after 15, 20 and 25 min for commercial tablets processed at production scale. Samples of 18 batches of biconvex tablets from a production-scale design of experiments study into exploring the design space of a commercial tablet manufacturing process were used. The tablet production involved the process steps of high-shear wet granulation, fluid-bed drying and subsequent compaction. The 18 batches were produced using a 4 factor split plot design to study the effects of process changes on the disintegration time. Non-destructive and contactless terahertz transmission measurements of the whole tablets without prior sample preparation were performed to measure the effective refractive index and absorption coefficient of 6 tablets per batch. The disintegration time (R (2) = 0.86) and API dissolved after 15 min (R (2) = 0.96) linearly correlates with the effective refractive index, n eff, measured at terahertz frequencies. In contrast, no such correlation could be established from conventional hardness measurements. The magnitude of n eff represents the optical density of the sample and thus it reflects both changes in tablet porosity as well as granule density. For the absorption coefficient, α eff, we observed a better correlation with dissolution after 20 min (R (2) = 0.96) and a weaker correlation with disintegration (R (2) = 0.83) compared to n eff. The measurements of n eff and α eff provide promising predictors for the disintegration and dissolution time of tablets. The high penetration power of terahertz radiation makes it possible to sample a significant volume proportion of a tablet without any prior sample preparation. Together with the short measurement time (seconds), the potential to

  13. Formulation of a modified release metformin. HCl matrix tablet: influence of some hydrophilic polymers on release rate and in-vitro evaluation

    Directory of Open Access Journals (Sweden)

    John Rojas

    2011-09-01

    Full Text Available Metformin hydrochloride is an antidiabetic agent which improves glucose tolerance in patients with type 2 diabetes and reduces basal plasma levels of glucose. In this study, a simplex centroid experimental design with 69 runs was used to select the best combination of some hydrophilic polymers that rendered a 24 h in-vitro release profile of metformin.HCl. The Korsmeyer-Peppas model was used to model the dissolution profiles since it presented the best fit to the experimental data. Further, a cubic model predicted the best formulation of metformin.HCl containing polyvinyl pyrrolidone, ethyl cellulose, hydroxypropyl methyl cellulose, carrageenan, sodium alginate, and gum arabic at 6.26, 68.7, 6.26, 6.26, 6.26 and 6.26 % levels, respectively. The validation runs confirmed the accuracy of the cubic model with six components for predicting the best set of components which rendered a once-a-day modified release hydrophilic matrix tablet in compliance with the USP specifications.O cloridrato de metformina é um agente antidiabético que melhora a tolerância à glicose em pacientes com diabetes tipo 2 e reduz os níveis plasmáticos basais de glicose. Neste estudo, um projeto experimental do tipo "centróide simplex" com 69 tomadas foi usado para selecionar a melhor combinação de alguns polímeros hidrofílicos que gerou um perfil de liberação da metformina.HCl de 24 horas. O modelo Korsmeyer-Peppas foi usado para modelar os perfis de dissolução, uma vez que apresentou os melhores ajustes aos dados experimentais. Além disso, um modelo cúbico previu a melhor formulação de metformina.HCl sendo aquela contendo polivinilpirrolidona, etilcelulose, hidroxipropilmetil celulose, carragena, alginato de sódio e goma arábica nos níveis 6.26, 68.7, 6.26, 6.26, 6.26 e 6.26 %, respectivamente. As corridas de validação confirmaram a precisão do modelo cúbico com os seis componentes para prever o melhor conjunto de componentes que originou uma

  14. FORMULATION AND EVALUATION OF CONTROLLED POROSITY OSMOTIC TABLETS OF LORNOXICAM

    Directory of Open Access Journals (Sweden)

    A. Uma Maheswari*, K. Elango, Daisy Chellakumari, K. Saravanan and Anglina Jeniffer Samy

    2012-06-01

    Full Text Available The aim of the present study is to formulate and evaluate controlled release formulation of lornoxicam based on osmotic technology. Lornoxicam, a potent non-steroidal anti-inflammatory drug (NSAID with shorter half life, makes the development of sustained release (SR dosage forms extremely advantageous. However, due to its weak acidic nature, its release from SR delivery system is limited to the lower GIT which consequently leads to a delayed onset of its analgesic action. Basic pH modifier tromethamine and wicking agent SLS were incorporated into the core tablet to create basic environmental pH inside the tablets, which provide complete drug release that starts in the stomach to rapidly alleviate the painful symptoms and continue in the intestine to maintain protracted analgesic effect. The effect of different formulation variables namely level of osmogen (mannitol in the core tablet and level of pore former (sorbitol in the coating membrane on in-vitro release was studied. Lornoxicam release from controlled porosity osmotic pump was directly proportional to the pore former (sorbitol and level of osmogen (mannitol. Drug release from the developed formulations was independent of pH and agitational intensity and was dependent on osmotic pressure of the release media. Results of SEM studies showed the formation of pores in the membrane from where the drug release occurred. The optimized formulation was found to release the drug in zero order and found to be stable upon stability studies.

  15. Study on Preparation of Cefradine Sustain-release Tablet%头孢拉定缓释制剂的制备及释放特征研究

    Institute of Scientific and Technical Information of China (English)

    虢红梅; 杨建林

    2015-01-01

    目的:头孢拉定为第1代半合成头孢菌素,为了满足临床特殊用途,进行缓释片的研究。方法采用羟丙甲纤维素(HPMC)、丙烯酸树脂Ⅱ号等缓释材料制备头孢拉定缓释制剂,并考察丙烯酸树脂Ⅱ号含量、剂型、释放介质等对体外累积释放率的影响。结果头孢拉定缓释片体外释药测定结果符合缓释制剂要求。结论头孢拉定缓释片与Higuchi方程拟合较好(在PH=1.2人工胃液中线性回归系数为0.9887,在PH=7.4人工肠液中为0.9935),是骨架溶蚀和药物扩散的综合效应过程。%Objective Cefradine is the first generation of half synthetic cePhalosPorin. To study the cefradine sustain-release tablet for sPecific usage in the clinic. Methods Sustained-release materials,such as HPMC and Eudragit Ⅱwere adoPted to PrePare the cefra-dine sustained-release dosage forms,and the effects of acrylic resin content,dosage forms and release medium on the cumulative drug release were studied. Results The cefradine sustained-release tablets met the requirements of sustained-release. Conclusion The cefradine sustained-release tablets fit well with the Higuchi equation ( PH=1. 2,R2=0. 988 7,PH=7. 4,R2=0. 994 3 ) ,which is a comPrehensive Process of skeleton dissolution and drug diffusion.

  16. Sustained-release liquisolid compact tablets containing artemether-lumefantrine as alternate-day regimen for malaria treatment to improve patient compliance

    Directory of Open Access Journals (Sweden)

    Nnamani PO

    2016-11-01

    Full Text Available Petra Obioma Nnamani,1,2 Agatha Adaora Ugwu,1 Emmanuel Chinedu Ibezim,1 Franklin Chimaobi Kenechukwu,1 Paul Achile Akpa,1 John-Dike Nwabueze Ogbonna,1 Nicholas Chinedu Obitte,3 Amelia Ngozi Odo,4 Maike Windbergs,2 Claus-Michael Lehr,2,5,6 Anthony Amaechi Attama1 1Drug Delivery and Nanomedicines Research Group, Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Nigeria, Nsukka, Nigeria; 2Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS, Helmholtz Centre for Infection Research, Saarland University, Saarbrücken, Germany; 3Department of Pharmaceutical Technology and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, 4Department of Human Kinetics and Health Education, University of Nigeria, Nsukka, Nigeria; 5PharmBioTec GmbH, 6Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany Abstract: The present study aimed to develop low-dose liquisolid tablets of two antimalarial drugs artemether–lumefantrine (AL from a nanostructured lipid carrier (NLC of lumefantrine (LUM and estimate the potential of AL as an oral delivery system in malariogenic Wistar mice. LUM-NLCs were prepared by hot homogenization using Precirol® ATO 5/Transcutol® HP and tallow fat/Transcutol® HP optimized systems containing 3:1 ratios of the lipids, respectively, as the matrices. LUM-NLC characteristics, including morphology, particle size, zeta potential, encapsulation efficiency, yield, pH-dependent stability, and interaction studies, were investigated. Optimized LUM-NLCs were mixed with artemether powder and other dry ingredients and the resultant powder evaluated for micromeritics. Subsequent AL liquisolid tablets were tested for in vitro drug release and in vivo antiplasmodial activity in mice infected with Plasmodium berghei berghei (NK 65. Results showed that optimized LUM-NLC were stable, spherical, polydispersed but nanometric. Percentage

  17. Sex differences in the pharmacokinetics and bioequivalence of the delayed-release combination of doxylamine succinate-pyridoxine hydrochloride; implications for pharmacotherapy in pregnancy.

    Science.gov (United States)

    Koren, Gideon; Vranderick, Manon; Gill, Simerpal K; Macleod, Stuart

    2013-12-01

    Most bioequivalence (BE) studies are conducted in males with the assumption that variability in pharmacokinetics is similar between the sexes. The purpose of this single-center, reference replicate study was to determine the effect of sex on the pharmacokinetics and BE of doxylamine-pyridoxine 10 mg-10 mg delayed-release tablets. Healthy males (n = 12) and non-pregnant females (n = 12) were administered two tablets, and blood sampling was conducted from 1 hour pre-dose until 72 hours post-dose. After 21 days, dose administration and blood sampling were re-conducted. All analytes were measured using liquid chromatography-tandem mass-spectrometry. Pharmacokinetic parameters were calculated for each study period using standard, non-compartmental methods, and differences were assessed using ANOVA. BE testing was conducted using the relative 90% confidence interval for the AUC0-t for each analyte. Females had significantly larger AUC0-t for doxylamine, 1,550 ng h/mL (coefficient of variance [CV = 19%]) versus 1,272 ng h/mL (CV = 21%; P ≤ .05), and pyridoxine, 35 ng h/mL, (CV = 43%) versus 25 ng h/mL (CV = 31%; P ≤ .05) compared to males. A higher Cmax for doxylamine was observed in females, 107 ng/mL (CV = 16%), compared to males, 86 ng/mL (CV = 15%) (P ≤ .05). BE testing did not demonstrate bioequivalence between males and females. Pharmacokinetic differences observed between the sexes have implications for future BE studies using doxylamine-pyridoxine.

  18. HIGH MOLECULAR CELLULOSE ESTERS. MECHANISM OF ACTION IN SUSTAINED RELEASE MATRIX TABLETS. DISSOLUTION PROFILE OF ACTIVE DRUG DEPENDING ON MOLECULAR WEIGHT AND HYDROPHILIC PROPERTIES OF POLYMERS

    Directory of Open Access Journals (Sweden)

    S. V. Trofimov

    2015-01-01

    Full Text Available This article reviews cellulose esters as important excipients in development of dosage forms with sustained release. We have studied modern methods of drug development, based on technological, and physical and chemical properties of excipients to provide a sustained release effect and the mechanism of interaction between active substance and excipients for justification of choice of the optimum prolonging agent in compliance with desirable result. Different cellulose esters were used as model excipients. They were hydroxypropylmethylcellulose (HPMC and hydroxyethylcellulose (HEC. we have studied an effect of molecular weight and hydrophilic properties on dissolution rate of active substance from the tablets with sustained release.

  19. Prescriber utilization of dalfampridine extended release tablets in multiple sclerosis: a retrospective pharmacy and medical claims analysis

    Directory of Open Access Journals (Sweden)

    Jara M

    2014-12-01

    Full Text Available Michele Jara,1 Matthew F Sidovar,2 Herbert R Henney III2 1Drug Safety and Risk Management, 2Clinical Development and Medical Affairs, Acorda Therapeutics, Inc, Ardsley, NY, USA Purpose: This study aimed to characterize the prescribing of dalfampridine extended release (D-ER 10 mg tablet treatment in people with multiple sclerosis (MS. Methods: A retrospective cohort study was performed using Medco pharmacy and medical claims. Medical claims were used to identify MS patients with more than one prescription for D-ER with 1 year of prior continuous enrollment (n=704. These patients were matched 2:1 on age, sex, and health insurance source with a comparison group of MS patients who were treatment naïve for D-ER (n=1,403. Categorical data were analyzed by Χ2 test; ordinal data by Wilcoxon rank sum test; and continuous data by Student’s t-test. Results: Most patients were women aged 45–64 years. In the year preceding D-ER initiation, the prevalence of seizure and renal impairment was numerically lower in the D-ER cohort relative to those who were D-ER naïve (seizure: 3.1% versus 4.7%, respectively; renal impairment: 4.3% versus 5.1%, respectively; however, prescriptions for antiepileptic drugs in the two cohorts were comparable. In the year preceding treatment initiation, 62% of the D-ER cohort was prescribed MS-specific disease-modifying therapies relative to 45% who were D-ER naïve. Conclusion: Seizure and renal impairment rates among D-ER-naïve patients were consistent with published literature, yet rates among those prescribed D-ER during the year preceding treatment initiation were slightly lower than rates among D-ER-naïve patients. Given that D-ER is contraindicated in patients with history of seizure or moderate or severe renal impairment, lower rates may indicate that risk-minimization strategies contributed to the lower prevalence. Keywords: disease-modifying therapy, database, seizures, renal impairment, pharma­coepidemiology

  20. Preparation of Ibuprofen Sustained-release Tablet and Its Release Rate in Vitro%布洛芬缓释片的制备及其体外释放度考察

    Institute of Scientific and Technical Information of China (English)

    王平; 肖昌录; 袁训贤

    2011-01-01

    OBJECTIVE: To study and prepare Ibuprofen sustained-release tablets and to establish determination method for release rate of it in vitro. METHODS: Ibuprofen sustained-release tablet was prepared using hydrophilic gel framework material. The content of Ibuprofen sustained release tablets was determined by HPLC. Ac coding to stirring basket method stated in Chinese Pharmacopeia (2010 edition), phosphate buffer solution was used as solvent at rotating speed of 150 r·min-1 to determine release rate of 3 batches of samples in vitro. Repeatability of different batches and homogeneity of the same batch of samples (1, 3, 6, 8 h)were investigated. RESULTS: 3 batches of sustained-release tablet released completely within 8 h with sound repeatability. The RSDs of dissolution rate of the same batch of samples at 1, 3, 6, 8 h were 0.45%, 1.89%, 1.88%, 1.31%. There was small difference among different batches. CONCLUSION: Established preparation method is simple and stable, and the method for in vitro dissolution rate determination is convenient, rapid and easy to do.%目的:研制布洛芬缓释片并建立其体外释放度测定方法.方法:以亲水性凝胶骨架材料羟丙基甲基纤维素制备布洛芬缓释片.采用高效液相色谱法测定其含量,根据2010年版篮法,以磷酸盐缓冲液为溶出介质、转速为150 r·min-1测定3批样品的体外释放度,进行批闻重现性和同一批样品的均一性(1、3、6、8h)考察.结果:所制3批缓释片在8 h内释放基本完成,批间重现性良好;同一批样品在1、3、6、8 h各取样时间点,释放度的RSD值分别为0.45%、1.89%、1.88%、1.3l%,批间差异小.结论:布洛芬缓释片的制备方法简单、质量稳定,建立的体外释放度测定方法简便、快速,易于操作.

  1. 琥珀酸美托洛尔缓释微丸型片剂的制备与体外释放度考察%Preparation and in vitro Release of Metoprolol Succinate Sustained-release Pellet Tablets

    Institute of Scientific and Technical Information of China (English)

    谢向阳; 邢传峰; 李银科; 李旸; 陈鹰

    2014-01-01

    Objective To prepare metoprolol succinate sustained-release pellet tablets,and to investigate their in vitro drug release behavior. Methods Metoprolol succinate sustained-release pellets were prepared by fluid bed coating technology,while the sustained-release pellet tablets were prepared by direct compression of sustained-release pellets and suitable excipients. The release behavior similarity was investigated between the reference and self-prepared tablets in release media. Similar factor( F 2 )was used to evaluate the similarity of release curves. Re-sults The size of blank sugar pellets was 250-350 μm. With Kollicoat SR 30D as the coating material,the coating level was 20%,the plasticizer content was 20%,the anti-tacking agent content was 50%,and the tableting pressure was 80 kN. The value of F 2 was more than 50,and the release behavior was similar. Conclusion The release behav-ior of metoprolol succinate sustained-release pellet tablets is quite satisfactory. This method of preparation may be used in industrial production.%目的:制备琥珀酸美托洛尔缓释微丸型片剂,并对其体外释放度进行考察。方法采用流化床包衣法制备琥珀酸美托洛尔缓释微丸,将缓释微丸与适合的辅料混合后采用直接压片法制备琥珀酸美托洛尔微丸型片剂,并采用F2相似因子法评价自制制剂和参比制剂在释放介质中的体外释放行为。结果选用空白蔗糖丸芯粒径为250~350μm,以Kollicoat SR 30D为微丸的衣膜材料,包衣增重为20%,增塑剂用量为20%,滑石粉用量为50%,压片压力为80 kN时,自制制剂和参比制剂F 2相似因子值大于50,说明2种制剂体外释放行为相似。结论制备的琥珀酸美托洛尔缓释微丸型片剂的释药行为较好,有望应用于工业生产。

  2. Development and potential application of an oral ColoPulse infliximab tablet with colon specific release : A feasibility study

    NARCIS (Netherlands)

    Maurer, Jacoba M.; Hofmana, Susan; Schellekens, Reinout C.A.; Tonnis, Wouter F.; Dubois, Annelien O.T.; Woerdenbag, Herman J.; Hinrichs, Wouter L.J.; Kosterink, Jos G.W.; Frijlink, Henderik W.

    2016-01-01

    The monoclonal antibody infliximab is one of the cornerstones in the treatment of Crohn's disease. Local delivery of infliximab would be an alternative to overcome the inherent disadvantages of intravenous therapy. For this purpose 5mg infliximab tablets were developed. To stabilize the antibody dur

  3. Preparation and in vitro release of ketoprofen sustained-release pellet tablets%酮洛芬微丸缓释片的制备及体外释放度考察

    Institute of Scientific and Technical Information of China (English)

    李海刚; 袁中文; 关世侠; 周郁斌; 胡波; 叶小玲; 杨艳

    2011-01-01

    目的:制备一种酮洛芬缓释片剂.方法:采用挤出-滚圆法制备酮洛芬微丸,用Eudragit(R) RS 30D和Eudragit(R) RL30D包衣.再将包衣微丸与酮洛芬原药压片,最终制成酮洛芬缓释片.结果:体外释放度实验显示,制备的酮洛芬缓释片在2h内能释药30%,剩余70%药物在随后的10h内缓慢释放.结论:用本方法制备酮洛芬缓释片,工艺简便,易于操作.%OBJECTIVE To prepare detoprofen sustained-release tablets. METHODS Extrusion-spheronization technique was introduced to prepare ketoprofen pellets and Eudragir? RS 30D and Eudragit? RL 30D were used as coating materials. Even mix the coated pellets with ketoprofen to prepare ketoprofen sustained-release tablets. RESULTS The data obtained proved that the formulation was useful for a sustained-release of ketoprofen, due to the percentage released in two hours was 30% and in the later ten hours was 70%. CONCLUSION The preparation technology is reliable and easy to operate.

  4. Pharmacokinetic Studies in Healthy Subjects for the Development of an Extended-Release Tablet Formulation of Guaifenesin: A 505(b)(2) New Drug Application Approval.

    Science.gov (United States)

    Vilson, Lineau; Owen, Joel S

    2013-01-01

    Guaifenesin is an expectorant used to improve mucociliary clearance (MCC) and relieve chest congestion from upper respiratory tract infections. Immediate-release (IR) guaifenesin requires dosing every 4 hours to maintain efficacy because of the drug's short half-life. Extended-release (ER) guaifenesin has been developed to prolong efficacy and reduce dosing frequency. As part of the 505(b)(2) new drug application (NDA), the pharmacokinetics (PK) of an ER bi-layer tablet formulation of guaifenesin (Mucinex®) and bioequivalence to an over-the-counter (OTC) monograph IR formulation were evaluated in healthy subjects. In one study, subjects received 1,200 mg ER guaifenesin every 12 hours or 400 mg IR guaifenesin every 4 hours for 6 days. Steady-state exposures were equivalent between the two products, as demonstrated by AUC and Cmax . In another study, subjects received a single dose of 600 mg (fasted) or 1,200 mg (fasted or fed) ER bi-layer tablet formulations. AUC and Cmax were equivalent between both states for the 1,200 mg ER dose. However, Tmax of 1,200 mg ER guaifenesin was later in the fed than the fasted state. ER guaifenesin is bioequivalent to corresponding OTC monograph doses of IR guaifenesin. ER guaifenesin offers a convenient 12-hour dosing alternative to 4-hour dosing of IR guaifenesin. © The Author(s) 2013.

  5. Formulation design and evaluation of Cefuroxime axetil 125 mg immediate release tablets using different concentration of sodium lauryl sulphate as solubility enhancer

    Directory of Open Access Journals (Sweden)

    Fozia Israr

    2014-12-01

    Full Text Available Cefuroxime axetil immediate release tablets were formulated by direct compression method with different percentages of sodium lauryl sulphate (SLS such as 0.5, 1.0, 1.5 and also without SLS. Resulting batches of tablets were evaluated by both pharmacopeial and non-pharmacopeial methods to ascertain the physico-mechanical properties. Dissolution test were carried out in different medium like 0.07 M HCl, distilled water, 0.1M HCl of pH 1.2 and phosphate buffers at pH 4.5 and 6.8 to observe the drug release against the respective concentration of SLS used. Later, test formulations were compared by f1(dissimilarity and f2(similarity factors using a reference brand of cefuroxime axetil. Significant differences (p<0.05 in dissolution rate were recorded with the change in concentration of SLS in different media. Test formulation T3 containing 1% SLS was found to be best optimized formulation based on assay, disintegration, dissolution and similarity and dissimilarity factors.

  6. Calcification prevention tablets

    Science.gov (United States)

    Lindsay, Geoffrey A.; Hasting, Michael A.; Gustavson, Michael A.

    1991-01-01

    Citric acid tablets, which slowly release citric acid when flushed with water, are under development by the Navy for calcification prevention. The citric acid dissolves calcium carbonate deposits and chelates the calcium. For use in urinals, a dispenser is not required because the tablets are non-toxic and safe to handle. The tablets are placed in the bottom of the urinal, and are consumed in several hundred flushes (the release rate can be tailored by adjusting the formulation). All of the ingredients are environmentally biodegradable. Mass production of the tablets on commercial tableting machines was demonstrated. The tablets are inexpensive (about 75 cents apiece). Incidences of clogged pipes and urinals were greatly decreased in long term shipboard tests. The corrosion rate of sewage collection pipe (90/10 Cu/Ni) in citric acid solution in the laboratory is several mils per year at conditions typically found in traps under the urinals. The only shipboard corrosion seen to date is of the yellow brass urinal tail pieces. While this is acceptable, the search for a nontoxic corrosion inhibitor is underway. The shelf life of the tablets is at least one year if stored at 50 percent relative humidity, and longer if stored in sealed plastic buckets.

  7. Compound Metformin/Glipizide Bilayer Extended Release Tablets: Development and in Vitro Release%复方二甲双胍/格列吡嗪双层缓释片:设计与体外释放

    Institute of Scientific and Technical Information of China (English)

    欧阳德方; 聂淑芳; 孟晋; 杨星钢; 宋志全; 潘卫三

    2005-01-01

    Aim In this study, compound metformin/glipizide bilayer extended release tablets were formulated with hydroxypropyl methylcellulose (HPMC) by wet granulation technique in order to tackle the problems associated with the multidrug therapy of non-insulin dependent diabetes mellitus. Methods High-dose metformin is difficult to formulate into a tablet dosage form due to its poor compressibility and compactibility. In this study, the way to overcome the difficulty was to utilize stearic alcohol to prepare the tablet formulation. The influences of viscosity, amount of HPMC, and weight of fillers were investigated. The optimal formulation had acceptable physicochemical properties and released metformin and glipizide over 10 h. Results The data of metformin obtained from in vitro release fitted Higuchi kinetics best, while the release of glipizide in vitro was found to follow zero kinetics. Conclusion Compound metformin/glipizide bilayer extended release tablets have been successfully developed.%目的本文为了解决2型糖尿病中的多药治疗问题,用HPMC进行湿法制粒制备了复方二甲双胍/格列吡嗪双层缓释片.方法由于二甲双胍的压缩成型性较差,高剂量的二甲双胍很难压制成片.在实验中,采用十八醇克服了这一问题.研究了HPMC的黏度、用量和填充剂的用量对药物释放的影响.优化的处方具有较好的物理化学性质,其中二甲双胍和格列吡嗪缓释时间为10小时.结果二甲双胍的体外释放符合Higuchi方程, 而格列吡嗪的体外释放符合零级方程.结论本文成功地设计了一种新型的复方二甲双胍/格列吡嗪双层缓释片.

  8. The advantages of combination therapy on hypertension: development of immediate release perindopril-indapamide tablet and assessment of bioequivalence studies.

    Science.gov (United States)

    Ölçer, A; Ölçer, M; İnce, I; Karasulu, E

    2016-03-01

    Hypertension has a major associated risk for organ damage and mortality, which is further heightened in patients with prior cardiovascular events, comorbid diabetes mellitus, microalbuminuria and renal impairment. Convers Plus tablet including perindopril erbumine (PE), which is an angiotensin converting enzyme (ACE) inhibitor, and indapamide, which is diuretic, was designed as a combined tablet to succes in the treatment of hypertension. Physico-pharmaceutical properties and characterization studies were evaluated in vitro conditions. Later on in vivo study was planned as a cross-designed, randomized, open-labeled, single-dose, single-center study via peroral route in 24 healthy male subjects. In this study, bioequivalence with primary pharmacokinetical target parameters reference (Bipreterax 4/1.25 mg Tablet-S.A.Servier Benelux N.V.) and test (Convers Plus 4/1.25 mg Tablet-ARGESAN Pharmaceutical Company) tablets have been found bioequivalent. The results of pharmacokinetic parameters for perindopril, perindoprilat and indapamide were found as Cmax = 23.179 µg/mL, tmax = 0.729 h, t1/2 = 1.429 h; AUC0-t = 26.998 µgs/mL, AUC0-inf = 27.117 µgs/mL; Cmax = 1.834 µg/mL, tmax = 8.792 h, t1/2 = 40.699 h; AUC0-t = 54.828 µgs/mL, AUC0-inf = 77.113 µgs/mL; Cmax = 18.994 µg/mL, tmax = 3.417 h, t1/2 = 16.626 h and AUC0-t = 385.829 µgs/mL, AUC0-inf = 410.728 µgs/mL respectively. In conclusion, physico-pharmaceutical properties and results of clinical trials show that Convers Plus tablets have been found as bioequivalent for perindopril, perindoprilat and indapamide in terms of AUC and Cmax, in 90% confidence limits.

  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. 4-氨基吡啶凝胶骨架缓释片的制备及体外释放%Preparation and drug release in vitro of 4-aminopyridine hydrophilic matrics sustained release tablets

    Institute of Scientific and Technical Information of China (English)

    叶小玲; 关世侠; 周郁斌; 袁中文; 杨艳; 胡波; 卢舒凡; 张怡; 欧汝静

    2012-01-01

    OBJECTIVE To prepare 4-aminopyridine (4-AP) hydrophilic matrics sustained release tablets. METHODS The formula of 4-aminopyridine (4-AP) hydrophilic matrics sustained release tablets was optimized by orthogonal experiment with the kind of HPMC and the amount of HPMC and lactose as factors and with the in vitro release rates as index. Meanwhile, the verification test on the intra-and inter-batch release rates of the samples was performed. Weibull model was used to make in vitro release fitting curve, and the influence of in vitro release conditions on the drug release was investigated. RESULTS The optimum formula could be seen as follows: the ratios of HPMC K100LV and lactose were 54% and 16% respectively. The formula achieved a sustained drug release of up to 12h, and both the intra- batch homogenicity and the inter- batch reproducibility were satisfactory. Weibull curve fitting equations showed that the drug release met level 1 rate process. The results of in vitro release test showed that drug release rate could be affected by the stirring rate, while the kind of media and device had no significant effect on it. CONCLUSION The preparation procedure of self-prepared 4-aminopyridine hydrophilic matrics sustained release tablets is feasible and rcpeatablc. The tablets have obviously sustained property.%目的:制备4-氨基吡啶(4-aminopyridine,4-AP)亲水凝胶骨架缓释片.方法:以羟丙甲纤维素的规格、处方用量及乳糖处方用量为因素设计正交试验,以体外释放度为考察指标,优化4-AP凝胶骨架片的处方,并进行批内和批间体外释放度验证试验.采用Origin软件对筛选出的最优处方释放度进行Weibull曲线拟合.考察体外释放条件对药物释放的影响.结果:优化处方为HPMC规格为K100LV,处方用量为54%0,乳糖的处方用量为16%.所制得4-AP凝胶骨架片可持续释药12 h,批内释放均一性及批间重复性均良好.Weibull模型拟合方程得出药物释放符合一级

  11. In vitro conditions for the study of the in vivo performance of sustained-release theophylline matrix tablets administered in fasted conditions and with a high-fat diet.

    Science.gov (United States)

    Andonaegui, M T; Barría, J L; Thielemann, A M; Seitz, C; Gai, M N

    1999-11-01

    Dissolution profiles of theophylline (TP) from three types of sustained-release (SR) matrix tablets (plastic [PL], lipid [LP], and hydrophilic [HP]) in different dissolution media, with and without enzymes, were established. Also investigated was the influence of a treatment of the tablets with peanut oil prior to the dissolution test. The in vivo behavior of the tablets under the fasted state and with the concomitant administration with a high-fat diet was previously evaluated; the diet produced changes in the absorption profiles for the three matrix tablets in comparison with fasted administration. Level A correlations were obtained between cumulative percentage dissolved (CPD) and cumulative percentage absorbed (CPA). For the fasted condition, better correlations were obtained with water as the dissolution medium for the HP and LP matrix; for PL matrix, the best correlation was obtained with a medium with gradual change of pH. The pretreatment with peanut oil showed better correlations for the fed state.

  12. Application of Chemomic Release Kinetics to Evaluation of the Release Characteristics of Yinqiaojiedu Tablets%应用化合物组释放动力学方法评价银翘解毒片的释放特征

    Institute of Scientific and Technical Information of China (English)

    陈立兵; 王中华; 傅丹丹; 凌昳; 葛卫红; 顾景凯; YORK Peter; 邵群; 张继稳

    2008-01-01

    目的:考察中药化合物组释放动力学新理论在银翘解毒片释放特征评价中的适用性.方法:以Kalman滤波法为基础,进行紫外分光光度法测定银翘解毒片化合物组标准谱、线性、精密度、稳定性等方法学研究,测定银翘解毒片及其粉末的化合物组释放特征.结果:方法学结果表明,在0.112~1.120 mg生药/mL范围内银翘解毒片化合物组呈线性相关(r=0.999 7);高、中、低化合物组浓度测定的RSD分别为0.05%、0.07%和0.31%浓度分别为0.278,0.556,和1.120 mg生药/mL的供试液化合物组在24 h内稳定.结论:化合物组释放度能简洁、可视、直观地反映银翘解毒片多组分释放动力学特征,中药化合物组释放动力学新理论可以定量地揭示传统中药制剂的新内涵或其给药系统的活性组分释放特征.%AIM: To verify the applicability of a new theory for chemomic release kinetics of traditional Chinese medicines using the release characteristics of Yinqiaojiedu tablets.METHOD: The methodological studies of the preparation of chemomic standard spectrum, linearity, precision and stability tests of the chemomes of Yinqiaojiedu tablets were processed by UV spectrophotometry and Kalman filter methods.The chemomic release profiles of Yinqiaojiedu tablets and powders were determined.RESULT: The methodology studies indicated that there was a good linearity of chemomic concentration of Yinqiaojiedu tablets within the range 0.112 to 1.120 mg total herbs / mL (r=0.999 7).The values of RSD tested at three chemomic levels were 0.05 %, 0.07 % and 0.31% respectively.The chemomic solutions were stable for 24 h at concentrations of 0.278, 0.556, and 1.120 mg total herb / mL.CONCLUSION:The chemomic release profiles demonstrated multi-component release kinetics illustrated using a simple visualization approach.The new theory of chemomic release kinetics may advantageously provide a quantitative description for the release of the active

  13. 富马酸喹硫平缓释片在不同释放介质中的体外释放研究%Drug Release of Quetiapine Fumarate Sustained-release Tablets in Different Release Mediums in vitro

    Institute of Scientific and Technical Information of China (English)

    杨大龙; 杨意波; 卢定强; 谢浩; 严相平

    2013-01-01

    OBJECTIVE: To investigate release behavior of Quetiapine fumarate sustained-release tablets in vitro and its mechanism. METHODS: Taking foreign prepaf ations in the market as control, the similarity of release behavior of 2 preparations in 3 medium (water, 0.1 mol/L hydrochloric acid, pH 6.8 phosphate buffer solution) were analyzed with basket method. The release rates of them were determined by UV spectrophotometry, and similarity factor f2 was used to evaluate the similarity of release curves. Release behavior model was fitted for self-made preparation. RESULTS: In 3 kinds of mediums, similarity factor f2 of 2 preparations was more than 50; in vitro drug release of self-made preparation was consistent with Higuchi equation and Peppas equation in water and pH 6.8 phosphate buffer, and more consistent with first-order equation and Peppas equation in 0.1 mol/L hydrochloric acid. CONCLUSIONS: The release behavior of self-made preparation and reference preparation are similar in different release mediums, and the release mechanism is mainly diffusion mode.%目的:考察自制富马酸喹硫平缓释片的体外释放情况及其释放机制.方法:以国外上市制剂为参比,采用篮法进行2种制剂分别在3种释放介质(水、0.1 mol/L盐酸溶液、pH 6.8磷酸盐缓冲液)中体外释放行为的相似性比较;采用紫外分光光度法测定释放度,以相似因子(f2)进行相似度评价;并对自制制剂进行释放行为模型的拟合.结果:在3种释放介质中,2种制剂比较,f2值均大于50;自制制剂在水和pH 6.8磷酸盐缓冲液中体外释放拟合模型更接近Higuchi方程和Peppas方程,在0.1 mol/L盐酸溶液中更接近一级方程和Peppas方程.结论:自制制剂与参比制剂在不同释放介质中的体外释放行为一致,释放机制以扩散为主.

  14. Design and release characteristics of sustained release tablet containing metformin HCl Planejamento e características de liberação de comprimidos de liberação controlada de cloridrato de metformina

    Directory of Open Access Journals (Sweden)

    Subal Chandra Basak

    2008-09-01

    Full Text Available Metformin hydrochloride (metformin HCl was formulated as a hydrophobic matrix sustained release tablet employing wax materials and the sustained release behavior of the fabricated tablet was investigated. Sustained release matrix tablets containing 500 mg metformin HCl were developed using different bees wax combinations. The tablets were prepared by wet granulation technique. The formulation was optimized on the basis of acceptable tablet properties and in vitro drug release. The resulting formulation produced monolithic tablets with optimum hardness, uniform thickness, consistent weight uniformity and low friability. Statistically significant differences were found among the drug release profile from different bees wax combination matrices. The results of dissolution studies indicated that formulations F-III, F-IV and F-V (bees wax and cetyl alcohol combination matrices, exhibited drug release pattern very close to theoretical release profile. Applying kinetic equation models, the mechanism of release of the drug from the three formulations was found to be followed Higuchi model, as the plots showed high linearity, with correlation coefficient (R² value of 0.98 or more. Tablet matrices containing cetyl alcohol gave better release of the drug than other materials studied. However, the rate of release varied with amount of cetyl alcohol in the matrix. The 'n' value lies below 0.5 (Korsmeyer-Peppas model demonstrating that the mechanism controlling the drug release was the quasi Fickian. Therefore, the results of the kinetic study obtained permit us to conclude that the fabricated hydrophobic matrix tablets, in this case, delivers the drug through diffusion dominated mechanism.O cloridrato de metformina (metformina.HCl foi formulado como comprimido de liberação controlada, empregando materiais cerosos como matriz hidrofóbica, e o comportamento dessa formulação foi investigado. Comprimidos com matriz de liberação controlada contendo 500 mg

  15. Study on in vitro release of Yizhi osmotic pump tablets%自制益智方渗透泵片的体外释放度考察

    Institute of Scientific and Technical Information of China (English)

    王艳明; 杜守颖; 翟永松; 陆洋; 王文峰

    2012-01-01

    目的:考察激光打孔的孔径与释放条件对自制益智方渗透泵片体外释放的影响.方法:处方量主药与辅料混合均匀,70%乙醇制粒、压片、包衣,衣膜增重7%,熟化,激光打孔器双面打孔,制备孔径为0.2、0.4、0.6、0.8、1.0mm激光打孔片剂.考察不同测定方法(转篮法、桨法)、不同孔径、不同转速、不同渗透压条件下释放度,并比较4种有效成分(人参皂苷Rg1、人参皂苷Rb1、人参皂苷R1、桅子苷)释放度,探索其释放规律.结果:转篮法测定该渗透泵片,释放度重复性较好;激光打孔孔径为0.2-0.6mm时,近恒速释放;在50r/min转速条件下,0.4mm孔径片中4种成分12h累积释放度均达到了85%以上;释药度随着释放介质渗透压的升高而减少;4种检测成分间释放度相似因子均大于50; 0.4mm孔径,转篮法50r/min条件下,10h释放较符合零级释放方程y=9.1034t+4.5482(r=0.9915).结论:转篮法适于测定益智渗透泵片的释放度,激光打孔孔径对释放度有一定影响,衣膜内外渗透压是片剂释放动力,4种有效成分释放度相似,该制剂的释放符合零级释放方程.%Objective: To study the effect of diameter of laser drilling apertures and release conditions on the in vitro release of self-made Yizhi osmotic pump tablets. Methods: Drugs and excipients were mixed uniformly, granulated with 70% alcohol as binder, then compressed into tablets, coated, drilled by laser beam bilaterally with apertures size at 0.2,0.4,0.6,0.8 and 1.0 mm respectively. Release behaviors were investigated with different measuring methods (rotating basket method, oar method), at different apertures sizes, different rotating speeds and different osmotic pressure; release behaviors of four effective components were also compared and investigated. Results: Release with rotating basket method showed good reproducibility; Release rate was nearly constant when laser drilling apertures ranged from 0.2 to 0

  16. Effect of food on the pharmacokinetics of canagliflozin/metformin (150/1,000 mg) immediate-release fixed-dose combination tablet in healthy participants.

    Science.gov (United States)

    Murphy, Joseph; Wang, Shean-Sheng; Stieltjes, Hans; Wajs, Ewa; Devineni, Damayanthi

    2015-03-01

    To assess the effect of food on the pharmacokinetics (PK) of canagliflozin and metformin following administration of a canagliflozin/metformin (150/1,000 mg) immediate-release (IR) fixed-dose combination (FDC) tablet. A randomized, open-label, singlecenter, single-dose, 2-period, 2-sequence crossover study was conducted in healthy participants. Participants were randomized to 2 sequences of fasted and fed (or vice versa) administration of one 150/1,000 mg canagliflozin/metformin IR FDC, with 10-14 day washout between treatments PK parameters (AUC, Cmax, tmax, t1/2) were assessed for canagliflozin and metformin. Safety was evaluated. When comparing the IR FDC tablet administered with and without food, PK parameters of canagliflozin were bioequivalent as the 90% confidence intervals (CIs) for log-transformed AUClast, AUC∞, and Cmax were within the bioequivalence limits of 80-125%. For metformin, overall exposure was similar under fed and fasted conditions as geometric mean ratios for AUC and associated 90% CI were contained within the bioequivalence limits, but geometric mean Cmax decreased by 16% in the fed compared to fasted state. Both treatments were well tolerated with similar adverse events and most common were gastrointestinal events, generally attributed to metformin. Food did not affect canagliflozin bioavailability parameters (Cmax and AUCs) or AUCs of metformin. The Cmax of metformin was decreased by 16%, which is not considered clinically meaningful. The canagliflozin/metformin FDC tablet is recommended to be taken with meals to reduce the symptoms of gastrointestinal intolerability associated with metformin.

  17. Controlled release of ropinirole hydrochloride from a multiple barrier layer tablet dosage form: effect of polymer type on pharmacokinetics and IVIVC.

    Science.gov (United States)

    Malewar, Nikhil; Avachat, Makarand; Pokharkar, Varsha; Kulkarni, Shirish

    2013-09-01

    The purpose of the present study was to control in vitro burst effect of the highly water-soluble drug, ropinirole hydrochloride to reduce in vivo dose dumping and to establish in vitro-in vivo correlation. The pharmacokinetics of two entirely different tablet formulation technologies is also explored in this study. For pharmacokinetics study, FDA recommends at least 10% difference in drug release for formulations to be studied but here a different approach was adopted. The formulations F8A and F9A having similar dissolution profiles among themselves and with Requip® XL™ (f 2 value 72, 77, 71 respectively) were evaluated. The C max of formulation F8A comprising hypromellose 100,000 cP was 1005.16 pg/ml as compared to 973.70 pg/ml of formulation F9A comprising hypromellose 4000 cP irrespective of T max of 5 and 5.75 h, respectively. The difference in release and extent of absorption in vivo was due to synergistic effect of complex RH release mechanism; however, AUC0-t and AUC0-∞ values were comparable. The level A correlation using the Wagner-Nelson method supported the findings where R (2) was 0.7597 and 0.9675 respectively for formulation F8A and F9A. Thus, in vivo studies are required for proving the therapeutic equivalency of different formulation technologies even though f 2 ≥ 50. The technology was demonstrated effectively at industrial manufacturing scale of 200,000 tablets.

  18. 左乙拉西坦缓释片的制备与体内外相关性研究%Preparation and in vitro-in vivo correlation in Beagle dogs of levetiracetam sustained-release tablets

    Institute of Scientific and Technical Information of China (English)

    伍衢; 王悦; 王永禄; 李学明; 毛利娟

    2011-01-01

    Objective: To prepare levetiracetam sustained release tablets, and investigate in vitro-in vivo correlation in Beagle dogs. Methods: Mixed HPMC and EC matrix was used to prepare levetiracetam sustained release tablets. The in vitro release characteristics and in vivo pharmacokinetics in dogs of the tablets were investigated. Results: Higuchi model was optimal for the description of drug release profile. The mean elimination half-lives (t1/2 ) after administration of conventional tablets, reference sustained release tablets and our sustained release tablets were (2.09±0.45), (5.35±0.76) and (7.44±1.48) h, respectively. The peak levels were (1.184± 0. 38) , (3. 87 ± 0. 37 ) and (4. 07 ± 0. 56) hj AUCs were calculated to be ( 175. 40 ± 15. 47 ) , (240. 93 ± 19.73) and (251.47 ± 13. 22) μg·h·Ml-1, respectively. Conclusion: The levetiracetam sustained release tablets exhibit the sustained release characteristics in vitro, and show a good correction in vitro release and in vivo absorption.%目的:研制左乙拉西坦缓释片并考察其体外释放及犬体内药动学.方法:以羟丙甲基纤维素,乙基纤维素为混合骨架材料制备日服一次的缓释片,测定其体外释放度和Beagle犬口服单剂量缓释片后血浆中药物的浓度,推算药动学参数.结果:自制缓释片体外释放符合Higuchi模型.左乙拉西坦普通片,上市缓释片和自制缓释片的有关药动学参数如下:t1/2分别为(2.09±0.45),(5.35±0.76),(7.44±1.48)h,T( peak)分别为(1.184±0.38),(3.87±0.37),(4.07±0.56)h,AUC分别为为(175.40±15.47),(240.93±19.73),(251.47±13.22) μg·h·mL-1.结论:自制缓释片具体良好的缓释特性.体外释放和体内吸收有良好的相关性.

  19. The Influence of High Drug Loading in Xanthan Tablets and Media with Different Physiological pH and Ionic Strength on Swelling and Release.

    Science.gov (United States)

    Mikac, Urša; Sepe, Ana; Baumgartner, Saša; Kristl, Julijana

    2016-03-07

    The formation of a gel coat around xanthan (Xan) tablets, empty or loaded with pentoxifylline (PF), and its release in media differing in pH and ionic strength by NMR, MR imaging, and two release methods were studied. The T1 and T2 NMR relaxation times in gels depend predominantly on Xan concentration; the presence of PF has negligible influence on them. It is interesting that the matrix swelling is primarily regulated by Xan despite high drug loading (25%, 50%). The gastric pH and high ionic strength of the media do not influence the position of the penetration and swelling fronts but do affect the erosion front and gel thickness. The different release profiles obtained in mixing and nonmixing in vitro methods are the consequence of matrix hydration level and erosion at the surface. In water and in diluted acid medium with low ionic strength, the main release mechanism is erosion, whereas in other media (pH 1.2, μ ≥ 0.20 M), anomalous transport dominates as was found out by fitting of measured data with theoretical model. Besides the in vitro investigation that mimics gastric conditions, mathematical modeling makes the product development more successful.

  20. Comparative of Therapeutic Efficacy of Oxycodone Hydrochloride Sustained-release Tablets vs. Morphine Sulfate Sustained-release Tablets for Severe Cancer Pain Control with Rectal Administration%盐酸羟考酮缓释片与硫酸吗啡缓释片直肠给药控制重度癌性疼痛的疗效比较

    Institute of Scientific and Technical Information of China (English)

    滕箭; 杨梅英; 沈季元; 王建华; 毛睿

    2012-01-01

    目的:比较盐酸羟考酮缓释片与硫酸吗啡缓释片经直肠给药治疗重度癌性疼痛的疗效和不良反应.方法:将102例伴有中、重度疼痛的癌症患者随机分为A组(50例)与B组(52例),分别经直肠给予盐酸羟考酮缓释片和硫酸吗啡缓释片,比较2组药物起效时间、癌痛类型和药品不良反应的差异.结果:A组患者治疗1、3h时的疼痛与B组同期比较,差异有统计学意义(P<0.05),2组内脏痛和躯体痛比较差异分别有统计学意义(P<0.05),2组的不良反应如恶心、呕吐、便秘比较分别有显著性差异(P<0.05),A组均优于B组.结论:盐酸羟考酮缓释片经直肠给药控制重度癌性疼痛,安全、有效、简便.%OBJECTIVE: To compare the efficacy and adverse drug reactions of oxycodone hydrochloride sustained-release tablets (Oxycontin, Oxycodone hydrochloride prolonged-release tablets) and Morphine sulfate sustained-release tablets (MS Contin, Morphine sulfate) with rectal administration in the treatment of severe cancer pain. METHODS: Clinical information of 102 cases of moderate to severe cancer pain were analyzed, and they were divided into 2 groups. 50 cases were given oxycodone hydrochloride sustained-release tablets with rectal administration group A and 52 cases were given morphine sulfate sustained-release tablets group B. The differences of onset time, the type of cancer pain and side effects were compared between 2 groups. RESULTS: There was statistical significance in the difference of cancer pain between 2 groups, after 1 h and 3 h treatment (P<0.05), there were statistical significance in the differences of visceral pain and somatic pain between 2 groups (P<0.05) ; there were significant differences in adverse drug reactions between 2 groups, such as nausea, vomiting, constipation (P<0.05), and group A was better than group B. CONCLUSION: As for non-hospitalized patients, dying patients and not oral due to various reasons, transrectal

  1. Clinical comparative study of oxycodone sustained-release tablet versus morphine tablet in dose titration therapy on moderate and severe chronic cancer pain%羟考酮缓释片和吗啡片用于中重度癌痛滴定的对比研究

    Institute of Scientific and Technical Information of China (English)

    沈俊俊; 潘月芬; 钟丽萍; 齐全

    2016-01-01

    目的:观察比较羟考酮缓释片和吗啡片用于中重度癌痛滴定的疗效及不良反应。方法选取60例既往未使用阿片类药物的中重度癌痛患者,按随机数字表法分为两组羟考酮缓释片组和吗啡片组,每组30例。羟考酮缓释片组以羟考酮缓释片10 mg/次、1次/12 h行疼痛滴定,吗啡片组以吗啡片5或10 mg作为初始剂量按需给药行疼痛滴定,24 h后均转换为羟考酮缓释片,观察1周,记录疼痛控制情况及不良反应。结果滴定期间羟考酮缓释片组日爆发痛次数、日给药次数明显少于吗啡组[(1.27±1.53)次比(4.87±1.98)次、(3.37±1.78)次比(5.10±2.20)次],差异有统计学意义(P<0.05)。滴定后第1天羟考酮缓释片组疼痛缓解率明显高于吗啡片组[83.33%(25/30)比60.00%(18/30)],差异有统计学意义(P<0.05);而滴定后第3天两组疼痛缓解率比较差异无统计学意义(P>0.05)。滴定后第1天羟考酮缓释片组爆发痛发生率明显少于吗啡片组[23.33%(7/30)比53.33%(16/30)],疼痛达到稳态率明显高于吗啡片组[86.67%(26/30)比63.33%(19/30)],差异有统计学意义(P<0.05)。而两组滴定后第3天爆发痛发生率和疼痛达到稳态率、疼痛达到稳态所需时间、不良反应发生率比较差异无统计学意义(P>0.05)。结论羟考酮缓释片用于中重度癌痛滴定的疼痛缓解率及不良反应与吗啡片类似,但较吗啡片更快止痛,并减少滴定期间爆发痛次数,减轻患者滴定过程的痛苦,具有时效优势,值得应用推广。%Objective To observe the clinical effect and adverse reaction of oxycodone sustained-release tablet and morphine tablet in dose titration therapy on moderate and severe chronic cancer pain. Methods Sixty patients suffering from moderate and severe cancer pain, without using opioid drugs, were divided into oxycodone sustained-release

  2. Relative Bioavailability of Sustained Release Tablets of Tramadol Hydrochloride%盐酸曲马多缓释片的相对生物利用度研究

    Institute of Scientific and Technical Information of China (English)

    葛庆华; 王浩; 张小红; 刘戈; 周臻

    2001-01-01

    18名男性健康受试者,随机交叉口服两种盐酸曲马多缓释片,采用反相高效液相色谱-荧光检测法测定血浆药物浓度。单剂量口服100 mg两种缓释片的Cmax为205.0±51.3和193.5±44.0 ng/ml;Tmax为5.6±2.1和5.8±2.6 h;t1/2为7.3±2.6和7.3±2.8 h。供试制剂的相对生物利用度为97.36±10.01%。多剂量口服两种缓释片达稳态后的峰谷比为1.42±0.17和1.44±0.22;波动度为36.09±12.78和34.37±14.22%。经统计处理均无显著性差异(P>0.05)。经双单侧t检验,两种缓释片具有生物等效性。%The pharmacokinetics and relative bioavailability of two brands of sustained release tramadol hydrochloride tablets administrated orally by 18 healthy male volunteers were investigated, according to a randomized crossover design. The plasma concentration of tramadol hydrochloride was determined by RP-HPLC method with fluorescence detection. The pharmacokinetic parameters for the single oral dose of 100 mg sustained release tramadol hydrochloride tablets were Cmax 205.0±51.3 and 193.5±44.0 ng/ml; Tmax 5.6±2.1 and 5.8±2.6 h;t1/2 7.3±2.6 and 7.3±2.8 h, for tested and reference tablets, respectively. The relative bioavailability for the tested tablets was 97.36±10.01%. For the multiple dosing, the concentration peak-trough ratio (PTR) were 1.42±0.17 and 1.44±0.22, the degree of fluctuation (DF) were 36.09±12.78 and 34.37±14.22%, respectively. The results of two-one-sided t test showed that the tablets of two brands were bioequivalent.

  3. Effect of nifedipine controlled-release tablet combined with valsartan treatment on serological indicators in type 2 diabetic nephropathy patients with hypertension

    Institute of Scientific and Technical Information of China (English)

    Song Chen; Bo Gu; Han-Qing Wang; Bei-Ye Dong; Yang Yi; Ying-Dan Zhao; Yi Xuan; LI Song-yang; Jun Ma

    2016-01-01

    Objective:To analyze the effect of nifedipine controlled-release tablet combined with valsartan treatment on serological indicators in type 2 diabetic nephropathy patients with hypertension. Methods:A total of 96 cases of type 2 diabetic nephropathy with hypertension were included in the research, and according to different clinical treatment plans, all patients were randomly divided into nifedipine group, valsartan group and combined treatment group, 32 cases in each group. After different treatment, peripheral venous blood was drawn to detect the differences in values of serum renal function-related indicators, renal blood vessel-related indicators and illness-related indexes.Results: Serum CysC, Hcy, Chemerin and RBP-4 values of combined treatment group were significantly lower than those of nifedipine group and valsartan group (P<0.05); serum COMP, TM, vWF and mALB values of combined treatment group were significantly lower than those of nifedipine group and valsartan group while Ang-1 and Ang-2 values were higher than those of nifedipine group and valsartan group (P<0.05); serum Ghrelin, TGF-β1 and ALD values of combined treatment group were significantly lower than those of nifedipine group and valsartan group while APN and miR-21 values were higher than those of nifedipine group and valsartan group (P<0.05).Conclusions: Nifedipine controlled-release tablet combined with valsartan treatment of type 2 diabetic nephropathy patients with hypertension can effectively optimize the illness and inhibit the progression of renal failure, and it has positive clinical significance.

  4. Determination of the content of nicergoline in release tablets by RP-HPLC%RP-HPLC测定尼麦角林缓释片的含量

    Institute of Scientific and Technical Information of China (English)

    邬卫东; 温爱平

    2013-01-01

    Objective:To establish a method for determination of contents in Nicergoline Release Tablets. Methods:An RP-HPLC method was used with Agilent ZORBAX C8 (250mm×4.6mm,5μm) column; the mobile phase consisted of acetonitrile -0.05mol/L phosphate buffer (42∶58) and UV detection at 280 nm. Results:Nicergoline showed good linear relationship in the range of 0.243~0.973μg (γ=1.0000). The average recovery was 99.8%, RSD was 0.64%(n=6). Conclusions:This method is rapid, simple and reproducible, The method can be used for the quality control of nicergoline release tablets.%目的:建立尼麦角林缓释片的含量测定方法。方法:采用RP-HPLC法,以Agilent ZORBAX C8(250mm×4.6mm,5μm)为色谱柱;乙腈-0.05mol/L磷酸盐缓冲液(42∶58)为流动相;检测波长280nm。结果:尼麦角林在0.243~0.973μg范围内,与峰面积呈良好的线性关系(γ=1.0000);平均回收率为99.8%,RSD为0.64%(n=6)。结论:该法快速、简便、重现性好,可用于尼麦角林缓释片的质量控制。

  5. Study on detection method of niacin release rate in lovastatin and niacin ustained-release tablets%洛伐他汀烟酸缓释片中烟酸释放度检测方法研究

    Institute of Scientific and Technical Information of China (English)

    蒋艳霞; 秦晶晶; 焦志斌

    2013-01-01

    目的 建立洛伐他汀烟酸缓释片中烟酸释放度的最佳检测方法.方法 参照ADVICOR中烟酸释放度测定方法,将水做为释放介质,温度(37±0.5)℃,转速为100 r/min,作为本实验中烟酸的释放条件;照中紫外-可见分光光度法(2010版附录Ⅳ A),选用262 nm作为烟酸溶出量紫外检测波长.结果 烟酸的溶出量不受辅料影响;浓度在11.01-27.13 μg/ml范围内回收率大于99.70%;体外24 h内烟酸的稳定性良好;在3.88-23.28 μg/ml浓度范围内,紫外吸光度与溶液浓度呈良好的线性关系;烟酸释放均一性没有显著差异.结论 此方法适合洛伐他汀烟酸缓释片中烟酸释放度的测定.%Objective To establish an optimal detection method of niacin in lovastatin and niacin sustained-release tablets. Methods Referring to the detection method of the release rate of niacin in ADVICOR(R) , niacin release conditions were as follows: water as the release medium,( 37 ±0.5 )℃ ,100 r/min. According to UV-Vis spectrophotometry in Chinese Pharmacopoeia( 2010 version of Appendix ⅣA ) , niacin detection wavelength was set at 262 nm. Results Niacin release rate was not affected by the excipients. Recovery rate was more than 99. 70% at the concentrations of 11.01- 27. 13 μg/ml. Nician stability in vitro was good in 24 h. It showed a good linear relationship between UV absorbance and the solution concentration in the range of 3. 88 - 23. 28 μg/ml. Niacin release homogeneity was not significantly different. Conclusion This method is suitable for detecting the niacin release rate in lovastatin and niacin sustained-release tablets.

  6. Assessing the long-term clinical benefit of prolonged-release fampridine tablets in a real-world setting: a review of 67 cases

    Directory of Open Access Journals (Sweden)

    Prugger M

    2013-10-01

    Full Text Available Michael Prugger, Thomas Berger Neuroimmunology and Multiple Sclerosis Clinic and Research Unit, Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria Purpose: To assess the long-term effects of prolonged-release (PR fampridine tablets (dalfampridine extended release in clinical practice in patients with multiple sclerosis (MS with walking impairment. Patients and methods: MS patients with walking impairment deemed candidates for treatment with PR-fampridine tablets were included in this case series. Clinical assessments included the Expanded Disability Status Scale (EDSS, Timed 25-Foot Walk (T25FW, 12-item Multiple Sclerosis Walking Scale (MSWS-12, EuroQoL-5D, and the Fatigue Severity Scale (FSS. The T25FW was videotaped at each visit. Assessments were performed at baseline and after 4 weeks of treatment with PR-fampridine tablets 10 mg twice daily. Clinical benefit of treatment was defined as any improvement in T25FW or MSWS-12 score at 4 weeks. Patients who demonstrated clinical benefit continued treatment and were assessed at 3 and 6 months. Results: Among all patients (N = 67; mean MS duration, 16.5 years; mean EDSS score, 4.8; mean T25FW, 13.9 seconds, 65, 52, and 48 completed the 4-week, 3-month, and 6-month visits, respectively. After 4 weeks, 50.7% and 32.8% of patients walked ≥10% and ≥20% faster, respectively; and in 65.7% of patients, MSWS-12 scores improved. Three patients experienced adverse events (nausea, n = 2, insomnia, n = 1 that resulted in discontinuation of treatment. After 6 months, 38.8% and 16.4% of patients walked ≥10% and ≥20% faster versus baseline, respectively; and in 59.7% of patients, MSWS-12 scores improved. Among patients who demonstrated clinical benefit of treatment at 6 months, FSS scores improved on average by 1 point and MSWS-12 scores by 10 points. Three case studies showing different outcomes of PR-fampridine treatment are detailed with a visual depiction of the changes

  7. Comparisons of drug efficacy and time-effect among magnesium valproate,sustained-release magnesium valproate tablet and depakine chrono for epilepsy An experiment of determining cortical convulsive threshold in rats undergoing electrical stimulation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    BACKGROUND:Scholars have investigated the differences in drug metabolism and pharmacodynamics between valproate and its sustained-release tablets only from the angle of pharmaceutical sciences or clinical practice.Whether the fact that differences in drug efficacy and time-effect of different doses of valproate and different types of sustained-release valproate tablets at the same concentration can be quantitatively reflected by determining the changes in convulsive threshold pre- and post-administration in rat models of determining the convulsive threshold developed by direct cortical electrical stimulation remains unclear.OBJECTIVE:This study aimed to compare the drug efficacy and time-effect among magnesium valproate,sustained-release magnesium valproate tablet and depakine chrono in the treatment of epilepsy by determining the convulsive threshold of rat models created by direct cortical electrical stimulation,and human serum drug concentration before and after administration.DESIGN:A controlled observational experiment.SETTING:Research Institute of Epilepsy,Shanxi Medical University.MATERIALS:Adult health male SD rats of clean grade,weighing 200 - 220 g,provided by the Laboratory Animal Center of Shanxi Medical University.The protocol was carried out in accordance with requests from Animal Ethics Committees for guidance.Magnesium valproate (Lot No.041004) and sustained-release magnesium valproate tablet (Lot No.050501) were produced in Hunan Xiangzhong Pharmaceutical Co.,Ltd.METHODS:This study was carried out in the Laboratory for Epilepsy,Shanxi Medical University between June and August 2005.①All the SD rats were created into models for determining cortical convulsive threshold.They were randomly divided into 4 groups with 20 rats in each:magnesium valproate tablet group,sustained-release magnesium valproate tablet group,depakine chrono group and control group.After being modeled,the rats in the first 3 groups were intragastrically administrated with

  8. Development of novel core-shell dual-mesoporous silica nanoparticles for the production of high bioavailable controlled-release fenofibrate tablets.

    Science.gov (United States)

    Zhao, Zongzhe; Gao, Yu; Wu, Chao; Hao, Yanna; Zhao, Ying; Xu, Jie

    2016-01-01

    Novel core-shell dual-mesoporous silica nanoparticles (DMSN) were successfully prepared as a carrier in order to improve the dissolution of fenofibrate and obtain an oral highly bioavailable controlled-release drug delivery system using the osmotic pump technology. Fenofibrate was loaded into DMSN by an adsorption method. The solid state properties of fenofibrate in DMSN, before and after drug loading, were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption analysis (BET), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC). In vitro release tests showed that DMSN increased the dissolution rate of fenofibrate and produced zero-order release in push-pull osmotic pump tablets (OPT). The relative bioavailability of OPT was 186.9% in comparison with the commercial reference product. In summary, osmotic pump technology in combination with solid dispersion technology involving nanometer materials is a promising way for achieving the oral delivery of poorly water-soluble drugs.

  9. 布洛芬缓释片人体生物等效性研究%Human Bioequivalence of Ibuprofen Sustained Release Tablet

    Institute of Scientific and Technical Information of China (English)

    苏方华; 陈燕; 庞日兰

    2014-01-01

    Objective To study the human bioequivalence of Ibuprofen Sustained Release Tablet. Methods 20 cases of male volunteers were selected from March 2012 to March 2013 and divided into the observation group(10 cases)and the control group(10 cases)ac-cording to the random digital table. The observation group took oral Ibuprofen Sustained Release Tablet,while the control group took oral Ibuprofen Sustained Release Capsule(fenbid). The blood drug concentration was determined by HPLC,which was fitted by the 3p97 pharmacokinetic program and compared with the pharmacokinetic parameters. Results Compared with the control group,the observation group had significant differences in Cmax,AUC0 -24 and AUC0 -∞ levels,all showing the statistical significance( P ﹤ 0. 05). The peak concentration change in the observation group was more gentle and the effect of drug sustained release was better,the relative bioavail-ability(F value)was 103. 7%. Conclusion Compared with the reference preparation,Ibuprofen Sustained Release Tablet can better play the sustained release effect with the broad application prospects in clinic,which is worthy of further research.%目的:研究布洛芬缓释片的人体生物等效性。方法2012年11月至2013年8月,选择20例男性志愿者,按随机数字表法随机分成观察组和对照组,各10例。观察组服用布洛芬缓释片,对照组服用布洛芬缓释胶囊(芬必得)。采用高效液相色谱( HPLC )法测定血药浓度,经3p97型药代动力学方案拟合并对比药代动力学参数。结果与对照组相比,观察组在峰浓度( Cmax)、0~24 h药时曲线下面积( AUC0-24)以及 AUC0-∞等水平差异均显著( P﹤0.05)。观察组峰浓度变化较平缓,且药物缓释效果较好,相对生物利用度( F值)为103.7%。结论与参比制剂相比,布洛芬缓释片可更好地发挥缓释效果,临床应用前景广阔,值得深入研究。

  10. A structure parameter for porous pharmaceutical tablets obtained with the aid of Wiener bounds for effective permittivity and terahertz time-delay measurement.

    Science.gov (United States)

    Bawuah, Prince; Chakraborty, Mousumi; Ervasti, Tuomas; Zeitler, J Axel; Ketolainen, Jarkko; Gane, Patrick A C; Peiponen, Kai-Erik

    2016-06-15

    A structure parameter that can be used to predict the pattern of arrangement of porous inclusions in pharmaceutical tablets is introduced. By utilizing the effective refractive index of a pharmaceutical tablet obtained from terahertz time-domain measurements, we have shown that there exists a promising correlation between the calculated structural parameter and the porosity of training sets of pharmaceutical tablets, having well-defined characterization. Knowing of the structural arrangement, i.e. combined constituent skeletal-pore elements in series, parallel or mixed within porous media, could serve as a basis for understanding the ingress and permeation of liquids in such media. In the realm of pharmaceutical applications, such knowledge of the structural arrangement of air voids within a medicinal tablet could enable correlation with mechanical strength and dissolution behaviour in aqueous systems.

  11. 阿魏酸钠羟丙甲纤维素片剂的体外释药描述%Description of the release of sodium ferulate from hydroxypropyl methylcellulose based matrix tablets in vitro

    Institute of Scientific and Technical Information of China (English)

    李凤前; 胡晋红

    2004-01-01

    Aim To elucidate the mechanism and to present suitable models for the release of sodium ferulate (SF) from hydroxypropyl methylcellulose (HPMC) based matrix tablets. Methods The characteristics and mechanisms of drug release were analyzed from the point of thermodynamic, swelling and diffusion effect. Despite the classical equation of Higuchi, the semi-empirical power law and quadratic curve were also adopted to analogize the release of SF from HPMC based tablets in vitro. Results The first release stage of SF was mainly controlled by Fick diffusion, and the rest SF released mainly according to case II transport process caused by the swelling effect of HPMC. The decreased Ts of HPMC, resulted from the entered water, enhanced the release of SF. The power law was possible for the first released 60 % SF, but unfit for the last 40 % SF. The quadratic curve expressed equation can illuminate the release of SF. Conclusion For the HPMC system, drug release undertakes the Fick diffusion process followed by the extend of polymer chain. The nonlinear quadratic equation might he valuable to explain the entire drug release from HPMC-hased delivery system.

  12. 富马酸喹硫平骨架缓释片的研发%Development and Research of Quetiapine Fumarate Matrix Sustained-Release Tablets

    Institute of Scientific and Technical Information of China (English)

    何广卫; 苏峰; 许国琴; 许慧雷

    2014-01-01

    Using f2 similarity factor and comprehensive score of the cumulate release rate as response value , single factor test and orthogonal experimental design were used to determine the viscosity and dosage of HPMC as matrix materials and dosage of lactose as diluents and sodium citrate as pH regulators and magnesium stearate as lubricants .The optimal formulation (1 000 units) was quetiapine fumarate 230 g, HPMC K100Lv 180 g, HPMC K4M 60 g, lactose 50 g, sodium citrate 75 g and magnesium stearate 6 g.The dissolution profile in difference pH media was consistent with reference listed drug ( f2≥50 ) , and the sustained -release tablets in vitro release fitted to the Higuchi model and Ritger -Peppas equation , the release mechanism in vitro was diffusion combined with corrosion.%以HPMC为骨架缓释材料,乳糖为填充剂,枸橼酸钠为pH调节剂,硬脂酸镁为润滑剂,采用单因素试验和正交实验设计方法,通过f2相似因子和累积释放度综合评分进行评价,最终确定富马酸喹硫平缓释片的处方组成为:富马酸喹硫平230 g, HPMC K100Lv 180 g, HPMC K4M 60 g,乳糖50 g,柠檬酸钠75 g,硬脂酸镁6 g。自研缓释片释放行为与原研制剂一致( f2≥50),且符合Higuchi模型和Ritger-Peppas方程,表明药物释放机制是扩散与溶蚀并存的双重机制。

  13. Can semipermeable membranes coating materials influence in vivo performance for paliperidone tri-layer ascending release osmotic pump tablet: In vitro evaluation and in vivo pharmacokinetics study

    Directory of Open Access Journals (Sweden)

    Guangjing Li

    2015-04-01

    Full Text Available One purpose of this study was to develop a paliperidone (PAL tri-layer ascending release push–pull osmotic pump (TA-PPOP tablet which could meet the needs of clinical applications. And another purpose was to investigate whether different coating materials influenced in vivo performance of TA-PPOP. The ascending release mechanism of this tri-layer delivery system on theory was elaborated. TA-PPOP was prepared by means of coating with cellulose acetate (CA or ethyl cellulose (EC. Several important influence factors such as different core tablet compositions and different coating solution ingredients involved in the formulation procedure were investigated. The optimization of formulation and process was conducted by comparing different in vitro release behaviors of PAL. In vitro dissolution studies indicated that both the two formulations of different coating materials were able to deliver PAL at an ascending release rate during the whole 24 h test. The in vivo pharmacokinetics study showed that both self-made PPOP tablets with different coating had a good in vitro-in vivo correlation (IVIVC and were bioequivalent with the brand product, which demonstrated no significant influence of the coating materials on the in vivo release acceleration of TA-PPOP.

  14. Formulation and Evaluation of a Sustained-Release Tablets of Metformin Hydrochloride Using Hydrophilic Synthetic and Hydrophobic Natural Polymers

    OpenAIRE

    K J Wadher; Kakde, R. B.; M J Umekar

    2011-01-01

    Metformin hydrochloride has relatively short plasma half-life, low absolute bioavailability. The need for the administration two to three times a day when larger doses are required can decrease patient compliance. Sustained release formulation that would maintain plasma level for 8-12 h might be sufficient for daily dosing of metformin. Sustained release products are needed for metformin to prolong its duration of action and to improve patient compliances. The overall objective of this study ...

  15. 帕利哌酮缓释片用于精神分裂症复发的研究进展%Research progress of paliperidone extended-release tablet applied in schizophrenia relapse

    Institute of Scientific and Technical Information of China (English)

    黄宇

    2014-01-01

    帕利哌酮缓释片是目前临床常用的一种非典型抗精神病药物,临床作用机制是主要通过阻断全部的5-羟色胺2A(5-HT2A)受体和部分多巴胺D2(DA2)受体,进而发挥抗精神病的作用。近年来,随着帕利哌酮缓释片在临床上被广泛应用,许多临床研究提示帕利哌酮缓释片可有效控制精神分裂症患者的阳性症状、改善阴性症状和认知损害、提高患者的耐受性和依从性。帕利哌酮缓释片起效快,且可有效改善对其他非典型抗精神病药治疗无效患者的临床效果,为精神分裂症患者的全面康复提供有效的治疗。近年来的统计观察发现,帕利哌酮缓释片应用于急性期及首发精神分裂症患者的临床效果较好,临床治愈率满意,但帕利哌酮缓释片对精神分裂症复发的效果如何尚未报道。本院通过对住院或门诊复发精神分裂症患者应用帕利哌酮缓释片的观察,评价帕利哌酮缓释片治疗精神分裂症复发的临床效果。本研究对帕利哌酮缓释片治疗精神分裂症复发的研究进行综述。%Paliperidone extended-release tablet is used as a common atypical antipsychotic drugs,and its clinical mechanism of action is mainly blocking all 5-HT2A receptor and partial DA2 receptor in order to play the role of anti psychotic.In recent years,with the extensive use of paliperidone extended-release tablet in the clinic,many study showed that paliperidone extended-release tablet can effectively control the positive symptoms of patients with schizophrenia,improve negative symptoms and cognitive impairment and improve the tolerance and compliance pa-tients.Paliperidone extended-release tablet with rapid action can effectively improve the clinical efficacy of other pa-tients treated inefficiently by other atypical antipsychotics therapy,and it can provide effective treatment for the com-prehensive rehabilitation of patients with schizophrenia

  16. Optimization of metoprolol tartrate modified-release matrix tablet formulation using Eudragit NE as binder for metoprolol fluid bed granulation

    Directory of Open Access Journals (Sweden)

    Ioan Tomuta

    2012-01-01

    Full Text Available The aim of this experimental work was to investigate the possibility of obtaining hydroxypropyl methylcellulose (HPMC hydrophilic matrix extended-release dosage forms with metoprolol by using aqueous dispersions of Eudragit NE, as binders in fluid bed granulation. To evaluate the influence of formulation variables (levels of HPMC-Methocel K100 M and Surelease E7 19010 on drug release during a period of time of 12 hours, and on the kinetic release, a full factorial experimental design with two factors and three levels was used. The formulation factors were the granulation polymer concentration and the matrix-forming polymer concentration. The obtained results have shown that the percentage of the drug released during the 12 hours is influenced both by the Methocel ratio and the Eudragit NE ratio; increasing the ratios of Eudragit and Methocel leads to the decrease of the percentage of the released drug. The influence of Eudragit NE percentage is maximum at four and six hours, but the influence of Methocel K100 M concentration is almost the same at all sampling times; all studied formulations showed a kinetic release that fitted best with the Peppas model.

  17. Development of In Vitro-In Vivo Correlation for Amorphous Solid Dispersion Immediate-Release Suvorexant Tablets and Application to Clinically Relevant Dissolution Specifications and In-Process Controls.

    Science.gov (United States)

    Kesisoglou, Filippos; Hermans, Andre; Neu, Colleen; Yee, Ka Lai; Palcza, John; Miller, Jessica

    2015-09-01

    Although in vitro-in vivo correlations (IVIVCs) are commonly pursued for modified-release products, there are limited reports of successful IVIVCs for immediate-release (IR) formulations. This manuscript details the development of a Multiple Level C IVIVC for the amorphous solid dispersion formulation of suvorexant, a BCS class II compound, and its application to establishing dissolution specifications and in-process controls. Four different 40 mg batches were manufactured at different tablet hardnesses to produce distinct dissolution profiles. These batches were evaluated in a relative bioavailability clinical study in healthy volunteers. Although no differences were observed for the total exposure (AUC) of the different batches, a clear relationship between dissolution and Cmax was observed. A validated Multiple Level C IVIVC against Cmax was developed for the 10, 15, 20, 30, and 45 min dissolution time points and the tablet disintegration time. The relationship established between tablet tensile strength and dissolution was subsequently used to inform suitable tablet hardness ranges within acceptable Cmax limits. This is the first published report for a validated Multiple Level C IVIVC for an IR solid dispersion formulation demonstrating how this approach can facilitate Quality by Design in formulation development and help toward clinically relevant specifications and in-process controls. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  18. 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

  19. Population pharmacokinetics of the 5-hydroxymethyl metabolite of tolterodine after administration of fesoterodine sustained release tablet in Western and East Asian populations.

    Science.gov (United States)

    Oishi, Masayo; Tomono, Yoshiro; Yamagami, Hidetomi; Malhotra, Bimal

    2014-08-01

    This analysis was conducted to investigate factors that affect 5-hydroxymethyl tolterodine (5-HMT) pharmacokinetics after administration of fesoterodine sustained release tablets to Westerners and East Asians. Ten pharmacokinetic studies and three efficacy/safety studies in overactive bladder (OAB) patients were pooled for the population pharmacokinetic analysis. The plasma 5-HMT concentration data were described by a 1-compartment model with first order absorption and a lag time. Creatinine clearance (CLCR), hepatic impairment, CYP2D6 genotype, and concomitant medication with CYP3A inhibitor/inducer were identified as influential covariates. It was estimated that decreasing of CLCR from 80 to 15 mL/min resulted in a 39.5% reduction in 5-HMT apparent oral clearance (CL/F). Hepatic impairment, CYP2D6 poor metabolizer, and CYP3A inhibitor were estimated to reduce CL/F by about 60%, 40%, and 50%, respectively. CYP3A inducer resulted in about fourfold increase in CL/F. Although sex and Japanese ethnicity were selected as covariates on CL/F, each resulted in only about 10% decrease and increase of CL/F, respectively. Of the influential covariates of 5-HMT CL/F, CLCR, hepatic impairment, CYP2D6 genotype, and concomitant medication with CYP3A inhibitor/inducer were of significance, whereas sex and Japanese ethnicity covariates were considered not to have clinically significant impact on exposures of 5-HMT. © 2014, The American College of Clinical Pharmacology.

  20. 吲达帕胺缓释片疑致糖代谢紊乱%Disorder of glucose metabolism induced by indapamide sustained-release tablet

    Institute of Scientific and Technical Information of China (English)

    杨宝; 杨四涛; 夏洪颖; 普燕芳

    2013-01-01

    1例64岁女性患者,因高血压给予吲达帕胺缓释片(2.5 mg,qd)降压,用药3周后,患者出现口渴、多尿、消瘦、体质量下降5 kg,血糖13.4 mmol· L-1,尿糖(++++)。停药3 d后,患者血糖、尿糖恢复正常,口渴、多尿症状消失。%One 64-year-old female patient with hypertension was given indapamide sustained-release tablets 2.5 mg once a day. Three weeks later, the patient developed thirst, polyuria, marasmus. The weight decreased 5 kg. Her blood glucose was 13.4 mmol· L-1, and the urine sugar showed (++++). The drug was stopped. Three days later, her blood glucose and urine sugar returned to normal, the symptoms of thirst and polyuria disappeared.

  1. A binary concrete crack self-healing system containing oxygen-releasing tablet and bacteria and its Ca(2+)-precipitation performance.

    Science.gov (United States)

    Zhang, J L; Wang, C G; Wang, Q L; Feng, J L; Pan, W; Zheng, X C; Liu, B; Han, N X; Xing, F; Deng, X

    2016-12-01

    A strategy to supply molecular oxygen for microbial calcium precipitation was developed for the first time. Firstly, a controlled oxygen-releasing tablet (ORT) containing CaO2 and lactic acid with a suitable ratio of 9:1 was developed. It can provide a stable oxygen supply and maintain pH in the range of 9.5-11.0 for 45 days while contacting with water. In the presence of oxygen, a self-healing bacterium H4 spores germinated more effectively and maintained high metabolic activity. Furthermore, H4 vegetative cells induced 50 % more calcium precipitation than that obtained without oxygen supply. Finally, a binary self-healing system containing bacterial spores and ORT was established. The calcium precipitation experiments showed that H4 in the binary self-healing system precipitated 27.5 mM calcium with oxygen supply after 32 days and dissolved oxygen (DO) concentration of the solution decreased from 15 to 4 mg l(-1), while only 6.9 mM calcium precipitation was obtained without oxygen supply. This work can disclose the effect of oxygen on microbial calcium precipitation and further lay a foundation for the establishment of ternary self-healing system containing bacteria, ORT, and nutrients, which will be promising for the self-healing of cracks deep inside the concrete structure.

  2. 复方非洛地平/酒石酸美托洛尔渗透泵控释片的研制%Preparation of osmotic pump controlled release tablets of compound felodipine with metoprolol tartrate

    Institute of Scientific and Technical Information of China (English)

    颜琨; 李志平; 刘洪玉; 姚蕊; 梅兴国

    2011-01-01

    目的 制备复方非洛地平/酒石酸美托洛尔渗透泵控释片,并优选最佳处方.方法 采用高效液相色谱法测定不同处方制剂累积释药百分率,建立体外评价方法,并通过相似因子和正交设计筛选出最佳处方.结果 渗透泵片的片芯处方、包衣增重是影响释药的主要因素.优化的处方为15 mg聚氧乙烯、45 mg NaCl、11%包衣增重.结论 按优化处方制备的渗透泵控释片符合零级释放特征,且两种药物释放同步.%Objective To prepare osmotic pump controlled release tablets of felodipine with metoprolol tartrate and to optimize the formulation. Methods The cumulative rates of drug release of differently formulated preparations were measured by HPLC method. The tablets were evaluated in vitro to select the best formula using similarity factors and orthogonal design. Results The formulation of core tablets and different coating weights of membrane showed marked effects on drug release. The selected formula was 15 mg PEO,45 mg NaC1 and 11% weight gain of coat. Conclusion The osmotic pump tablets of the selected formula release simultaneously felodipine and metoprolol tartrate according to zero order kinetics.

  3. Characterisation of a novel, multifunctional, co-processed excipient and its effect on release profile of paracetamol from tablets prepared by direct compression

    Directory of Open Access Journals (Sweden)

    Sylvester Okhuelegbe Eraga

    2015-09-01

    Conclusions: The drug-excipient ratios of 1:3 and 1:4 gave pharmaceutically acceptable tablets that met the British Pharmacopoeia specifications. The t50% value of the 1:4 batch of tablets may find its usefulness in formulating drugs for which a fast onset of action is desired.

  4. Clinical recommendation on paliperidone extended-release tablet in schizophrenia therapy%帕利哌酮缓释片临床用药指导意见

    Institute of Scientific and Technical Information of China (English)

    舒良; 蔡焯基; 吉中孚; 江开达; 司天梅; 张鸿燕; 梅其一; 贾福军; 陆峥

    2011-01-01

    精神分裂症是一组病因未明的精神疾病,其病程迁延,易慢性化,多数患者会出现精神残疾.目前的治疗目标不仅是控制症状,还要改善患者的社会功能.文中综述了帕利哌酮缓释片的药理特点,并就其临床使用提出指导意见.帕利哌酮缓释片是一种新型第二代抗精神病药,其有效成分帕利哌酮是利培酮的活性代谢产物,同时OROS控释技术可以带来平稳的血药浓度.帕利哌酮缓释片起效迅速,能够全面有效控制症状,安全性良好,同时可以显著改善患者的社会功能.%Schizophrenia is a group of disabling disorders with uncertain cause. Its course can be presented as one episode or span into a chronic state, ultimately requiring lifelong treatment. The treatment goals of schizophrenia are to rapidly control symptoms, and to gain a result of improved personal and social functioning. In this paper, clinical recommendation on paliperidone extended-release (ER) tablet in schizophrenia therapy was reviewed. Paliperidone ER is a recently developed atypical antipsychotic drug available for the treatment of schizo-phrenia. Paliperidone (9-hydroxy risperidone) is the major active metabolite of risperidone. By the unique extended-release delivery system, paliperidone ER can steadily deliver paliperidone and maintain steady plasma concentrations. It is efficacious in improving symptoms and social functioning of schizophrenia patients, and is well tolerated.

  5. NEW STABILITY INDICATING RP-LC METHOD FOR SIMULTANEOUS QUANTIFICATION OF RELATED IMPURITIES OF LAMIVUDINE, TENOFOVIR DISOPEOXIL FUMARATE AND NEVIRAPINE IN EXTENDED RELEASE TABLET DOSAGE FORMS

    Directory of Open Access Journals (Sweden)

    Lanka A.Rama Prasad

    2012-11-01

    Full Text Available The objective of the current study was to develop and validate precise, specific and stability-indicating reverse phase LC method for the simultaneous quantitative determination of Lamivudine, Tenofovir disoproxil fumarate and Nevirapine and their related impurities. The determination was done for extended release tablets dosage form where Tenofovir and Lamivudine are formulated into immediate release and Nevirapine into extended relase. The pharmaceutical formulation along with individual active ingredients was subjected to stress conditions of hydrolysis (acid and base, oxidation and thermal degradation as per International Conference on Harmonization (ICH prescribed stress conditions to show the stability-indicating power of the method. It was found Tenofovir disoproxil fumarate is very sensitive to various stress conditions and readily degrades into Monoester impurity. The chromatographic conditions were optimized using an impurity-spiked solution and the samples generated from forced degradation studies. Regression analysis shows an r value (correlation coefficient of greater than 0.997 for individual active drug substances and their all the related impurities. The chromatographic separation was achieved on a core shell technology C18 stationary phase. The method employed a linear gradient elution and the detection wavlength was set at 260 nm. The mobile phases consists of buffer and acetonitrile delivered at a flow rate of 0.8 mL•min–1. The stress samples were assayed against a qualified reference standard and the mass balance was found to be close to 98.5%. The developed RP-LC method was validated with respect to linearity, accuracy, precision and robustness.

  6. Study on the Formulation Optimization and Preparation Technology of Pioglitazone Hydrocloride Sustained-release Tablets%盐酸吡格列酮缓释片处方筛选及工艺研究

    Institute of Scientific and Technical Information of China (English)

    陈吉生; 陈燕忠; 庄文斌; 黎行山

    2012-01-01

    OBJECTIVE: To screen the formulation of Pioglitazone hydrocloride sustained-release tablets, and to optimize the preparation technology of it. METHODS: The type, amount and preparation technology of matrix material, bulking agent, and adhesive were investigated by determining accumulative rate of pioglitazone at different time in PBS to determine the formulation and preparation technology of tablet core. RESULTS: The tablet core was prepared with HPMC(K15M) as matrix material, microcrys-taline celulose as the bulking agent and 70% ethanol solution of 2% HPMC(E5) as adhesive material for Pioglitazone hydrocloride sustained-release tablets. The tablet was prepared by film coating method using 70% ethanol solution of Opadry as film coating material. Accumulative drug release rate of prepared 3 batches of samples were all more than 90% in 12 h. CONCLUSION: The preparation method is simple and the tablet is up to the requirements of sustained-release preparation.%目的:对盐酸吡格列酮缓释片进行处方筛选及工艺研究.方法:通过测定不同时间吡格列酮在pH6.8磷酸盐缓冲液中的累积释药率,对缓释骨架材料、填充剂、黏合剂的种类或规格、用量及工艺等进行考察,确立片芯处方及制备工艺.结果:片芯处方以羟丙基甲基纤维素(HPMC) (K15M)为骨架材料,微晶纤维素为填充剂,2%HPMC(E5)的70%乙醇溶液为黏合剂;制备工艺采用薄膜包衣法,以欧巴代的70%乙醇溶液作为薄膜包衣材料;所制3批样品12h的累积释药率均在90%以上.结论:本制剂工艺简单,符合缓释制剂要求.

  7. 左金胃漂浮缓释片多组分体内释放研究%Study on Multicomponent In Vivo Releasing Rules of Zuojin Gastric Floating Sustained-release Tablet

    Institute of Scientific and Technical Information of China (English)

    杨颂; 刘文; 陈大业; 施小伟; 王群; 宋颖

    2013-01-01

    目的:研究左金胃漂浮缓释片多组分的体内释放行为。方法:不同时间点取家兔胃内容物,处理并制备供试品溶液,采用高效液相色谱法建立各个时间点及全溶样品的图谱,计算体内累积释放度,采用相似因子法评价指标成分之间及指标成分与制剂之间的释放行为。结果:在10 h内,小檗碱与吴茱萸内酯、吴茱萸次碱的相似因子分别为52、61.5,与制剂的相似因子为66.4,吴茱萸内酯与吴茱萸次碱的相似因子为70,与制剂的相似因子分别为46.5、53.7。结论:在10 h内,小檗碱的释放行为与吴茱萸内酯、吴茱萸次碱及制剂相似;吴茱萸次碱与吴茱萸内酯及制剂的释放行为相似;而吴茱萸内酯与制剂的释放行为不一致。%This article was aimed to study the multicomponent in vivo releasing rules of Zuojin Gastric Floating Sus-tained-release Tablet. Stomach contents of rabbits were collected at different times and then prepared into solutions for the study. The HPLC was used to establish fingerprints of each time and fingerprints of completely dissolved samples. The in vivo releasing rates were calculated. The evaluation was made on releasing behaviors among index components as well as between index components and preparations. The results showed that within 10 h, the f2 of berberine and limonin, rutaecarpine, preparation were 52, 61.5, 66.4, respectively. The f2 of limonin and rutae-carpine, preparation were 70, 46.5, 53.7, respectively. It was concluded that within 10 h, the releasing behavior of berberine and limonin, rutaecarpine, preparation was similar. The releasing behavior of rutaecarpine and limonin, preparation was similar. However, the releasing behavior of limonin and preparation was different.

  8. Estudio de bioequivalencia de dos formulaciones de tabletas de carbamazepina de liberación retardada Study of bioequivalence of two carbamazepine retard-release tablet formulations

    Directory of Open Access Journals (Sweden)

    2000-03-01

    Full Text Available En 12 voluntarios sanos se efectuó un estudio de bioequivalencia de dos preparados comerciales de carbamazepina en tabletas de liberación retardada. Este estudio permitió comparar la biodisponibilidad de la formulación de referencia Tegretol® Retard de Ciba Geigy elaborado en Colombia por Novartis, y la formulación de prueba Carbamazepina MK Retard, de Tecnoquímicas. Para evaluar la bioequivalencia se determinaron las curvas de concentración plasmática vs tiempo de las dos formulaciones y se calcularon las áreas bajo la curva (AUC y las concentraciones máximas (Cmáx. Para la formulación de prueba el intervalo de confianza del 90% para el AUC estuvo entre 95.7 y 100.7% y para el C(máx entre el 88.6 y el 106.1%. Para ambas determinaciones el rango de aceptación, según normas internacionales, está entre 80 y 125% de la formulación de referencia. Esto demuestra la bioequivalencia de las dos formulaciones. A study of the bioequivalence of two comercial carbamazepine retard-release formulations was carried out in 12 healthy volunteers. Studies of bioequivalence allow to compare the bioavailability of the innovator formulation with generic, alternative or branch formulations. In order to evaluate the bioequivalence, plasma carbamazepine concentration/time curves were obtained for the Tegretol® Retard Tablets –reference formulationand for the test formulation; the area under each curve and the maximum concentration were calculated. After the calculation, statistical analysis of data for the area under the curve of the Carbamazepine Retard Tablets –test formulation, was between 95.7% and 100.7 % and the maximum concentration of the test formulation was between 88.6% and 106.1%; both parameters with the 90% confidence interval. Since the acceptance range was determined to be between 80.0% and 125.0% of the reference formulation, we concluded from this study that the two formulations are bioequivalent.

  9. 国产布洛芬缓释片的体内外相关性%In vivo and vitro correlation of domestic sustained release tablet of ibuprofen

    Institute of Scientific and Technical Information of China (English)

    李雪宁; 陈伟力

    2001-01-01

    OBJECTIVE To study in vivo and vitro correlation of domesticsustained release tablet of ibuprofen.METHODS The dissolution of ibuprofen was determined in vitro according to CP(1995,II) and the blood concentration in vivo by HPLC. The 3P97 program was used to calculate the pharmacokinetic parameters of ibuprofen. RESULTS The dissolution of ibuprofen was 77.44% within 7h, the AUC, Cmax, Tmax were (150.2±34.8) μg·h·ml-1,(22.7±5.3) μg·ml-1 and (3.5±0.7) h respectively. CONCLUSIONS There was significant correlation between in vitro dissolution and in vivo absorption of the tablet.%目的:对国产布洛芬缓释片的体内外相关性进行研究。方法:体外释放度采用中国药典1995年版二部的转篮法,体内血药浓度用HPLC法和3P97程序计算药动学参数。结果:在7h时平均累积释放77.44%;10名男性健康志愿者口服单剂量600mg布洛芬缓释片的体内过程符合开放一室模型,AUC,Cmax,Tmax分别为(150.2±34.8)μg·h·ml-1,(22.7±5.3)μg·ml-1和(3.5±0.7)h。结论:将体外释放百分率即释放度(F)对体内吸收分数(f)回归得回归方程为:f=-33.45+1.745F(r=0.988,n=4),对相关系数进行检验,两者之间存在显著相关性(P<0.05)。

  10. Application of felodipine sustained-release tablets in the hypertension treatment in China%非洛地平缓释片在中国高血压患者治疗中的应用

    Institute of Scientific and Technical Information of China (English)

    邬瑾

    2016-01-01

    背景:非洛地平缓释片每日仅需服用1次,具有平坦的血浆-浓度曲线,且起效平稳、口服吸收度好,生物利用度高,患者的依从性好。目的:介绍非洛地平缓释片在国内高血压治疗中的应用状况。方法:应用计算机检索CNKI中国期刊全文数据库,纳入文献时间限定为2005-01-01/2016-07-01。在题名中检索包含“非洛地平缓释片,高血压”的文献,得到174篇;检索主题包含“非洛地平缓释片,材料”的文献,得到22篇,均为中文。按纳入排除标准选择30篇文献进行分析。结果与结论:非洛地平缓释片在国内高血压治疗中已经得到了广泛的应用,尤其是对轻中度原发性高血压的降压效果良好,其疗效与硝苯地平缓释片、美托洛尔缓释片及贝那普利片等降压药相似。非洛地平缓释片的主要不良反应有头痛、面部潮红、心悸、踝部水肿等,但一般都很轻微。对于非洛地平缓释片单药控制不良的高血压患者,可随机联合β受体阻滞剂、血管紧张素转换酶抑制剂、利尿剂等不同类型降压药,同样能够获得较好的降压效果。复方非洛地平缓释片目前也已经在临床上应用,数个多中心双盲随机对照试验已经证实了复方非洛地平缓释片的降压有效性及安全性,对于单药治疗效果不佳的原发性高血压患者,复方非洛地平缓释片也是一个可选的治疗方案。%BACKGROUND:Felodipine sustained-release tablets are taken oral y once daily, which not only exhibit a flat plasma-concentration curve, but also have characteristics of stable effect-acting, good absorption in vivo, high bioavailability and good compliance. OBJECTIVE:To introduce the application status of felodipine sustained-release tablets in the hypertensive treatment of China. METHODS:A computer-based research of CNKI database was performed for literatures published from January 1, 2005

  11. Study on in vitro release and bioequivalence in Beagle dogs of ambroxol hydrochloride push-pull osmotic pump controlled-release tablets%盐酸氨溴索双层渗透泵控释片体外释放及Beagle犬生物等效性

    Institute of Scientific and Technical Information of China (English)

    马银玲; 赵锋; 金晓利; 王静; 曹德英

    2011-01-01

    目的:研究自制片的体外释药行为及体内生物等效性.方法:采用相似因子(f2)为评价指标,考察自制片的体外释放行为;采用单剂量交叉试验考察Beagle犬口服自制片与参比制剂的生物等效性及体内外相关性.结果:自制片体外释放零级特征明显(r=0.992 1)且释药完全(90%).犬体内两制剂生物等效,相对生物利用度(100.0±12.6)%,自制片体内外相关性良好(r=0.98).结论:盐酸氨溴索双层渗透泵控释片具有很好的开发前景.%OBJECTIVE In vitro release and bioequivalence of self-made tablets were evaluated. METHODS Using similar factor (f2) as evaluate index, in vitro release of self-made tablets were evaluated. In vivo study, ultilizing Beagle dogs orally single-dose crossing administrated, the bioequivalence between the self-made controlled-release tablets and marketed sustained capsules and the correlation coefficient between the fraction of absorption in vivo and the release rate in vitro were investigated. RESULTS Self-made tablets possessed character of zero-order release (r = 0.992 1) and drug release completely(90%) in vitro release. The relative bioavailability was (100. 0 ± 12. 6) %. The correlation coefficient between the fraction of absorption in vivo and the release rate in vitro was 0. 98. CONCLUSION Ambroxol hydrochloride push-pull osmotic pump controlled-releasetablets have much developing potential.

  12. In vitro and in vivo evaluation of single-unit commercial conventional tablet and sustained-release capsules compared with multiple-unit polystyrene microparticle dosage forms of ibuprofen

    OpenAIRE

    Tamilvanan, Shunmugaperumal; Sa, Biswanath

    2006-01-01

    The major aims of the present study were (1) to select a multiple-unit formulation that matched the in vitro dissolution profile of single-unit sustained-release commercial capsules, (2) to compare the sustaining/controlling efficacy of the selected multiple-unit formulation with that of the single-unit commercial conventional tablet and sustained-release capsules, and (3) to determine whether an in vitro-in vivo correlation exists for single- and multiple-unit formulations. Ibuprofen (20%–60...

  13. 响应面法优化富马酸喹硫平缓释片处方%Optimization of the Formulation of Fumarate Quetiapine Sustained-release Tablets by Response Surface Methodology

    Institute of Scientific and Technical Information of China (English)

    沈艳; 任丽莉; 王丞; 陈建龙; 陈国广

    2012-01-01

    OBJECTIVE:To optimize the formulation of Fumarate quetiapine sustained-release tablets. METHODS:Using comprehensive score of the cumulate release rate behavior as response value, response surface methodology of 3 factors and 3 levels was used to determine the viscosity and dosage of HPMC and the dose of natrium citricum and lactose, and to explore drug release mechanism in vitro. RESULTS: HPMC K15M was selected as framework material, and the dosage of it was 13.5% ; the doses of sodium citrate and lactose were 9.5% and 14%. Sustained-release tablets in vitro release fitted to the Higuchi equation, the release behavior in vitro is diffusion combined with corrosion. CONCLUSION: The optimized preparation process of Fumarate quetiapine sustained-release tablet is stable, feasible and the tablets have sustained-release behavior.%目的:优化富马酸喹硫平缓释片处方.方法:以累积释放度综合评分作为响应值,采用3因素3水平的响应面法,确定富马酸喹硫平缓释片处方中羟丙甲纤维素(HPMC)的黏度、用量与枸橼酸钠、乳糖的用量,并探讨其体外释药机制.结果:骨架材料选择HPMC K15M,考虑到实际操作便利确定其用量为13.5%,枸橼酸钠用量为9.5%,乳糖用量为14%.缓释片体外释放符合Higuchi方程,释药机制为扩散和溶蚀并存的双重机制.结论:筛选所得的富马酸喹硫平缓释片处方工艺稳定可行,有一定的缓释作用.

  14. Tablet Weaving

    Science.gov (United States)

    Kren, Margo

    1976-01-01

    Article described a weaving technique called tablet weaving, an ancient textile process that provides opportunity for making a variety of items, such as guitar straps, belts, and decorative bands. (Author/RK)

  15. 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

  16. Influence of cellulose polymers type on in vitro controlled release tablets containing theophylline Desenvolvimento e avaliação de comprimidos matriciais de teofilina baseados em ésteres da celulose

    Directory of Open Access Journals (Sweden)

    Evelyn Ojoe

    2007-12-01

    Full Text Available In this study, the effect of ethylcellulose (EC and 6 types of hydroxypropylmethylcellulose (Methocel® K100M, K100MPRCR, K15MPRCR, K4MPRCR, K4M PR and E4MCR on release profile of theophylline from matrix tablets was evaluated. Formulations tablets were prepared by either wet granulation or direct compression technique. The tablets were evaluated for physical characteristics and in vitro release of drug was performed as described in USP 30 ed. (Test 3. All formulations with cellulose polymer produced tablets easily and with physicals characteristics in accordance with official limits. Drug dissolution tests showed that formulations with 15% of Methocel® K4MPR, 15% of Methocel® K4MPRCR and 30% of Ethocel® N10STD, obtained by direct compression method, complied with official specifications, in terms of release profile and diffusion was the main mechanism involved in theophylline delivery.Os efeitos das variáveis das formulações na liberação da teofilina a partir da hidroxipropilmetilcelulose (HPMC e etilcelulose (EC em comprimidos matriciais foram estudados. Formulações de comprimidos foram preparadas pelos métodos da granulação úmida ou compressão direta usando diferentes viscosidades de HPMC. Propriedades físico-químicas dos comprimidos e liberação do fármaco foram estudadas conforme dissolução descrita no Teste 3 da Farmacopéia Americana 30ed. Ensaios "in vitro" mostraram que as formulações com 15% de Methocel® K4MPR, 15% de Methocel® K4MPRCR e 30% de Ethocel® N10STD obtidas por compressão direta apresentaram bom perfil de liberação de teofilina e a difusão foi o principal mecanismo envolvido na liberação.

  17. 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.

  18. 甲硝唑结肠定位缓释片与普通片人体药代动力学对比研究%Pharmacokinetic comparison of metronidazole colon-targeted sustained-release tablets with conventional tablets in healthy volunteers

    Institute of Scientific and Technical Information of China (English)

    毛锐; 徐楠; 秦永平; 王颖; 南峰; 向瑾; 余勤; 梁茂植

    2013-01-01

    plasma was determined by RP-HPLC method, and the pharmacokinetic parameters were calculated by DAS 2.0 software. Statistical analysis was performed by SPSS 17.0 program. Results; The main pharmacokinetic parameters of metronidazole test and reference preparations after a single dose were as follows; Tmax(19.50±3.43) h and (1.52 ±0.56) h, Cmax( 1.083 ±0.710) mg·L-1 and (4.536+0.964) mg·L-1, AUC0-t(22.69 + 15.96) mg·L-1·h and (62.90 + 14.51) mg·L-1·h, t1/2z (10.60 ± 1.62) h and (9.83 ±2.02) h,CL/F (25.22 ±44.90) L·h-1 and (3.21 ±0.70) L·h-1, V/F (378.59 ±661.63) L and (44. 18 ±7.90) L, respectively. The parameters after the multi-dose were: Tmax(11.25 ±4.58) h and (1.05 ±0.57) h, Cmax(3.84 ± 1.32) mg·L-1 and (7.96 ±1.33) mg·L-1, AUC0-t( 116. 81 ±46.90) mg·L-1·h and (115.48 ±31.64) mg·L-1·h, AUCss(39. 88 ±14.33) mg·L-1·h and (60.07+12.03) mg·L-1·h, t1/2z (10.65+1.64) h and (10.13 ±2.27) h, CL/F (1.97 ±0.82) L·h-1 and (1.80+0.55) L·h-1, Vz/F (29.49 ± 11. 04) L and (24.94 ±4.45) L, respectively. Conclusion; Metronidazole colon-targeted sustained-release tablets have delayed Tmax and lower Cmax in healthy Chinese volunteers, showing the typical sustained release characteristics.

  19. 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.

  20. 磷酸川芎嗪缓释片的研制及兔体内生物利用度测定%Preparation of Sustained-Release Tetramethylpyrazine Phosphate Tablet and its Bioavailability on Rabbits

    Institute of Scientific and Technical Information of China (English)

    金昔陆; 陈滨凌; 吴卫江; 顾铮; 江明华; 张智波; 董纪昌

    2000-01-01

    Purpose To prepare the sustained-release tablet of tetramethylpyrazine phosphate with hydroxypropylmethylcelluose(HPMC) as matrix material. Methods The paddle method and the HPLC method were erspectively used determined the cumulative drug released in vitro and the serum concentration in vivo. Results The cumulative drug released in the first hour was about 20%, while in 12 hours it was above 85%. Drug release behavior can be best described by Higuchi equation, and the release rate decreased as the viscosity and/or the amount of HPMC increased. Compared with the market tablet on the rabbits, the sustained release tablet had the decreased peak concentration (P < 0.05 ); the prolonged peak time and mean residence time (P< 0.05). Conclusions The matrix tablet was a good sustained-release dosage form and it had a good in vitro-in vivo correlation.%目的 以羟丙甲纤维素(HPMC)为骨架材料制备持续释药12h的磷酸川芎嗪缓释片。方法 分别采用中国药典1995年版溶出度测定法第2法及高效液相色谱法测定缓释片的体外释放度及兔体内生物利用度。结果 缓释片体外1h释药20%左右,12h释药85%以上,12 h内释药平稳,释药曲线符合Higuchi方程,体外释药受HPMC类型、黏度、用量影响较大。缓释片与市售常释片相比,兔体内峰浓度降低,达峰时间延迟,平均滞留时间延长,吸收程度生物等效。结论 缓释片体内外缓释效果良好,并具有良好的体内外相关性。

  1. Study on ranitidine bismuth citrate intra-gastric floating sustained-release tablets%枸橼酸铋雷尼替丁胃漂浮缓释片的研究

    Institute of Scientific and Technical Information of China (English)

    任新荣; 王志国; 叶冠豪; 冯汉林

    2011-01-01

    Objective To prepare ranitidine bismuth citrate intra-gastric floating sustained-release tablets with hydroxypropylmethylcellulose( HPMC ) as the matrix material. Methods The effects of the specification of HPMC、the amount of stearic acid and Polyvinyl polypyrrolidone( PVPP) 、solidity on the floation and release behavior were investigated by single-factor tests to optimize the formulation; The stability of tablets were examined. Results HPMC (20% ) ,stearic acid ( 35% ) and PVPP ( 2% ) were selected as excipients of the tablets. The beginning floating time of ranitidine bismuth citrate intra-gastric floating sustained-release tablets was less than 10 min,lasting for more than 20 h. The tablets had good behavior of floating and release characteristics. Conclusion The preparation process is simple, which is worth further development and application in the clinic.%目的 以羟丙甲基纤维素(HPMC)为骨架材料研制枸橼酸铋雷尼替丁胃漂浮缓释片.方法 采用单因素法考察HPMC的规格、硬脂酸的用量、交联聚维酮的用量及片剂硬度对片子漂浮性能和释放度的影响,筛选处方;并对研制样品进行初步稳定性实验.结果 优选处方为(ω):骨架材料羟丙甲基纤维索20%,助漂剂硬脂酸35%,交联聚维酮2%.所制得的枸橼酸铋雷尼替丁胃漂浮缓释片10 min内起漂.续漂时间在20 h以上,体外释放均匀缓慢达到了缓释的效果.结论 该制剂制备工艺简单,值得推广使用.

  2. Development of time controlled chronomodulated tablet with swelling and rupturable layers: Optimization of factors influencing lag-time and drug release

    OpenAIRE

    Desai, Mayur; Rishad R. Jivani; Patel, Laxman D; Jivani, Noordin P; Sonagara, Bhavin

    2012-01-01

    Introduction: A tablet system consisting of cores coated with two layers of swelling and rupturable coatings was prepared and evaluated as time controlled chronomodulated tablet. Materials and Methods: Cores containing Montelukast sodium as model drug were prepared by direct compression and then coated sequentially with an inner swelling layer containing a HPMC E 5 and an outer rupturable layer of Eudragit RL/RS (1:1). A three-factor, two-level, full factorial design was used to investigate t...

  3. Evaluating the effect of coating equipment on tablet film quality using terahertz pulsed imaging

    DEFF Research Database (Denmark)

    Haaser, Miriam; Naelapaa, Kaisa; Gordon, Keith C

    2013-01-01

    In this study, terahertz pulsed imaging (TPI) was employed to investigate the effect of the coating equipment (fluid bed and drum coater) on the structure of the applied film coating and subsequent dissolution behaviour. Six tablets from every batch coated with the same delayed release coating...... formulation under recommended process conditions (provided by the coating polymer supplier) were mapped individually to evaluate the effect of coating device on critical coating characteristics (coating thickness, surface morphology and density). Although the traditional coating quality parameter (weight gain......) indicated no differences between both batches, TPI analysis revealed a lower mean coating thickness (CT) for tablets coated in the drum coater compared to fluid bed coated tablets (p...

  4. Matrix tablets: the effect of hydroxypropyl methylcellulose/anhydrous dibasic calcium phosphate ratio on the release rate of a water-soluble drug through the gastrointestinal tract I. In vitro tests.

    Science.gov (United States)

    Mamani, Pseidy L; Ruiz-Caro, Roberto; Veiga, María D

    2012-12-01

    Different hydroxypropyl methylcellulose (HPMC)/anhydrous dibasic calcium phosphate (ADCP) matrix tablets have been developed aiming to evaluate the influence of both components ratio in the control release of a water-soluble drug (theophylline). In order to characterise the matrix tablets, swelling, buoyancy and dissolution studies have been carried out in different aqueous media (demineralised water, progressive pH medium, simulated gastric fluid, simulated intestinal fluid and simulated colonic fluid). The HPMC/ADCP ratio has turned out to be the determinant in the matrix behaviour: the HPMC characteristic swelling behaviour was modulated, in some cases, by the ADCP characteristic acidic dissolution. When the HPMC/ADCP ratio was ≥0.69, buoyancy, continuous swelling and low theophylline dissolution rate from the matrices (H1, H2 and H3) were observed in all dissolution media. Consequently, these formulations could be adequate as gastro-retentive drug delivery systems. Additionally, HPMC/ADCP ratio ≤0.11 (H5 and H6) induces a pH-dependent drug release which could be applied to design control drug release enteric formulations (with a suitable enteric coating). Finally, a HPMC/ADCP ratio between 0.11 and 0.69 (H4) yield a gastrointestinal controlled drug release, due to its time-dependent buoyancy (7 h) and a total drug delivery in 17 h in simulated colonic fluid.

  5. Impact of active ingredients on the swelling properties of orally disintegrating tablets prepared by microwave treatment.

    Science.gov (United States)

    Sano, Syusuke; Iwao, Yasunori; Kimura, Susumu; Noguchi, Shuji; Itai, Shigeru

    2014-07-01

    The impact of different active pharmaceutical ingredients (APIs) loading on the properties of orally disintegrating tablets (ODTs) prepared according to our previously reported microwave (MW) treatment process was evaluated using famotidine (FAM), acetaminophen (AAP), and ibuprofen (IBU). None of the APIs interrupted the tablet swelling during the MW treatment and the tablet hardness were improved by more than 20 N. MW treatment, however, led to a significant increase in the disintegration time of the ODTs containing IBU, but it had no impact on that of the ODTs containing FAM or AAP. This increased disintegration time of the ODTs containing IBU was attributed to the relatively low melting point of IBU (Tm=76 °C), with the IBU particles melting during the MW treatment to form agglomerates, which interrupted the penetration of water into the tablets and delayed their disintegration. The effects of the MW treatment on the chemical stability and dissolution properties of ODTs were also evaluated. The results revealed that MW treatment did not promote the degradations of FAM and AAP or delay their release from the ODTs, while dissolution of the ODTs containing IBU delayed by MW treatment. Based on these results, the MW method would be applicable to the preparation of ODTs containing APIs with melting points higher than 110 °C. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. 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...

  7. Optimizing the preparation of doxycycline hydrochloride sustained release tablet using response surface methodology%响应面法优化盐酸多西环素缓释片处方工艺

    Institute of Scientific and Technical Information of China (English)

    喻佰启; 王永禄; 殷海翔; 王栋; 吕贝贝; 李学明

    2014-01-01

    目的:利用响应面分析法优化盐酸多西环素缓释片处方。方法通过单因素考察确定对释放度影响最大的3个因素:羟丙基甲基纤维素(hydroxypropyl methyl cellulose,HPMC)的用量、粘合剂聚乙烯吡咯烷酮-K30(polyvinylpyrrolidone-K30,PVP-K30)的浓度、乳糖与微晶纤维素(microcrystalline cellulose,MCC)的比例,以2 h、4 h、8 h 的释放度综合评分作为响应值,利用 Box-Benhnken中心组合实验设计原理,采用三因素三水平的响应面分析法,确定各处方的用量。结果筛选得到优化的处方为:HPMC K15质量分数为片重的30%、粘合剂PVP-K30浓度为10%、乳糖与MCC比例为13,其体外释药行为较理想。结论筛选所得的盐酸多西环素缓释片处方工艺稳定可行。%Objective In this article Response Surface Analysis(RSA)was applied to optimize the formulation of doxycycline hydrochloride sustained release tablet.Methods Single factor exploration was used to determine the three factors which have the greatest impact on the release rate.The three factors were the dosage of the HPMC in the total weight of the tablet,the concentration of PVP-K30,and the ratio of lactose to microcrystalline cellulose,respectively.The composite score of the release behaviour was taken as the response value.The dosage of the ingredients were determined by Box-Benhnke design principles and 3 factors and 3 levels.Results The optimized formulation and process are as follows:the dosage of the HPMC in the total weight of the tablet was 30%;the concentration of PVP-K30 was 10%,and the ratio of lactose to microcrystalline cellulose was 13.The release behavior in vitro is ideal.Conclusion The optimized preparation process of doxycycline hydrochloride sustained release tablet is stable,highly efficient and suitable for industrial production.

  8. 复方丹参脉冲片的制备工艺及体外释药特性研究%Preparation and release characterization in vitro of pulsed-release tablets of compound Danshen

    Institute of Scientific and Technical Information of China (English)

    李元波; 薛立安; 殷建华; 彭熙琳; 侯世祥

    2009-01-01

    目的:根据冠心病发病的时辰节律性,以复方丹参方的药效物质和作用机制为基础,制备复方丹参脉冲片并考察其体外释药特性.方法:脉冲片由含有复方丹参药物、丁二酸、羧甲基淀粉钠、乳糖和微晶纤维素的片芯外包3层衣膜构成,内层为隔离层,由Eudragit RL 100构成;中间层为溶胀层,由HPMC E5构成;外层为控释层,由Eudragit RS 100,RL 100和EC的混合物构成.结果:5种有效成分丹参素、原儿茶醛、人参皂苷Rg_1,Rb_1、三七皂苷R_1以相近的释药规律释药,脉冲片在膨胀作用的基础上,利用渗透泵、有机酸诱导和扩散机理在设定的时滞后快速释药.结论:成功制得一定时滞后快速释放的复方丹参脉冲片用于冠心病的防治,可减少"心血管事件"发生的几率.%Objective: To prepare pulsed-release tablet (PTS) according to the rhythm of coronary heart disease based on efficacy material and the mechanism of compound Danshen. Method: PTS were achieved by coating the core which contains drugs, CMS-Na, lactose, succinic acid and MCC with separation layer (Eudragit RL), swelling layer (HPMC E5), and controlled-release membrane (Eudragit RS-RL-EC). Result: The results of in vitro experiments showed that no difference was observed among the profiles of Danshensu, protocatechuic aldehyde, ginsenoside Rg_1, Rb_1, notoginsenoside R_1 release from the two-step release system. And it indicated that swelling was the basis and prerequisite for drug release from PTS, and the diffusion, organic acid-induced, and osmotic pumping mechanism were involved in drug release, but the latter they were the dominant factors. Conclusion: Successfully obtained the PTS of a certain lag-time behind the rapid release which indicate that after bed time administration of such device, the drug plasma concentration-time curve CAN meet the requirements of chronotherapy of cardiovascular disease.

  9. 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.

  10. Process analytical technology: chemometric analysis of Raman and near infra-red spectroscopic data for predicting physical properties of extended release matrix tablets.

    Science.gov (United States)

    Shah, Rakhi B; Tawakkul, Mobin A; Khan, Mansoor A

    2007-05-01

    The purpose of this work was to develop a correlation between pharmaceutical properties such as hardness, porosity, and content with prediction models employed using Raman and near infra-red (NIR) spectroscopic methods. Metoprolol tartrate tablets were prepared by direct compression and wet granulation methods. NIR spectroscopy and chemical imaging, and Raman spectra were collected, and hardness, porosity, and dissolution were measured. The NIR PLS model showed a validated correlation coefficient of >0.90 for the predicted versus measured porosity, hardness, and amount of drug with raw and second derivative NIR spectra. Raman spectra correlated porosity of the tablets using raw data for directly compressed tablets and wet granulated tablets (r(2) > 0.90). A very close root-mean square error of calibration (RMSEC) and root-mean square error of prediction (RMSEP) values were found in all the cases indicating validity of the calibration models. Raman spectroscopy was used for the first time to predict physical quality attribute such as porosity successfully. Chemical imaging utilizing NIR detector also demonstrated to show physical changes due to compression differences. In conclusion, sensor technologies can be potentially used to predict physical parameters of the matrix tablets.

  11. 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

  12. Microstructure of Tablet-Pharmaceutical Significance, Assessment, and Engineering.

    Science.gov (United States)

    Sun, Changquan Calvin

    2017-05-01

    To summarize the microstructure - property relationship of pharmaceutical tablets and approaches to improve tablet properties through tablet microstructure engineering. The main topics reviewed here include: 1) influence of material properties and manufacturing process parameters on the evolution of tablet microstructure; 2) impact of tablet structure on tablet properties; 3) assessment of tablet microstructure; 4) development and engineering of tablet microstructure. Microstructure plays a decisive role on important pharmaceutical properties of a tablet, such as disintegration, drug release, and mechanical strength. Useful information on mechanical properties of a powder can be obtained from analyzing tablet porosity-pressure data. When helium pycnometry fails to accurately measure true density of a water-containing powder, non-linear regression of tablet density-pressure data is a useful alternative method. A component that is more uniformly distributed in a tablet generally exerts more influence on the overall tablet properties. During formulation development, it is highly recommended to examine the relationship between any property of interest and tablet porosity when possible. Tablet microstructure can be engineered by judicious selection of formulation composition, including the use of the optimum solid form of the drug and appropriate type and amount of excipients, and controlling manufacturing process.

  13. 羟考酮控释片用于滴定中度癌痛的疗效观察%Effect of the Titration of Oxycodone Controlled-release Tablets on Moderate Pain

    Institute of Scientific and Technical Information of China (English)

    张颖一; 韩廷; 汪颖; 刘璐; 王宁; 王雅杰

    2011-01-01

    目的 评价盐酸羟考酮控释片对中度癌性疼痛滴定期的疗效优势.方法 本研究选取67例无阿片类药物使用史的中度癌痛患者,随机分为两组,A组(35例)使用盐酸羟考酮控释片5mg作为初始剂量对其进行滴定,B组(32例)使用硫酸吗啡控释片10mg滴定,达到疼痛明显缓解或完全缓解后进入维持期.观察期4天,以服药后1h的NRS评分(numerical rating scale,数字模拟评分法)为主要观察指标,将两组疗效进行对比.结果 给药1h后盐酸羟考酮控释片组中有1例患者疼痛获得完全缓解,12例症状明显缓解,11例达到中度缓解,总有效率高达68.6% ;硫酸吗啡控释片组有4例获得明显缓解,10例疼痛中度缓解,总有效率43.8%.服药第4天两组患者疼痛总缓解率均在90%左右.结论 在迅速缓解疼痛方面,盐酸羟考酮控释片组具有优势;而在维持期控制疼痛方面,两组疗效相当.%Objective To evaluate the efficacy advantage of oxycodone hydrochloride controlled - release tablets for moderate cancer pain. Methods This study selected 67 patients suffering from moderate pain without a history of opioid. They were randomly divided into 2 groups. A group (35 cases) used the oxycodone hydrochloride controlled - release tablets 5mg as the initial dose for titration, and B group ( 32 cases) used the morphine sulfate controlled - release tablets 10mg. All of them entered the maimenance phase after been titrated to achieve obvious relief or complete relief of pain. Within 4 - day observation period, we got the NRS score ( Numerical Rating Scale,digital analog scale) [2] the first hour after taking the pills as the main observation index to compare the two groupa. Results In the group of oxycodone hydrochloride controlled - release tablets, 1 patient achieved complete relief after 1 hour administration, 12 were obviously relieved, and 11 were moderate relieved The total efficiency was up to 68.6% . At the same time, in the

  14. TABLET COATING TECHNIQUES: CONCEPTS AND RECENT TRENDS

    OpenAIRE

    Gupta Ankit; Bilandi Ajay; Kataria Mahesh Kumar; Khatri Neetu

    2012-01-01

    Tablet coating is a common pharmaceutical technique of applying a thin polymer-based film to a tablet or a granule containing active pharmaceutical ingredients (APIs). Solid dosage forms are coated for a number of reasons, the most important of which is controlling the release profiles. The amount of coating on the surface of a tablet is critical to the effectiveness of the oral dosage form. Tablets are usually coated in horizontal rotating pans with the coating solution sprayed onto the free ...

  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. 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

  17. In vitro and in vivo evaluation of single-unit commercial conventional tablet and sustained-release capsules compared with multiple-unit polystyrene microparticle dosage forms of Ibuprofen.

    Science.gov (United States)

    Tamilvanan, Shunmugaperumal; Sa, Biswanath

    2006-09-01

    The major aims of the present study were (1) to select a multiple-unit formulation that matched the in vitro dissolution profile of single-unit sustained-release commercial capsules, (2) to compare the sustaining/controlling efficacy of the selected multiple-unit formulation with that of the single-unit commercial conventional tablet and sustained-release capsules, and (3) to determine whether an in vitro-in vivo correlation exists for single- and multiple-unit formulations. Ibuprofen (20%-60% wt/wt)-loaded multiple-unit polystyrene microparticles were prepared by an emulsion-solvent evaporation method from an aqueous system. The in vitro release profiles obtained in phosphate buffer of pH 6.8 for drug-loaded polystyrene microparticles and for commercial sustained-release capsules (Fenlong-SR, 400 mg) were compared. Since the microparticles with 30% ibuprofen load showed a release profile comparable to that of the Fenlong-SR release profile, the microparticles with this drug load were considered to be the optimized/selected formulation and, therefore, were subjected to stability study and in vivo study in human volunteers. A single-dose oral bioavailability study revealed significant differences in C(max), T(max), t(1/2a), t(1/2e), K(a), K(e), and AUC between the conventional tablet and optimized or Fenlong-SR capsule dosage forms. However, all the parameters, with the exception of K(a) along with relative bioavailability (F) and retard quotient (R(Delta)), obtained from the optimized ibuprofen-loaded microparticles were lower than that obtained from the commercial Fenlong-SR formulation. Furthermore, linear relationship obtained between the percentages dissolved and absorbed suggests a means to predict in vivo absorption by measuring in vitro dissolution.

  18. 尼莫地平双层渗透泵片的制备及其体外释放度考察%Preparation and in Vitro Release of Nimodipine Two-layer Osmotic Pump Tablets

    Institute of Scientific and Technical Information of China (English)

    张冠男; 白靖; 曹德英

    2012-01-01

    目的:制备尼莫地平双层渗透泵控释片,并考察其体外释放度.方法:以体外累积释放度作为评价指标,以含药层助悬剂聚氧化乙烯(PEO)200000的用量、促渗剂氯化钠的用量、致孔剂聚乙二醇(PEG)2000的含量及包衣增重为考察因素,采用正交设计优化尼莫地平双层渗透泵控释片的处方;参照《中国药典》释放度测定法第二法测定其体外释放度.结果:最优处方为含药层PEO 200000 80 mg,氯化钠10 mg,助推层PEO 5000000 40 mg,PEG 2000用量8%,包衣增重8%.所制片剂释药速率恒定,12 h的体外累积释放度达90%以上.结论:尼莫地平双层渗透泵片工艺稳定,体外释放行为在12 h内具有明显的零级释放特征(r=0.990 3),达到了控释要求.%OBJECTIVE: To prepare Nimodipine two-layer osomatic pump tablets and to study the in vitro release of it. METHODS: The preparation formula of Nimodipine two-layer osomatic pump tablets was optimized by orthogonal design with accumulative release rate as index using the amount of PEO 200000 and osmotic promoter NaCl, the content of PEG 2000 and the weight growth of coating membrane as factors. The in vitro release of preparation was determined in accordance with the method stated in Chinese Pharmacopeia. RESULTS: The optimal formula was as follows: PEO 200000 in drug-containing layer of 80 mg, NaCl of 10 mg, PEO 5000000 in push layer of 40 mg, PEG 2000 of 8%, weight gain for coating membrane of 8%. The release rate was constant, the accumulative release rate was above 90% in 12 h. CONCLUSION: The preparation of Nimodipine two-layer osomatic pump tablets is stable, and the in vitro drug release shows excellent zero-release profile within 12 h (r=0.990 3), and in line with controlled requirements.

  19. 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

  20. Microspheres and tablet in capsule system: A novel chronotherapeutic system of ketorolac tromethamine for site and time specific delivery

    Science.gov (United States)

    Shahi, Priya; Kumari, Neeraj; Pathak, Kamla

    2015-01-01

    The objective of the present work was to develop a novel delivery system of ketorolac tromethamine (KT) for dual pulse release based on microspheres and tablet in capsule system (MATICS) as a treatment modality for rheumatoid arthritis. The design consisted of an impermeable hard gelatin capsule body, in which a core tablet was (second pulse) placed in the bottom and sealed with a hydrogel plug (HP2). The body was locked with enteric coated cap filled with KT microspheres (first pulse). The microspheres for first pulse were selected by screening the formulations (M1–M6), and M1 with least particle size of 96.38 ± 0.05 μm, highest drug loading of 25.10% ± 0.28% and maximum CDR of 89.32% ± 0.21% was adjudged as the best formulation. The HP2 tablet was selected based on its capability for maintaining a lag period of 6 h. The selection criterion of the second pulse (core tablet: T3) was its disintegration time of 4.02 ± 0.53 min and CDR of 99.10% ± 0.32% in 30 min. All the optimized formulations were assembled in accordance with the proposed design to form pulsatile MATICS and evaluated for in vitro release. MATICS displayed delayed sustained CDR of 80.15% in 8 h from the first pulse (microspheres) after a lag time of 2 h, followed by 97.05% KT release from second pulse (core tablet) in simulated colonic fluid within 10 h. Conclusively, in vitro pulsatile release was a rational combination of delayed sustained and immediate release of KT that has the potential to combat the pain at night and morning stiffness. Incorporation of two pulses in one system offers a reduction in dose frequency and better pain management. PMID:26258058

  1. 硫酸吗啡控释片联合丁丙诺啡舌下含片用于中重度癌痛患者的疗效观察%Efficacy of combination of morphine sulfate controlled-release tablet and buprenorphine sublingual tablet in moderate to severe cancer pain patient

    Institute of Scientific and Technical Information of China (English)

    周亮; 孙亮; 王海燕; 董彦鹏; 武林鑫; 孙莉

    2015-01-01

    目的 观察硫酸吗啡控释片联合丁丙诺啡治疗中重度癌痛的临床疗效,探讨临床合理治疗晚期癌痛的有效方法. 方法 选择止痛门诊的癌症晚期疼痛患者,视觉模拟评分(visual analog scale,VAS)>3分,用单一吗啡控释片治疗后,VAS评分仍>3分,止痛效果欠佳的150例患者,采用随机数字表法分为两组,每组75例:吗啡控释片组(M组),使用单一硫酸吗啡控释片;吗啡控释片联合丁丙诺啡组(MB组),采用硫酸吗啡控释片+丁丙诺啡.通过对两组止痛效果、副作用、生活质量及患者对镇痛治疗满意度的比较,探讨联合用药治疗晚期癌痛的优点和可行性. 结果 联合用药较单一用药镇痛效果显著,中重度VAS评分例数明显减少(M组/MB组:中度26/10,重度4/0)(P<0.05);恶心、呕吐等副作用的发生例数明显减少(M组/MB组:恶性呕吐12/2,嗜睡4/2,呼吸抑制9/4,排尿困难8/3,便秘8/4)(P<0.05);患者对镇痛效果的满意度明显提高(M组/MB组:很满意10/14,满意36/47)(P<0.05);生活质量明显改善[M组/MB组:睡眠(5.5±1.2)/(4.6±0.7),情绪(5.4±0.5)/(4.6±1.2),日常活动(5.1±0.4)/(4.9±0.5),社交活动(5.5±0.4)/(4.8±1.6)](P<0.05).结论 硫酸吗啡控释片联合丁丙诺啡治疗晚期癌痛可以提高镇痛效果,降低副作用的发生率,提高患者的生活质量.%Objective To investigate the efficacy of combination of morphine sulfate controlled-release tablet and buprenorphine sublingual tablet in patients with moderate to severe cancer pain,and explore effective analgesic therapies for advanced cancer pain patients.Methods One hundred and fifty patients with advanced cancer pain whose visual analog scale (VAS) scores were greater than 3 points and VAS scores were still greater than 3 points after treated with controlled-release tablet of morphine alone were randomly divided into two groups (n=75):controlled-release morphine tablet alone group (M group) and conbination use

  2. Hydrochloride oxycodone sustained-release tablet for titration in cancer pain management%盐酸羟考酮缓释片用于癌痛治疗的滴定

    Institute of Scientific and Technical Information of China (English)

    杨平(综述); 王昆(审校)

    2015-01-01

    Oxycodone sustained-release tablet is a new formulation of potent opioids, which are characterized by their exact anal-gesic effect, high safety for oral administration, and slight adverse drug reaction. Oxycodone improves the quality of life of patients with cancer pains and is among the selected drugs used for controlling moderate and severe cancer pains. Relief from prolonged pain is achieved by adjusting the dose of Oxycontin (oxycodone hydrochloride) sustained-release tablet according to its pharmacological char-acteristics. The details are reviewed in this article.%盐酸羟考酮缓释片作为一种新型的强阿片类镇痛药,镇痛效果确切、口服安全性高、不良反应轻微,持续应用可提高癌痛患者的生存质量,是临床治疗中重度癌痛的首选药物之一。针对盐酸羟考酮缓释片治疗癌痛的药理特点,近年国内外将其用于癌痛治疗过程中的剂量调整,取得了很好的效果,本文对此进行综述。

  3. 饮食对石杉碱甲缓释片药代动力学的影响研究%Effect of Food Intake on Pharmacokinetics of Huperzine A Sustained--Release Tablets in Healthy Volunteers

    Institute of Scientific and Technical Information of China (English)

    魏振满; 丁晋彪; 胡琳; 陈红鸽; 吴荣荣; 刘万卉; 沙春洁

    2011-01-01

    Objective To assess the effect of high protein and fat diet on the pharmacokinetic profiles of Huperzine A Sustained - Release Tablets by LC - MS - MS. Methods The study was conducted according to an open,randomized,2 - period crossover design with a 7 - day washout interval,which was administrated with a Huperzine A Sustained - Release Tablets on an empty stomach or after meal. The plasma concentrations were determined by LC - MS/MS. Pharmacokinetic parameters were obtained using DAS program. Results The major pharmacokinetic parameters of the single doses study on an empty stomach and after meal were as follows: Cmax were (0. 873 ±0. 117 )ng/mL and ( 1. 07 ±0. 19 )ng/mL, tmax were ( 4. 6±2. 3 )h and ( 6. 0±1. 8 )h. AUCo_ t were ( 18. 7 ±3. 0 )ng · h/mL and ( 19. 4±3. 7 )ng · h/mL, AUC0_∞ were ( 20. 2±3. 5 )ng · h/mL and ( 20. 6±3. 9)ng · h/mL, respectively. As compared with fasting state, the relative bioavailability of fed state was determined as (97.5 ±10. 8 )% , Cmax increased and tmax delayed slightly. Conclusion This method is sensitive,convenient and proved to be suitable for clinical investigation of huperzine A pharmacokinetics. High protein and fat diet could influence Huperzine A Sustained-Release Tablets’s tmax and Cmax slightly.%目的 评价饮食对健康人体口服石杉碱甲缓释片药代动力学的影响.方法 12名受试者随机分为2组,6名受试者空腹12口服石杉碱甲缓释片200μg,另6名进高脂餐后口服石杉碱甲缓释片200μg.第1周期结束后,经过7 d的清洗期,两组受试者交叉试验.采用液相色谱-串联质谱法测定血浆药物浓度,药代动力学参数采用DAS软件处理.结果 进食前后口服石杉碱甲缓释片的血药峰浓度(Cmax)分别为(0.873±0.117)ng/mL和(1.07±0.19)ng/mL,达峰时间(tmzx)分别为(4.6 ±2.3)h和(6.0 ±1.8)h,O~t药时曲线下面积(AUCo-t)分别为(18.7±3.0)ng·h/mL和(19.4±3.7)ng·h/mL,O~∞药时曲线下面积(AUCo-∞)分别为(20

  4. Determining the polymer threshold amount for achieving robust drug release from HPMC and HPC matrix tablets containing a high-dose BCS class I model drug: in vitro and in vivo studies.

    Science.gov (United States)

    Klančar, Uroš; Baumgartner, Saša; Legen, Igor; Smrdel, Polona; Kampuš, Nataša Jeraj; Krajcar, Dejan; Markun, Boštjan; Kočevar, Klemen

    2015-04-01

    It is challenging to achieve mechanically robust drug-release profiles from hydrophilic matrices containing a high dose of a drug with good solubility. However, a mechanically robust drug release over prolonged period of time can be achieved, especially if the viscosity and amount of the polymer is sufficiently high, above the "threshold values." The goal of this research was to determine the hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC) polymer threshold amount that would enable robust drug release from matrix tablets containing a high dose of levetiracetam as a class I model drug according to the Biopharmaceutical Classification System (BCS). For this purpose, formulations containing HPC or HPMC of similar viscosity range, but in different amounts, were prepared. Based on the dissolution results, two final formulations were selected for additional in vitro and in vivo evaluation to confirm the robustness and to show bioequivalence. Tablets were exposed to various stress conditions in vitro with the use of different mechanically stress-inducing dissolution methods. The in vitro results were compared with in vivo results obtained from fasted and fed bioequivalence studies. Under both conditions, the formulations were bioequivalent and food had a negligible influence on the pharmacokinetic parameters C max and area under the curve (AUC). It was concluded that the drug release from both selected formulations is mechanically robust and that HPC and HPMC polymers with intrinsic viscosities above 9 dL/g and in quantities above 30% enable good mechanical resistance, which ensures bioequivalence. In addition, HPC matrices were found to be more mechanically robust compared to HPMC.

  5. Bioequivalence of nicotinic acid sustained-release tablets in healthy volunteers%烟酸缓释片在健康人体的生物等效性

    Institute of Scientific and Technical Information of China (English)

    葛苗苗; 卫乐乐; 方凯; 黄露; 黎维勇

    2011-01-01

    目的 研究烟酸缓释片(广谱凋血脂药)在健康人体的药代动力学,并评价其生物等效性.方法 30名男性健康志愿者随机交叉单剂量口服试验制剂或参比制剂1.5 g,用高效液相色谱-串联质谱法测定血浆中烟酸浓度.结果 单剂量口服烟酸试验制剂或参比制剂1.5 g,药代动力学参数如下:AUC0-t分别为(20.05±16.29),(21.61±18.06)μg·h·mL-1;AUC0-∞分别为(20.81±16.30),(22.81±18.47)μg·h·mL-1;Cmax分别为(8.72±6.81),(9.57±8.22)μg·mL-1;tmax分别为(4.41±1.34),(4.31±1.29)h;t1/2分别为(4.00±4.90),(2.91±3.39)h,烟酸缓释片的相对生物利用度为(96.6±30.9)%.结论 受试制剂与参比制剂生物等效.%Objective To study the pharmacokinetics of nicotinic acid sustained-release tablets in healthy volunteers and evaluate the bioequivalence. Methods Single oral dose ( 1.5 g of test and reference formulations) were given to 30 volunteers in an open randomized crossover way.The concentrations of nicotinic acid in plasma were determined by HPLC- MS/MS. The pharmacokinetic parameters were calculated and the bioequivalence of two formulations were evaluated by DAS program.Results The main pharmacokinetic parameters of test and reference preparations obtained from single oral dose were as follows: AUC0-t were (20. 05±16.29),(21.61 ± 18.06) μg · h · mL-1;AUC0-∞ were (20. 81 ± 16. 30 ), ( 22. 81 ± 18.47 ) μg · h · mL - 1; Cmax were ( 8. 72 ±6.81),(9.57 ±8.22) μg · mL-1;tmax were(4.41 ± 1.34), (4.31 ±1.29)h; t1/2 were ( 4. 00 ±4.90),(2.91 ±3.39)h. Conclusion The two preparations were bioequivalent.

  6. Efficacy Comparison of Oxycodone Hydrochloride Controlled-release Tablets and Tramadol Hydrochloride Sustained-release Tablets in the Treatment of Moderate Cancer Pain%盐酸羟考酮缓释片与曲马多缓释片治疗中度癌痛的近期疗效比较

    Institute of Scientific and Technical Information of China (English)

    张锦丰; 杨权烈; 吴国武; 郭维新; 张英燕; 古银芳; 叶敏

    2014-01-01

    目的:比较盐酸羟考酮缓释片(奥施康定)与曲马多缓释片(奇曼丁)治疗中度癌痛的近期疗效。方法将100例伴有中度癌痛患者随机分为奥施康定组和奇曼丁组,每组50例,分别接受奥施康定和奇曼丁的治疗。结果奥施康定组治疗后第3、7、10天的NRS评分均较奇曼丁组低,且奥施康定组治疗后第3天NRS评分下降幅度较奇曼丁组明显( P﹤0.05);奥施康定组的CR率和有效率分别为34.0%和100.0%,明显高于奇曼丁组的10.0%和84.0%(P﹤0.05);2组毒副反应发生率比较差异均无统计学意义(P﹥0.05)。结论与奇曼丁相比,应用奥施康定治疗中度癌痛患者,能更快更有效缓解疼痛,而未增加毒副反应。%Objective To compare the efficacy and tolerability of oxycodone hydrochloride controlled-release tab-lets( oxycodone)and tramadol hydrochloride sustained-release tablets( tramadol)in the treatment of patients with moderate cancer pain. Methods A total of 100 patients with moderate cancer pain were randomly divided into two groups,50 patients of the oxycodone group was treated with oxycodone,and 50 patients of the tramadol group was treated with tramadol. Results The NRS scorce in the oxy-codone group had declined more significantly than the tramadol group,and the decrease was statistically significant in the first three days (P﹤0. 05). The CR rate and the response rate in the oxycodone group were significantly better than those of the tramadol group (34.0% vs10.0% and100.0% vs84.0%)(P﹤0.05).There was no statistic significant difference in the toxicity incidences be-tween the two groups(P﹥0. 05). Conclusion Compared with tramadol,oxycodone is faster and more effective to relieve pain,and don’t increase the toxicities.

  7. Evaluation of quick disintegrating calcium carbonate tablets.

    Science.gov (United States)

    Fausett, H; Gayser, C; Dash, A K

    2000-07-02

    The purpose of this investigation was to develop a rapidly disintegrating calcium carbonate (CC) tablet by direct compr