Biowaiver monograph for immediate-release solid oral dosage forms: acetylsalicylic acid.

Science.gov (United States)

Dressman, Jennifer B; Nair, Anita; Abrahamsson, Bertil; Barends, Dirk M; Groot, D W; Kopp, Sabine; Langguth, Peter; Polli, James E; Shah, Vinod P; Zimmer, Markus

2012-08-01

A biowaiver monograph for acetylsalicylic acid (ASA) is presented. Literature and experimental data indicate that ASA is a highly soluble and highly permeable drug, leading to assignment of this active pharmaceutical ingredient (API) to Class I of the Biopharmaceutics Classification System (BCS). Limited bioequivalence (BE) studies reported in the literature indicate that products that have been tested are bioequivalent. Most of the excipients used in products with a marketing authorization in Europe are not considered to have an impact on gastrointestinal motility or permeability. Furthermore, ASA has a wide therapeutic index. Thus, the risks to the patient that might occur if a nonbioequivalent product were to be incorrectly deemed bioequivalent according to the biowaiver procedure appear to be minimal. As a result, the BCS-based biowaiver procedure can be recommended for approval of new formulations of solid oral dosage forms containing ASA as the only API, including both multisource and reformulated products, under the following conditions: (1) excipients are chosen from those used in ASA products already registered in International Conference on Harmonization and associated countries and (2) the dissolution profiles of the test and the comparator products comply with the BE guidance. Copyright © 2012 Wiley Periodicals, Inc.

Continuous powder feeding for pharmaceutical solid dosage form manufacture: a short review.

Science.gov (United States)

Blackshields, Caroline A; Crean, Abina M

2018-07-01

There has been a noticeable shift from pharmaceutical batch processing towards a more continuous mode of manufacture for solid oral dosage forms. Continuous solid oral dose processes would not be possible in the absence of a highly accurate feeding system. The performance of feeders defines the content of formulations and is therefore a critical operation in continuous manufacturing of solid dosage forms. It was the purpose of this review to review the role of the initial powder feeding step in a continuous manufacturing process. Different feeding mechanisms are discussed with a particular emphasis on screw controlled loss in weight (LIW) feeding. The importance of understanding the physical properties of the raw materials and its impact on the feeding process is reviewed. Prior knowledge of materials provides an initial indication of how the powders will behave through processing and facilitates in the selection of the most suitable (i) feeder (capacity), (ii) feeding mechanism, and (iii) in the case of screw feeder - screw type. The studies identified in this review focus on the impact of material on powder feeding performance.

Material Considerations for Fused-Filament Fabrication of Solid Dosage Forms

Directory of Open Access Journals (Sweden)

Evert Fuenmayor

2018-04-01

Full Text Available Material choice is a fundamental consideration when it comes to designing a solid dosage form. The matrix material will ultimately determine the rate of drug release since the physical properties (solubility, viscosity, and more of the material control both fluid ingress and disintegration of the dosage form. The bulk properties (powder flow, concentration, and more of the material should also be considered since these properties will influence the ability of the material to be successfully manufactured. Furthermore, there is a limited number of approved materials for the production of solid dosage forms. The present study details the complications that can arise when adopting pharmaceutical grade polymers for fused-filament fabrication in the production of oral tablets. The paper also presents ways to overcome each issue. Fused-filament fabrication is a hot-melt extrusion-based 3D printing process. The paper describes the problems encountered in fused-filament fabrication with Kollidon® VA64, which is a material that has previously been utilized in direct compression and hot-melt extrusion processes. Formulation and melt-blending strategies were employed to increase the printability of the material. The paper defines for the first time the essential parameter profile required for successful 3D printing and lists several pre-screening tools that should be employed to guide future material formulation for the fused-filament fabrication of solid dosage forms.

21 CFR 520.1696 - Penicillin oral dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin oral dosage forms. 520.1696 Section 520.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1696 Penicillin oral...

21 CFR 520.45 - Albendazole oral dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Albendazole oral dosage forms. 520.45 Section 520.45 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.45 Albendazole oral...

21 CFR 520.905 - Fenbendazole oral dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fenbendazole oral dosage forms. 520.905 Section 520.905 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Fenbendazole oral dosage forms. ...

Zein as a Pharmaceutical Excipient in Oral Solid Dosage Forms: State of the Art and Future Perspectives.

Science.gov (United States)

Berardi, Alberto; Bisharat, Lorina; AlKhatib, Hatim S; Cespi, Marco

2018-05-07

Zein is the main storage protein of corn and it has several industrial applications. Mainly in the last 10-15 years, zein has emerged as a potential pharmaceutical excipient with unique features. Zein is a natural, biocompatible and biodegradable material produced from renewable sources. It is insoluble, yet due to its amphiphilic nature, it has self-assembling properties, which have been exploited for the formation of micromicroparticle and nanoparticle and films. Moreover, zein can hydrate so it has been used in swellable matrices for controlled drug release. Other pharmaceutical applications of zein in oral drug delivery include its incorporation in solid dispersions of poorly soluble drugs and in colonic drug delivery systems. This review describes the features of zein significant for its use as a pharmaceutical excipient for oral drug delivery, and it summaries the literature relevant to macroscopic zein-based oral dosage forms, i.e. tablets, capsules, beads and powders. Particular attention is paid to the most novel formulations and applications of zein. Moreover, gaps of knowledge as well as possible venues for future investigations on zein are highlighted.

Drop-on-Demand System for Manufacturing of Melt-based Solid Oral Dosage: Effect of Critical Process Parameters on Product Quality.

Science.gov (United States)

Içten, Elçin; Giridhar, Arun; Nagy, Zoltan K; Reklaitis, Gintaras V

2016-04-01

The features of a drop-on-demand-based system developed for the manufacture of melt-based pharmaceuticals have been previously reported. In this paper, a supervisory control system, which is designed to ensure reproducible production of high quality of melt-based solid oral dosages, is presented. This control system enables the production of individual dosage forms with the desired critical quality attributes: amount of active ingredient and drug morphology by monitoring and controlling critical process parameters, such as drop size and product and process temperatures. The effects of these process parameters on the final product quality are investigated, and the properties of the produced dosage forms characterized using various techniques, such as Raman spectroscopy, optical microscopy, and dissolution testing. A crystallization temperature control strategy, including controlled temperature cycles, is presented to tailor the crystallization behavior of drug deposits and to achieve consistent drug morphology. This control strategy can be used to achieve the desired bioavailability of the drug by mitigating variations in the dissolution profiles. The supervisor control strategy enables the application of the drop-on-demand system to the production of individualized dosage required for personalized drug regimens.

Transforming lipid-based oral drug delivery systems into solid dosage forms: an overview of solid carriers, physicochemical properties, and biopharmaceutical performance.

Science.gov (United States)

Tan, Angel; Rao, Shasha; Prestidge, Clive A

2013-12-01

The diversity of lipid excipients available commercially has enabled versatile formulation design of lipid-based drug delivery systems for enhancing the oral absorption of poorly water-soluble drugs, such as emulsions, microemulsions, micelles, liposomes, niosomes and various self-emulsifying systems. The transformation of liquid lipid-based systems into solid dosage forms has been investigated for several decades, and has recently become a core subject of pharmaceutical research as solidification is regarded as viable means for stabilising lipid colloidal systems while eliminating stringent processing requirements associated with liquid systems. This review describes the types of pharmaceutical grade excipients (silica nanoparticle/microparticle, polysaccharide, polymer and protein-based materials) used as solid carriers and the current state of knowledge on the liquid-to-solid conversion approaches. Details are primarily focused on the solid-state physicochemical properties and redispersion capacity of various dry lipid-based formulations, and how these relate to the in vitro drug release and solubilisation, lipid carrier digestion and cell permeation performances. Numerous in vivo proof-of-concept studies are presented to highlight the viability of these dry lipid-based formulations. This review is significant in directing future research work in fostering translation of dry lipid-based formulations into clinical applications.

A Novel Disintegration Tester for Solid Dosage Forms Enabling Adjustable Hydrodynamics.

Science.gov (United States)

Kindgen, Sarah; Rach, Regine; Nawroth, Thomas; Abrahamsson, Bertil; Langguth, Peter

2016-08-01

A modified in vitro disintegration test device was designed that enables the investigation of the influence of hydrodynamic conditions on disintegration of solid oral dosage forms. The device represents an improved derivative of the compendial PhEur/USP disintegration test device. By the application of a computerized numerical control, a variety of physiologically relevant moving velocities and profiles can be applied. With the help of computational fluid dynamics, the hydrodynamic and mechanical forces present in the probe chamber were characterized for a variety of device moving speeds. Furthermore, a proof of concept study aimed at the investigation of the influence of hydrodynamic conditions on disintegration times of immediate release tablets. The experiments demonstrated the relevance of hydrodynamics for tablet disintegration, especially in media simulating the fasted state. Disintegration times increased with decreasing moving velocity. A correlation between experimentally determined disintegration times and computational fluid dynamics predicted shear stress on tablet surface was established. In conclusion, the modified disintegration test device is a valuable tool for biorelevant in vitro disintegration testing of solid oral dosage forms. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Determination of the mechanical properties of solid and cellular polymeric dosage forms by diametral compression.

Science.gov (United States)

Blaesi, Aron H; Saka, Nannaji

2016-07-25

At present, the immediate-release solid dosage forms, such as the oral tablets and capsules, are granular solids. They release drug rapidly and have adequate mechanical properties, but their manufacture is fraught with difficulties inherent in processing particulate matter. Such difficulties, however, could be overcome by liquid-based processing. Therefore, we have recently introduced polymeric cellular (i.e., highly porous) dosage forms prepared from a melt process. Experiments have shown that upon immersion in a dissolution medium, the cellular dosage forms with polyethylene glycol (PEG) as excipient and with predominantly open-cell topology disintegrate by exfoliation, thus enabling rapid drug release. If the volume fraction of voids of the open-cell structures is too large, however, their mechanical strength is adversely affected. At present, the common method for determining the tensile strength of brittle, solid dosage forms (such as select granular forms) is the diametral compression test. In this study, the theory of diametral compression is first refined to demonstrate that the relevant mechanical properties of ductile and cellular solids (i.e., the elastic modulus and the yield strength) can also be extracted from this test. Diametral compression experiments are then conducted on PEG-based solid and cellular dosage forms. It is found that the elastic modulus and yield strength of the open-cell structures are about an order of magnitude smaller than those of the non-porous solids, but still are substantially greater than the stiffness and strength requirements for handling the dosage forms manually. This work thus demonstrates that melt-processed polymeric cellular dosage forms that release drug rapidly can be designed and manufactured to have adequate mechanical properties. Copyright © 2016. Published by Elsevier B.V.

Microbial quality of some herbal solid dosage forms

African Journals Online (AJOL)

STORAGESEVER

2010-03-15

Mar 15, 2010 ... Key words: Microbial quality, herbal, contamination, solid dosage form ... The type of dosage form, packaging, manufacturing and expiration dates of subject solid herbal .... According to WHO report (2002), Salmonella food.

[Oral films as perspective dosage form].

Science.gov (United States)

Walicová, Veronika; Gajdziok, Jan

Oral films, namely buccal mucoadhesive films and orodispersible films represent innovative formulations for administration of a wide range of drugs. Oral films show many advantageous properties and are intended for systemic drug delivery or for local treatment of the oral mucosa. In both cases, the film represents a thin layer, which could be intended to adhere to the oral mucosa by means of mucoadhesion; or to rapid dissolution and subsequent swallowing without the need of liquid intake, in the case of orodispersible films. Main constitutive excipients are film-forming polymers, which must in the case of mucoadhesive forms remain on the mucosa within the required time interval. Oral films are currently available on the pharmaceutical market and could compete with conventional oral dosage forms in the future. oral cavity oral films buccal mucoadhesive films orodispersible films film-forming polymers.

Overview of PAT process analysers applicable in monitoring of film coating unit operations for manufacturing of solid oral dosage forms.

Science.gov (United States)

Korasa, Klemen; Vrečer, Franc

2018-01-01

Over the last two decades, regulatory agencies have demanded better understanding of pharmaceutical products and processes by implementing new technological approaches, such as process analytical technology (PAT). Process analysers present a key PAT tool, which enables effective process monitoring, and thus improved process control of medicinal product manufacturing. Process analysers applicable in pharmaceutical coating unit operations are comprehensibly described in the present article. The review is focused on monitoring of solid oral dosage forms during film coating in two most commonly used coating systems, i.e. pan and fluid bed coaters. Brief theoretical background and critical overview of process analysers used for real-time or near real-time (in-, on-, at- line) monitoring of critical quality attributes of film coated dosage forms are presented. Besides well recognized spectroscopic methods (NIR and Raman spectroscopy), other techniques, which have made a significant breakthrough in recent years, are discussed (terahertz pulsed imaging (TPI), chord length distribution (CLD) analysis, and image analysis). Last part of the review is dedicated to novel techniques with high potential to become valuable PAT tools in the future (optical coherence tomography (OCT), acoustic emission (AE), microwave resonance (MR), and laser induced breakdown spectroscopy (LIBS)). Copyright © 2017 Elsevier B.V. All rights reserved.

Fourteen days oral administration of therapeutic dosage of some ...

African Journals Online (AJOL)

Fourteen days oral administration of therapeutic dosage of some antibiotics reduced serum testosterone in male rats. FO Awobajo, Y Raji, II Olatunji-Bello, FT Kunle-Alabi, AO Adesanya, TO Awobajo ...

Approaches for Establishing Clinically Relevant Dissolution Specifications for Immediate Release Solid Oral Dosage Forms.

Science.gov (United States)

Hermans, Andre; Abend, Andreas M; Kesisoglou, Filippos; Flanagan, Talia; Cohen, Michael J; Diaz, Dorys A; Mao, Y; Zhang, Limin; Webster, Gregory K; Lin, Yiqing; Hahn, David A; Coutant, Carrie A; Grady, Haiyan

2017-11-01

This manuscript represents the perspective of the Dissolution Analytical Working Group of the IQ Consortium. The intent of this manuscript is to highlight the challenges of, and to provide a recommendation on, the development of clinically relevant dissolution specifications (CRS) for immediate release (IR) solid oral dosage forms. A roadmap toward the development of CRS for IR products containing active ingredients with a non-narrow therapeutic window is discussed, within the context of mechanistic dissolution understanding, supported by in-human pharmacokinetic (PK) data. Two case studies present potential outcomes of following the CRS roadmap and setting dissolution specifications. These cases reveal some benefits and challenges of pursuing CRS with additional PK data, in light of current regulatory positions, including that of the US Food and Drug Administration (FDA), who generally favor this approach, but with the understanding that both industry and regulatory agency perspectives are still evolving in this relatively new field. The CRS roadmap discussed in this manuscript also describes a way to develop clinically relevant dissolution specifications based primarily on dissolution data for batches used in pivotal clinical studies, acknowledging that not all IR product development efforts need to be supported by additional PK studies, albeit with the associated risk of potentially unnecessarily tight manufacturing controls. Recommendations are provided on what stages during the life cycle investment into in vivo studies may be valuable. Finally, the opportunities for CRS within the context of post-approval changes, Modeling and Simulation (M&S), and the application of biowaivers, are briefly discussed.

78 FR 30197 - Oral Dosage Form New Animal Drugs; Clindamycin; Enrofloxacin

Science.gov (United States)

2013-05-22

...-0002] Oral Dosage Form New Animal Drugs; Clindamycin; Enrofloxacin AGENCY: Food and Drug Administration...- Tallaght, Dublin Oral Drops. 940. 24, Ireland. 200-551........ Putney, Inc., 400 Enrofloxacin Original....812 Enrofloxacin. (a) Specifications. Each tablet contains 22.7, 68.0, or 136.0 milligrams (mg) of...

21 CFR 520.1448 - Monensin oral dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Monensin oral dosage forms. 520.1448 Section 520.1448 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... distance the spots travel from the starting line divided by the distance the solvent front travels from the...

Semi-Solid and Solid Dosage Forms for the Delivery of Phage Therapy to Epithelia

Science.gov (United States)

Petrovski, Steve; Chan, Hiu Tat; Angove, Michael J.; Tucci, Joseph

2018-01-01

The delivery of phages to epithelial surfaces for therapeutic outcomes is a realistic proposal, and indeed one which is being currently tested in clinical trials. This paper reviews some of the known research on formulation of phages into semi-solid dosage forms such as creams, ointments and pastes, as well as solid dosage forms such as troches (or lozenges and pastilles) and suppositories/pessaries, for delivery to the epithelia. The efficacy and stability of these phage formulations is discussed, with a focus on selection of optimal semi-solid bases for phage delivery. Issues such as the need for standardisation of techniques for formulation as well as for assessment of efficacy are highlighted. These are important when trying to compare results from a range of experiments and across different delivery bases. PMID:29495355

76 FR 59023 - Oral Dosage Form New Animal Drugs; Tylosin

Science.gov (United States)

2011-09-23

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Tylosin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

77 FR 3927 - Oral Dosage Form New Animal Drugs; Deracoxib

Science.gov (United States)

2012-01-26

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Deracoxib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

76 FR 18648 - Oral Dosage Form New Animal Drugs; Robenacoxib

Science.gov (United States)

2011-04-05

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Robenacoxib AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

76 FR 40808 - Oral Dosage Form New Animal Drugs; Amprolium

Science.gov (United States)

2011-07-12

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Amprolium AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

77 FR 15960 - Oral Dosage Form New Animal Drugs; Pergolide

Science.gov (United States)

2012-03-19

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Pergolide AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

75 FR 67031 - Oral Dosage Form New Animal Drugs; Domperidone

Science.gov (United States)

2010-11-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2010-N-0002] Oral Dosage Form New Animal Drugs; Domperidone AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

76 FR 78149 - Oral Dosage Form New Animal Drugs; Estriol

Science.gov (United States)

2011-12-16

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 520 [Docket No. FDA-2011-N-0003] Oral Dosage Form New Animal Drugs; Estriol AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and Drug Administration (FDA) is amending the animal drug...

Effects of pharmaceutical processing on pepsin activity during the formulation of solid dosage forms.

Science.gov (United States)

Kristó, Katalin; Pintye-Hódi, Klára

2013-02-01

The main aim of this study was to investigate the effects of pharmaceutical technological methods on pepsin activity during the formulation of solid dosage forms. The circumstances of direct compression and wet granulation were modeled. During direct compression, the heat and the compression force must be taken into consideration. The effects of these parameters were investigated in three materials (pure pepsin, and 1:1 (w/w) pepsin-tartaric acid and 1:1 (w/w) pepsin-citric acid powder mixtures). It was concluded that direct compression is appropriate for the formulation of solid dosage forms containing pepsin through application without acids or with acids at low compression force. The effects of wet granulation were investigated with a factorial design for the same three materials. The factors were time, temperature and moisture content. There was no significant effect of the factors when acids were not applied. Temperature was a significant factor when acids were applied. The negative effect was significantly higher for citric acid than for tartaric acid. It was found that wet granulation can be utilized for the processing of pepsin into solid dosage forms under well-controlled circumstances. The application of citric acid is not recommended during the formulation of solid dosage forms through wet granulation. A mathematically based optimization may be necessary for preformulation studies of the preparation of dosage forms containing sensitive enzymes.

Optimal Antibiotic Dosage for Chronic Kidney Disease Patient: A Pharmacological Manual for Oral Clinicians.

Science.gov (United States)

Chidambaram, Ramasamy

2015-01-01

Chronic kidney disease, (CKD) a gradual and inevitable deterioration in renal function, is the disease with the most associations in dentistry. Dosage adjustment is one amongst the vital elements to be familiar with during their oral care. CKD patients take extended duration to filter out medications, therefore dosage must always be tailored under the supervision of nephrologist. The relished benefits from antibiotic could transform as anti-microbial resistance on their abuse and nephrotoxic when contraindicated drugs are encouraged. New patented drug belonging to oxazoliodine group has driven the researchers to handle the emerging AMR. The present communication discusses the pharmacological factors influencing in prescribing the antibiotics for CKD patient from the dentist's point of view. The formulas destined for calculating the optimal dosage of antibiotics have been documented to aid oral physicians.

Package selection for moisture protection for solid, oral drug products.

Science.gov (United States)

Waterman, Kenneth C; MacDonald, Bruce C

2010-11-01

This review describes how best to select the appropriate packaging options for solid, oral drug products based on both chemical and physical stability, with respect to moisture protection. This process combines an accounting for the initial moisture content of dosage form components, moisture transfer into (out of) packaging based on a moisture vapor transfer rate (MVTR), and equilibration between drug products and desiccants based on their moisture sorption isotherms to provide an estimate of the instantaneous relative humidity (RH) within the packaging. This time-based RH is calculationally combined with a moisture-sensitive Arrhenius equation (determined using the accelerated stability assessment program, ASAP) to predict the drug product's chemical stability over time as a function of storage conditions and packaging options. While physical stability of dosage forms with respect to moisture has been less well documented, a process is recommended based on the threshold RH at which changes (e.g., dosage form dissolution, tablet hardness, drug form) become problematic. The overall process described allows packaging to be determined for a drug product scientifically, with the effect of any changes to storage conditions or packaging to be explicitly accounted for. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

ORODISPERSIBLE TABLET: A Patient Friendly Dosage Form (a Review

Directory of Open Access Journals (Sweden)

C. K. Rameesa

2015-03-01

Full Text Available Background: The most common and preferred route of drug administration is through the oral route. Orodispersible tablets are gaining importance among novel oral drug delivery system as they have improved patient compliance and have some additional advantages compared to other formulation. They are also solid unit dosage forms, which disintegrate in the mouth within a minute in the presence of saliva due to superdisintegrants in the formulation. Thus this type of drug delivery helps a proper per oral administration in pediatric and geriatric population where swallowing is a matter of trouble. Various scientists have prepared orodispersible tablets by following various methods. However, the most common method is the direct compression method. Other special methods are Freeze Drying,Tablet Molding, Sublimation, Spray Drying, Mass extrusion, Phase transition process, etc. Since these tablets dissolve directly in the mouth, so, their taste is also an important factor. Various approaches have been taken in order to mask the bitter taste of the drug. A number of scientists have explored several drugs in this field. Like all other solid dosage forms, they are also evaluated in the field of hardness, friability, wetting time, moisture uptake, disintegration test and dissolution test.

Unveiling multiple solid-state transitions in pharmaceutical solid dosage forms using multi-series hyperspectral imaging and different curve resolution approaches

DEFF Research Database (Denmark)

Alexandrino, Guilherme L; Amigo Rubio, Jose Manuel; Khorasani, Milad Rouhi

2017-01-01

Solid-state transitions at the surface of pharmaceutical solid dosage forms (SDF) were monitored using multi-series hyperspectral imaging (HSI) along with Multivariate Curve Resolution – Alternating Least Squares (MCR-ALS) and Parallel Factor Analysis (PARAFAC and PARAFAC2). First, the solid-stat...

Dissolution and oral bioavailability enhancement of praziquantel by solid dispersions.

Science.gov (United States)

Liu, Yanyan; Wang, Tianzi; Ding, Wenya; Dong, Chunliu; Wang, Xiaoting; Chen, Jianqing; Li, Yanhua

2018-06-01

The aim of the present investigation was to enhance the solubility, dissolution, and oral bioavailability of praziquantel (PZQ), a poorly water-soluble BCS II drug (Biopharmaceutical Classification System), using a solid dispersion (SD) technique involving hydrophilic copolymers. The SD formulations were prepared by a solvent evaporation method with PZQ and PEG 4000 (polyethylene glycol 4000), PEG 6000, or P 188 polymers at various weight ratios or a combination of PEG 4000/P 188. The optimized SD formulation, which had the highest solubility in distilled water, was further characterized by its surface morphology, crystallinity, and dissolution in 0.1 M HCl with 0.2% w/v of sodium dodecyl sulfate (SDS). X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) revealed the amorphous form of PZQ in the SDs. Moreover, at an oral dosage of 5 mg/kg PZQ, the SDs had higher C max values and areas under the curve (AUCs) compared to those of commercial PZQ tablets. Preparation of PZQ-loaded SDs using PEG 4000/P 188 is a promising strategy to improve the oral bioavailability of PZQ.

Oral Solid Dosage Form Disintegration Testing - The Forgotten Test.

Science.gov (United States)

Al-Gousous, Jozef; Langguth, Peter

2015-09-01

Since its inception in the 1930s, disintegration testing has become an important quality control (QC) test in pharmaceutical industry, and disintegration test procedures for various dosage forms have been described by the different pharmacopoeias, with harmonization among them still not quite complete. However, because of the fact that complete disintegration does not necessarily imply complete dissolution, much more research has been focused on dissolution rather than on disintegration testing. Nevertheless, owing to its simplicity, disintegration testing seems to be an attractive replacement to dissolution testing as recognized by the International Conference on Harmonization guidelines, in some cases. Therefore, with proper research being carried out to overcome the associated challenges, the full potential of disintegration testing could be tapped saving considerable efforts allocated to QC testing and quality assurance. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

An introduction to fast dissolving oral thin film drug delivery systems: a review.

Science.gov (United States)

Kathpalia, Harsha; Gupte, Aasavari

2013-12-01

Many pharmaceutical companies are switching their products from tablets to fast dissolving oral thin films (OTFs). Films have all the advantages of tablets (precise dosage, easy administration) and those of liquid dosage forms (easy swallowing, rapid bioavailability). Statistics have shown that four out of five patients prefer orally disintegrating dosage forms over conventional solid oral dosages forms. Pediatric, geriatric, bedridden, emetic patients and those with Central Nervous System disorders, have difficulty in swallowing or chewing solid dosage forms. Many of these patients are non-compliant in administering solid dosage forms due to fear of choking. OTFs when placed on the tip or the floor of the tongue are instantly wet by saliva. As a result, OTFs rapidly hydrate and then disintegrate and/or dissolve to release the medication for local and/or systemic absorption. This technology provides a good platform for patent non- infringing product development and for increasing the patent life-cycle of the existing products. The application of fast dissolving oral thin films is not only limited to buccal fast dissolving system, but also expands to other applications like gastroretentive, sublingual delivery systems. This review highlights the composition including the details of various types of polymers both natural and synthetic, the different types of manufacturing techniques, packaging materials and evaluation tests for the OTFs.

Particle Engineering Via Mechanical Dry Coating in the Design of Pharmaceutical Solid Dosage Forms.

Science.gov (United States)

Qu, Li; Morton, David A V; Zhou, Qi Tony

2015-01-01

Cohesive powders are problematic in the manufacturing of pharmaceutical solid dosage forms because they exhibit poor flowability, fluidization and aerosolization. These undesirable bulk properties of cohesive powders represent a fundamental challenge in the design of efficient pharmaceutical manufacturing processes. Recently, mechanical dry coating has attracted increasing attention as it can improve the bulk properties of cohesive powders in a cheaper, simpler, safer and more environment-friendly way than the existing solvent-based counterparts. In this review, mechanical dry coating techniques are outlined and their potential applications in formulation and manufacturing of pharmaceutical solid dosage forms are discussed. Reported data from the literature have shown that mechanical dry coating holds promise for the design of superior pharmaceutical solid formulations or manufacturing processes by engineering the interfaces of cohesive powders in an efficient and economical way.

A novel validated stability indicating high performance liquid chromatographic method for estimation of degradation behavior of ciprofloxacin and tinidazole in solid oral dosage

Directory of Open Access Journals (Sweden)

Bhupendrasinh K Vaghela

2013-01-01

Full Text Available Objective: The objective of current investigation was to study the degradation behavior of Ciprofloxacin and Tinidazole. The study was performed as per International Conference on Harmonization recommended stress condition. A novel stability-indicating reverse phase HPLC method was developed for the determination of Ciprofloxacin and Tinidazole purity in the presence of its impurities and forced degradation products. This method is also capable to separate placebo peaks as well in pharmaceutical dosage forms. The solid oral dosage form was subjected to the stress conditions such as oxidative, acid, base hydrolysis, heat and photolytic degradation. Materials and Methods: The method was developed using Waters symmetry shield, Reverse Phase (RP C18, 250mm x 4.6mm, 5΅ as a stationary phase. The mobile phase containing a gradient mixture of solvent A and B. 10mM phosphate buffer, adjusted pH 3.0 with phosphoric acid was used as a buffer. Buffer pH 3.0 was used as solvent A and buffer pH 3.0: Acetonitrile in the ratio of 20: 80 v/v were used as solvent B. The eluted compounds were monitored 278 nm (Ciprofloxacin, 317 nm (Tinidazole. The run time was 50 minute. Results: In the precision study the % RSD for the result of Ciprofloxacin, Tinidazole and its impurities was below 10%. The method was linear with the correlation coefficient greater than 0.997. The percentage recoveries were calculated and observed from 93.0% to 106.7%.The peak purity of Ciprofloxacin, Tinidazole peak had not shown any flag, thus proved the stability-indicating power of the method. Conclusion: The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness.

Dissolution testing of orally disintegrating tablets.

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Kraemer, Johannes; Gajendran, Jayachandar; Guillot, Alexis; Schichtel, Julian; Tuereli, Akif

2012-07-01

For industrially manufactured pharmaceutical dosage forms, product quality tests and performance tests are required to ascertain the quality of the final product. Current compendial requirements specify a disintegration and/or a dissolution test to check the quality of oral solid dosage forms. These requirements led to a number of compendial monographs for individual products and, at times, the results obtained may not be reflective of the dosage form performance. Although a general product performance test is desirable for orally disintegrating tablets (ODTs), the complexity of the release controlling mechanisms and short time-frame of release make such tests difficult to establish. For conventional oral solid dosage forms (COSDFs), disintegration is often considered to be the prerequisite for subsequent dissolution. Hence, disintegration testing is usually insufficient to judge product performance of COSDFs. Given the very fast disintegration of ODTs, the relationship between disintegration and dissolution is worthy of closer scrutiny. This article reviews the current status of dissolution testing of ODTs to establish the product quality standards. Based on experimental results, it appears that it may be feasible to rely on the dissolution test without a need for disintegration studies for selected ODTs on the market. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

The knowledge, attitudes and beliefs of patients and their healthcare professionals around oral dosage form modification: A systematic review of the qualitative literature.

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Mc Gillicuddy, Aoife; Kelly, Maria; Crean, Abina M; Sahm, Laura J

The objective of this systematic review was to synthesize the available qualitative evidence on the knowledge, attitudes and beliefs of adult patients, healthcare professionals and carers about oral dosage form modification. A systematic review and synthesis of qualitative studies was undertaken, utilising the thematic synthesis approach. The following databases were searched from inception to September 2015: PubMed, Medline (EBSCO), EMBASE, CINAHL, PsycINFO, Web of Science, ProQuest Databases, Scopus, Turning Research Into Practice (TRIP), Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews (CDSR). Citation tracking and searching the references lists of included studies was also undertaken. Grey literature was searched using the OpenGrey database, internet searching and personal knowledge. An updated search was undertaken in June 2016. Studies meeting the following criteria were eligible for inclusion; (i) used qualitative data collection and analysis methods; (ii) full-text was available in English; (iii) included adult patients who require oral dosage forms to be modified to meet their needs or; (iv) carers or healthcare professionals of patients who require oral dosage forms to be modified. Two reviewers independently appraised the quality of the included studies using the Critical Appraisal Skills Programme Checklist. A thematic synthesis was conducted and analytical themes were generated. Of 5455 records screened, seven studies were eligible for inclusion; three involved healthcare professionals and the remaining four studies involved patients. Four analytical themes emerged from the thematic synthesis: (i) patient-centred individuality and variability; (ii) communication; (iii) knowledge and uncertainty and; (iv) complexity. The variability of individual patient's requirements, poor communication practices and lack of knowledge about oral dosage form modification, when combined with the complex and multi

Development and characterization of an atorvastatin solid dispersion formulation using skimmed milk for improved oral bioavailability

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Ankush Choudhary

2012-08-01

Full Text Available Atorvastatin has low aqueous solubility resulting in low oral bioavailability (12% and thus presents a challenge in formulating a suitable dosage form. To improve the aqueous solubility, a solid dispersion formulation of atorvastatin was prepared by lyophilization utilising skimmed milk as a carrier. Six different formulations were prepared with varying ratios of drug and carrier and the corresponding physical mixtures were also prepared. The formation of a solid dispersion formulation was confirmed by differential scanning calorimetry and X-ray diffraction studies. The optimum drug-to-carrier ratio of 1:9 enhanced solubility nearly 33-fold as compared to pure drug. In vitro drug release studies exhibited a cumulative release of 83.69% as compared to 22.7% for the pure drug. Additionally, scanning electron microscopy studies suggested the conversion of crystalline atorvastatin to an amorphous form. In a Triton-induced hyperlipidemia model, a 3-fold increase in the lipid lowering potential was obtained with the reformulated drug as compared to pure drug. These results suggest that solid dispersion of atorvastatin using skimmed milk as carrier is a promising approach for oral delivery of atorvastatin.

Dry coating of solid dosage forms: an overview of processes and applications.

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Foppoli, Anastasia Anna; Maroni, Alessandra; Cerea, Matteo; Zema, Lucia; Gazzaniga, Andrea

2017-12-01

Dry coating techniques enable manufacturing of coated solid dosage forms with no, or very limited, use of solvents. As a result, major drawbacks associated with both organic solvents and aqueous coating systems can be overcome, such as toxicological, environmental, and safety-related issues on the one hand as well as costly drying phases and impaired product stability on the other. The considerable advantages related to solventless coating has been prompting a strong research interest in this field of pharmaceutics. In the article, processes and applications relevant to techniques intended for dry coating are analyzed and reviewed. Based on the physical state of the coat-forming agents, liquid- and solid-based techniques are distinguished. The former include hot-melt coating and coating by photocuring, while the latter encompass press coating and powder coating. Moreover, solventless techniques, such as injection molding and three-dimensional printing by fused deposition modeling, which are not purposely conceived for coating, are also discussed in that they would open new perspectives in the manufacturing of coated-like dosage forms.

Evidence for oral agmatine sulfate safety--a 95-day high dosage pilot study with rats.

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Gilad, Gad M; Gilad, Varda H

2013-12-01

Agmatine, decarboxylated arginine, exerts beneficial effects in various experimental disease models. Clinical trials indicate the safety and effectiveness of short-term (up to 21 days) high dose regimens of oral agmatine sulfate, but longer term studies are lacking. This pilot study undertook to assess the safety of a longer term high dosage oral agmatine sulfate in laboratory rats. Adult Wistar rats consumed 5.3 g/l agmatine sulfate in their drinking water for 95 days, a regimen estimated to result in a daily dosage of absorbed agmatine of about 100mg/kg. Animals' body weight, water consumption and blood pressure were periodically measured, and general cage behavior, fur appearance, urination and feces appearance monitored. These parameters were also determined at 20 days after treatment cessation (day 115). On days 95 and 115, animals were euthanized for gross necropsy assessment. Agmatine-treated rats showed slight, but significant reductions in body weight and blood pressure, and reduced water consumption during treatment, which recovered completely within 20 days after treatment cessation. Otherwise, no abnormal behaviors or organ pathologies were observed. These findings are first to suggest apparent safety of sub-chronic high dosage dietary agmatine sulfate in laboratory rats, thus lending further support to the therapeutic applications of agmatine. Copyright © 2013 Elsevier Ltd. All rights reserved.

The effect of miscellaneous oral dosage forms on the environmental pollution of sulfonamides in pig holdings.

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Stahl, Jessica; Zessel, Katrin; Schulz, Jochen; Finke, Jan Henrik; Müller-Goymann, Christel Charlotte; Kietzmann, Manfred

2016-04-01

Due to antibiotic treatment of humans and animals, the prevalence of bacterial resistances increases worldwide. Especially in livestock farming, large quantities of faeces contaminated with antibiotics pose a risk of the carryover of the active ingredient to the environment. Accordingly, the aim of the present study was the evaluation of the benefit of different oral dosage forms (powder, pellets, granula) in pigs concerning the environmental pollution of sulfadiazine. Two subtherapeutic dosages were evaluated in powder mixtures to gain information about their potential to pollute the pig barn. Furthermore, a new group of pigs was kept in the stable after powder feeding of another pig group to determine the possible absorption of environmentally distributed antibiotics. Pigs were orally treated with three dosage forms. Simultaneously, sedimentation and airborne dust were collected and plasma and urine levels were determined. All formulations result in comparable plasma and urine levels, but massive differences in environmental pollution (powder > pellets, granula). Pigs housing in a contaminated barn exhibit traces of sulfadiazine in plasma and urine. Using pharmaceutical formulations like pellets or granula, the environmental pollution of sulfonamides can significantly be diminished due to massive dust reduction during feeding.

Artificial Neural Networks in Evaluation and Optimization of Modified Release Solid Dosage Forms

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Zorica Djurić

2012-10-01

Full Text Available Implementation of the Quality by Design (QbD approach in pharmaceutical development has compelled researchers in the pharmaceutical industry to employ Design of Experiments (DoE as a statistical tool, in product development. Among all DoE techniques, response surface methodology (RSM is the one most frequently used. Progress of computer science has had an impact on pharmaceutical development as well. Simultaneous with the implementation of statistical methods, machine learning tools took an important place in drug formulation. Twenty years ago, the first papers describing application of artificial neural networks in optimization of modified release products appeared. Since then, a lot of work has been done towards implementation of new techniques, especially Artificial Neural Networks (ANN in modeling of production, drug release and drug stability of modified release solid dosage forms. The aim of this paper is to review artificial neural networks in evaluation and optimization of modified release solid dosage forms.

Microstructural effects in drug release by solid and cellular polymeric dosage forms: A comparative study.

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Blaesi, Aron H; Saka, Nannaji

2017-11-01

In recent studies, we have introduced melt-processed polymeric cellular dosage forms to achieve both immediate drug release and predictable manufacture. Dosage forms ranging from minimally-porous solids to highly porous, open-cell and thin-walled structures were prepared, and the drug release characteristics investigated as the volume fraction of cells and the excipient molecular weight were varied. In the present study, both minimally-porous solid and cellular dosage forms consisting of various weight fractions of Acetaminophen drug and polyethylene glycol (PEG) excipient are prepared and analyzed. Microstructures of the solid forms and the cell walls range from single-phase solid solutions of the excipient and a small amount of drug molecules to two-phase composites of the excipient and tightly packed drug particles. Results of dissolution experiments show that the minimally-porous solid forms disintegrate and release drug by slow surface erosion. The erosion rate decreases as the drug weight fraction is increased. By contrast, the open-cell structures disintegrate rapidly by viscous exfoliation, and the disintegration time is independent of drug weight fraction. Drug release models suggest that the solid forms erode by convective mass transfer of the faster-eroding excipient if the drug volume fraction is small. At larger drug volume fractions, however, the slower-eroding drug particles hinder access of the free-flowing fluid to the excipient, thus slowing down erosion of the composite. Conversely, the disintegration rate of the cellular forms is limited by diffusion of the dissolution fluid into the excipient phase of the thin cell walls. Because the wall thickness is of the order of the drug particle size, and the particles are enveloped by the excipient during melt-processing, the drug particles cannot hinder diffusion through the excipient across the walls. Thus the disintegration time of the cellular forms is mostly unaffected by the volume fraction of drug

Solid-state dependent dissolution and oral bioavailability of piroxicam in rats.

Science.gov (United States)

Lust, Andres; Laidmäe, Ivo; Palo, Mirja; Meos, Andres; Aaltonen, Jaakko; Veski, Peep; Heinämäki, Jyrki; Kogermann, Karin

2013-01-23

The aim of this study was to gain understanding about the effects of different solid-state forms of a poorly water-soluble piroxicam on drug dissolution and oral bioavailability in rats. Three different solid-state forms of piroxicam were studied: anhydrate I (AH), monohydrate (MH), and amorphous form in solid dispersion (SD). In addition, the effect of a new polymeric excipient Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) on oral bioavailability of piroxicam was investigated. Significant differences in the dissolution and oral bioavailability were found between the solid-state forms of piroxicam. Amorphous piroxicam in SD showed the fastest dissolution in vitro and a solid-state transformation to MH in the dissolution medium. Despite the presence of solid-state transformation, SD exhibited the highest rate and extent of oral absorption in rats. Oral bioavailability of other two solid-state forms decreased in the order AH and MH. The use of Soluplus® was found to enhance the dissolution and oral bioavailability of piroxicam in rats. The present study shows the importance of solid-state form selection for oral bioavailability of a poorly water-soluble drug. Copyright © 2012 Elsevier B.V. All rights reserved.

Type of oral solid medication packaging and medication preparation time in nursing homes: A direct observation study.

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Cready, C M; Hudson, C; Dreyer, K

2017-12-01

Medication administration is a substantial portion of the workday in nursing homes, with the medication preparation step being the most time-consuming. However, little is known about how medication preparation time is affected by the type of packaging used for oral solid medications (ie, tablets/capsules). We examined the effects of two types of packaging. As fewer steps are associated with strip packaging compared to bingo card packaging, we hypothesized that the increase in medication preparation seconds per resident with each additional oral solid medication would be smaller when strip packaging was used. A total of 430 medication preparations conducted by eight nurses during the regularly scheduled morning medication administration period in two nursing homes-using strip packaging and bingo card packaging, respectively-were observed. Each medication preparation observation was matched to its corresponding medication administration record and observations averaged across resident. Using the resident sample (N=149), we estimated three regression models (adjusting the standard errors for the clustering of resident by nurse). The first model regressed medication preparation seconds on the number of oral solid medications. The second model added the type of packaging used and the control variables (type of unit [long-term care, post-acute care], the number of one-half pills and the dosage form diversity in the preparation). To test our hypothesis, the third model added an interaction term between the number of oral solid medications and the type of packaging used. As hypothesized, all else equal, the number of oral solid medications tended to increase medication preparation time per resident in both nursing homes, but the increase was smaller in the strip packaging nursing home (Ppackaging nursing home increased medication preparation by an average of 13 seconds (b=13.077), whereas each oral solid medication administered in the strip packaging nursing home

New applications to computerized tomography: analysis of solid dosage forms produced by pharmaceutical industry

International Nuclear Information System (INIS)

Oliveira Junior, Jose Martins de; Martins, Antonio Cesar Germano

2009-01-01

Full text: In recent years, computerized tomography (CT) has been used as a new probe to study solid dosage forms (tablets) produced by pharmaceutical industry. This new approach to study tablet and powder, or granulation, properties used in pharmaceutical industry is very suitable. First because CT can generate information that traditional technologies used in this kind of analysis can not, such as, density distribution of internal structures and tablet dimensions, pore size distribution, particle shape information, and also investigation of official and unofficial (counterfeit) copies of solid dosage forms. Second because CT is a nondestructive technique, allowing the use of tablets or granules in others analysis. In this work we discus how CT can be used to acquire and reconstruct internal microstructure of tablets and granules. CT is a technique that is based on attenuation of X-rays passing through matter. Attenuation depends on the density and atomic number of the material that is scanned. In this work, a micro-CT X-ray scanner (manufactured by the group of Applied Nuclear Physics at University of Sorocaba) was used to obtain three-dimensional images of the tablets and granules for nondestructive analysis. These images showed a non uniform density distribution of material inside some tablets, the morphology of some granules analyzed, the integrity of the liquid-filled soft-gelatin capsule and so on. It could also be observed that the distribution of different constituents presents an osmotic controlled-release dosage form. The present work shows that it is possible to use X-ray microtomography to obtain useful qualitative and quantitative information on the structure of pharmaceutical dosage forms. (author)

Polymer adhesion predictions for oral dosage forms to enhance drug administration safety. Part 3: Review of in vitro and in vivo methods used to predict esophageal adhesion and transit time.

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Drumond, Nélio; Stegemann, Sven

2018-05-01

The oral cavity is frequently used to administer pharmaceutical drug products. This route of administration is seen as the most accessible for the majority of patients and supports an independent therapy management. For current oral dosage forms under development, the prediction of their unintended mucoadhesive properties and esophageal transit profiles would contribute for future administration safety, as concerns regarding unintended adhesion of solid oral dosage forms (SODF) during oro-esophageal transit still remain. Different in vitro methods that access mucoadhesion of polymers and pharmaceutical preparations have been proposed over the years. The same methods might be used to test non-adhesive systems and contribute for developing safe-to-swallow technologies. Previous works have already investigated the suitability of non-animal derived in vitro methods to assess such properties. The aim of this work was to review the in vitro methodology available in the scientific literature that used animal esophageal tissue to evaluate mucoadhesion and esophageal transit of pharmaceutical preparations. Furthermore, in vivo methodology is also discussed. Since none of the in vitro methods developed are able to mimic the complex swallowing process and oro-esophageal transit, in vivo studies in humans remain as the gold standard. Copyright © 2018 Elsevier B.V. All rights reserved.

76 FR 25696 - Guidance for Industry on Dosage Delivery Devices for Orally Ingested OTC Liquid Drug Products...

Science.gov (United States)

2011-05-05

... are manufacturing, marketing, or distributing orally ingested over-the-counter (OTC) liquid drug... overdoses that can result from the use of dosage delivery devices with markings that are inconsistent or... because of ongoing concerns about potentially serious accidental drug overdoses that can result from the...

On the exfoliating polymeric cellular dosage forms for immediate drug release.

Science.gov (United States)

Blaesi, Aron H; Saka, Nannaji

2016-06-01

The most prevalent pharmaceutical dosage forms at present-the oral immediate-release tablets and capsules-are granular solids. Though effective in releasing drug rapidly, development and manufacture of such dosage forms are fraught with difficulties inherent to particulate processing. Predictable dosage form manufacture could be achieved by liquid-based processing, but cast solid dosage forms are not suitable for immediate drug release due to their resistance to fluid percolation. To overcome this limitation, we have recently introduced cellular dosage forms that can be readily prepared from polymeric melts. It has been shown that open-cell structures comprising polyethylene glycol 8000 (PEG 8k) excipient and a drug exfoliate upon immersion in a dissolution medium. The drug is then released rapidly due to the large specific surface area of the exfoliations. In this work, we vary the molecular weight of the PEG excipient and investigate its effect on the drug release kinetics of structures with predominantly open-cell topology. We demonstrate that the exfoliation rate decreases substantially if the excipient molecular weight is increased from 12 to 100kg/mol, which causes the drug dissolution time to increase by more than a factor of ten. A model is then developed to elucidate the exfoliation behavior of cellular structures. Diverse transport processes are considered: percolation due to capillarity, diffusion of dissolution medium through the cell walls, and viscous flow of the saturated excipient. It is found that the lower exfoliation rate and the longer dissolution time of the dosage forms with higher excipient molecular weight are primarily due to the greater viscosity of the cell walls after fluid penetration. Copyright © 2016 Elsevier B.V. All rights reserved.

Significance of excipients to enhance the bioavailability of poorly water-soluble drugs in oral solid dosage forms: A Review

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Vadlamudi, Manoj Kumar; Dhanaraj, Sangeetha

2017-11-01

Nowadays most of the drug substances are coming into the innovation pipeline with poor water solubility. Here, the influence of excipients will play a significant role to improve the dissolution of poorly aqueous soluble compounds. The drug substance needs to be dissolved in gastric fluids to get the better absorption and bioavailability of an orally administered drug. Dissolution is the rate-controlling stage for drugs which controls the rate and degree of absorption. Usually, poorly soluble oral administrated drugs show a slower dissolution rate, inconsistent and incomplete absorption which can lead to lower bioavailability. The low aqueous solubility of BCS class II and IV drugs is a major challenge in the drug development and delivery process. Several technologies have been used in an attempt to progress the bioavailability of poorly water-soluble drug compounds which include solid dispersions, lipid-based formulations, micronization, solvent evaporation, co-precipitation, ordered mixing, liquid-solid compacts, solvent deposition inclusion complexation, and steam aided granulation. In fact, most of the technologies require excipient as a carrier which plays a significant role in improving the bioavailability using Hypromellose acetate succinate, Cyclodextrin, Povidone, Copovidone, Hydroxypropyl cellulose, Hydroxypropyl methylcellulose, Crospovidone, Starch, Dimethylacetamide, Polyethylene glycol, Sodium lauryl sulfate, Polysorbate, Poloxamer. Mesoporous silica and so on. This review deliberates about the excipients significance on bioavailability enhancement of drug products in a single platform along with pragmatically proved applications so that user can able to select the right excipients as per the molecule.

Oral delivery of medications to companion animals: palatability considerations.

Science.gov (United States)

Thombre, Avinash G

2004-06-23

There is an increased need for highly palatable solid oral dosage forms for companion animals, which are voluntarily accepted by the dog or cat, either from a feeding bowl or from the outstretched hand of the pet owner. Such dosage forms represent an emerging trend in companion animal formulations with major impact on medical needs such as convenience and compliance, particularly for chronically administered medications, and on marketing needs such as product differentiation. This review focuses on the science of taste, food and flavor preferences of dogs and cats, and palatability testing, in the context of applying these principles to the development of an oral palatable tablet for companion animals.

Oral medicines for children in the European paediatric investigation plans.

Directory of Open Access Journals (Sweden)

Diana A van Riet-Nales

Full Text Available INTRODUCTION: Pharmaceutical industry is no longer allowed to develop new medicines for use in adults only, as the 2007 Paediatric Regulation requires children to be considered also. The plans for such paediatric development called Paediatric Investigation Plans (PIPs are subject to agreement by the European Medicines Agency (EMA and its Paediatric Committee (PDCO. The aim of this study was to evaluate the key characteristics of oral paediatric medicines in the PIPs and the changes implemented as a result of the EMA/PDCO review. METHODS: All PIPs agreed by 31 December 2011 were identified through a proprietary EMA-database. PIPs were included if they contained an agreed proposal to develop an oral medicine for children 0 to 11 years. Information on the therapeutic area (EMA classification system; target age range (as defined by industry and pharmaceutical characteristics (active substance, dosage form(s as listed in the PIP, strength of each dosage form, excipients in each strength of each dosage form was extracted from the EMA website or the EMA/PDCO assessment reports. RESULTS: A hundred and fifty PIPs were included corresponding to 16 therapeutic areas and 220 oral dosage forms in 431 strengths/compositions. Eighty-two PIPs (37% included tablets, 44 (20% liquids and 35 (16% dosage forms with a specific composition/strength that were stored as a solid but swallowed as a liquid e.g. dispersible tablets. The EMA/PDCO review resulted in an increase of 13 (207 to 220 oral paediatric dosage forms and 44 (387 to 431 dosage forms with a specific composition/strength. For many PIPs, the target age range was widened and the excipient composition and usability aspects modified. CONCLUSION: The EMA/PDCO review realized an increase in the number of requirements for the development of oral dosage forms and a larger increase in the number of dosage forms with a specific composition/strength, both targeting younger children. Changes to their pharmaceutical

Improved oral absorption of tacrolimus by a solid dispersion with hypromellose and sodium lauryl sulfate.

Science.gov (United States)

Jung, Hyuck Jun; Ahn, Hye In; Park, Ji Yeon; Ho, Myoung Jin; Lee, Dae Ro; Cho, Ha Ra; Park, Jun Seo; Choi, Yong Seok; Kang, Myung Joo

2016-02-01

A novel surfactant-incorporated hydroxypropyl methylcellulose (HPMC) solid dispersion (SD) system was constructed in order to facilitate the release rate and oral absorption of tacrolimus (FK506), a poorly water-soluble immunosuppressant. Several emulsifiers including sodium lauryl sulfate (SLS), as drug release promotors, were employed with HPMC to fabricate SD using the solvent wetting method. The solid state characteristics using differential scanning calorimetry and X-ray powder diffraction, revealed that FK506 was molecularly distributed within all dispersions in amorphous form. The dissolution rates of FK506 in SLS-incorporated SDs were much higher than those in SDs prepared with HPMC alone, and even with stearoyl polyoxyl-32 glycerides or tocopheryl polyethylene glycol 1000 succinate. In particular, the greatest dissolution enhancement was obtained from the SD consisting of the drug, HPMC, and SLS in a weight ratio of 1:1:3, providing a 50-fold higher drug concentration within 15 min, compared with HPMC SD. In vivo absorption study in rats demonstrates that the optimized formula remarkably increased the oral absorption of FK506, providing about 4.0-fold greater bioavailability (p<0.05) compared with the marketed product (Prograf®, Astellas Pharma). These data suggest that a novel SLS/HPMC SD may be an advantageous dosage form of FK506, boosting the dissolution and absorption in gastrointestinal tract. Copyright © 2015 Elsevier B.V. All rights reserved.

Micropellets coated with Kollicoat® Smartseal 30D for taste masking in liquid oral dosage forms.

Science.gov (United States)

Dashevskiy, Andriy; Mohylyuk, Valentyn; Ahmed, Abid Riaz; Kolter, Karl; Guth, Felicitas; Bodmeier, Roland

2017-09-01

The objective of this study was to develop delivery systems for taste masking based on multiparticulates coated with Kollicoat ® Smartseal 30D formulated as liquid oral suspensions. Coating of particles containing bitter drugs with Kollicoat ® Smartseal reduced drug leaching into aqueous medium, especially when increasing pH, therefore can be used for the formulation of liquid dosage forms. Application of an intermediate layer of ion exchange resins between drug layer and coating can further decrease drug leaching into aqueous vehicle that is beneficial in terms of taste masking. Using optimized compositions of liquid vehicles such as addition of sugar alcohols and ion exchange resin, reconstitutable or ready-to-use liquid dosage forms with micropellets can be developed with bitter taste protection after redispersion lasting longer than 3 weeks, which exceeds the usual period of application.

Discrete element method (DEM) simulations of stratified sampling during solid dosage form manufacturing.

Science.gov (United States)

Hancock, Bruno C; Ketterhagen, William R

2011-10-14

Discrete element model (DEM) simulations of the discharge of powders from hoppers under gravity were analyzed to provide estimates of dosage form content uniformity during the manufacture of solid dosage forms (tablets and capsules). For a system that exhibits moderate segregation the effects of sample size, number, and location within the batch were determined. The various sampling approaches were compared to current best-practices for sampling described in the Product Quality Research Institute (PQRI) Blend Uniformity Working Group (BUWG) guidelines. Sampling uniformly across the discharge process gave the most accurate results with respect to identifying segregation trends. Sigmoidal sampling (as recommended in the PQRI BUWG guidelines) tended to overestimate potential segregation issues, whereas truncated sampling (common in industrial practice) tended to underestimate them. The size of the sample had a major effect on the absolute potency RSD. The number of sampling locations (10 vs. 20) had very little effect on the trends in the data, and the number of samples analyzed at each location (1 vs. 3 vs. 7) had only a small effect for the sampling conditions examined. The results of this work provide greater understanding of the effect of different sampling approaches on the measured content uniformity of real dosage forms, and can help to guide the choice of appropriate sampling protocols. Copyright © 2011 Elsevier B.V. All rights reserved.

Optimization and Evaluation of Desloratadine Oral Strip: An Innovation in Paediatric Medication

OpenAIRE

Singh, Harmanpreet; Kaur, Mandeep; Verma, Hitesh

2013-01-01

Patients, especially children, are the most difficult to treat in all groups of population mainly because they can not swallow the solid dosage form. Due to this reason they are often prescribed liquid dosage forms. But these formulations have their own disadvantages (lack of dose accuracy during administration, spitting by children, spillage, lack of stability, difficulty in transportation, etc.). Oral strip technology is one such technology to surpass these disadvantages. Desloratadine, a d...

In vitro dissolution of generic immediate-release solid oral dosage forms containing BCS class I drugs: comparative assessment of metronidazole, zidovudine, and amoxicillin versus relevant comparator pharmaceutical products in South Africa and India.

Science.gov (United States)

Reddy, Nallagundla H S; Patnala, Srinivas; Löbenberg, Raimar; Kanfer, Isadore

2014-10-01

Biowaivers are recommended for immediate-release solid oral dosage forms using dissolution testing as a surrogate for in vivo bioequivalence studies. Several guidance are currently available (the World Health Organization (WHO), the US FDA, and the EMEA) where the conditions are described. In this study, definitions, criteria, and methodologies according to the WHO have been applied. The dissolution performances of immediate-release metronidazole, zidovudine, and amoxicillin products purchased in South African and Indian markets were compared to the relevant comparator pharmaceutical product (CPP)/reference product. The dissolution performances were studied using US Pharmacopeia (USP) apparatus 2 (paddle) set at 75 rpm in each of three dissolution media (pH1.2, 4.5, and 6.8). Concentrations of metronidazole, zidovudine, and amoxicillin in each dissolution media were determined by HPLC. Of the 11 metronidazole products tested, only 8 could be considered as very rapidly dissolving products as defined by the WHO, whereas 2 of those products could be considered as rapidly dissolving products but did not comply with the f 2 acceptance criteria in pH 6.8. All 11 zidovudine products were very rapidly dissolving, whereas in the case of the 14 amoxicillin products tested, none of those products met any of the WHO criteria. This study indicates that not all generic products containing the same biopharmaceutics classification system (BCS) I drug and in similar strength and dosage form are necessarily in vitro equivalent. Hence, there is a need for ongoing market surveillance to determine whether marketed generic products containing BCS I drugs meet the release requirements to confirm their in vitro bioequivalence to the respective reference product.

Submicron Emulsions and Their Applications in Oral Delivery.

Science.gov (United States)

Mundada, Veenu; Patel, Mitali; Sawant, Krutika

2016-01-01

A "submicron emulsion" is an isotropic mixture of drug, lipids, and surfactants, usually with hydrophilic cosolvents and with droplet diameters ranging from 10 to 500 nm. Submicron emulsions are of increasing interest in medicine due to their kinetic stability, high solubilizing capacity, and tiny globule size. Because of these properties, they have been applied in various fields, such as personal care, cosmetics, health care, pharmaceuticals, and agrochemicals. Submicron emulsions are by far the most advanced nanoparticulate systems for the systemic delivery of biologically active agents for controlled drug delivery and targeting. They are designed mainly for pharmaceutical formulations suitable for various routes of administration like parenteral, ocular, transdermal, and oral. This review article describes the marked potential of submicron emulsions for oral drug delivery owing to their numerous advantages like reduced first pass metabolism, inhibition of P-glycoprotein efflux system, and enhanced absorption via intestinal lymphatic pathway. To overcome the limitations of liquid dosage forms, submicron emulsions can be formulated into solid dosage forms such as solid self-emulsifying systems. This article covers various types of submicron emulsions like microemulsion, nanoemulsion, and self-emulsifying drug delivery system (SEDDS), and their potential pharmaceutical applications in oral delivery with emphasis on their advantages, limitations, and advancements.

Nanofibrous solid dosage form of living bacteria prepared by electrospinning

Directory of Open Access Journals (Sweden)

I. Wagner

2014-05-01

Full Text Available The aim of this work was to investigate the suitability of electrospinning for biodrug delivery and to develop an electrospinning-based method to produce vaginal drug delivery systems. Lactobacillus acidophilus bacteria were encapsulated into nanofibers of three different polymers (polyvinyl alcohol and polyvinylpyrrolidone with two different molar masses. Shelf life of the bacteria could be enhanced by the exclusion of water and by preparing a solid dosage form, which is an advantageous and patient-friendly way of administration. The formulations were stored at –20, 7 and 25°C, respectively. Viability testing showed that the nanofibers can provide long term stability for huge amounts of living bacteria if they are kept at (or below 7°C. Furthermore, all kinds of nanowebs prepared in this work dissolved instantly when they got in contact with water, thus the developed biohybrid nanowebs can provide new potential ways for curing bacterial vaginosis.

Dropwise additive manufacturing of pharmaceutical products for solvent-based dosage forms.

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Hirshfield, Laura; Giridhar, Arun; Taylor, Lynne S; Harris, Michael T; Reklaitis, Gintaras V

2014-02-01

In recent years, the US Food and Drug Administration has encouraged pharmaceutical companies to develop more innovative and efficient manufacturing methods with improved online monitoring and control. Mini-manufacturing of medicine is one such method enabling the creation of individualized product forms for each patient. This work presents dropwise additive manufacturing of pharmaceutical products (DAMPP), an automated, controlled mini-manufacturing method that deposits active pharmaceutical ingredients (APIs) directly onto edible substrates using drop-on-demand (DoD) inkjet printing technology. The use of DoD technology allows for precise control over the material properties, drug solid state form, drop size, and drop dynamics and can be beneficial in the creation of high-potency drug forms, combination drugs with multiple APIs or individualized medicine products tailored to a specific patient. In this work, DAMPP was used to create dosage forms from solvent-based formulations consisting of API, polymer, and solvent carrier. The forms were then analyzed to determine the reproducibility of creating an on-target dosage form, the morphology of the API of the final form and the dissolution behavior of the drug over time. DAMPP is found to be a viable alternative to traditional mass-manufacturing methods for solvent-based oral dosage forms. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Curcumin-Artemisinin Coamorphous Solid: Xenograft Model Preclinical Study

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M. K. Chaitanya Mannava

2018-01-01

Full Text Available Curcumin is a natural compound present in Indian spice turmeric. It has diverse pharmacological action but low oral solubility and bioavailability continue to limit its use as a drug. With the aim of improving the bioavailability of Curcumin (CUR, we evaluated Curcumin-Pyrogallol (CUR-PYR cocrystal and Curcumin-Artemisinin (CUR-ART coamorphous solid. Both of these solid forms exhibited superior dissolution and pharmacokinetic behavior compared to pure CUR, which is practically insoluble in water. CUR-ART coamorphous solid showed two fold higher bioavailability than CUR-PYR cocrystal (at 200 mg/kg oral dose. Moreover, in simulated gastric and intestinal fluids (SGF and SIF, CUR-ART is stable up to 3 and 12 h, respectively. In addition, CUR-PYR and CUR-ART showed no adverse effects in toxicology studies (10 times higher dose at 2000 mg/kg. CUR-ART showed higher therapeutic effect and inhibited approximately 62% of tumor growth at 100 mg/kg oral dosage of CUR in xenograft models, which is equal to the positive control drug, doxorubicin (2 mg/kg by i.v. administration.

Effect of formulation variables on insulin localisation within solid lipid nanoparticles

OpenAIRE

Thong, Li Ming

2016-01-01

There has been a lot of interest on solid lipid nanoparticles (SLNs) as these colloidal submicron drug dosage forms present a promising frontier in drug delivery. It is possible to incorporate susceptible drugs such as protein intended for oral delivery. Here, we aim to develop an oral delivery system based on SLNs to deliver the peptide hormone, insulin using the double emulsion (W/O/W) solvent evaporation technique for formulating the SLNs. The choice of lipids was carefully selected to inc...

QR encoded smart oral dosage forms by inkjet printing.

Science.gov (United States)

Edinger, Magnus; Bar-Shalom, Daniel; Sandler, Niklas; Rantanen, Jukka; Genina, Natalja

2018-01-30

The use of inkjet printing (IJP) technology enables the flexible manufacturing of personalized medicine with the doses tailored for each patient. In this study we demonstrate, for the first time, the applicability of IJP in the production of edible dosage forms in the pattern of a quick response (QR) code. This printed pattern contains the drug itself and encoded information relevant to the patient and/or healthcare professionals. IJP of the active pharmaceutical ingredient (API)-containing ink in the pattern of QR code was performed onto a newly developed porous and flexible, but mechanically stable substrate with a good absorption capacity. The printing did not affect the mechanical properties of the substrate. The actual drug content of the printed dosage forms was in accordance with the encoded drug content. The QR encoded dosage forms had a good print definition without significant edge bleeding. They were readable by a smartphone even after storage in harsh conditions. This approach of efficient data incorporation and data storage combined with the use of smart devices can lead to safer and more patient-friendly drug products in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

Multicomponent chemical imaging of pharmaceutical solid dosage forms with broadband CARS microscopy.

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Hartshorn, Christopher M; Lee, Young Jong; Camp, Charles H; Liu, Zhen; Heddleston, John; Canfield, Nicole; Rhodes, Timothy A; Hight Walker, Angela R; Marsac, Patrick J; Cicerone, Marcus T

2013-09-03

We compare a coherent Raman imaging modality, broadband coherent anti-Stokes Raman scattering (BCARS) microscopy, with spontaneous Raman microscopy for quantitative and qualitative assessment of multicomponent pharmaceuticals. Indomethacin was used as a model active pharmaceutical ingredient (API) and was analyzed in a tabulated solid dosage form, embedded within commonly used excipients. In comparison with wide-field spontaneous Raman chemical imaging, BCARS acquired images 10× faster, at higher spatiochemical resolution and with spectra of much higher SNR, eliminating the need for multivariate methods to identify chemical components. The significant increase in spatiochemical resolution allowed identification of an unanticipated API phase that was missed by the spontaneous wide-field method and bulk Raman spectroscopy. We confirmed the presence of the unanticipated API phase using confocal spontaneous Raman, which provided spatiochemical resolution similar to BCARS but at 100× slower acquisition times.

Enhancement of bioavailability of ketoprofen using dry elixir as a novel dosage form.

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Ahn, H J; Kim, K M; Kim, C K

1998-07-01

To enhance the dissolution rate and bioavailability of poorly water-soluble ketoprofen, a novel oral dosage form of ketoprofen, termed ketoprofen dry elixir, was developed by the spray-drying technique. Ketoprofen, dextrin, and sodium lauryl sulfate were dissolved in an ethanol-water mixture (20:25 w/w) and thereafter spray-dried to form the ketoprofen dry elixir. Comparative studies on the in vitro dissolution and in vivo adsorption of ketoprofen in the form of dry elixir and powder were carried out. Ketoprofen in the dry elixir completely dissolved within 5 min. On the other hand, only about 50.1% of ketoprofen powder alone dissolved during 60 min. The initial dissolution rate of ketoprofen in the dry elixir markedly increased in distilled water at 37 degrees C, becoming fourfold higher than that of ketoprofen powder alone. The maximal plasma concentration of ketoprofen (Cmax) and the area under the concentration-time curve from zero to 8 hr (AUC0-8 hr) after the oral administration of dry elixir increased about 3.2- (24.6 versus 7.6 micrograms/ml) and 2.2-(38.4 versus 17.3 micrograms hr/ml) fold compared with powder alone. It was obvious that ketoprofen dry elixir might be a useful solid dosage form to improve the dissolution rate and bioavailability of poorly water-soluble ketoprofen.

PAT: From Western solid dosage forms to Chinese materia medica preparations using NIR-CI.

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Zhou, Luwei; Xu, Manfei; Wu, Zhisheng; Shi, Xinyuan; Qiao, Yanjiang

2016-01-01

Near-infrared chemical imaging (NIR-CI) is an emerging technology that combines traditional near-infrared spectroscopy with chemical imaging. Therefore, NIR-CI can extract spectral information from pharmaceutical products and simultaneously visualize the spatial distribution of chemical components. The rapid and non-destructive features of NIR-CI make it an attractive process analytical technology (PAT) for identifying and monitoring critical control parameters during the pharmaceutical manufacturing process. This review mainly focuses on the pharmaceutical applications of NIR-CI in each unit operation during the manufacturing processes, from the Western solid dosage forms to the Chinese materia medica preparations. Finally, future applications of chemical imaging in the pharmaceutical industry are discussed. Copyright © 2015 John Wiley & Sons, Ltd.

Predicting the oral pharmacokinetic profiles of multiple-unit (pellet) dosage forms using a modeling and simulation approach coupled with biorelevant dissolution testing: case example diclofenac sodium.

Science.gov (United States)

Kambayashi, Atsushi; Blume, Henning; Dressman, Jennifer B

2014-07-01

The objective of this research was to characterize the dissolution profile of a poorly soluble drug, diclofenac, from a commercially available multiple-unit enteric coated dosage form, Diclo-Puren® capsules, and to develop a predictive model for its oral pharmacokinetic profile. The paddle method was used to obtain the dissolution profiles of this dosage form in biorelevant media, with the exposure to simulated gastric conditions being varied in order to simulate the gastric emptying behavior of pellets. A modified Noyes-Whitney theory was subsequently fitted to the dissolution data. A physiologically-based pharmacokinetic (PBPK) model for multiple-unit dosage forms was designed using STELLA® software and coupled with the biorelevant dissolution profiles in order to simulate the plasma concentration profiles of diclofenac from Diclo-Puren® capsule in both the fasted and fed state in humans. Gastric emptying kinetics relevant to multiple-units pellets were incorporated into the PBPK model by setting up a virtual patient population to account for physiological variations in emptying kinetics. Using in vitro biorelevant dissolution coupled with in silico PBPK modeling and simulation it was possible to predict the plasma profile of this multiple-unit formulation of diclofenac after oral administration in both the fasted and fed state. This approach might be useful to predict variability in the plasma profiles for other drugs housed in multiple-unit dosage forms. Copyright © 2014 Elsevier B.V. All rights reserved.

Physiological parameters for oral delivery and in vitro testing.

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Mudie, Deanna M; Amidon, Gordon L; Amidon, Gregory E

2010-10-04

Pharmaceutical solid oral dosage forms must undergo dissolution in the intestinal fluids of the gastrointestinal tract before they can be absorbed and reach the systemic circulation. Therefore, dissolution is a critical part of the drug-delivery process. The rate and extent of drug dissolution and absorption depend on the characteristics of the active ingredient as well as properties of the dosage form. Just as importantly, characteristics of the physiological environment such as buffer species, pH, bile salts, gastric emptying rate, intestinal motility, and hydrodynamics can significantly impact dissolution and absorption. While significant progress has been made since 1970 when the first compendial dissolution test was introduced (USP apparatus 1), current dissolution testing does not take full advantage of the extensive physiologic information that is available. For quality control purposes, where the question is one of lot-to-lot consistency in performance, using nonphysiologic test conditions that match drug and dosage form properties with practical dissolution media and apparatus may be appropriate. However, where in vitro-in vivo correlations are desired, it is logical to consider and utilize knowledge of the in vivo condition. This publication critically reviews the literature that is relevant to oral human drug delivery. Physiologically relevant information must serve as a basis for the design of dissolution test methods and systems that are more representative of the human condition. As in vitro methods advance in their physiological relevance, better in vitro-in vivo correlations will be possible. This will, in turn, lead to in vitro systems that can be utilized to more effectively design dosage forms that have improved and more consistent oral bioperformance.

Non-Conventional Applications of Computerized Tomography: Analysis of Solid Dosage Forms Produced by Pharmaceutical Industry

International Nuclear Information System (INIS)

Martins de Oliveira, Jose Jr.; Germano Martins, Antonio Cesar

2010-01-01

X-ray computed tomography (CT) refers to the cross-sectional imaging of an object measuring the transmitted radiation at different directions. In this work, we describe a non-conventional application of computerized tomography: visualization and improvements in the understanding of some internal structural features of solid dosage forms. A micro-CT X-ray scanner, with a minimum resolution of 30 μm was used to characterize some pharmaceutical tablets, granules, controlled-release osmotic tablet and liquid-filled soft-gelatin capsules. The analysis presented in this work are essentially qualitative, but quantitative parameters, such as porosity, density distribution, tablets dimensions, etc. could also be obtained using the related CT techniques.

Buccal Dosage Forms: General Considerations for Pediatric Patients.

Science.gov (United States)

Montero-Padilla, Soledad; Velaga, Sitaram; Morales, Javier O

2017-02-01

The development of an appropriate dosage form for pediatric patients needs to take into account several aspects, since adult drug biodistribution differs from that of pediatrics. In recent years, buccal administration has become an attractive route, having different dosage forms under development including tablets, lozenges, films, and solutions among others. Furthermore, the buccal epithelium can allow quick access to systemic circulation, which could be used for a rapid onset of action. For pediatric patients, dosage forms to be placed in the oral cavity have higher requirements for palatability to increase acceptance and therapy compliance. Therefore, an understanding of the excipients required and their functions and properties needs to be particularly addressed. This review is focused on the differences and requirements relevant to buccal administration for pediatric patients (compared to adults) and how novel dosage forms can be less invasive and more acceptable alternatives.

Optimization and Evaluation of Desloratadine Oral Strip: An Innovation in Paediatric Medication

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Harmanpreet Singh

2013-01-01

Full Text Available Patients, especially children, are the most difficult to treat in all groups of population mainly because they can not swallow the solid dosage form. Due to this reason they are often prescribed liquid dosage forms. But these formulations have their own disadvantages (lack of dose accuracy during administration, spitting by children, spillage, lack of stability, difficulty in transportation, etc.. Oral strip technology is one such technology to surpass these disadvantages. Desloratadine, a descarboethoxy derivative of loratadine, is a second generation antihistaminic drug approved for usage in allergic rhinitis among paediatric population and is available in markets as suspension. An attempt has been made to design and optimize the oral strip containing desloratadine as an active ingredient. Oral strip was optimized with the help of optimal experimental design using polymer concentration, plasticizer type, and plasticizer concentration as independent variables. Prepared oral strips were evaluated for physicochemical parameter, mechanical strength parameters, disintegration time, dissolution, surface pH, and moisture sorption tendency. Optimized formulation was further evaluated by scanning electron microscopy, moisture content, and histological alteration in oral mucosa. Accelerated stability studies were also carried out for optimized formulations. Results were analysed with the help of various statistical tools at and .

Polymer adhesion predictions for oral dosage forms to enhance drug administration safety. Part 2: In vitro approach using mechanical force methods.

Science.gov (United States)

Drumond, Nélio; Stegemann, Sven

2018-06-01

Predicting the potential for unintended adhesion of solid oral dosage forms (SODF) to mucosal tissue is an important aspect that should be considered during drug product development. Previous investigations into low strength mucoadhesion based on particle interactions methods provided evidence that rheological measurements could be used to obtain valid predictions for the development of SODF coatings that can be safely swallowed. The aim of this second work was to estimate the low mucoadhesive strength properties of different polymers using in vitro methods based on mechanical forces and to identify which methods are more precise when measuring reduced mucoadhesion. Another aim was to compare the obtained results to the ones achieved with in vitro particle interaction methods in order to evaluate which methodology can provide stronger predictions. The combined results correlate between particle interaction methods and mechanical force measurements. The polyethylene glycol grades (PEG) and carnauba wax showed the lowest adhesive potential and are predicted to support safe swallowing. Hydroxypropyl methylcellulose (HPMC) along with high molecular grades of polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) exhibited strong in vitro mucoadhesive strength. The combination of rheological and force tensiometer measurements should be considered when assessing the reduced mucoadhesion of polymer coatings to support safe swallowing of SODF. Copyright © 2018 Elsevier B.V. All rights reserved.

A possible method using baseline hormonal levels to prescribe the appropriate oral therapeutic radioiodine dosage for Graves' disease

International Nuclear Information System (INIS)

Nakajo, Masayuki; Tsuchimochi, Shinsaku; Jinguji, Megumi; Tanabe, Hiroaki; Umanodan, Tomoichi; Nakabeppu, Yoshiaki

2007-01-01

The purpose of this study was to retrospectively examine the correlations of hormonal ratios with radioiodine I-131 therapeutic parameters and the potentiality of prescribing the therapeutic I-131 target dosage for an individual patient with Graves' disease using baseline serum levels of thyroid hormones. Serum T3, T4, and FT4 levels 6 and 12 months after I-131 therapy/baseline levels (hormonal ratios) were calculated for a total of 68 therapeutic courses in 57 patients with Graves' disease. The therapeutic parameters were absorbed dose (Gy), dose concentration (μCi/g) and oral dose (mCi). Linear regression analysis was performed for correlating hormonal ratios (X) and therapeutic parameters (Y). Significant (P<0.05) negative correlations of the hormonal ratios were observed with absorbed dose (R -0.50 for T3, -0.61 for T4, and -0.46 for FT4 at 6 months, and -0.29 for T3, -0.44 for T4 at 12 months) and dose concentration (R -0.57 for T3, -0.58 for T4, and -0.49 for FT4 at 6 months and -0.27 for T3, -0.27 for T4 at 12 months), but not with oral dose at 6 months and 12 months or the absorbed dose and dose concentration for FT4 at 12 months. The correlations were higher at 6 months than at 12 months and in serum T4 than in serum T3 and FT4. The formulae for serum T4 at 6 months were as follows: Y (Gy)=109-53X and Y (μCi/g)=109-52X. These results suggest that the hormonal ratios are significantly correlated with the absorbed dose and dose concentration. The formulae for serum T4 at 6 months may serve to prescribe the individual oral dosage for Graves' disease, although the correlation coefficients are about -0.6. (author)

Enhanced oral bioavailability and controlled release of dutasteride by a novel dry elixir.

Science.gov (United States)

Jang, Dong-Jin; Kim, Sung Tae; Oh, Euichaul; Ban, Eunmi

2014-01-01

To develop a solid dosage form of dutasteride for improving its oral bioavailability, a novel dry elixir (DE) system was fabricated. DEs incorporating dextrin and/or xanthan gum were prepared using spray-drying and evaluated by morphology, ethanol content, crystallinity, dissolution and oral bioavailability. DEs were spherical with a smooth surface and had an average particle size of 20-25 μm. The ethanol content could be easily varied by controlling the spray-drying temperature. The dissolution profiles of dutasteride from each DE proved to be much faster than that of dutasteride powder due to the amorphous state and a high amount of incorporated ethanol. In particular, the pharmacokinetic profiles of dutasteride were significantly altered depending on the proportions of dextrin and xanthan gum. Blood concentrations of dutasteride from DE formulations were similar to those of market products and much greater than those of native dutasteride. Interestingly, the dissolution and pharmacokinetic profiles were easily controlled by changing the ratio of dextrin to xanthan gum. The data suggests that a DE using dextrin and/or xanthan gum could provide an applicable solid dosage form to improve the dissolution and bio-availability of dutasteride as well as to modulate its pharmacokinetics.

Emergence of 3D Printed Dosage Forms: Opportunities and Challenges.

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Alhnan, Mohamed A; Okwuosa, Tochukwu C; Sadia, Muzna; Wan, Ka-Wai; Ahmed, Waqar; Arafat, Basel

2016-08-01

The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such an extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry.

Metabolism and elimination of methyl, iso- and n-butyl paraben in human urine after single oral dosage.

Science.gov (United States)

Moos, Rebecca K; Angerer, Jürgen; Dierkes, Georg; Brüning, Thomas; Koch, Holger M

2016-11-01

Parabens are used as preservatives in personal care and consumer products, food and pharmaceuticals. Their use is controversial because of possible endocrine disrupting properties. In this study, we investigated metabolism and urinary excretion of methyl paraben (MeP), iso-butyl paraben (iso-BuP) and n-butyl paraben (n-BuP) after oral dosage of deuterium-labeled analogs (10 mg). Each volunteer received one dosage per investigated paraben separately and at least 2 weeks apart. Consecutive urine samples were collected over 48 h. In addition to the parent parabens (free and conjugated) which are already used as biomarkers of internal exposure and the known but non-specific metabolites, p-hydroxybenzoic acid (PHBA) and p-hydroxyhippuric acid (PHHA), we identified new, oxidized metabolites with hydroxy groups on the alkyl side chain (3OH-n-BuP and 2OH-iso-BuP) and species with oxidative modifications on the aromatic ring. MeP represented 17.4 % of the dose excreted in urine, while iso-BuP represented only 6.8 % and n-BuP 5.6 %. Additionally, for iso-BuP, about 16 % was excreted as 2OH-iso-BuP and for n-BuP about 6 % as 3OH-n-BuP. Less than 1 % was excreted as ring-hydroxylated metabolites. In all cases, PHHA was identified as the major but non-specific metabolite (57.2-63.8 %). PHBA represented 3.0-7.2 %. For all parabens, the majority of the oral dose captured by the above metabolites was excreted in the first 24 h (80.5-85.3 %). Complementary to the parent parabens excreted in urine, alkyl-chain-oxidized metabolites of the butyl parabens are introduced as valuable and contamination-free biomarkers of exposure.

Preparation and in Vivo Evaluation of a Dutasteride-Loaded Solid-Supersaturatable Self-Microemulsifying Drug Delivery System

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Min-Soo Kim

2015-05-01

Full Text Available The purpose of this study was to prepare a dutasteride-loaded solid-supersaturatable self-microemulsifying drug delivery system (SMEDDS using hydrophilic additives with high oral bioavailability, and to determine if there was a correlation between the in vitro dissolution data and the in vivo pharmacokinetic parameters of this delivery system in rats. A dutasteride-loaded solid-supersaturatable SMEDDS was generated by adsorption of liquid SMEDDS onto Aerosil 200 colloidal silica using a spray drying process. The dissolution and oral absorption of dutasteride from solid SMEDDS significantly increased after the addition of hydroxypropylmethyl cellulose (HPMC or Soluplus. Solid SMEDDS/Aerosil 200/Soluplus microparticles had higher oral bioavailability with 6.8- and 5.0-fold higher peak plasma concentration (Cmax and area under the concentration-time curve (AUC values, respectively, than that of the equivalent physical mixture. A linear correlation between in vitro dissolution efficiency and in vivo pharmacokinetic parameters was demonstrated for both AUC and Cmax values. Therefore, the preparation of a solid-supersaturatable SMEDDS with HPMC or Soluplus could be a promising formulation strategy to develop novel solid dosage forms of dutasteride.

Dropwise additive manufacturing of pharmaceutical products for melt-based dosage forms.

Science.gov (United States)

Içten, Elçin; Giridhar, Arun; Taylor, Lynne S; Nagy, Zoltan K; Reklaitis, Gintaras V

2015-05-01

The US Food and Drug Administration introduced the quality by design approach and process analytical technology guidance to encourage innovation and efficiency in pharmaceutical development, manufacturing, and quality assurance. As part of this renewed emphasis on the improvement of manufacturing, the pharmaceutical industry has begun to develop more efficient production processes with more intensive use of online measurement and sensing, real-time quality control, and process control tools. Here, we present dropwise additive manufacturing of pharmaceutical products (DAMPP) as an alternative to conventional pharmaceutical manufacturing methods. This mini-manufacturing process for the production of pharmaceuticals utilizes drop on demand printing technology for automated and controlled deposition of melt-based formulations onto edible substrates. The advantages of drop-on-demand technology, including reproducible production of small droplets, adjustable drop sizing, high placement accuracy, and flexible use of different formulations, enable production of individualized dosing even for low-dose and high-potency drugs. In this work, DAMPP is used to produce solid oral dosage forms from hot melts of an active pharmaceutical ingredient and a polymer. The dosage forms are analyzed to show the reproducibility of dosing and the dissolution behavior of different formulations. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Development of a stability-indicating high performance liquid chromatography method for assay of erythromycin ethylsuccinate in powder for oral suspension dosage form

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Fahimeh Kamarei

2014-12-01

Full Text Available In this study an effective method was developed to assay erythromycin ethylsuccinate for an oral suspension dosage form. The chromatographic separation was achieved on an X-Terra™ C18 analytical column. A mixture of acetonitrile–ammonium dihydrogen phosphate buffer (0.025 mol L-1 (60:40, V/V (pH 7.0 was used as the mobile phase, effluent flow rate monitored at 1.0 mL min−1, and UV detection at 205 nm. In forced degradation studies, the effects of acid, base, oxidation, UV light and temperature were investigated showing no interference in the peak of drug. The proposed method was validated in terms of specificity, linearity, robustness, precision and accuracy. The method was linear at concentrations ranging from 400 to 600 μg mL−1, precise (intra- and inter-day relative standard deviations <0.65, accurate (mean recovery; 99.5%. The impurities and degradation products of erythromycin ethylsuccinate were selectively determined with good resolution in both the raw material and the final suspension forms. The method could be useful for both routine analytical and quality control assays of erythromycin ethylsuccinate in commercial powder for an oral suspension dosage form and it could be a very powerful tool to investigate the chemical stability of erythromycin ethylsuccinate.

Integrity of the oral tissues in patients with solid-organ transplants.

Science.gov (United States)

Rojas, Gonzalo; Bravo, Loreto; Cordero, Karina; Sepúlveda, Luis; Elgueta, Leticia; Díaz, Juan Carlos; Urzúa, Blanca; Morales, Irene

2012-01-01

The relationship between the use of immunosuppressants in solid-organ transplant patients and oral tissue abnormalities has been recognized. The objective of this study was to determine the state of oral tissue integrity in renal, heart, and liver transplant patients who are on continuous medical and dental control. Forty patients of both sexes were clinically evaluated at the Clinical Hospital of the University of Chile to identify pathologies of oral mucosa, gingival enlargement (GE), decayed, missing, filled teeth (DMFT) index, and salivary flow. The average age of the transplant subjects was 49.4 years, and the age range was 19 to 69 years. Most subjects maintained a good level of oral hygiene, and the rate mean of DMFT was 14.7. The degree of involvement of the oral mucosa and GE was low (10%). Unlike other studies, the frequency of oral mucosal diseases and GE was low despite the fact that these patients were immunosuppressed. Care and continuous monitoring seem to be of vital importance in maintaining the oral health of transplant patients.

Integrity of the Oral Tissues in Patients with Solid-Organ Transplants

Directory of Open Access Journals (Sweden)

Gonzalo Rojas

2012-01-01

Full Text Available The relationship between the use of immunosuppressants in solid-organ transplant patients and oral tissue abnormalities has been recognized. The objective of this study was to determine the state of oral tissue integrity in renal, heart, and liver transplant patients who are on continuous medical and dental control. Forty patients of both sexes were clinically evaluated at the Clinical Hospital of the University of Chile to identify pathologies of oral mucosa, gingival enlargement (GE, decayed, missing, filled teeth (DMFT index, and salivary flow. The average age of the transplant subjects was 49.4 years, and the age range was 19 to 69 years. Most subjects maintained a good level of oral hygiene, and the rate mean of DMFT was 14.7. The degree of involvement of the oral mucosa and GE was low (10%. Unlike other studies, the frequency of oral mucosal diseases and GE was low despite the fact that these patients were immunosuppressed. Care and continuous monitoring seem to be of vital importance in maintaining the oral health of transplant patients.

Development and Validation of RP-HPLC Method for the Simultaneous Determination of Rabeprazole Sodium and Itopride Hydrochloride in Solid Dosage Form

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Rajesh Sharma

2010-01-01

Full Text Available A simple, sensitive, precise, accurate, rapid and reproducible reverse phase high performance liquid chromatographic procedure is developed for simultaneous determination of rabeprazole sodium and itopride hydrochloride in solid dosage form. The mobile phase used was a combination of acetonitrile: buffer (35:65 v/v and the pH was adjusted to 7.0 ± 0.1 by addition of triethylamine. The detection of the capsule dosage form was carried out at 266 nm and a flow rate employed was 1 mL/min. Linearity was obtained in the concentration range of 2 to 16 μg/mL of rabeprazole sodium and 5 to 55 μg/mL of itopride hydrochloride with a correlation coefficient of 0.9992 and 0.9996 respectively. The results of the analysis were validated statistically and recovery studies confirmed the accuracy of the proposed method.

Effect of Calcium Ions on the Disintegration of Enteric-Coated Solid Dosage Forms.

Science.gov (United States)

Al-Gousous, Jozef; Langguth, Peter

2016-02-01

To investigate the effect of calcium ions on the disintegration of enteric-coated dosage forms, disintegration testing was performed on enteric-coated aspirin tablets in the presence and absence of calcium in the test media. The results show that the presence of calcium ions retards the disintegration of enteric-coated dosage forms. This finding, which has not been reported in scientific literature, sheds light on the importance of conducting well-designed detailed investigations into the potential of calcium from dietary sources, calcium supplements, antacids, and/or phosphate binders affecting the absorption of drugs formulated into enteric-coated dosage forms. Moreover, it shows the necessity to investigate the potential of the occurrence of additional nutrient-excipient interactions. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process.

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Ha, Eun-Sol; Kim, Jeong-Soo; Baek, In-Hwan; Yoo, Jin-Wook; Jung, Yunjin; Moon, Hyung Ryong; Kim, Min-Soo

2015-01-01

In the present study, solid dispersion nanoparticles with a hydrophilic polymer and surfactant were developed using the supercritical antisolvent (SAS) process to improve the dissolution and oral absorption of megestrol acetate. The physicochemical properties of the megestrol acetate solid dispersion nanoparticles were characterized using scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction, and a particle-size analyzer. The dissolution and oral bioavailability of the nanoparticles were also evaluated in rats. The mean particle size of all solid dispersion nanoparticles that were prepared was nanoparticles. Hydroxypropylmethyl cellulose (HPMC) solid dispersion nanoparticles significantly increased the maximum dissolution when compared with polyvinylpyrrolidone K30 solid dispersion nanoparticles. The extent and rate of dissolution of megestrol acetate increased after the addition of a surfactant into the HPMC solid dispersion nanoparticles. The most effective surfactant was Ryoto sugar ester L1695, followed by D-α-tocopheryl polyethylene glycol 1000 succinate. In this study, the solid dispersion nanoparticles with a drug:HPMC:Ryoto sugar ester L1695 ratio of 1:2:1 showed >95% rapid dissolution within 30 minutes, in addition to good oral bioavailability, with approximately 4.0- and 5.5-fold higher area under the curve (0-24 hours) and maximum concentration, respectively, than raw megestrol acetate powder. These results suggest that the preparation of megestrol acetate solid dispersion nanoparticles using the supercritical antisolvent process is a promising approach to improve the dissolution and absorption properties of megestrol acetate.

Effect of lead acetate administered orally at different dosage levels ...

African Journals Online (AJOL)

The project was conducted to evaluate the effect of lead administered as lead acetate at different dosage levels via drinking water in broiler chicks. Thirty-five healthy chicks were divided into seven groups (five chicks each) and one group was kept as un-medicated control. Groups A, B, C, D, E and F were medicated with ...

Determination of methadone hydrochloride in a maintenance dosage formulation.

Science.gov (United States)

Hoffmann, T J; Thompson, R D

1975-07-01

A colorimetric method for direct quantitative assay of methadone hydrochloride in liquid oral dosage forms is presented. The procedure involves the formation of a dye complex with bromothymol blue buffer solution. The resultant complex is extracted with benzene and measured spectrophotometrically. Duplicate tests on the formulation showed 99.2% of the labeled amount of methadone.

Solid dispersions in oncology: a solution to solubility-limited oral drug absorption

NARCIS (Netherlands)

Sawicki, Emilia

2017-01-01

This thesis discusses the formulation method solid dispersion and how it works to resolve solubility-limited absorption of orally dosed anticancer drugs. Dissolution in water is essential for drug absorption because only dissolved drug molecules are absorbed. The problem is that half of the arsenal

Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit® E

Directory of Open Access Journals (Sweden)

Youngseok Cho

2015-05-01

Full Text Available The present study aimed to investigate the effect of Eudragit® E/HCl (E-SD on the degradation of sirolimus in simulated gastric fluid (pH 1.2 and to develop a new oral formulation of sirolimus using E-SD solid dispersions to enhance oral bioavailability. Sirolimus-loaded solid dispersions were fabricated by a spray drying process. A kinetic solubility test demonstrated that the sirolimus/E-SD/TPGS (1/8/1 solid dispersion had a maximum solubility of 196.7 μg/mL within 0.5 h that gradually decreased to 173.4 μg/mL after 12 h. According to the dissolution study, the most suitable formulation was the sirolimus/E-SD/TPGS (1/8/1 solid dispersion in simulated gastric fluid (pH 1.2, owing to enhanced stability and degree of supersaturation of E-SD and TPGS. Furthermore, pharmacokinetic studies in rats indicated that compared to the physical mixture and sirolimus/HPMC/TPGS (1/8/1 solid dispersion, the sirolimus/E-SD/TPGS (1/8/1 solid dispersion significantly improved oral absorption of sirolimus. E-SD significantly inhibited the degradation of sirolimus in a dose-dependent manner. E-SD also significantly inhibited the precipitation of sirolimus compared to hydroxypropylmethyl cellulose (HPMC. Therefore, the results from the present study suggest that the sirolimus-loaded E-SD/TPGS solid dispersion has great potential in clinical applications.

Disintegration of chemotherapy tablets for oral administration in patients with swallowing difficulties.

Science.gov (United States)

Siden, Rivka; Wolf, Matthew

2013-06-01

The administration of oral chemotherapeutic drugs can be problematic in patients with swallowing difficulties. Inability to swallow solid dosage forms can compromise compliance and may lead to poor clinical outcome. The current technique of tablet crushing to aid in administration is considered an unsafe practice. By developing a technique to disintegrate tablets in an oral syringe, the risk associated with tablet crushing can be avoided. The purpose of this study was to determine the feasibility of using disintegration in an oral syringe for the administration of oral chemotherapeutic tablets. Eight commonly used oral chemotherapeutic drugs were tested. Tablets were placed in an oral syringe and allowed to disintegrate in tap water. Various volumes and temperatures were tested to identify which combination allows for complete disintegration of the tablet in the shortest amount of time. The oral syringe disintegration method was considered feasible if disintegration occurred in ≤15 min and in ≤20 mL of water and the dispersion passed through an oral syringe tip. The following tablets were shown to disintegrate within 15 min and in disintegration test. Disintegrating oral chemotherapeutic tablets in a syringe provides a closed system to administer hazardous drugs and allows for the safe administration of oral chemotherapeutic drugs in a tablet form to patients with swallowing difficulties.

Quality of 'Climax' blueberries after low dosage electron beam irradiation

International Nuclear Information System (INIS)

Miller, W.R.; McDonald, R.E.; McCollum, T.G.; Smittle, B.J.

1994-01-01

Fruit of 'Climax' rabbiteye blueberries (Vaccinium ashei Reade) were irradiated by a linear accelerator at 0, 0.25, 0.5, 0.75, 1.0, and 1.25 kGy and evaluated for various quality attributes after storage for 1, 3, 7, or 14 days at 1C plus 2 days at 15C, respectively. Weight loss increased during storage and averaged 4.2% after the final inspection and was not affected by irradiation dosage. About 5% of total berries were decayed after 14 days at 1C, about 6% after the final inspection at 15C, but decay was not affected by the level of irradiation. Electrolyte leakage, skin color, total soluble solids, acidity, and pH were also not affected by irradiation dosage. There was a significant decline in berry firmness, flavor, and texture as dosage increased. Berries treated at 1.0 kGy or above were softer and had lower flavor and texture preference scores than berries treated at lower dosages or nontreated berries

Comparative pharmacokinetic study of dosage forms with morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate

Directory of Open Access Journals (Sweden)

I. V. Bushueva

2014-12-01

] acetate elimination from the body of the animal occurs within 1 hour, and then only trace amount of the drug substanceis detected in serum. After oral and rectal dosage forms of morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate its maximum concentration in the blood of laboratory animals is recorded at 60 minutes after administration of the capsules and suppositories respectively. Thereafter, for 2-2, 5 it is supported at a high level. At the same time, no significant differences in the kinetics of the drug administered dose. 24 hours after single oral administration and rectal capsules and suppositories of morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate is not detected in the serum. Comparative analysis of the pharmacokinetics of morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate depending on the kind of administration and the dosage form shows that after oral administration in capsule form, and rectal administration as a suppository absorption rate constants, elimination, half-life periods floor suction and depending on the dose administered differ slightly. Also, almost no relationship between dose and orally administered rectally morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate and total quantities (of plasma clearance, since the difference between the drug administered in doses of 5 times the value of the latter increased only 1.2 times. Degree of morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate absolute bioavailability after oral and rectal administration, is practically independent from the dose. The magnitude of this indicator for rectal suppository almost 3 times higher than that for oral capsules of morpholinium 2-[5-(pyridin-4-yl-1,2,4-triazol-3-ylthio] acetate. This indicates the great promise of his rectal dosage form. Conclusion. The degree of its absolute bioavailability for rectal dosage form doesn’t depend on administered dose and is nearly twice higher than for the oral solid

Contraceptive Use Affects Overall Olfactory Performance: Investigation of Estradiol Dosage and Duration of Intake.

Directory of Open Access Journals (Sweden)

Kathrin Kollndorfer

Full Text Available The influence of female sex steroids on cognitive performance and sensory perception has been investigated for decades. However, previous research that studied olfaction revealed inconsistent results. The main aim of this study was to investigate the effects of different ethinyl estradiol (EE concentrations of oral contraceptives and duration of intake on olfactory function. Forty-two healthy women, with regular intake of either high or low EE dosage over at least one year and up to 15 years participated in this study. Results revealed a significant concordance between a priori categorization in the two groups with high and low EE dosage and data-driven hierarchical clustering (p = 0.008. Furthermore, significantly higher olfactory performance was observed in women using low-dose products compared to women using high-dosed products (p = 0.019. These findings indicate different effects of pill use with regard to EE concentration. We therefore strongly recommend the acquisition of information about EE dosage of oral contraceptives to reduce potential confounding factors when investigating sensory systems.

Novel Nanostructured Solid Materials for Modulating Oral Drug Delivery from Solid-State Lipid-Based Drug Delivery Systems.

Science.gov (United States)

Dening, Tahnee J; Rao, Shasha; Thomas, Nicky; Prestidge, Clive A

2016-01-01

Lipid-based drug delivery systems (LBDDS) have gained significant attention in recent times, owing to their ability to overcome the challenges limiting the oral delivery of poorly water-soluble drugs. Despite the successful commercialization of several LBDDS products over the years, a large discrepancy exists between the number of poorly water-soluble drugs displaying suboptimal in vivo performances and the application of LBDDS to mitigate their various delivery challenges. Conventional LBDDS, including lipid solutions and suspensions, emulsions, and self-emulsifying formulations, suffer from various drawbacks limiting their widespread use and commercialization. Accordingly, solid-state LBDDS, fabricated by adsorbing LBDDS onto a chemically inert solid carrier material, have attracted substantial interest as a viable means of stabilizing LBDDS whilst eliminating some of the various limitations. This review describes the impact of solid carrier choice on LBDDS performance and highlights the importance of appropriate solid carrier material selection when designing hybrid solid-state LBDDS. Specifically, emphasis is placed on discussing the ability of the specific solid carrier to modulate drug release, control lipase action and lipid digestion, and enhance biopharmaceutical performance above the original liquid-state LBDDS. To encourage the interested reader to consider their solid carrier choice on a higher level, various novel materials with the potential for future use as solid carriers for LBDDS are described. This review is highly significant in guiding future research directions in the solid-state LBDDS field and fostering the translation of these delivery systems to the pharmaceutical marketplace.

76 FR 78815 - Oral Dosage Form New Animal Drugs; Cyclosporine

Science.gov (United States)

2011-12-20

..., Inc. The NADA provides for the veterinary prescription use of cyclosporine oral solution, USP.... FOR FURTHER INFORMATION CONTACT: Angela K.S. Clarke, Center for Veterinary Medicine (HFV-112), Food... (cyclosporine oral solution, USP (MODIFIED)) by veterinary prescription for the control of feline allergic...

Klucel™ EF and ELF polymers for immediate-release oral dosage forms prepared by melt extrusion technology.

Science.gov (United States)

Mohammed, Noorullah Naqvi; Majumdar, Soumyajit; Singh, Abhilasha; Deng, Weibin; Murthy, Narasimha S; Pinto, Elanor; Tewari, Divya; Durig, Thomas; Repka, Michael A

2012-12-01

The objective of this research work was to evaluate Klucel™ hydroxypropylcellulose (HPC) EF and ELF polymers, for solubility enhancement as well as to address some of the disadvantages associated with solid dispersions. Ketoprofen (KPR), a Biopharmaceutics Classification System class II drug with poor solubility, was utilized as a model compound. Preliminary thermal studies were performed to confirm formation of a solid solution/dispersion of KPR in HPC matrix and also to establish processing conditions for hot-melt extrusion. Extrudates pelletized and filled into capsules exhibited a carrier-dependent release with ELF polymer exhibiting a faster release. Tablets compressed from milled extrudates exhibited rapid release owing to the increased surface area of the milled extrudate. Addition of mannitol (MNT) further enhanced the release by forming micro-pores and increasing the porosity of the extrudates. An optimized tablet formulation constituting KPR, MNT, and ELF in a 1:1:1 ratio exhibited 90% release in 15 min similar to a commercial capsule formulation. HPC polymers are non-ionic hydrophilic polymers that undergo polymer-chain-length-dependent solubilization and can be used to enhance solubility or dissolution rate of poorly soluble drugs. Dissolution/release rate could be tailored for rapid-release applications by selecting a suitable HPC polymer and altering the final dosage form. The release obtained from pellets was carrier-dependent and not drug-dependent, and hence, such a system can be effectively utilized to address solubility or precipitation issues with poorly soluble drugs in the gastrointestinal environment.

Development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process

Directory of Open Access Journals (Sweden)

Ha ES

2015-08-01

Full Text Available Eun-Sol Ha,1 Jeong-Soo Kim,2 In-hwan Baek,3 Jin-Wook Yoo,1 Yunjin Jung,1 Hyung Ryong Moon,1 Min-Soo Kim1 1College of Pharmacy, Pusan National University, 2Dong-A ST Co Ltd, Yongin, 3College of Pharmacy, Kyungsung University, Busan, South Korea Abstract: In the present study, solid dispersion nanoparticles with a hydrophilic polymer and surfactant were developed using the supercritical antisolvent (SAS process to improve the dissolution and oral absorption of megestrol acetate. The physicochemical properties of the megestrol acetate solid dispersion nanoparticles were characterized using scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction, and a particle-size analyzer. The dissolution and oral bioavailability of the nanoparticles were also evaluated in rats. The mean particle size of all solid dispersion nanoparticles that were prepared was <500 nm. Powder X-ray diffraction and differential scanning calorimetry measurements showed that megestrol acetate was present in an amorphous or molecular dispersion state within the solid dispersion nanoparticles. Hydroxypropylmethyl cellulose (HPMC solid dispersion nanoparticles significantly increased the maximum dissolution when compared with polyvinylpyrrolidone K30 solid dispersion nanoparticles. The extent and rate of dissolution of megestrol acetate increased after the addition of a surfactant into the HPMC solid dispersion nanoparticles. The most effective surfactant was Ryoto sugar ester L1695, followed by d-a-tocopheryl polyethylene glycol 1000 succinate. In this study, the solid dispersion nanoparticles with a drug:HPMC:Ryoto sugar ester L1695 ratio of 1:2:1 showed >95% rapid dissolution within 30 minutes, in addition to good oral bioavailability, with approximately 4.0- and 5.5-fold higher area under the curve (0–24 hours and maximum concentration, respectively, than raw megestrol acetate powder. These results suggest that the preparation of megestrol

Pharmaceutical development of an intravenous dosage form of diacetylmorphine hydrochloride

NARCIS (Netherlands)

Klous, Marjolein G.; Nuijen, Bastiaan; van den Brink, Wim; van Ree, Jan M.; Beijnen, Jos H.

2004-01-01

A solid dosage form for multiple use was developed for parenteral administration of diacetylmorphine in a clinical trial on co-prescription of heroin to heroin addicts. A 300-mg/mL diacetylmorphine hydrochloride solution was lyophilised as 10-mL aliquots in 30-mL glass vials, to be reconstituted to

Enhanced oral bioavailability of felodipine by novel solid self-microemulsifying tablets.

Science.gov (United States)

Jing, Boyu; Wang, Zhiyuan; Yang, Rui; Zheng, Xia; Zhao, Jia; Tang, Si; He, Zhonggui

2016-01-01

The novel self-microemulsifying (SME) tablets were developed to enhance the oral bioavailability of a poor water-soluble drug felodipine (FDP). Firstly, FDP was dissolved in the optimized liquid self-microemusifying drug delivery systems (SMEDDS) containing Miglyol® 812, Cremophor® RH 40, Tween 80 and Transcutol® P, and the mixture was solidified with porous silicon dioxide and crospovidone as adsorbents. Then after combining the solidified powders with other excipients, the solid SME tablets were prepared by wet granulation-compression method. The prepared tablets possessed satisfactory characterization; the droplet size of the SME tablets following self-emulsification in water was nearly equivalent to the liquid SMEDDS (68.4 ± 14.0 and 64.4 ± 12.0 nm); differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) analysis demonstrated that FDP in SME tablets had undergone a polymorphism transition from a crystal form to an amorphous state, which was further confirmed by transmission electron microscopy (TEM). A similar dissolution performance of SME tablets and liquid SMEDDS was also obtained under the sink condition (85% within 10 min), both significantly higher than commercial tablets. The oral bioavailability was evaluated for the SME tablets, liquid SMEDDS and commercial conventional tablets in the fasted beagle dogs. The AUC of FDP from the SME tablets was about 2-fold greater than that of conventional tablets, but no significant difference was found when compared with the liquid SMEDDS. Accordingly, these preliminary results suggest that this formulation approach offers a useful large-scale producing method to prepare the solid SME tablets from the liquid SMEDDS for oral bioavailability equivalent enhancement of poorly soluble FDP.

Oral ketamine for children with chronic pain: a pilot phase 1 study

Science.gov (United States)

Bredlau, Amy-Lee; McDermott, Michael P.; Adams, Heather; Dworkin, Robert H; Venuto, Charles; Fisher, Susan; Dolan, James G; Korones, David N

2013-01-01

Objective To assess whether oral ketamine aids is is safe at higher dosages for sedating children and whether it may be an option for control of chronic pain in children. Study design A prospective study was performed on 12 children with chronic pain to identify the maximum tolerated dosage of oral ketamine. Participants were given 14 days of oral ketamine, three times daily, at dosages ranging from 0.25–1.5 mg/kg/dose. Participants were assessed for toxicity and for pain severity at baseline and on day 14 of treatment. Results Two participants, both treated at 1.5 mg/kg/dose, experienced dose-limiting toxicities (sedation and anorexia). One participant, treated at 1 mg/kg/dose, opted to stop ketamine treatment due to new pain on treatment. Nine participants completed their course of ketamine treatment. Of these 12 children, 5 experienced improvement in their pain scores, two with complete resolution of pain, lasting for more than 4 weeks off ketamine treatment. Conclusion Oral ketamine at dosages of 0.25–1 mg/kg/dose appears to be safe when given for 14 days to children with chronic pain. PMID:23403253

Instrumental and sensory quantification of oral coatings retained after swallowing semi-solid foods

NARCIS (Netherlands)

Prinz, J.F.; Huntjens, L.; Wijk, de R.A.

2006-01-01

After a mouthful of food has been swallowed, some food material is always retained in the mouth. With semi-solid foods this is in the form of a coating that adheres to the oral mucosa. The amount and location of this material may play an important role in food sensations. In this study two

How to stabilize cilazapril-containing solid dosage forms? The optimization of a final drug formulation

Directory of Open Access Journals (Sweden)

Katarzyna Regulska

2017-03-01

. It was suggested that in the manufacture of cilazapril-containing solid dosage forms the procedure of wet granulation should be avoided while hygroscopic excipients should be substituted by their non-hygroscopic counterparts.

A novel solid dosage form of rifampicin and isoniazid with improved functionality.

Science.gov (United States)

Gohel, Mukesh C; Sarvaiya, Krishnakant G

2007-08-24

The aim of the present investigation was to develop a novel dosage form of rifampicin and isoniazid to minimize degradation of rifampicin in acidic medium and to modulate the release of rifampicin in the stomach and isoniazid in the intestine. Gastroretentive tablets of rifampicin (150 mg) were prepared by the wet granulation method using hydroxypropyl methylcellulose, calcium carbonate, and polyethylene glycol 4000. The granules and tablets of rifampicin were characterized. Hard gelatin capsules (size 4) containing a compacted mass of isoniazid (150 mg) and dicalcium phosphate (75 mg) were enteric coated. Two tablets of rifampicin and 1 capsule (size 4) of isoniazid were put into a hard gelatin capsule (size 00). The in vitro drug release and in vitro drug degradation studies were performed. Rifampicin was released over 4 hours by zero-order kinetics from the novel dosage form. More than 90% of isoniazid was released in alkaline medium in 30 minutes. The results of dissolution studies with the US Pharmacopeia XXIII method revealed that a substantial amount of rifampicin was degraded from the immediate release capsule containing rifampicin and isoniazid powder owing to drug accumulation in the dissolution vessel and also to the presence of isoniazid. The degradation of rifampicin to 3-formyl rifampicin SV (3FRSV) was arrested (3.6%-4.8% degradation of rifampicin at 4 hours) because of the minimization of physical contact between the 2 drugs and controlled release of rifampicin in acidic medium in the modified Rossett-Rice apparatus. This study concludes that the problem of rifampicin degradation can be alleviated to a certain extent by this novel dosage form.

Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability

Directory of Open Access Journals (Sweden)

Guo S

2016-04-01

over 2.5-fold compared to RTV solution. Conclusion: We successfully discovered and developed novel ISNPs to manufacture RTV ISNP granules that were reconstitutable, stable, and palatable, and improved RTV bioavailability. The novel ISNP nanotechnology is a platform to manufacture oral solid dosage forms for poorly water-soluble drugs, especially for pediatric formulation development. Keywords: ritonavir, pediatric formulation, taste, pharmacokinetics, lipid formulation, drug loading

Physicochemical characterization of berberine chloride: a perspective in the development of a solution dosage form for oral delivery.

Science.gov (United States)

Battu, Sunil Kumar; Repka, Michael A; Maddineni, Sindhuri; Chittiboyina, Amar G; Avery, Mitchell A; Majumdar, Soumyajit

2010-09-01

The objective of the present research was to evaluate the physicochemical characteristics of berberine chloride and to assess the complexation of drug with 2-hydroxypropyl-β-cyclodextrin (HPβCD), a first step towards solution dosage form development. The parameters such as log P value were determined experimentally and compared with predicted values. The pH-dependent aqueous solubility and stability were investigated following standard protocols at 25°C and 37°C. Drug solubility enhancement was attempted utilizing both surfactants and cyclodextrins (CDs), and the drug/CD complexation was studied employing various techniques such as differential scanning calorimetry, Fourier transform infrared, nuclear magnetic resonance, and scanning electron microscopy. The experimental log P value suggested that the compound is fairly hydrophilic. Berberine chloride was found to be very stable up to 6 months at all pH and temperature conditions tested. Aqueous solubility of the drug was temperature dependent and exhibited highest solubility of 4.05 ± 0.09 mM in phosphate buffer (pH 7.0) at 25°C, demonstrating the effect of buffer salts on drug solubility. Decreased drug solubility was observed with increasing concentrations of ionic surfactants such as sodium lauryl sulfate and cetyl trimethyl ammonium bromide. Phase solubility studies demonstrated the formation of berberine chloride-HPβCD inclusion complex with 1:1 stoichiometry, and the aqueous solubility of the drug improved almost 4.5-fold in the presence of 20% HPβCD. The complexation efficiency values indicated that the drug has at least threefold greater affinity for hydroxypropyl-β-CD compared to randomly methylated-β-CD. The characterization techniques confirmed inclusion complex formation between berberine chloride and HPβCD and demonstrated the feasibility of developing an oral solution dosage form of the drug.

21 CFR 520.530 - Cythioate oral liquid.

Science.gov (United States)

2010-04-01

... greyhounds or in animals that are pregnant, sick, under stress, or recovering from surgery. Federal law... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.530 Cythioate oral liquid. (a...

Improved Dissolution and Oral Bioavailability of Celecoxib by a Dry Elixir System.

Science.gov (United States)

Cho, Kwan Hyung; Jee, Jun-Pil; Yang, Da A; Kim, Sung Tae; Kang, Dongjin; Kim, Dae-Young; Sim, Taeyong; Park, Sang Yeob; Kim, Kyeongsoon; Jang, Dong-Jin

2018-02-01

The purpose of this study was to develop and evaluate a dry elixir (DE) system for enhancing the dissolution rate and oral bioavailability of celecoxib. DE system has been used for improving solubility, oral bioavailability of poorly water-soluble drugs. The encapsulated drugs or solubilized drugs in the matrix are rapidly dissolved due to the co-solvent effect, resting in both an enhanced dissolution and bioavailability. DEs containing celecoxib were prepared by spray-drying method and characterized by morphology, drug/ethanol content, drug crystallinity, dissolution rate and oral bioavailability. The ethanol content and drug content in DE system could be easily altered by controlling the spraydrying conditions. The dissolution profile of celecoxib from DE proved to be much higher than that of celecoxib powder due to the nano-structured matrix, amorphous state and encapsulated ethanol. The bioavailability of celecoxib from DEs was compared with celecoxib powder alone and commercial product (Celebrex®) in rats. In particular, blood concentrations of celecoxib form DE formulation were much greater than those of native celecoxib and market product. The data demonstrate that the DE system could provide an useful solid dosage form to enhance the solubility, dissolution rate and oral bioavailability of celecoxib.

75 FR 26646 - Oral Dosage Form New Animal Drugs; Orbifloxacin Suspension

Science.gov (United States)

2010-05-12

.... The NADA provides for the veterinary prescription use of an oral suspension containing orbifloxacin... 12, 2010. FOR FURTHER INFORMATION CONTACT: Melanie R. Berson, Center for Veterinary Medicine (HFV-110..., filed NADA 141-305 that provides for veterinary prescription use of ORBAX (orbifloxacin) Oral Suspension...

Pasteurization as a tool to control the bio-burden in solid herbal dosage forms: A pilot study of formulating Ashoka tablets with an industrial perspective.

Science.gov (United States)

Pushpalatha, Hulikal Basavarajaiah; Pramod, Kumar; Sundaram, Ramachandran; Shyam, Ramakrishnan

2014-10-01

Irradiation and use of preservatives are routine procedures to control bio-burden in solid herbal dosage forms. Use of steam or pasteurization is even though reported in the literature, not many studies are available with respect to its application in reducing the bio-burden in herbal drug formulations. Hence, we undertook a series of studies to explore the suitability of pasteurization as a method to reduce bio-burden during formulation and development of herbal dosage forms, which will pave the way for preparing preservative-free formulations. Optimized Ashoka (Saraca indica) tablets were formulated and developed. The optimized formula was then subjected to pasteurization during formulation, with an aim to keep the microbial count well within the limits of pharmacopoeial standards. Then, three variants of the optimized Ashoka formulation - with preservative, without preservative and formulation without preservative and subjected to pasteurization, were compared by routine in-process parameters and stability studies. The results obtained indicate that Ashoka tablets manufactured by inclusion of the pasteurization technique not only showed the bio-burden to be within the limits of pharmacopoeial standards, but also exhibited the compliance with other parameters, such as stability and quality. The outcome of this pilot study shows that pasteurization can be employed as a distinctive method for reducing bio-burden during the formulation and development of herbal dosage forms, such as tablets.

Long-term (5 years), high daily dosage of dietary agmatine--evidence of safety: a case report.

Science.gov (United States)

Gilad, Gad M; Gilad, Varda H

2014-11-01

There is presently a great interest in the therapeutic potential of agmatine, decarboxylated arginine, for various diseases. Recent clinical studies have already shown that oral agmatine sulfate given for up to 3 weeks provides a safe and, as compared with current therapeutics, more effective treatment for neuropathic pain. These studies have ushered in the use of dietary agmatine as a nutraceutical. However, in view of information paucity, assessment of long-term safety of oral agmatine treatment is now clearly required. The authors of this report undertook to assess their own health status during ongoing consumption of a high daily dosage of oral agmatine over a period of 4-5 years. A daily dose of 2.67 g agmatine sulfate was encapsulated in gelatin capsules; the regimen consists of six capsules daily, each containing 445 mg, three in the morning and three in the evening after meals. Clinical follow-up consists of periodic physical examinations and laboratory blood and urine analyses. All measurements thus far remain within normal values and good general health status is sustained throughout the study period, up to 5 years. This case study shows for the first time that the recommended high dosage of agmatine may be consumed for at least 5 years without evidence of any adverse effects. These initial findings are highly important as they provide significant evidence for the extended long-term safety of a high daily dosage of dietary agmatine--a cardinal advantage for its utility as a nutraceutical.

Dependence of surface smoothing, sputtering and etching phenomena on cluster ion dosage

CERN Document Server

Song, J H; Choi, W K

2002-01-01

The dependence of surface smoothing and sputtering phenomena of Si (1 0 0) solid surfaces irradiated by CO sub 2 cluster ions on cluster-ion dosage was investigated using an atomic force microscope. The flux and total ion dosage of impinging cluster ions at the acceleration voltage of 50 kV were fixed at 10 sup 9 ions/cm sup 2 s and were scanned from 5x10 sup 1 sup 0 to 5x10 sup 1 sup 3 ions/cm sup 2 , respectively. The density of hillocks induced by cluster ion impact was gradually increased with the dosage up to 5x10 sup 1 sup 1 ions/cm sup 2 , which caused that the irradiated surface became rough from 0.4 to 1.24 nm in root-mean-square roughness (sigma sub r sub m sub s). At the boundary of the ion dosage of 10 sup 1 sup 2 ions/cm sup 2 , the density of the induced hillocks was decreased and sigma sub r sub m sub s was about 1.21 nm, not being deteriorated further. At the dosage of 5x10 sup 1 sup 3 ions/cm sup 2 , the induced hillocks completely disappeared and the surface became very flat as much as sigma...

[Pharmacokinetics and relative bioavailability of THC and THC-solid dispersion orally to mice at single dose].

Science.gov (United States)

Liao, Li; Hua, Hua; Zhao, Jun-Ning; Luo, Heng; Yang, An-Dong

2014-03-01

To establish a fast sensitive, reproducible LC-MS/MS method to study pharmacokinetic properties of THC, and compare relative bioavailability of THC and its solid dispersion in mice. 200 mice were divided randomly into two groups, and administered orally with THC and THC-solid dispersion after fasting (calculate on THC:400 mg x kg(-1)), used HPLC-MS/MS method to determine the THC concentration of each period at the following times: baseline ( predose ), 15, 30, 45 min, 1, 1.5, 2, 3, 4, 6, 24 h after dosing. Calculating the pharmacokinetic parameters according to the C-t curv, and then use the Phoenix WinNonlin software for data analysis. The calibration curves were linear over the range 9.06-972 microg x L(-1) for THC (R2 = 0.999). The limit of detection (LOD) was 0.7 microg x L(-1), respectively. The average extraction recoveries for THC was above 75%, The methodology recoveries were between 79% and 108%. The intra-day and inter-day RSD were less than 13%, the stability test showed that the plasma samples was stable under different conditions (RSD THC and THC-solid dispersion orally to mice shows as fllows: T(max), were 60 and 15 min, AUC(0-t) were 44 500.43 and 57 497.81 mg x L(-1) x min, AUC(0-infinity) were 51 226.00 and 68 031.48 mg x L(-1) x min, MRT(0-infinity) were 596.915 6, 661.747 7 min, CL(z)/F were 0.007 809 and 0.005 88 L x min(-1) x kg(-1). Compared with THC, the MRT and t1/2 of the THC-solid dispersion were all slightly extended, the t(max) was significantly reduced, AUC(0-24 h), AUC(0-infinity) and C(max) were all significantly higher, the relative bioavailability of THC-solid dispersion is 1.34 times of THC. The results of the experiment shows that the precision, accuracy, recovery and applicability were found to be adequate for the pharmacokinetic studies. After oral administration to mice, the relative bioavailability of THC-solid dispersion show significant improvement compared to THC.

Oral mucositis in patients treated with chemotherapy for solid tumors: a retrospective analysis of 150 cases

NARCIS (Netherlands)

Raber-Durlacher, J. E.; Weijl, N. I.; Abu Saris, M.; de Koning, B.; Zwinderman, A. H.; Osanto, S.

2000-01-01

The incidence and the severity of chemotherapy-associated oral mucositis were determined in a retrospective analysis of 150 patients with various solid tumors. In addition, possible risk factors for the development of mucositis were identified. Patients were treated with chemotherapeutic regimens

Gestational Diabetes Mellitus Management with Oral Hypoglycemic Agents

Science.gov (United States)

Ryu, Rachel J.; Hays, Karen E.; Hebert, Mary F.

2014-01-01

Oral hypoglycemic agents such as glyburide (second generation sulfonylurea) and metformin (biguanide) are attractive alternatives to insulin due to lower cost, ease of administration, and better patient adherence. The majority of evidence from retrospective and prospective studies suggests comparable efficacy and safety of oral hypoglycemic agents such as glyburide and metformin as compared to insulin when used in the treatment of women with gestational diabetes mellitus (GDM). Glyburide and metformin have altered pharmacokinetics during pregnancy and both agents cross the placenta. In this article, we review the efficacy, safety and dosage of oral hypoglycemic agents for the treatment of gestational diabetes mellitus. Additional research is needed to evaluate optimal dosage for glyburide and metformin during pregnancy. Comparative studies evaluating the effects of glyburide and metformin on long-term maternal and fetal outcomes are also needed. PMID:25315294

Oral transmucosal drug delivery for pediatric use.

Science.gov (United States)

Lam, Jenny K W; Xu, Yingying; Worsley, Alan; Wong, Ian C K

2014-06-01

The formulation of medicines for children remains a challenge. An ideal pediatric formulation must allow accurate dose administration and be in a dosage form that can be handled by the target age group. It is also important to consider the choices and the amount of excipients used in the formulation for this vulnerable age group. Although oral formulations are generally acceptable to most pediatric patients, they are not suitable for drugs with poor oral bioavailability or when a rapid clinical effect is required. In recent years, oral transmucosal delivery has emerged as an attractive route of administration for pediatric patients. With this route of administration, a drug is absorbed through the oral mucosa, therefore bypassing hepatic first pass metabolism and thus avoiding drug degradation or metabolism in the gastrointestinal tract. The high blood flow and relatively high permeability of the oral mucosa allow a quick onset of action to be achieved. It is a simple and non-invasive route of drug administration. However, there are several barriers that need to be overcome in the development of oral transmucosal products. This article aims to provide a comprehensive review of the current development of oral transmucosal delivery specifically for the pediatric population in order to achieve systemic drug delivery. The anatomical and physiological properties of the oral mucosa of infants and young children are carefully examined. The different dosage forms and formulation strategies that are suitable for young patients are discussed. © 2013.

Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers

Directory of Open Access Journals (Sweden)

Chih-Hung Lin

2017-04-01

Full Text Available Chemical and enzymatic barriers in the gastrointestinal (GI tract hamper the oral delivery of many labile drugs. The GI epithelium also contributes to poor permeability for numerous drugs. Drugs with poor aqueous solubility have difficulty dissolving in the GI tract, resulting in low bioavailability. Nanomedicine provides an opportunity to improve the delivery efficiency of orally administered drugs. Solid lipid nanoparticles (SLNs are categorized as a new generation of lipid nanoparticles consisting of a complete solid lipid matrix. SLNs used for oral administration offer several benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. The nontoxic excipients and sophisticated material engineering of SLNs tailor the controllable physicochemical properties of the nanoparticles for GI penetration via mucosal or lymphatic transport. In this review, we highlight the recent progress in the development of SLNs for disease treatment. Recent application of oral SLNs includes therapies for cancers, central nervous system-related disorders, cardiovascular-related diseases, infection, diabetes, and osteoporosis. In addition to drugs that may be active cargos in SLNs, some natural compounds with pharmacological activity are also suitable for SLN encapsulation to enhance oral bioavailability. In this article, we systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for drug- and natural compound-loaded SLNs.

Recent advances in oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers.

Science.gov (United States)

Lin, Chih-Hung; Chen, Chun-Han; Lin, Zih-Chan; Fang, Jia-You

2017-04-01

Chemical and enzymatic barriers in the gastrointestinal (GI) tract hamper the oral delivery of many labile drugs. The GI epithelium also contributes to poor permeability for numerous drugs. Drugs with poor aqueous solubility have difficulty dissolving in the GI tract, resulting in low bioavailability. Nanomedicine provides an opportunity to improve the delivery efficiency of orally administered drugs. Solid lipid nanoparticles (SLNs) are categorized as a new generation of lipid nanoparticles consisting of a complete solid lipid matrix. SLNs used for oral administration offer several benefits over conventional formulations, including increased solubility, enhanced stability, improved epithelium permeability and bioavailability, prolonged half-life, tissue targeting, and minimal side effects. The nontoxic excipients and sophisticated material engineering of SLNs tailor the controllable physicochemical properties of the nanoparticles for GI penetration via mucosal or lymphatic transport. In this review, we highlight the recent progress in the development of SLNs for disease treatment. Recent application of oral SLNs includes therapies for cancers, central nervous system-related disorders, cardiovascular-related diseases, infection, diabetes, and osteoporosis. In addition to drugs that may be active cargos in SLNs, some natural compounds with pharmacological activity are also suitable for SLN encapsulation to enhance oral bioavailability. In this article, we systematically introduce the concepts and amelioration mechanisms of the nanomedical techniques for drug- and natural compound-loaded SLNs. Copyright © 2017. Published by Elsevier B.V.

Prednisone raw material characterization and formulation development

OpenAIRE

Leonardo Henrique Toehwé; Livia Deris Prado; Helvécio Vinícius Antunes Rocha

2018-01-01

ABSTRACT Solid dosage forms for oral use, particularly tablets, are the most highly used dosage forms in therapy because they are easily administered, have high productivity and relatively low cost and provide a more stable drug to form a semi-solid net. Numerous parameters influence the quality of the final dosage form. In this study, the dissolution profile of 20-mg prednisone tablets bioequivalent to the reference product and three test formulations were evaluated using stability testing. ...

Orally-dissolving film for sublingual and buccal delivery of ropinirole.

Science.gov (United States)

Lai, Ka Lun; Fang, Yuan; Han, Hao; Li, Qingqing; Zhang, Shuai; Li, Ho Yin; Chow, Shing Fung; Lam, Tai Ning; Lee, Wai Yip Thomas

2018-03-01

Ropinirole is a very important treatment option for Parkinson's disease (PD), a major threat to the aging population. However, this drug undergoes extensive first-pass metabolism, resulting in a low oral bioavailability. Moreover, the necessity of frequent administration due to the short half-life of ropinirole may jeopardize patient compliance. Indeed, taking this drug in solid oral dosage forms (e.g. Tablet) can be a challenge because of the tremor, rigidity, limited mobility, and impaired drug absorption experienced by PD patients. In light of these, there is a pressing need to devise formulations for the delivery of ropinirole that allow simple and easy administration and fast drug action, as well as avoidance of first-pass metabolism and overcoming the challenge of impaired absorption due to gastrointestinal dysfunctions, etc. Herein, we seek to overcome all these challenges via sublingual or buccal delivery of orally-dissolving films. Accordingly, we aimed to fabricate and characterize orally-dissolving films of ropinirole and assess their in vivo pharmacokinetics after sublingual and buccal administration. The ropinirole oral film was non-toxic and exhibited fast disintegration and dissolution and was physically stable for at least 28 days. Upon buccal/sublingual administration of the oral films, ropinirole reached the systemic circulation within 15 min and bioavailability was significantly improved, which may be attributable to avoidance of first-pass metabolism via absorption through the oral cavity. In conclusion, our ropinirole oral film improved bioavailability after sublingual or buccal administration. This formulation potentially overcomes biopharmaceutical challenges and provide a convenient means of administration of ropinirole or other anti-PD drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Importance of levonorgestrel dose in oral contraceptives for effects on coagulation

NARCIS (Netherlands)

Kluft, C.; Maat, M.P.M. de; Heinemann, L.A.J.; Spannagl, M.; Schramm, W.

1999-01-01

Combined oral contraceptives show clear differences in effect on the tissue factor-initiated coagulation test of activated protein C resistance, which is dependent on the presence and dosage of levonorgestrel. Multiphasic levonorgestrol oral contraceptives differ from monophasic contraceptives and

Dissolution and bioavailability enhancement of alpha-asarone by solid dispersions via oral administration.

Science.gov (United States)

Deng, Li; Wang, Yu; Gong, Tao; Sun, Xun; Zhang, Zhi-Rong

2017-11-01

Alpha (α)-asarone (1-propenyl-2,4,5-methoxybenzol) (ARE) has been extensively used to treat chronic obstructive pulmonary diseases (COPD), bronchial asthma, pneumonia, and epilepsy. Due to its poor solubility and bioavailability, ARE was clinically administered via intravenous injection. However, severe allergies were often reported due to the presence of solublizers in the injection formulation. In our study, we sought to explore the biopharmaceutical classification of ARE, elucidate the mechanisms behind ARE absorption, and to develop a viable formulation to improve the oral bioavailability of ARE. ARE was not a P-glycoprotein substrate, which was absorbed in the passive mode without site specificity in the gastrointestinal tract. Solid dispersions prepared using hydrophilic matrix materials such as Pluronic F68, and polyethylene glycol (PEG) of varying molecular weights (PEG4K, PEG10K, and PEG20K) were proven to significantly improve the dissolution of ARE in vitro and the oral bioavailability of ARE in rats, which represent a promising strategy for the oral administration of ARE and other BCS II compounds.

Enhancement of solubility and bioavailability of ambrisentan by solid dispersion using Daucus carota as a drug carrier: formulation, characterization, in vitro, and in vivo study.

Science.gov (United States)

Deshmane, Subhash; Deshmane, Snehal; Shelke, Santosh; Biyani, Kailash

2018-06-01

Ambrisentan is an US FDA approved drug, it is the second oral endothelin A receptor antagonist known for the treatment of pulmonary arterial hypertension, but its oral administration is limited due to its poor water solubility. Hence, the objective of the investigation was focused on enhancement of solubility and bioavailability of ambrisentan by solid dispersion technique using natural Daucus carota extract as drug carrier. Drug carrier was evaluated for solubility, swelling index, viscosity, angle of repose, hydration capacity, and acute toxicity test (LD 50 ). Ambrisentan was studied for the saturation solubility, phase solubility, and Gibbs free energy change. Compatibility of drug and the natural carrier was confirmed by DSC, FTIR, and XRD. Solid dispersions were evaluated for drug content, solubility, morphology, in vitro, and in vivo study. Screening of the natural carrier showed the desirable properties like water solubility, less swelling index, less viscosity, and acute toxicity study revealed no any clinical symptoms of toxicity. Drug and carrier interaction study confirmed the compatibility to consider its use in the formulation. Formed particles were found to be spherical with smooth surface. In vitro studies revealed higher drug release from the solid dispersion than that of the physical mixture. Bioavailability study confirms the increased absorption and bioavailability by oral administration of solid dispersion. Hence, it can be concluded that the natural Daucus carota extract can be the better alternative source for the preparation of solid dispersion and/or other dosage forms for improving solubility and bioavailability.

Recent advances and perspectives in topical oral anesthesia.

Science.gov (United States)

Franz-Montan, Michelle; Ribeiro, Lígia Nunes de Morais; Volpato, Maria Cristina; Cereda, Cintia Maria Saia; Groppo, Francisco Carlos; Tofoli, Giovana Randomille; de Araújo, Daniele Ribeiro; Santi, Patrizia; Padula, Cristina; de Paula, Eneida

2017-05-01

Topical anesthesia is widely used in dentistry to reduce pain caused by needle insertion and injection of the anesthetic. However, successful anesthesia is not always achieved using the formulations that are currently commercially available. As a result, local anesthesia is still one of the procedures that is most feared by dental patients. Drug delivery systems (DDSs) provide ways of improving the efficacy of topical agents. Areas covered: An overview of the structure and permeability of oral mucosa is given, followed by a review of DDSs designed for dental topical anesthesia and their related clinical trials. Chemical approaches to enhance permeation and anesthesia efficacy, or to promote superficial anesthesia, include nanostructured carriers (liposomes, cyclodextrins, polymeric nanoparticle systems, solid lipid nanoparticles, and nanostructured lipid carriers) and different pharmaceutical dosage forms (patches, bio- and mucoadhesive systems, and hydrogels). Physical methods include pre-cooling, vibration, iontophoresis, and microneedle arrays. Expert opinion: The combination of different chemical and physical methods is an attractive option for effective topical anesthesia in oral mucosa. This comprehensive review should provide the readers with the most relevant options currently available to assist pain-free dental anesthesia. The findings should be considered for future clinical trials.

Oral Cryotherapy for Preventing Oral Mucositis in Patients Receiving Cancer Treatment.

Science.gov (United States)

Riley, Philip; McCabe, Martin G; Glenny, Anne-Marie

2016-10-01

In patients receiving treatment for cancer, does oral cryotherapy prevent oral mucositis? Oral cryotherapy is effective for the prevention of oral mucositis in adults receiving fluorouracil-based chemotherapy for solid cancers, and for the prevention of severe oral mucositis in adults receiving high-dose melphalan-based chemotherapy before hematopoietic stem cell transplantation (HSCT).

Intravenous voriconazole after toxic oral administration

NARCIS (Netherlands)

Alffenaar, J.W.C.; Van Assen, S.; De Monchy, J.G.R.; Uges, D.R.A.; Kosterink, J.G.W.; Van Der Werf, T.S.

In a male patient with rhinocerebral invasive aspergillosis, prolonged high-dosage oral administration of voriconazole led to hepatotoxicity combined with a severe cutaneous reaction while intravenous administration in the same patient did not. High concentrations in the portal blood precipitate

The Active Metabolite of Warfarin (3'-Hydroxywarfarin) and Correlation with INR, Warfarin and Drug Weekly Dosage in Patients under Oral Anticoagulant Therapy: A Pharmacogenetics Study.

Science.gov (United States)

Gemmati, Donato; Burini, Francesco; Talarico, Anna; Fabbri, Matteo; Bertocco, Cesare; Vigliano, Marco; Moratelli, Stefano; Cuneo, Antonio; Serino, Maria Luisa; Avato, Francesco Maria; Tisato, Veronica; Gaudio, Rosa Maria

2016-01-01

Warfarin oral anticoagulant therapy (OAT) requires regular and frequent drug adjustment monitored by INR. Interindividual variability, drug and diet interferences, and genetics (VKORC1 and CYP2C9) make the maintenance/reaching of stable INR a not so easy task. HPLC assessment of warfarin/enantiomers was suggested as a valid monitoring-tool along with INR, but definite results are still lacking. We evaluated possible correlations between INR, warfarin/3'-hydroxywarfarin, and drug weekly dosage aimed at searching novel alternatives to OAT monitoring. VKORC1/CYP2C9 pharmacogenetics investigation was performed to account for the known influence on warfarin homeostasis. 133 OAT patients were recruited and assessed for warfarin/3'-hydroxywarfarin serum levels (HPLC), INR, and VKORC1 and CYP2C9 genotypes. A subgroup of 52 patients were monitored in detail (5 consecutive controls; c0-c4) till the target INR was reached. Correlation analyses were performed in both groups. In the whole OAT group both warfarin and 3'-hydroxywarfarin correlate with INR at comparable degree (r2 = 0.0388 and 0.0362 respectively). Conversely, warfarin weekly dosage better correlates with warfarin than with 3'-hydroxywarfarin (r2 = 0.0975 and r2 = 0.0381 respectively), but considering together warfarin plus 3'-hydroxywarfarin the correlation strongly increased (r2 = 0.1114; ppharmacogenetics studies confirmed that patients carrying the VKORC1 variant-allele required lower warfarin maintenance dosage and that the combination of VKORC1 and CYP2C9 yielded a warfarin responsive index (WRI) inversely related to the number variant alleles. Our results overall suggest that 3'-hydroxywarfarin monitoring could be of great advantage in INR monitoring respect to classical warfarin assessment showing significant contribution also in multivariate analysis. Therefore, additional active metabolites should be recognized and investigated as novel useful indicators.

A review on oral liquid as an emerging technology in controlled drug delivery system.

Science.gov (United States)

Torne, Sangmesh Raosaheb; Sheela, Angappan; Sarada, N C

2017-12-03

The oral liquid drug delivery system (OLDDS) remains as the primary choice of dosage form, though challenging, for the pharmaceutical scientists. In the last two decades, Oral Liquid Controlled Release (OLCR) formulation has gained a lot of attention because of its advantages over the conventional dosage forms. The world of nanotechnology has paved multiple ways to administer the drug through oral cavity in liquid dosage form with an additional advantage of control over the release. In the current study, the various approaches towards the same have been discussed comprehensively to understand the different mechanisms of OLCR. This review also emphasizes on the existing techniques and the developments that have been made to improve on its efficacy including various formulation related factors. It also provides valuable insights into the role of polymers in the development of OLCR formulation that can be used in the management of Gastroesophageal reflux disease (GERD). Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A new modified wetting test and an alternative disintegration test for orally disintegrating tablets.

Science.gov (United States)

Hooper, Patrick; Lasher, Jason; Alexander, Kenneth S; Baki, Gabriella

2016-02-20

Industrial manufacturing of solid oral dosage forms require quality tests, such as friability, hardness, and disintegration. The United States Pharmacopeia (USP) disintegration test uses 900mL of water. However, recent studies of orally disintegrating tablets (ODTs) have shown that this volume does not accurately portray the oral environment. In our study, various tests were conducted with a more moderate amount of water that accurately resembles the oral environment. A simulated wetting test was performed to calculate the water absorption ratio. Results showed that wetting was comparable to disintegration. Although the wetting test worked for most types of ODTs, it had limitations that produced inaccurate results. This led to the use of a modified shaking water bath test. This test was found to work for all types of ODT products and was not subject to the limitations of the wetting test. The shake test could provide disintegration times rather than water permeation times; however, it could not be used to calculate the water absorption ratio. A strong correlation was observed between the standardized shake test and the USP disintegration times for the tablets. This shake test could be used during the development stages and quality tests for ODTs with relative ease. Copyright © 2015 Elsevier B.V. All rights reserved.

Mucoadhesive oral films: The potential for unmet needs.

Science.gov (United States)

Silva, Branca M A; Borges, Ana Filipa; Silva, Cláudia; Coelho, Jorge F J; Simões, Sérgio

2015-10-15

Oral drug delivery is the most common route of drug administration. Nevertheless, there are some important limitations that reinforce the need for developing new drug delivery systems. Mucoadhesive oral films (MOF) are promising dosage forms that adhere to the oral mucosa and deliver the drug through it, which present several advantages. These include: bypassing the hepatic first pass effect, fast onset of action, ease of transportation and handling. The use of such dosage form is beneficial for drugs that have poor oral bioavailability and also for drugs that need to be rapidly absorbed. In spite of the known benefits, the number of marketed MOF is still quite small. This review explores the products under development and corresponding clinical trials in respect to their status, therapeutic indication, companies involved and technologies. In this way, it was possible to identify the preferred therapeutic indications, new research and market trends as well as future prospects of MOF. Moreover, it is reasonable to expect an increase in the number of products on the market due to their great potential to satisfy unmet medical needs. Copyright © 2015 Elsevier B.V. All rights reserved.

Antiretroviral solid drug nanoparticles with enhanced oral bioavailability: production, characterization, and in vitro-in vivo correlation.

Science.gov (United States)

McDonald, Tom O; Giardiello, Marco; Martin, Philip; Siccardi, Marco; Liptrott, Neill J; Smith, Darren; Roberts, Phill; Curley, Paul; Schipani, Alessandro; Khoo, Saye H; Long, James; Foster, Alison J; Rannard, Steven P; Owen, Andrew

2014-03-01

Nanomedicine strategies have produced many commercial products. However, no orally dosed HIV nanomedicines are available clinically to patients. Although nanosuspensions of drug particles have demonstrated many benefits, experimentally achieving >25 wt% of drug relative to stabilizers is highly challenging. In this study, the emulsion-templated freeze-drying technique for nanoparticles formation is applied for the first time to optimize a nanodispersion of the leading non-nucleoside reverse transcriptase inhibitor efavirenz, using clinically acceptable polymers and surfactants. Dry monoliths containing solid drug nanoparticles with extremely high drug loading (70 wt% relative to polymer and surfactant stabilizers) are stable for several months and reconstitute in aqueous media to provide nanodispersions with z-average diameters of 300 nm. The solid drug nanoparticles exhibit reduced cytoxicity and increased in vitro transport through model gut epithelium. In vivo studies confirm bioavailability benefits with an approximately four-fold higher pharmacokinetic exposure after oral administration to rodents, and predictive modeling suggests dose reduction with the new formulation may be possible. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy

DEFF Research Database (Denmark)

Heinz, Andrea; Strachan, Clare J; Gordon, Keith C

2009-01-01

OBJECTIVES: Solid-state transformations may occur during any stage of pharmaceutical processing and upon storage of a solid dosage form. Early detection and quantification of these transformations during the manufacture of solid dosage forms is important since the physical form of an active...... pharmaceutical ingredient can significantly influence its processing behaviour, including powder flow and compressibility, and biopharmaceutical properties such as solubility, dissolution rate and bioavailability. KEY FINDINGS: Vibrational spectroscopic techniques such as infrared, near-infrared, Raman and, most...... multivariate approaches where even overlapping spectral bands can be analysed. SUMMARY: This review discusses the applications of different vibrational spectroscopic techniques to detect and monitor solid-state transformations possible for crystalline polymorphs, hydrates and amorphous forms of pharmaceutical...

Soft gelatin capsules (softgels).

Science.gov (United States)

Gullapalli, Rampurna Prasad

2010-10-01

It is estimated that more than 40% of new chemical entities (NCEs) coming out of the current drug discovery process have poor biopharmaceutical properties, such as low aqueous solubility and/or permeability. These suboptimal properties pose significant challenges for the oral absorption of the compounds and for the development of orally bioavailable dosage forms. Development of soft gelatin capsule (softgel) dosage form is of growing interest for the oral delivery of poorly water soluble compounds (BCS class II or class IV). The softgel dosage form offers several advantages over other oral dosage forms, such as delivering a liquid matrix designed to solubilize and improve the oral bioavailability of a poorly soluble compound as a unit dose solid dosage form, delivering low and ultra-low doses of a compound, delivering a low melting compound, and minimizing potential generation of dust during manufacturing and thereby improving the safety of production personnel. However, due to the very dynamic nature of the softgel dosage form, its development and stability during its shelf-life are fraught with several challenges. The goal of the current review is to provide an in-depth discussion on the softgel dosage form to formulation scientists who are considering developing softgels for therapeutic compounds.

Formulation and process considerations affecting the stability of solid dosage forms formulated with methacrylate copolymers.

Science.gov (United States)

Petereit, H U; Weisbrod, W

1999-01-01

General considerations concerning the stability of coated dosage forms are discussed, in order to avoid predictable interactions which may cause long-term stability problems. As polymers themselves maintain a high chemical stability and a low reactivity, instability phenomena mainly have to be explained by interactions of low molecular weight substances or physical changes. Possible interactions of functional groups can be predicted easily and insulating subcoates are proper countermeasures. Impurities, remaining in the polymeric material from the manufacturing process, may accelerate the hydrolysis of sensitive drugs. Instabilities of coated dosage forms are mainly based on physical interactions, caused by improper formulations of coating suspensions (i.e. plasticizers or pigments) or the film coating process. Residual moisture or solvents, probably enclosed in the core and migrating over time, may increase the permeability of coatings, due to plasticizing effects. The functionality of coatings from aqueous dispersions is linked to coalescence of latex particles. Thus any incomplete film formation, caused by too high or too low coating temperatures, may result in high permeable coatings. During storage, preferably under stress conditions this process will continue and thus change the release profile. Therefore bed temperatures of 10-20 degrees C above MFT must ensure the formation of homogeneous polymer layers during the coating process. Stability test procedures and packaging materials also need to be adapted to the physicochemical properties of the dosage form, in order to get meaningful results in stability tests.

Soluplus®/TPGS-based solid dispersions prepared by hot-melt extrusion equipped with twin-screw systems for enhancing oral bioavailability of valsartan.

Science.gov (United States)

Lee, Jae-Young; Kang, Wie-Soo; Piao, Jingpei; Yoon, In-Soo; Kim, Dae-Duk; Cho, Hyun-Jong

2015-01-01

Soluplus(®) (SP) and D-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS)-based solid dispersion (SD) formulations were developed by hot-melt extrusion (HME) to improve oral bioavailability of valsartan (VST). HME process with twin-screw configuration for generating a high shear stress was used to prepare VST SD formulations. The thermodynamic state of the drug and its dispersion in the polymers were evaluated by solid-state studies, including Fourier-transform infrared, X-ray diffraction, and differential scanning calorimetry. Drug release from the SD formulations was assessed at pH values of 1.2, 4.0, and 6.8. Pharmacokinetic study was performed in rats to estimate the oral absorption of VST. HME with a high shear rate produced by the twin-screw system was successfully applied to prepare VST-loaded SD formulations. Drug amorphization and its molecular dispersion in the polymer matrix were verified by several solid-state studies. Drug release from SD formulations was improved, compared to the pure drug, particularly at pH 6.8. Oral absorption of drug in rats was also enhanced in SP and TPGS-based SD groups compared to that in the pure drug group. SP and TPGS-based SDs, prepared by the HME process, could be used to improve aqueous solubility, dissolution, and oral absorption of poorly water-soluble drugs.

Pharmaceutical development of an oral tablet formulation containing a spray dried amorphous solid dispersion of docetaxel or paclitaxel

NARCIS (Netherlands)

Sawicki, Emilia; Beijnen, Jos H|info:eu-repo/dai/nl/071919570; Schellens, Jan H M|info:eu-repo/dai/nl/073926272; Nuijen, Bastiaan

2016-01-01

Previously, it was shown in Phase I clinical trials that solubility-limited oral absorption of docetaxel and paclitaxel can be drastically improved with a freeze dried solid dispersion (fdSD). These formulations, however, are unfavorable for further clinical research because of limitations in

Thermal Analysis by Structural Characterization as a Method for Assessing Heterogeneity in Complex Solid Pharmaceutical Dosage Forms.

Science.gov (United States)

Alhijjaj, Muqdad; Reading, Mike; Belton, Peter; Qi, Sheng

2015-11-03

Characterizing inter- and intrasample heterogeneity of solid and semisolid pharmaceutical products is important both for rational design of dosage forms and subsequent quality control during manufacture; however, most pharmaceutical products are multicomponent formulations that are challenging in this regard. Thermal analysis, in particular differential scanning calorimetry, is commonly used to obtain structural information, such as degree of crystallinity, or identify the presence of a particular polymorph, but the results are an average over the whole sample; it cannot directly provide information about the spatial distribution of phases. This study demonstrates the use of a new thermo-optical technique, thermal analysis by structural characterization (TASC), that can provide spatially resolved information on thermal transitions by applying a novel algorithm to images acquired by hot stage microscopy. We determined that TASC can be a low cost, relatively rapid method of characterizing heterogeneity and other aspects of structure. In the examples studied, it was found that high heating rates enabled screening times of 3-5 min per sample. In addition, this study demonstrated the higher sensitivity of TASC for detecting the metastable form of polyethylene glycol (PEG) compared to conventional differential scanning calorimetry (DSC). This preliminary work suggests that TASC will be a worthwhile additional tool for characterizing a broad range of materials.

Gamma scintigraphy in the evaluation of pharmaceutical dosage forms

International Nuclear Information System (INIS)

Davis, S.S.; Hardy, J.G.; Newman, S.P.; Wilding, I.R.

1992-01-01

Gamma-scintigraphy is applied extensively in the development and evaluation of pharmaceutical drug delivery systems. It is used particularly for monitoring formulations in the gastrointestinal and respiratory tracts. The radiolabelling is generally achieved by the incorporation of an appropriate technetium-99m or indium-111 labelled radiopharmaceutical into the formulation. In the case of complex dosage forms, such as enteric-coated tablets, labelling is best undertaken by the addition of a non-radioactive tracer such as samarium-152 or erbium-170 followed by neutron activation of the final product. Systems investigated include tablets and multiparticulates for oral administration, enemas and suppositories, metered dose inhalers and nebulisers, and nasal sprays and drops. Gamma-scintigraphy provides information on the deposition, dispersion and movement of the formulation. The combination of such studies with the assay of drug levels in blood or urine specimens, pharmacoscintigraphy, provides information concerning the sites of drug release and absorption. Data acquired from the scintigraphic evaluation of pharmaceutical dosage forms are now being used increasingly at all stages of product development, from the assessment of prototype delivery systems to supporting the product licence application. (orig.)

Gamma scintigraphy in the evaluation of pharmaceutical dosage forms

Energy Technology Data Exchange (ETDEWEB)

Davis, S.S.; Hardy, J.G.; Newman, S.P.; Wilding, I.R. (Pharmaceutical Profiles Ltd., Nottingham (United Kingdom))

1992-11-01

Gamma-scintigraphy is applied extensively in the development and evaluation of pharmaceutical drug delivery systems. It is used particularly for monitoring formulations in the gastrointestinal and respiratory tracts. The radiolabelling is generally achieved by the incorporation of an appropriate technetium-99m or indium-111 labelled radiopharmaceutical into the formulation. In the case of complex dosage forms, such as enteric-coated tablets, labelling is best undertaken by the addition of a non-radioactive tracer such as samarium-152 or erbium-170 followed by neutron activation of the final product. Systems investigated include tablets and multiparticulates for oral administration, enemas and suppositories, metered dose inhalers and nebulisers, and nasal sprays and drops. Gamma-scintigraphy provides information on the deposition, dispersion and movement of the formulation. The combination of such studies with the assay of drug levels in blood or urine specimens, pharmacoscintigraphy, provides information concerning the sites of drug release and absorption. Data acquired from the scintigraphic evaluation of pharmaceutical dosage forms are now being used increasingly at all stages of product development, from the assessment of prototype delivery systems to supporting the product licence application. (orig.).

Improving maraviroc oral bioavailability by formation of solid drug nanoparticles.

Science.gov (United States)

Savage, Alison C; Tatham, Lee M; Siccardi, Marco; Scott, Trevor; Vourvahis, Manoli; Clark, Andrew; Rannard, Steve P; Owen, Andrew

2018-05-17

Oral drug administration remains the preferred approach for treatment of HIV in most patients. Maraviroc (MVC) is the first in class co-receptor antagonist, which blocks HIV entry into host cells. MVC has an oral bioavailability of approximately 33%, which is limited by poor permeability as well as affinity for CYP3A and several drug transporters. While once-daily doses are now the favoured option for HIV therapy, dose-limiting postural hypotension has been of theoretical concern when administering doses high enough to achieve this for MVC (particularly during coadministration of enzyme inhibitors). To overcome low bioavailability and modify the pharmacokinetic profile, a series of 70 wt% MVC solid drug nanoparticle (SDN) formulations (containing 30 wt% of various polymer/surfactant excipients) were generated using emulsion templated freeze-drying. The lead formulation contained PVA and AOT excipients ( MVC SDN PVA/AOT ), and was demonstrated to be fully water-dispersible to release drug nanoparticles with z-average diameter of 728 nm and polydispersity index of 0.3. In vitro and in vivo studies of MVC SDN PVA/AOT showed increased apparent permeability of MVC, compared to a conventional MVC preparation, with in vivo studies in rats showing a 2.5-fold increase in AUC (145.33 vs. 58.71 ng h ml -1 ). MVC tissue distribution was similar or slightly increased in tissues examined compared to the conventional MVC preparation, with the exception of the liver, spleen and kidneys, which showed statistically significant increases in MVC for MVC SDN PVA/AOT . These data support a novel oral format with the potential for dose reduction while maintaining therapeutic MVC exposure and potentially enabling a once-daily fixed dose combination product. Copyright © 2018. Published by Elsevier B.V.

Intra-oral cone radiation therapy for selected carcinomas of the oral cavity

International Nuclear Information System (INIS)

Wang, C.C.; Doppke, K.P.; Biggs, P.J.

1983-01-01

A study of 101 patients with early carcinomas of the oral cavity, T1 and T2, treated by external cobalt 60 beam and/or intra-oral cone (IOC) radiation therapy between 1964 through 1980 was made. The two year disease-free survival rate, including surgical salvage, was 88% and the local control rate was 85%. The incidence of radiation complications, i.e., soft tissue ulceration and/or osteoradionecrosis, was 14% and varied with various tumor sites and radiation doses delivered. The present review shows that local control and radiation complications are closely related to radiation doses and varies with different tumor sites of the oral cavity. Radiation therapy dosages expressed in terms of TDF values for these lesions are herein recommended. With proper selections of lesions arising from the oral cavity, combined external beam and IOC radiation therapy has been found extremely efficacious in achieving good local tumor control and high survival rates with excellent cosmetic and functional results and minimum radiation sequalae

Semi-quantitative prediction of a multiple API solid dosage form with a combination of vibrational spectroscopy methods.

Science.gov (United States)

Hertrampf, A; Sousa, R M; Menezes, J C; Herdling, T

2016-05-30

Quality control (QC) in the pharmaceutical industry is a key activity in ensuring medicines have the required quality, safety and efficacy for their intended use. QC departments at pharmaceutical companies are responsible for all release testing of final products but also all incoming raw materials. Near-infrared spectroscopy (NIRS) and Raman spectroscopy are important techniques for fast and accurate identification and qualification of pharmaceutical samples. Tablets containing two different active pharmaceutical ingredients (API) [bisoprolol, hydrochlorothiazide] in different commercially available dosages were analysed using Raman- and NIR Spectroscopy. The goal was to define multivariate models based on each vibrational spectroscopy to discriminate between different dosages (identity) and predict their dosage (semi-quantitative). Furthermore the combination of spectroscopic techniques was investigated. Therefore, two different multiblock techniques based on PLS have been applied: multiblock PLS (MB-PLS) and sequential-orthogonalised PLS (SO-PLS). NIRS showed better results compared to Raman spectroscopy for both identification and quantitation. The multiblock techniques investigated showed that each spectroscopy contains information not present or captured with the other spectroscopic technique, thus demonstrating that there is a potential benefit in their combined use for both identification and quantitation purposes. Copyright © 2016 Elsevier B.V. All rights reserved.

Oral versus topical propranolol for management of superficial ...

African Journals Online (AJOL)

was treated with oral propranolol and group B (n = 24) was treated with propranolol .... months during treatment, or if any undesirable drawbacks .... dosage and the serum concentration of the drug in this route [29]. However, McMahon et al.

Piracetam relieves symptoms in progressive myoclonus epilepsy: a multicentre, randomised, double blind, crossover study comparing the efficacy and safety of three dosages of oral piracetam with placebo

Science.gov (United States)

Koskiniemi, M.; Van Vleymen, B.; Hakamies, L.; Lamusuo, S.; Taalas, J.

1998-01-01

OBJECTIVE—To compare the efficacy, tolerability, and safety of three daily dosage regimens of oral piracetam in patients with progressive myoclonus epilepsy.
METHODS—Twenty patients (12 men, eight women), aged 17-43 years, with classical Unverricht-Lundborg disease were enrolled in a multicentre, randomised, double blind trial of crossover design in which the effects of daily doses of 9.6 g, 16.8 g, and 24 g piracetam, given in two divided doses, were compared with placebo. The crossover design was such that patients received placebo and two of the three dosage regimens of piracetam, each for two weeks, for a total treatment period of six weeks and thus without wash out between each treatment phase. The primary outcome measure was a sum score representing the adjusted total of the ratings of six components of a myoclonus rating scale in which stimulus sensitivity, motor impairment, functional disability, handwriting, and global assessments by investigators and patients were scored. Sequential clinical assessments were made by the same neurologist in the same environment at the same time of day.
RESULTS—Treatment with 24 g/day piracetam produced significant and clinically relevant improvement in the primary outcome measure of mean sum score (p=0.005) and in the means of its subtests of motor impairment (p=0.02), functional disability (p=0.003), and in global assessments by both investigator (p=0.002) and patient (p=0.01). Significant improvement in functional disability was also found with daily doses of 9.6 g and 16.8 g. The dose-effect relation was linear and significant. More patients showed clinically relevant improvement with the highest dosage and, in individual patients, increasing the dose improved response. Piracetam was well tolerated and adverse effects were few, mild, and transient.
CONCLUSIONS—This study provides further evidence that piracetam is an effective and safe medication in patients with Unverricht-Lundborg disease. In addition

Influence of Postprandial Intragastric Pressures on Drug Release from Gastroretentive Dosage Forms.

Science.gov (United States)

Schneider, Felix; Hoppe, Melanie; Koziolek, Mirko; Weitschies, Werner

2018-05-29

Despite extensive research in the field of gastroretentive dosage forms, this "holy grail" of oral drug delivery yet remained an unmet goal. Especially under fasting conditions, the reproducible retention of dosage forms in the stomach seems to be an impossible task. This is why such systems are often advised to be taken together with food. But also the postprandial motility can contribute significantly to the failure of gastroretentive dosage forms. To investigate the influence of postprandial pressure conditions on drug release from such systems, we used a novel in vitro dissolution tool, the dissolution stress test device. With the aid of this device, we simulated three different intragastric pressure profiles that may occur after postprandial intake. These transit scenarios were based on recently obtained, postprandial SmartPill® data. The tested systems, Glumetza® 1000 and Madopar® HBS 125, are marketed dosage forms that are based on different approaches to achieve proper gastric retention. All three transit scenarios revealed a highly pressure-sensitive drug release behavior, for both drugs. For Madopar® HBS 125, nearly complete drug release was observed even after early occurring pressures. Glumetza® 1000 seemed to be more resistant to these, most likely due to incomplete wetting of the system. On the contrary to these findings, data from standard dissolution tests using the paddle apparatus displayed controlled drug release for both systems for about 6 h. Based on these results, it can be doubted that established gastroretentive systems stay intact over a longer period of time, even under postprandial conditions.

Screening computer-assisted dosage programs for anticoagulation with warfarin and other vitamin K antagonists: minimum safety requirements for individual programs

DEFF Research Database (Denmark)

Poller, L; Roberts, C; Ibrahim, S

2009-01-01

Based on the results of the previous European Action on Anticoagulation (EAA) multicenter study, a simplified minimum procedure is described for screening the safety and effectiveness of marketed programs for dosage of oral anticoagulant drugs (vitamin K antagonists). The aim was to demonstrate non...

Oral processing characteristics of solid savoury meal components, and relationship with food composition, sensory attributes and expected satiation.

Science.gov (United States)

Forde, C G; van Kuijk, N; Thaler, T; de Graaf, C; Martin, N

2013-01-01

The modern food supply is often dominated by a large variety of energy dense, softly textured foods that can be eaten quickly. Previous studies suggest that particular oral processing characteristics such as large bite size and lack of chewing activity contribute to the low satiating efficiency of these foods. To better design meals that promote greater feelings of satiation, we need an accurate picture of the oral processing characteristics of a range of solid food items that could be used to replace softer textures during a normal hot meal. The primary aim of this study was to establish an accurate picture of the oral processing characteristics of a set of solid savoury meal components. The secondary aim was to determine the associations between oral processing characteristics, food composition, sensory properties, and expected satiation. In a within subjects design, 15 subjects consumed 50 g of 35 different savoury food items over 5 sessions. The 35 foods represented various staples, vegetables and protein rich foods such a meat and fish. Subjects were video-recorded during consumption and measures included observed number of bites, number of chews, number of swallows and derived measures such as chewing rate, eating rate, bite size, and oral exposure time. Subjects rated expected satiation for a standard 200 g portion of each food using a 100mm and the sensory differences between foods were quantified using descriptive analysis with a trained sensory panel. Statistical analysis focussed on the oral processing characteristics and associations between nutritional, sensory and expected satiation parameters of each food. Average number of chews for 50 g of food varied from 27 for mashed potatoes to 488 for tortilla chips. Oral exposure time was highly correlated with the total number of chews, and varied from 27 s for canned tomatoes to 350 s for tortilla chips. Chewing rate was relatively constant with an overall average chewing rate of approximately 1 chew

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

Directory of Open Access Journals (Sweden)

Muhammad Zaman

2016-01-01

Full Text Available Oral route of drug administration is considered as the safest and easiest route of drug administration. Control release drug delivery system is the emerging trend in the pharmaceuticals and the oral route is most suitable for such kind of drug delivery system. Oral route is more convenient for It all age group including both pediatric and geriatrics. There are various systems which are adopted to deliver drug in a controlled manner to different target sites through oral route. It includes diffusion controlled drug delivery systems; dissolution controlled drug delivery systems, osmotically controlled drug delivery systems, ion-exchange controlled drug delivery systems, hydrodynamically balanced systems, multi-Particulate drug delivery systems and microencapsulated drug delivery system. The systems are formulated using different natural, semi-synthetic and synthetic polymers. The purpose of the review is to provide information about the orally controlled drug delivery system, polymers which are used to formulate these systems and characterizations of one of the most convenient dosage form which is the tablets. 

Comparative Studies on the Dissolution Profiles of Oral Ibuprofen Suspension and Commercial Tablets using Biopharmaceutical Classification System Criteria

Science.gov (United States)

Rivera-Leyva, J. C.; García-Flores, M.; Valladares-Méndez, A.; Orozco-Castellanos, L. M.; Martínez-Alfaro, M.

2012-01-01

In vitro dissolution studies for solid oral dosage forms have recently widened the scope to a variety of special dosage forms such as suspensions. For class II drugs, like Ibuprofen, it is very important to have discriminative methods for different formulations in physiological conditions of the gastrointestinal tract, which will identify different problems that compromise the drug bioavailability. In the present work, two agitation speeds have been performed in order to study ibuprofen suspension dissolution. The suspensions have been characterised relatively to particle size, density and solubility. The dissolution study was conducted using the following media: buffer pH 7.2, pH 6.8, 4.5 and 0.1 M HCl. For quantitative analysis, the UV/Vis spectrophotometry was used because this methodology had been adequately validated. The results show that 50 rpm was the adequate condition to discriminate the dissolution profile. The suspension kinetic release was found to be dependent on pH and was different compared to tablet release profile at the same experimental conditions. The ibuprofen release at pH 1.0 was the slowest. PMID:23626386

Taste-masking assessment of orally disintegrating tablets and lyophilisates with cetirizine dihydrochloride microparticles

Directory of Open Access Journals (Sweden)

Aleksandra Amelian

2017-12-01

Full Text Available Orally disintegrating tablets and oral lyophilisates are novel attractive dosage forms that disintegrate or dissolve in the buccal cavity within seconds without necessity of drinking. The major limitation in designing of these dosage forms is unpleasant taste of the drug substance. Cetirizine dihydrochloride is a H1-antihistamine substance indicated for the treatment of allergy. It is characterized by extremely bitter taste, therefore in order to deliver cetirizine dihydrochloride using orodispersible formulations, effective taste-masking is required. The aim of this study was to investigate whether microparticles containing cetirizine dihydrochloride could be successfully used to formulate orally disintegrating tablets by direct compression method and oral lyophilisates by freeze-drying process. Taste masking of cetirizine dihydrochloride was achieved by the spray-drying technique using Eudragit® E PO as the drug agent carrier. Based on the preliminary studies, optimal compositions of microparticles, tablets and lyophilisates were chosen. Obtained dosage forms were characterized for drug content, disintegration time and mechanical properties. In order to determine whether the microparticles subjected to direct compression and freeze-drying process effectively mask the bitter taste of cetirizine dihydrochloride, the in vivo and in vitro evaluation was performed. The results showed that designed formulates with microparticles containing cetirizine dihydrochloride were characterized by appropriate mechanical properties, uniformity of weight and thickness, short disintegration time, and the uniform content of the drug substance. Taste-masking assessment performed by three independent methods (e-tongue evaluation, human test panel and the in vitro drug release revealed that microparticles with Eudragit® E PO are effective taste – masking carriers of cetirizine dihydrochloride and might be used to formulate orally disintegrating tablets and oral

Determination of amphetamine-type stimulants in oral fluid by solid-phase microextraction and gas chromatography-mass spectrometry

International Nuclear Information System (INIS)

Souza, Daniele Z.; Boehl, Paula O.; Comiran, Eloisa; Mariotti, Kristiane C.; Pechansky, Flavio; Duarte, Paulina C.A.V.; De Boni, Raquel; Froehlich, Pedro E.; Limberger, Renata P.

2011-01-01

Graphical abstract: Highlights: → Propylchloroformate derivatization of amphetamine-type stimulants in oral fluid. → Direct immersion solid-phase microextraction/gas chromatography-mass spectrometry. → Linear range 2(4)-256 ng mL -1 , detection limits 0.5-2 ng mL -1 . → Accuracy 98-112%, precision TM device has been developed and validated. Thereunto, in-matrix propylchloroformate derivatization followed by direct immersion solid-phase microextraction and gas chromatography-mass spectrometry were employed. Deuterium labeled AMP was used as internal standard for all the stimulants and analysis was performed using the selected ion monitoring mode. The detector response was linear for the studied drugs in the concentration range of 2-256 ng mL -1 (neat oral fluid), except for FEN, whereas the linear range was 4-256 ng mL -1 . The detection limits were 0.5 ng mL -1 (MET), 1 ng mL -1 (MPH) and 2 ng mL -1 (DIE, AMP, FEN), respectively. Accuracy of quality control samples remained within 98.2-111.9% of the target concentrations, while precision has not exceeded 15% of the relative standard deviation. Recoveries with Quantisal TM device ranged from 77.2% to 112.1%. Also, the goodness-of-fit concerning the ordinary least squares model in the statistical inference of data has been tested through residual plotting and ANOVA. The validated method can be easily automated and then used for screening and confirmation of amphetamine-type stimulants in drivers' oral fluid.

In vitro models for the prediction of in vivo performance of oral dosage forms

NARCIS (Netherlands)

Kostewicz, E.S.; Abrahamsson, B.; Brewster, M.; Brouwers, J.; Butler, J.; Carlert, S.; Dickinson, P.A.; Dressman, J.; Holm, R.; Klein, S.; Mann, J.; McAllister, M.; Minekus, M.; Muenster, U.; Müllertz, A.; Verwei, M.; Vertzoni, M.; Weitschies, W.; Augustijns, P.

2014-01-01

Accurate prediction of the in vivo biopharmaceutical performance of oral drug formulations is critical to efficient drug development. Traditionally, in vitro evaluation of oral drug formulations has focused on disintegration and dissolution testing for quality control (QC) purposes. The connection

When and how should we teach the basic concepts of radiation beam dosage

International Nuclear Information System (INIS)

Brewin, T.B.

1977-01-01

The difficulty that many trainees, including those medically qualified, have in achieving a sound working grasp of certain basic principles of radiation beam dosage is often underestimated. Since any failure of understanding may seriously impair the efficiency of the team treating the patient, the discussion of these problems (and especially the monitoring of the results of such discussion by means of oral and written tests) deserves a high priority. Contrary to traditional practice, there would seem to be no good reason why teaching of radiation beam dosage, and the effect on dose-rate of changes in the treatment distance or in the amount of scattered radiation, should not begin in the very first week of training and be immediately integrated with discussion of the dose-rate information available at every radiotherapy unit when the patient is treated. A preliminary course of physics lectures does not usually make the understanding of these principles any easier and can be done either concurrently or later. For many radiotherapy trainees and for many doctors in other fields, comparison with drug dosage and with the brightness and scatter of ordinary light beams, avoiding technical terms so far as possible, may achieve a better initial understanding of basic principles than is achieved by mathematical equations and theoretical physics. (author)

When and how should we teach the basic concepts of radiation beam dosage

Energy Technology Data Exchange (ETDEWEB)

Brewin, T B [Institute of Radiotherapeutics and Oncology, Glasgow (UK)

1977-06-01

The difficulty that many trainees, including those medically qualified, have in achieving a sound working grasp of certain basic principles of radiation beam dosage is often underestimated. Since any failure of understanding may seriously impair the efficiency of the team treating the patient, the discussion of these problems (and especially the monitoring of the results of such discussion by means of oral and written tests) deserves a high priority. Contrary to traditional practice, there would seem to be no good reason why teaching of radiation beam dosage, and the effect on dose-rate of changes in the treatment distance or in the amount of scattered radiation, should not begin in the very first week of training and be immediately integrated with discussion of the dose-rate information available at every radiotherapy unit when the patient is treated. A preliminary course of physics lectures does not usually make the understanding of these principles any easier and can be done either concurrently or later. For many radiotherapy trainees and for many doctors in other fields, comparison with drug dosage and with the brightness and scatter of ordinary light beams, avoiding technical terms so far as possible, may achieve a better initial understanding of basic principles than is achieved by mathematical equations and theoretical physics.

Determination of amphetamine-type stimulants in oral fluid by solid-phase microextraction and gas chromatography-mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Souza, Daniele Z., E-mail: daniele.dzs@dpf.gov.br [Setor Tecnico-Cientifico, Superintendencia Regional do Departamento de Policia Federal no Rio Grande do Sul, 1365 Ipiranga Avenue, Azenha, Zip Code 90160-093 Porto Alegre, Rio Grande do Sul (Brazil); Programa de Pos-Graduacao em Ciencias Farmaceuticas, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul, 2752 Ipiranga Avenue, Santana, Zip Code 90610-000 Porto Alegre, Rio Grande do Sul (Brazil); Boehl, Paula O.; Comiran, Eloisa; Mariotti, Kristiane C. [Programa de Pos-Graduacao em Ciencias Farmaceuticas, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul, 2752 Ipiranga Avenue, Santana, Zip Code 90610-000 Porto Alegre, Rio Grande do Sul (Brazil); Pechansky, Flavio [Centro de Pesquisa em Alcool e Drogas (CPAD), Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, 2350, Ramiro Barcelos Street, Zip Code 90035-903 Porto Alegre, Rio Grande do Sul (Brazil); Duarte, Paulina C.A.V. [Secretaria Nacional de Politicas sobre Drogas (SENAD), Esplanada dos Ministerios, Block ' A' , 5th floor, Zip Code 70050-907 Brasilia, Distrito Federal (Brazil); De Boni, Raquel [Centro de Pesquisa em Alcool e Drogas (CPAD), Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, 2350, Ramiro Barcelos Street, Zip Code 90035-903 Porto Alegre, Rio Grande do Sul (Brazil); Froehlich, Pedro E.; Limberger, Renata P. [Programa de Pos-Graduacao em Ciencias Farmaceuticas, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul, 2752 Ipiranga Avenue, Santana, Zip Code 90610-000 Porto Alegre, Rio Grande do Sul (Brazil)

2011-06-24

Graphical abstract: Highlights: > Propylchloroformate derivatization of amphetamine-type stimulants in oral fluid. > Direct immersion solid-phase microextraction/gas chromatography-mass spectrometry. > Linear range 2(4)-256 ng mL{sup -1}, detection limits 0.5-2 ng mL{sup -1}. > Accuracy 98-112%, precision <15% of RSD, recovery 77-112%. > Importance of residual evaluation in checking model goodness-of-fit. - Abstract: A method for the simultaneous identification and quantification of amphetamine (AMP), methamphetamine (MET), fenproporex (FEN), diethylpropion (DIE) and methylphenidate (MPH) in oral fluid collected with Quantisal{sup TM} device has been developed and validated. Thereunto, in-matrix propylchloroformate derivatization followed by direct immersion solid-phase microextraction and gas chromatography-mass spectrometry were employed. Deuterium labeled AMP was used as internal standard for all the stimulants and analysis was performed using the selected ion monitoring mode. The detector response was linear for the studied drugs in the concentration range of 2-256 ng mL{sup -1} (neat oral fluid), except for FEN, whereas the linear range was 4-256 ng mL{sup -1}. The detection limits were 0.5 ng mL{sup -1} (MET), 1 ng mL{sup -1} (MPH) and 2 ng mL{sup -1} (DIE, AMP, FEN), respectively. Accuracy of quality control samples remained within 98.2-111.9% of the target concentrations, while precision has not exceeded 15% of the relative standard deviation. Recoveries with Quantisal{sup TM} device ranged from 77.2% to 112.1%. Also, the goodness-of-fit concerning the ordinary least squares model in the statistical inference of data has been tested through residual plotting and ANOVA. The validated method can be easily automated and then used for screening and confirmation of amphetamine-type stimulants in drivers' oral fluid.

A novel microdialysis-dissolution/permeation system for testing oral dosage forms

DEFF Research Database (Denmark)

Fong, Sophia Yui Kau; Poulsen, Jessie; Brandl, Martin

2016-01-01

A novel microdialysis-dissolution/permeation (M-D/P) system was developed for the biopharmaceutical assessment of oral drug formulations. This system consists of a side-by-side diffusion chamber, a microdialysis unit fixed within the dissolution chamber for continuous sampling, and a biomimetic P...

Sample preparation composite and replicate strategy for assay of solid oral drug products.

Science.gov (United States)

Harrington, Brent; Nickerson, Beverly; Guo, Michele Xuemei; Barber, Marc; Giamalva, David; Lee, Carlos; Scrivens, Garry

2014-12-16

In pharmaceutical analysis, the results of drug product assay testing are used to make decisions regarding the quality, efficacy, and stability of the drug product. In order to make sound risk-based decisions concerning drug product potency, an understanding of the uncertainty of the reportable assay value is required. Utilizing the most restrictive criteria in current regulatory documentation, a maximum variability attributed to method repeatability is defined for a drug product potency assay. A sampling strategy that reduces the repeatability component of the assay variability below this predefined maximum is demonstrated. The sampling strategy consists of determining the number of dosage units (k) to be prepared in a composite sample of which there may be a number of equivalent replicate (r) sample preparations. The variability, as measured by the standard error (SE), of a potency assay consists of several sources such as sample preparation and dosage unit variability. A sampling scheme that increases the number of sample preparations (r) and/or number of dosage units (k) per sample preparation will reduce the assay variability and thus decrease the uncertainty around decisions made concerning the potency of the drug product. A maximum allowable repeatability component of the standard error (SE) for the potency assay is derived using material in current regulatory documents. A table of solutions for the number of dosage units per sample preparation (r) and number of replicate sample preparations (k) is presented for any ratio of sample preparation and dosage unit variability.

Physical stabilization of low-molecular-weight amorphous drugs in the solid state: a material science approach.

Science.gov (United States)

Qi, Sheng; McAuley, William J; Yang, Ziyi; Tipduangta, Pratchaya

2014-07-01

Use of the amorphous state is considered to be one of the most effective approaches for improving the dissolution and subsequent oral bioavailability of poorly water-soluble drugs. However as the amorphous state has much higher physical instability in comparison with its crystalline counterpart, stabilization of amorphous drugs in a solid-dosage form presents a major challenge to formulators. The currently used approaches for stabilizing amorphous drug are discussed in this article with respect to their preparation, mechanism of stabilization and limitations. In order to realize the potential of amorphous formulations, significant efforts are required to enable the prediction of formulation performance. This will facilitate the development of computational tools that can inform a rapid and rational formulation development process for amorphous drugs.

Development of a solid self-microemulsifying drug delivery system (SMEDDS) for solubility enhancement of naproxen.

Science.gov (United States)

Čerpnjak, Katja; Zvonar, Alenka; Vrečer, Franc; Gašperlin, Mirjana

2015-01-01

Comparative evaluation of liquid and solid self-microemulsifying drug delivery systems (SMEDDS) as promising approaches for solubility enhancement. The aim of this work was to develop, characterize, and evaluate a solid SMEDDS prepared via spray-drying of a liquid SMEDDS based on Gelucire® 44/14 to improve the solubility and dissolution rate of naproxen. Various oils and co-surfactants in combination with Gelucire® 44/14 were evaluated during excipient selection study, solubility testing, and construction of (pseudo)ternary diagrams. The selected system was further evaluated for naproxen solubility, self-microemulsification ability, and in vitro dissolution of naproxen. In addition, its transformation into a solid SMEDDS by spray-drying using maltodextrin as a solid carrier was performed. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) were used to evaluate the physical characteristics of the solid SMEDDS obtained. The selected formulation of SMEDDS was comprised of Miglyol 812®, Peceol™, Gelucire® 44/14, and Solutol® HS 15. The liquid and solid SMEDDS formed a microemulsion after dilution with comparable average droplet size and exhibited uniform droplet size distribution. In the solid SMEDDS, liquid SMEDDS was adsorbed onto the surface of maltodextrin and formed smooth granular particles with the encapsulated drug predominantly in a dissolved state and partially in an amorphous state. Overall, incorporation of naproxen in SMEDDS, either liquid or solid, resulted in improved solubility and dissolution rate compared to pure naproxen. This study indicates that a liquid and solid SMEDDS is a strategy for solubility enhancement in the future development of orally delivered dosage forms.

Development and clinical application of oral dosage forms of taxanes

NARCIS (Netherlands)

Moes, J.J.

2013-01-01

Cancer is still one of the leading causes of death in the Western World. Despite the development and introduction of new anti-cancer agents, docetaxel and paclitaxel remain the cornerstone of adjuvant and metastatic chemotherapy against solid tumors. Taxanes belong to the class of anti-mitotic

Weight loss during therapy with olanzapine orally disintegrating tablets: two case reports.

Science.gov (United States)

Kozumplik, Oliver; Uzun, Suzana; Jakovljević, Miro

2009-03-01

The aim of this article is to report weight loss in patients with schizophrenia after switching from olanzapine standard oral tablet (SOT) to olanzapine orally disintegrating tablets (ODT). In the first case report, the patient was switched to olanzapine ODT in daily dosage of 20 mg, while in the second case report, the patient was switched to olanzapine ODT in daily dosage of 15 mg, and weight loss was similar (14 kg vs. 15 kg). Switching patients from olanzapine SOT to olanzapine ODT treatment resulted in significant weight loss that was maintained during 12 months in both case reports. Further controlled clinical investigations are necessary to evaluate change in weight during treatment with olanzapine ODT, and to improve our understanding of this change.

Pre-anthesis CPPU low dosage application increases 'Hayward' kiwifruit weight without affecting the other qualitative and nutritional characteristics.

Science.gov (United States)

Cruz-Castillo, J G; Baldicchi, A; Frioni, T; Marocchi, F; Moscatello, S; Proietti, S; Battistelli, A; Famiani, F

2014-09-01

In 2008, in Central Italy, a low dosage of CPPU solution, 4 μL L(-1) (6 hL/ha), was sprayed on the canopy of vines of 'Hayward' kiwifruit, at the "break of sepals", about one week before anthesis, to study its effects on fruit weight/size and on qualitative and nutritional characteristics. At harvest, CPPU, with respect to control, significantly increased the fresh weight by about 12% (+12.6 g fruit(-1)) and consequently the yield per vine, without affecting fruit shape, firmness, dry matter (%), total soluble solids, glucose, fructose, sucrose, starch, citrate, malate, vitamin C and soluble and insoluble oxalic acid. After 3 months of storage, CPPU-treated kiwifruits and the control fruit showed no difference in dry matter content, fruit firmness and total soluble solids. The results indicate that a low dosage of CPPU applied in pre-anthesis can improve fruit weight/size without any negative effect on fruit qualitative and nutritional characteristics. Copyright © 2014 Elsevier Ltd. All rights reserved.

Biowaiver monographs for immediate release solid oral dosage forms: acetaminophen (paracetamol).

NARCIS (Netherlands)

Kalantzi, L; Reppas, C; Dressman, J B; Amidon, G L; Junginger, H E; Midha, K K; Shah, V P; Stavchansky, S A; Barends, Dirk M

2006-01-01

Literature data are reviewed on the properties of acetaminophen (paracetamol) related to the biopharmaceutics classification system (BCS). According to the current BCS criteria, acetaminophen is BCS Class III compound. Differences in composition seldom, if ever, have an effect on the extent of

Effect of oral calcium and calcium + fluoride treatments on mouse bone properties during suspension

Science.gov (United States)

Simske, S. J.; Luttges, M. W.; Allen, K. A.; Spooner, B. S. (Principal Investigator)

1992-01-01

The bone effects of oral dosages of calcium chloride with or without supplementary sodium fluoride were assessed in antiorthostatically suspended mice. Two calcium dosages were used to replace half (3.1 mM) or all(6.3 mM) of the dietary calcium lost due to reduced food intake by the suspended mice. Two groups of 6.3 mM CaCl2-treated mice were additionally treated with 0.25 or 2.5 mM NaF. The results indicate that supplementation of the mouse drinking water with calcium salts prevents bone changes induced by short-term suspension, while calcium salts in combination with fluoride are less effective as fluoride dosage increases. However, the calcium supplements change the relationship between the femur mechanical properties and the mineral composition of the bone. Because of this, it appears that oral calcium supplements are effective through a mechanism other than simple dietary supplementation and may indicate a dependence of bone consistency on systemic and local fluid conditions.

[Understanding Oral and Nasal Mucosal Absorption of Fentanyl, and Rectal Absorption of Buprenorphine].

Science.gov (United States)

Shimoyama, Naohito; Shimoyama, Megumi; Kubota, Yukino; Kato, Yoko

2015-11-01

One of the key issues in the treatment of pain is to choose the appropriate route and dosage form of analgesics for each individual patient in pain. New drug forms of fentanyl absorbed by oral or nasal mucosa, and buprenorphine absorbed by rectal mucosa are described in this chapter. Only lipophilic opioids such as fentanyl and buprenorphine can be absorbed via the mucosa of oral or nasal cavity of the human body. The T max of rapid onset opioids (ROO) such as fentanyl buccal or sublingual tablets is the fastest among various dosage forms of opioid analgesics. However, such rapid increase in plasma concentration of fentanyl by ROO formulations may cause the risk of respiratory depression. Safe ways to use ROO analgesics are described.

Formulation and evaluation of a novel matrix-type orally disintegrating Ibuprofen tablet.

Science.gov (United States)

Tayebi, Hoda; Mortazavi, Seyed Alireza

2011-01-01

Orally disintegrating tablets (ODTs) are capable of turning quickly into a liquid dosage form in contact with the saliva, thus possessing the advantages of both the solid dosage forms particularly stability and liquid dosage forms specially ease of swallowing and pre-gastric absorption of drug. The aim of this study was to prepare a novel matrix-type buccal fast disintegrating ibuprofen tablet formulation using special polymers, water soluble excipients, super-disintegrants and quickly soluble granules. For this purpose different tablet formulations of ibuprofen were prepared. The amount of ibuprofen in each formulation was 100 mg. Eight groups of formulation were prepared (A-H series), accounting for a total number of 45 formulations. Formulations prepared were examined in terms of different physicochemical tests including powder/granule flowability, appearance, thickness, uniformity of weight, hardness, friability and disintegration time. Results of formulation F22a (in series F), was found to be acceptable, making it the chosen formulation for further studies. Then, by adding various flavorants and sweeteners to this formulation, complementary series of formulations, named G and H, were prepared. Following the comparison of their taste with each other through asking 10 volunteers, the most suitable formulation regarding the taste, being formulation F22s, was chosen as the ultimate formulation. This formulation had PVP, ibuprofen and croscarmellose as the intra-granular components and xylitol and saccharin as the extra-granular ingredients. Formulation F22s was found to be acceptable in terms of physicochemical tests conducted, showing quick disintegration within the buccal cavity, appropriate hardness and rather low friability. Hence formulation F22s was selected as the final formulation.

A benefit/risk approach towards selecting appropriate pharmaceutical dosage forms - an application for paediatric dosage form selection.

Science.gov (United States)

Sam, Tom; Ernest, Terry B; Walsh, Jennifer; Williams, Julie L

2012-10-05

The design and selection of new pharmaceutical dosage forms involves the careful consideration and balancing of a quality target product profile against technical challenges and development feasibility. Paediatric dosage forms present particular complexity due to the diverse patient population, patient compliance challenges and safety considerations of this vulnerable population. This paper presents a structured framework for assessing the comparative benefits and risks of different pharmaceutical design options against pre-determined criteria relating to (1) efficacy, (2) safety and (3) patient access. This benefit/risk framework has then been applied to three hypothetical, but realistic, scenarios for paediatric dosage forms in order to explore its utility in guiding dosage form design and formulation selection. The approach allows a rigorous, systematic and qualitative assessment of the merits and disadvantages of each dosage form option and helps identify mitigating strategies to modify risk. The application of a weighting and scoring system to the criteria depending on the specific case could further refine the analysis and aid decision-making. In this paper, one case study is scored for illustrative purposes. However, it is acknowledged that in real development scenarios, the generation of actual data considering the very specific situation for the patient/product/developer would come into play to drive decisions on the most appropriate dosage form strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

ANTITUBERCULOSIS DRUG DOSAGE FORMS: RANGE, KEY BENEFITS AND PROSPECTS OF TECHNOLOGICAL IMPROVEMENT

Directory of Open Access Journals (Sweden)

M. E. Kim

2016-01-01

Full Text Available Interest to research in the development of new formulations of antituberculosis drugs due to the high incidence of tuberculosis in the Republic of Kazakhstan and the Russian Federation nowadays, including with acquired drug resistance. The reason for the development of acquired drug resistance is to interrupt the treatment of patients is the high toxicity of antituberculosis drugs. The improving the efficiency of antituberculosis therapy remains one of the most pressing.The aim this study was to review the dosage forms of antituberculosis drugs currently used and the ways to improve them.Methods. The study was conducted on the basis of scientific analysis (eLibrary database, PubMed, Cyberleninca, patent (kzpatents, reference (Klifar, Drugs register and technical literature.Results. It was revealed that the antituberculosis drugs are available in the form of tablets, capsules, granules for oral use and injection solutions. The advantages and disadvantages of oral dosage forms of antituberculosis drugs: tablets, capsules, granules, syrups, suspensions are described. The importance of the development and implementation in practice of pediatric formulations of antituberculosis drugs is mentioned. The state of current research inhaled formulations for the treatment of tuberculosis is described. The prospects of directional inhalation exposure by immobilization of antituberculosis drugs in liposomes, niosomes, nanocapsules, micelles, micro- and nanoparticles are mentioned. The prospect of the rectal formulations use is described. The increase in interest in the molecular encapsulation of medicinal substances with cyclodextrins in connection with the possibility of increasing the bioavailability of active ingredients, reduce the harmful effects on the gastrointestinal tract, extension, elimination of interaction of incompatible components in combination preparations, the protection of unstable substances is

Toxic corneal epitheliopathy after intravitreal methotrexate and its treatment with oral folic acid.

Science.gov (United States)

Gorovoy, Ian; Prechanond, Tidarat; Abia, Maravillas; Afshar, Armin R; Stewart, Jay M

2013-08-01

To determine whether oral folic acid can ameliorate an iatrogenic, visually significant corneal epitheliopathy, which commonly occurs with intravitreal injections of methotrexate for the treatment of intraocular lymphoma. We report 2 cases of visually significant corneal epitheliopathy occurring after intravitreal injections of methotrexate for intraocular lymphoma. The first patient did not receive any treatment for the corneal disease, and the second patient with bilateral intraocular lymphoma received 1 mg of oral folic acid daily, a commonly used dosage for patients on systemic methotrexate. In the first patient without treatment, there was a complete regression of the corneal epithelial disease only when the frequency of intravitreal methotrexate was reduced from weekly to monthly as per a commonly used dosage regimen for methotrexate. In the second patient, the corneal disease improved 80% within 1 week of initiating oral folic acid for her eye already experiencing severe epitheliopathy during her weekly dosing regimen of methotrexate and also had significantly decreased epithelial disease in her second eye that started weekly intravitreal methotrexate several weeks after beginning oral folic acid. Currently, oral folic acid supplements are recommended for patients using systemic methotrexate to minimize drug toxicity. We suggest a similar use in patients undergoing intravitreal methotrexate injections to decrease toxic effects on the corneal epithelium.

Oral transmucosal drug delivery--current status and future prospects.

Science.gov (United States)

Sattar, Mohammed; Sayed, Ossama M; Lane, Majella E

2014-08-25

Oral transmucosal drug delivery (OTDD) dosage forms have been available since the 1980s. In contrast to the number of actives currently delivered locally to the oral cavity, the number delivered as buccal or sublingual formulations remains relatively low. This is surprising in view of the advantages associated with OTDD, compared with conventional oral drug delivery. This review examines a number of aspects related to OTDD including the anatomy of the oral cavity, models currently used to study OTDD, as well as commercially available formulations and emerging technologies. The limitations of current methodologies to study OTDD are considered as well as recent publications and new approaches which have advanced our understanding of this route of drug delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

Development and characterization of a gastroretentive dosage form composed of chitosan and hydroxyethyl cellulose for alendronate

OpenAIRE

Chen YC; Ho HO; Chiu CC; Sheu MT

2013-01-01

Ying-Chen Chen,1,* Hsiu-O Ho,1,* Chiao-Chi Chiu,1 Ming-Thau Sheu1,2 1School of Pharmacy, College of Pharmacy, Taipei Medical University, 2Clinical Research Center and Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan*These authors contributed equally to this workAbstract: In this study, alendronate, the most commonly used biphosphonate for treating osteoporosis, was formulated as gastroretentive dosage form (GRDF) tablets to enhance its oral bioav...

Curcumin-loaded self-nanomicellizing solid dispersion system: part I: development, optimization, characterization, and oral bioavailability.

Science.gov (United States)

Parikh, Ankit; Kathawala, Krishna; Song, Yunmei; Zhou, Xin-Fu; Garg, Sanjay

2018-05-29

Curcumin (CUR) is considered as one of the most bioactive molecules ever discovered from nature due to its proven anti-inflammatory and antioxidant in both preclinical and clinical studies. Despite its proven safety and efficacy, the clinical translation of CUR into a useful therapeutic agent is still limited due to its poor oral bioavailability. To overcome its limitation and enhance oral bioavailability by improving its aqueous solubility, stability, and intestinal permeability, a novel CUR formulation (NCF) was developed using the self-nanomicellizing solid dispersion strategy. From the initial screening of polymers for their potential to improve the solubility and stability, Soluplus (SOL) was selected. The optimized NCF demonstrated over 20,000-fold improvement in aqueous solubility as a result of amorphization, hydrogen bonding interaction, and micellization determined using differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance, dynamic light scattering, and transmission electron microscopy. Moreover, the greater stabilizing effect in alkaline pH and light was observed. Furthermore, significant enhancement of dissolution and permeability of CUR across everted sacs of rat small intestine were noticed. Pharmacokinetic studies demonstrated that the oral bioavailability of CUR was increased 117 and 17-fold in case of NCF and physical mixture of CUR and SOL compared to CUR suspension. These results suggest NCF identified as a promising new approach for repositioning of CUR for pharmaceutical application by enhancing the oral bioavailability of CUR. The findings herein stimulate further in vivo evaluations and clinical tests of NCF.

Solid formulation of a supersaturable self-microemulsifying drug delivery system for valsartan with improved dissolution and bioavailability.

Science.gov (United States)

Yeom, Dong Woo; Chae, Bo Ram; Kim, Jin Han; Chae, Jun Soo; Shin, Dong Jun; Kim, Chang Hyun; Kim, Sung Rae; Choi, Ji Ho; Song, Seh Hyon; Oh, Dongho; Sohn, Se Il; Choi, Young Wook

2017-11-07

In order to improve the dissolution and oral bioavailability of valsartan (VST), and reduce the required volume for treatment, we previously formulated a supersaturable self-microemulsifying drug delivery system (SuSMEDDS) composed of VST (80 mg), Capmul ® MCM (13.2 mg), Tween ® 80 (59.2 mg), Transcutol ® P (59.2 mg), and Poloxamer 407 (13.2 mg). In the present study, by using Florite ® PS-10 (119.1 mg) and Vivapur ® 105 (105.6 mg) as solid carriers, VST-loaded solidified SuSMEDDS (S-SuSMEDDS) granules were successfully developed, which possessed good flow properties and rapid drug dissolution. By introducing croscarmellose sodium (31 mg) as a superdisintegrant, S-SuSMEDDS tablets were also successfully formulated, which showed fast disintegration and high dissolution efficiency. Preparation of granules and tablets was successfully optimized using D-optimal mixture design and 3-level factorial design, respectively, resulting in percentage prediction errors of <10%. In pharmacokinetic studies in rats, the relative bioavailability of the optimized granules was 107% and 222% of values obtained for SuSMEDDS and Diovan ® powder, respectively. Therefore, we conclude that novel S-SuSMEDDS formulations offer great potential for developing solid dosage forms of a liquefied formulation such as SuSMEDDS, while improving oral absorption of drugs with poor water solubility.

X-ray diagnostics. Oral and intravenous cholegraphy

International Nuclear Information System (INIS)

1981-04-01

The standard deals with oral and intravenous cholegraphy. It includes information on indications, contraindications, prerequisites and preparations as well as on application and appropriate dosage of contrast media. Parameters on focussing, imaging conditions and on the program of taking radiographies are outlined. The necessity of special examinations according to findings as well as measures concerning radiation protection and hygiene are presented

In vitro models for the prediction of in vivo performance of oral dosage forms

DEFF Research Database (Denmark)

Kostewicz, Edmund S; Abrahamsson, Bertil; Brewster, Marcus

2014-01-01

Accurate prediction of the in vivo biopharmaceutical performance of oral drug formulations is critical to efficient drug development. Traditionally, in vitro evaluation of oral drug formulations has focused on disintegration and dissolution testing for quality control (QC) purposes. The connection...... of formulations that rely on complex intraluminal processes (e.g. solubilization, supersaturation, precipitation…) remains extremely challenging. Concomitantly, the increasing demand for complex formulations to overcome low drug solubility or to control drug release rates urges the development of new in vitro...

Preparation and evaluation of carvacrol pellets based on PVP solid-dispersion by extrusion-spheronization technique

Directory of Open Access Journals (Sweden)

Z. Taghizadeh*

2017-11-01

Full Text Available Background and objectives: Carvacrol is one of the main pharmacologically active components of Thymus vulgaris essential oil which has shown several therapeutic effects. There are few works regarding the formulation of essential oils as oral solid dosage forms due to their liquid nature, stability and technical problems. The aim of this study was to combine the solid-dispersion approach and extrusion-spheronization technique to produce pellets with desirable physico-mechanical and release properties. Methods: Solid dispersion matrix (30% of carvacrol in polyvinylpyrrolidone K30 was prepared by solvent evaporation. The matrix was mixed with Avicel and lactose and granulated by water. The wet mass was transformed into pellets by extrusion-spheronization. In order to compare the solid dispersion method with the classic approaches, another pellet formulation was prepared by absorption of carvacrol on Aerosil. The pellets were characterized for size (sieve analysis, shape factors (image analysis, mechanical strength, carvacrol content, and release rate (dissolution test. Accelerated stability test of formulations was also carried out. Results: Using suitable composition of solid dispersion matrix and granulation fluid, the pellets with desirable size and shape and mechanical properties could be produced. PVP-based pellets had higher mechanical strength, slower release rate and improved content and stability. The PVP ratio showed considerable effect on release properties of the pellets. Conclusion: Overall, the results revealed the feasibility of preparing desirable pellets containing carvacrol with acceptable content, stability and release properties which can be administered as hard gelatin capsules.

Pillbox

Data.gov (United States)

U.S. Department of Health & Human Services — The Pillbox website was developed to aid in the identification of unknown pills (oral solid dosage form medications). It combines images of pills with appearance and...

A Miniaturized Extruder to Prototype Amorphous Solid Dispersions: Selection of Plasticizers for Hot Melt Extrusion.

Science.gov (United States)

Lauer, Matthias E; Maurer, Reto; Paepe, Anne T De; Stillhart, Cordula; Jacob, Laurence; James, Rajesh; Kojima, Yuki; Rietmann, Rene; Kissling, Tom; van den Ende, Joost A; Schwarz, Sabine; Grassmann, Olaf; Page, Susanne

2018-05-19

Hot-melt extrusion is an option to fabricate amorphous solid dispersions and to enhance oral bioavailability of poorly soluble compounds. The selection of suitable polymer carriers and processing aids determines the dissolution, homogeneity and stability performance of this solid dosage form. A miniaturized extrusion device (MinEx) was developed and Hypromellose acetate succinate type L (HPMCAS-L) based extrudates containing the model drugs neurokinin-1 (NK1) and cholesterylester transfer protein (CETP) were manufactured, plasticizers were added and their impact on dissolution and solid-state properties were assessed. Similar mixtures were manufactured with a lab-scale extruder, for face to face comparison. The properties of MinEx extrudates widely translated to those manufactured with a lab-scale extruder. Plasticizers, Polyethyleneglycol 4000 (PEG4000) and Poloxamer 188, were homogenously distributed but decreased the storage stability of the extrudates. Stearic acid was found condensed in ultrathin nanoplatelets which did not impact the storage stability of the system. Depending on their distribution and physicochemical properties, plasticizers can modulate storage stability and dissolution performance of extrudates. MinEx is a valuable prototyping-screening method and enables rational selection of plasticizers in a time and material sparing manner. In eight out of eight cases the properties of the extrudates translated to products manufactured in lab-scale extrusion trials.

The Active Metabolite of Warfarin (3'-Hydroxywarfarin) and Correlation with INR, Warfarin and Drug Weekly Dosage in Patients under Oral Anticoagulant Therapy: A Pharmacogenetics Study

Science.gov (United States)

Talarico, Anna; Fabbri, Matteo; Bertocco, Cesare; Vigliano, Marco; Moratelli, Stefano; Cuneo, Antonio; Serino, Maria Luisa; Avato, Francesco Maria

2016-01-01

Objectives Warfarin oral anticoagulant therapy (OAT) requires regular and frequent drug adjustment monitored by INR. Interindividual variability, drug and diet interferences, and genetics (VKORC1 and CYP2C9) make the maintenance/reaching of stable INR a not so easy task. HPLC assessment of warfarin/enantiomers was suggested as a valid monitoring-tool along with INR, but definite results are still lacking. We evaluated possible correlations between INR, warfarin/3’-hydroxywarfarin, and drug weekly dosage aimed at searching novel alternatives to OAT monitoring. VKORC1/CYP2C9 pharmacogenetics investigation was performed to account for the known influence on warfarin homeostasis. Methods 133 OAT patients were recruited and assessed for warfarin/3’-hydroxywarfarin serum levels (HPLC), INR, and VKORC1 and CYP2C9 genotypes. A subgroup of 52 patients were monitored in detail (5 consecutive controls; c0-c4) till the target INR was reached. Correlation analyses were performed in both groups Results In the whole OAT group both warfarin and 3’-hydroxywarfarin correlate with INR at comparable degree (r2 = 0.0388 and 0.0362 respectively). Conversely, warfarin weekly dosage better correlates with warfarin than with 3’-hydroxywarfarin (r2 = 0.0975 and r2 = 0.0381 respectively), but considering together warfarin plus 3’-hydroxywarfarin the correlation strongly increased (r2 = 0.1114; pwarfarin (r2 = 0.2157 and r2 = 0.0549; p = 0.0005 and p = 0.0944 respectively) seeming less affected by drug adjustments in the subgroup of 52 patients who started OAT. The multivariate analyses aimed at estimating the true contribution of 3’-hydroxywarfarin on INR value ascribed it the unique significant value (p = 0.0021) in spite of warfarin who lost association. The pharmacogenetics studies confirmed that patients carrying the VKORC1 variant-allele required lower warfarin maintenance dosage and that the combination of VKORC1 and CYP2C9 yielded a warfarin responsive index (WRI

Detection time for THC in oral fluid after frequent cannabis smoking.

Science.gov (United States)

Andås, Hilde T; Krabseth, Hege-Merete; Enger, Asle; Marcussen, Bjarne N; Haneborg, An-Magritt; Christophersen, Asbjørg S; Vindenes, Vigdis; Øiestad, Elisabeth L

2014-12-01

The use of oral fluid for detecting drugs of abuse has become increasingly more frequent. Few studies have, however, investigated the detection times for drugs of abuse in oral fluid, compared with that of in urine or in blood. Cannabis is the world's most widely used drug of abuse, and the detection times for cannabis, in different types of matrixes, are therefore important information to the laboratories or institutions performing and evaluating drugs of abuse analyses. It is well known that frequent use of high dosages of cannabis, for longer periods of time, might lead to prolonged detection times for THC-COOH in urine. Cannabis intake is detected in oral fluid as THC, and a positive finding is considered to be a result of recent smoking, although some studies have already reported longer detection times. The aim of this study was to investigate the detection time for THC in oral fluid, collected from drug addicts admitted for detoxification. Findings in oral fluid were compared with findings in urine, among 26 patients admitted to a closed detoxification unit. The study, being the first in doing so, describes the concentration-time profiles for THC in oral fluid among chronic cannabis users, during monitored abstinence, using the Intercept collection kit. The study also includes the concentration-time profiles for creatinine-corrected THC-COOH ratios in urine samples, included to monitor for the possibility of new intakes. THC was detected in oral fluid collected from 11 of the 26 patients in the study. The elimination curves for THC in oral fluid revealed that negative samples could be interspersed among positive samples several days after cessation, whereas the THC-COOH concentrations in urine were decreasing. THC was, in this study, detected in oral fluid for up to 8 days after admission. The study shows that frequent use of high dosages of cannabis may lead to prolonged detection times, and that positive samples can be interspersed among negative samples

Physical Stability of Freeze-Dried Isomalt Diastereomer Mixtures

DEFF Research Database (Denmark)

Koskinen, Anna-Kaisa; Fraser-Miller, Sara J.; Bøtker, Johan P.

2016-01-01

Purpose Isomalt is a sugar alcohol used as an excipient in commercially available solid oral dosage forms. The potential of isomalt as a novel freeze-drying excipient was studied in order to increase knowledge of the behavior of isomalt when it is freeze-dried. Methods Isomalt was freeze-dried in......Purpose Isomalt is a sugar alcohol used as an excipient in commercially available solid oral dosage forms. The potential of isomalt as a novel freeze-drying excipient was studied in order to increase knowledge of the behavior of isomalt when it is freeze-dried. Methods Isomalt was freeze......-dried in four different diastereomer compositions and its physical stability was investigated with differential scanning calorimetry, Fourier-transform infrared and Raman spectroscopy, X-ray powder diffraction, Karl-Fischer titration and thermogravimetric analysis in order to verify the solid state form...... of the diastereomer compositions showed signs of physical instability when stored in the highest relative humidity condition. The four different crystalline diastereomer mixtures showed specific identifiable solid state properties. Conclusions Isomalt was shown to be a suitable excipient for freeze-drying. Preferably...

Potential hazards due to food additives in oral hygiene products.

Science.gov (United States)

Tuncer Budanur, Damla; Yas, Murat Cengizhan; Sepet, Elif

2016-01-01

Food additives used to preserve flavor or to enhance the taste and appearance of foods are also available in oral hygiene products. The aim of this review is to provide information concerning food additives in oral hygiene products and their adverse effects. A great many of food additives in oral hygiene products are potential allergens and they may lead to allergic reactions such as urticaria, contact dermatitis, rhinitis, and angioedema. Dental practitioners, as well as health care providers, must be aware of the possibility of allergic reactions due to food additives in oral hygiene products. Proper dosage levels, delivery vehicles, frequency, potential benefits, and adverse effects of oral health products should be explained completely to the patients. There is a necessity to raise the awareness among dental professionals on this subject and to develop a data gathering system for possible adverse reactions.

Scientific and Regulatory Considerations in Solid Oral Modified Release Drug Product Development.

Science.gov (United States)

Li, Min; Sander, Sanna; Duan, John; Rosencrance, Susan; Miksinski, Sarah Pope; Yu, Lawrence; Seo, Paul; Rege, Bhagwant

2016-11-01

This review presents scientific and regulatory considerations for the development of solid oral modified release (MR) drug products. It includes a rationale for patient-focused development based on Quality-by-Design (QbD) principles. Product and process understanding of MR products includes identification and risk-based evaluation of critical material attributes (CMAs), critical process parameters (CPPs), and their impact on critical quality attributes (CQAs) that affect the clinical performance. The use of various biopharmaceutics tools that link the CQAs to a predictable and reproducible clinical performance for patient benefit is emphasized. Product and process understanding lead to a more comprehensive control strategy that can maintain product quality through the shelf life and the lifecycle of the drug product. The overall goal is to develop MR products that consistently meet the clinical objectives while mitigating the risks to patients by reducing the probability and increasing the detectability of CQA failures.

Buccal bioadhesive drug delivery--a promising option for orally less efficient drugs.

Science.gov (United States)

Sudhakar, Yajaman; Kuotsu, Ketousetuo; Bandyopadhyay, A K

2006-08-10

Rapid developments in the field of molecular biology and gene technology resulted in generation of many macromolecular drugs including peptides, proteins, polysaccharides and nucleic acids in great number possessing superior pharmacological efficacy with site specificity and devoid of untoward and toxic effects. However, the main impediment for the oral delivery of these drugs as potential therapeutic agents is their extensive presystemic metabolism, instability in acidic environment resulting into inadequate and erratic oral absorption. Parenteral route of administration is the only established route that overcomes all these drawbacks associated with these orally less/inefficient drugs. But, these formulations are costly, have least patient compliance, require repeated administration, in addition to the other hazardous effects associated with this route. Over the last few decades' pharmaceutical scientists throughout the world are trying to explore transdermal and transmucosal routes as an alternative to injections. Among the various transmucosal sites available, mucosa of the buccal cavity was found to be the most convenient and easily accessible site for the delivery of therapeutic agents for both local and systemic delivery as retentive dosage forms, because it has expanse of smooth muscle which is relatively immobile, abundant vascularization, rapid recovery time after exposure to stress and the near absence of langerhans cells. Direct access to the systemic circulation through the internal jugular vein bypasses drugs from the hepatic first pass metabolism leading to high bioavailability. Further, these dosage forms are self-administrable, cheap and have superior patient compliance. Developing a dosage form with the optimum pharmacokinetics is a promising area for continued research as it is enormously important and intellectually challenging. With the right dosage form design, local environment of the mucosa can be controlled and manipulated in order to

Association between oral manifestations and inhaler use in asthmatic and chronic obstructive pulmonary disease patients

Directory of Open Access Journals (Sweden)

Bhargavi Krishna Ayinampudi

2016-01-01

Full Text Available Objectives: To examine the association between oral manifestations and type, frequency and duration of inhaler usage, also type and dosage of medication used in asthmatic and chronic obstructive pulmonary disease (COPD patients. Materials and Methods: A cross-sectional study was conducted on 250 patients of both sexes suffering from asthma and COPD who were using inhalers. Frequency of oral manifestation seen on the tongue, buccal mucosa, teeth, periodontium, palate, floor of the mouth, lips, and xerostomia in inhaler users depending on the type of inhaler, type and dosage of medication, frequency and duration of use of inhaler were examined. Chi-square test was used for statistical analysis and P 0.05. Gingivitis/gingival enlargement (53.6% and 51.5% was almost similar but periodontitis was higher in those using >500 μg. Significant association (P < 0.05 was observed with duration <1 year; oral manifestations seen were taste alterations (53.2% in tongue, ulcerations (63.6% in the buccal mucosa, teeth affected (87%, gingivitis/gingival enlargement (66.2%, and xerostomia (89.6%. Conclusions: As asthmatics and COPD patients are at a higher risk of developing oral diseases during inhalation therapy, it is necessary to educate patients on proper oral health care and maintenance.

Toxoplasma gondii oral infection induces intestinal inflammation and retinochoroiditis in mice genetically selected for immune oral tolerance resistance.

Directory of Open Access Journals (Sweden)

Raul Ramos Furtado Dias

Full Text Available Toxoplasmosis is a worldwide disease with most of the infections originating through the oral route and generates various pathological manifestations, ranging from meningoencephalitis to retinochoroiditis and inflammatory bowel disease. Animal models for these pathologies are scarce and have limitations. We evaluated the outcome of Toxoplasma gondii oral infection with 50 or 100 cysts of the ME-49 strain in two lines of mice with extreme phenotypes of susceptibility (TS or resistance (TR to immune oral tolerance. Therefore, the aim of this study was to evaluate the behaviour of TS and TR mice, orally infected by T. gondii, and determine its value as a model for inflammatory diseases study. Mortality during the acute stage of the infection for TR was 50% for both dosages, while 10 and 40% of the TS died after infection with these respective dosages. In the chronic stage, the remaining TS succumbed while TR survived for 90 days. The TS displayed higher parasite load with lower intestinal inflammation and cellular proliferation, notwithstanding myocarditis, pneumonitis and meningoencephalitis. TR presented massive necrosis of villi and crypt, comparable to inflammatory bowel disease, with infiltration of lymphoid cells in the lamina propria of the intestines. Also, TR mice infected with 100 cysts presented intense cellular infiltrate within the photoreceptor layer of the eyes, changes in disposition and morphology of the retina cell layers and retinochoroiditis. During the infection, high levels of IL-6 were detected in the serum of TS mice and TR mice presented high amounts of IFN-γ and TNF-α. Both mice lineages developed different disease outcomes, but it is emphasized that TR and TS mice presented acute and chronic stages of the infection, demonstrating that the two lineages offer an attractive model for studying toxoplasmosis.

Toxoplasma gondii Oral Infection Induces Intestinal Inflammation and Retinochoroiditis in Mice Genetically Selected for Immune Oral Tolerance Resistance

Science.gov (United States)

Dias, Raul Ramos Furtado; de Carvalho, Eulógio Carlos Queiroz; Leite, Carla Cristina da Silva; Tedesco, Roberto Carlos; Calabrese, Katia da Silva; Silva, Antonio Carlos; DaMatta, Renato Augusto; de Fatima Sarro-Silva, Maria

2014-01-01

Toxoplasmosis is a worldwide disease with most of the infections originating through the oral route and generates various pathological manifestations, ranging from meningoencephalitis to retinochoroiditis and inflammatory bowel disease. Animal models for these pathologies are scarce and have limitations. We evaluated the outcome of Toxoplasma gondii oral infection with 50 or 100 cysts of the ME-49 strain in two lines of mice with extreme phenotypes of susceptibility (TS) or resistance (TR) to immune oral tolerance. Therefore, the aim of this study was to evaluate the behaviour of TS and TR mice, orally infected by T. gondii, and determine its value as a model for inflammatory diseases study. Mortality during the acute stage of the infection for TR was 50% for both dosages, while 10 and 40% of the TS died after infection with these respective dosages. In the chronic stage, the remaining TS succumbed while TR survived for 90 days. The TS displayed higher parasite load with lower intestinal inflammation and cellular proliferation, notwithstanding myocarditis, pneumonitis and meningoencephalitis. TR presented massive necrosis of villi and crypt, comparable to inflammatory bowel disease, with infiltration of lymphoid cells in the lamina propria of the intestines. Also, TR mice infected with 100 cysts presented intense cellular infiltrate within the photoreceptor layer of the eyes, changes in disposition and morphology of the retina cell layers and retinochoroiditis. During the infection, high levels of IL-6 were detected in the serum of TS mice and TR mice presented high amounts of IFN-γ and TNF-α. Both mice lineages developed different disease outcomes, but it is emphasized that TR and TS mice presented acute and chronic stages of the infection, demonstrating that the two lineages offer an attractive model for studying toxoplasmosis. PMID:25437299

Formulation of avanafil in a solid self-nanoemulsifying drug delivery system for enhanced oral delivery.

Science.gov (United States)

Soliman, Kareem AbuBakr; Ibrahim, Howida Kamal; Ghorab, Mahmoud Mohammed

2016-10-10

Avanafil was incorporated into solid self-nanoemulsifying systems with the aim of improving its oral bioavailability. Labrafil, Labrafac, and Miglyol 812 N were investigated as oils, Tween 80 and Cremophor EL as surfactants, and Transcutol HP as a co-surfactant. Nine formulations produced clear solutions of 13.89-38.09nm globules after aqueous dilution. Adsorption of preconcentrate onto Aeroperl 300 Pharma at a 2:1 ratio had no effect on nanoemulsion particle size. Differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy indicated that avanafil was molecularly dispersed within the solid nanosystems. A formulation containing 10% Labrafil, 60% Tween 80, and 30% Transcutol HP had the highest drug loading (44.48mg/g) and an acceptable in vitro dissolution profile (96.42% within 30min). This formulation was chemically and physically stable for 6months under accelerated storage conditions and it produced a 3.2-fold increase in bioavailability in rabbits, as compared to conventional commercially available avanafil tablets (Spedra(®)). Copyright © 2016 Elsevier B.V. All rights reserved.

Formulation of cefuroxime axetil oral suspension and investigation of its pharmaceutical properties

OpenAIRE

Valizadeh, Hadi; Farajnia, Aynoor; Zakeri-Milani, Parvin

2011-01-01

Purpose: Cefuroxime is the second generation cephalosporin, which its intravenous and oral dosage forms are available. Oral route is the selective method for administration of most of the drugs. The aim of this study was formulating ‘for oral’ cefuroxime axetil suspensions. Methods: Minitab (ver.15) was used to design the formulations containing 125 mg of cefuroxime in 5 ml vehicle. After selecting the acceptable preparations, physical stability tests and other tests such as dissolution rate,...

Effect of warning symbols in combination with education on the frequency of erroneously crushing medication in nursing homes : An uncontrolled before and after study

NARCIS (Netherlands)

van Welie, Steven; Wijma, Linda; Beerden, Tim; van Doormaal, Jasperien; Taxis, Katja

2016-01-01

Objectives: Residents of nursing homes often have difficulty swallowing (dysphagia), which complicates the administration of solid oral dosage formulations. Erroneously crushing medication is common, but few interventions have been tested to improve medication safety. Therefore, we evaluated the

Herbal medicinal products in the treatment of pain as a symptom of osteoarthritis

Directory of Open Access Journals (Sweden)

Maksimović Zoran

2016-01-01

Full Text Available Herbal medicinal products which are used perorally in the treatment of minor articular pain include those obtained from willow bark, Salicis cortex, devil's claw root, Harpagophyti radix, nettle leaf and herb, Urticae folium/herba, meadowsweet flower and herb, Filipendulae ulmariae flos/herba, ash leaf, Fraxini folium, and blackcurrant leaf, Ribis nigri folium. They can be in the form of a herbal tea or solid and liquid dosage forms. Anti-inflammatory and/or analgetic action form/s basis for their therapeutic usage. Among mentioned herbal drugs, only willow bark, Salicis cortex, is employed for producing herbal medicinal products with well-established use (dry standardised hydroethanolic extract in the solid dosage form intended for oral application. Furthermore, traditional herbal medicines prepared from arnica flower, Arnicae flos, which are intended for dermal application (liquid and semi-solid dosage forms are used for symptomatic relief of rheumatic complaints, also because of their anti-inflammatory and analgetic effects. Owing to rubefacient activity, herbal medicinal products with well-established use based on the soft extracts of capsicum, Capsici frustus, (medicated plasters and semi-solid dosage forms for cutaneous use, as well as traditional herbal medicines based on rosemary leaf and oil, Rosmarini folium/aetheroleum, juniper oil, Juniperi aetheroleum, and eucalyptus oil, Eucalypti aetheroleum (bath additives and/or liquid and semi-solid dosage forms for dermal application, are used to decrease pain.

Improved Oral Bioavailability Using a Solid Self-Microemulsifying Drug Delivery System Containing a Multicomponent Mixture Extracted from Salvia miltiorrhiza

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Xiaolin Bi

2016-04-01

Full Text Available The active ingredients of salvia (dried root of Salvia miltiorrhiza include both lipophilic (e.g., tanshinone IIA, tanshinone I, cryptotanshinone and dihydrotanshinone I and hydrophilic (e.g., danshensu and salvianolic acid B constituents. The low oral bioavailability of these constituents may limit their efficacy. A solid self-microemulsifying drug delivery system (S-SMEDDS was developed to load the various active constituents of salvia into a single drug delivery system and improve their oral bioavailability. A prototype SMEDDS was designed using solubility studies and phase diagram construction, and characterized by self-emulsification performance, stability, morphology, droplet size, polydispersity index and zeta potential. Furthermore, the S-SMEDDS was prepared by dispersing liquid SMEDDS containing liposoluble extract into a solution containing aqueous extract and hydrophilic polymer, and then freeze-drying. In vitro release of tanshinone IIA, salvianolic acid B, cryptotanshinone and danshensu from the S-SMEDDS was examined, showing approximately 60%–80% of each active component was released from the S-SMEDDS in vitro within 20 min. In vivo bioavailability of these four constituents indicated that the S-SMEDDS showed superior in vivo oral absorption to a drug suspension after oral administration in rats. It can be concluded that the novel S-SMEDDS developed in this study increased the dissolution rate and improved the oral bioavailability of both lipophilic and hydrophilic constituents of salvia. Thus, the S-SMEDDS can be regarded as a promising new method by which to deliver salvia extract, and potentially other multicomponent drugs, by the oral route.

Formulation design of oral pediatric Acetazolamide suspension: dose uniformity and physico-chemical stability study.

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Santoveña, Ana; Suárez-González, Javier; Martín-Rodríguez, Cristina; Fariña, José B

2017-03-01

The formulation of an active pharmaceutical ingredient (API) as oral solution or suspension in pediatrics is a habitual practice, due to the non-existence of many commercialized medicines in pediatric doses. It is also the simplest way to prepare and administer them to this vulnerable population. The design of a formulation that assures the dose and the system stability depends on the physico-chemical properties of the API. In this study, we formulate a class IV API, Acetazolamide (AZM) as suspension for oral administration to pediatric population. The suspension must comply attributes of quality, safety and efficacy for this route of administration. We use simple compounding procedures, as well as fewer pure excipients, as recommended for children. Mass and uniformity content assays and physical and chemical stability studies were performed. To quantify the API an UPLC method was used. We verified the physico-chemical stability of the suspensions and that they passed the mass test of the European Pharmacopeia (EP), but not the dose uniformity test. This reveals that AZM must be formulated as liquid forms with a more complex system of excipients (not usually indicated in pediatrics), or otherwise solid forms capable of assuring uniformity of mass and dose for every dosage unit.

[Pharmaceutical advice concerning different pharmaceutical dosage forms].

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Szakonyi, Gergely; Zelkó, Romána

2010-01-01

The present paper summarizes the commonly applied types of drug uptake and the pharmacists' advice concerning a certain dosage form. The manuscript also deals with the modified release dosage forms and their abbreviations in the name of the marketing authorized products.

Low starting dosage of infliximab with possible escalating dosage in psoriatic arthritis gives the same treatment results as standard dosage of adalimumab or etanercept: results from the nationwide Icelandic ICEBIO registry

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Gudbjornsson B

2018-05-01

Full Text Available Bjorn Gudbjornsson,1,2 Arni Jon Geirsson,3,4 Niels Steen Krogh5 1Centre for Rheumatology Research, University Hospital, Reykjavik, Iceland; 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland; 3Department of Rheumatology, University Hospital, Reykjavik, Iceland; 4Laeknasetrid - Medical Clinic, University of Iceland, Reykjavik, Iceland; 5Zitelab Aps, Copenhagen, Denmark Objective: To explore differences in response to a low dosage regimen of infliximab with an escalating dosage in comparison to a standard dosage of etanercept and adalimumab in patients with psoriatic arthritis (PsA. Methods: Biologically naïve PsA patients who were beginning anti-TNF-α therapy were selected from the ICEBIO registry. Demographics and clinical differences were compared in four treatment groups: infliximab <4 mg/kg; infliximab >4 mg/kg; etanercept or adalimumab at baseline and on follow-up (6 and 12 months, last visit. The Kruskal–Wallis rank sum test was used for comparison of the groups and the Wilcoxon test to compare the two infliximab dosage regimens. Results: One hundred and eighty-five patients (61% female were identified; 84 patients received infliximab, 66 etanercept, and 35 adalimumab. A total of 19% of the patients treated with infliximab escalated their dosage ≥4 mg/kg. No significant differences were observed at baseline in respect to visual analog scale (VAS pain, VAS fatigue, Health Assessment Questionnaire, C-reactive protein (CRP, numbers of swollen or tender joints, or Disease Activity Score (DAS 28-CRP values. A similar treatment response was observed in all four treatment groups on follow-up. Conclusion: In respect to treatment effects, a low dosage of infliximab with possible escalating dosage is acceptable for the majority of PsA patients who are in need of biological treatment. Keywords: psoriatic arthritis, outcome, biological treatment, routine care, clinical nationwide registry

Lipid-based formulations for oral administration of poorly water-soluble drugs

DEFF Research Database (Denmark)

Mu, Huiling; Holm, René; Müllertz, Anette

2013-01-01

Lipid-based drug delivery systems have shown great potentials in oral delivery of poorly water-soluble drugs, primarily for lipophilic drugs, with several successfully marketed products. Pre-dissolving drugs in lipids, surfactants, or mixtures of lipids and surfactants omits the dissolving....../dissolution step, which is a potential rate limiting factor for oral absorption of poorly water-soluble drugs. Lipids not only vary in structures and physiochemical properties, but also in their digestibility and absorption pathway; therefore selection of lipid excipients and dosage form has a pronounced effect...

POTENTIAL HAZARDS DUE TO FOOD ADDITIVES IN ORAL HYGIENE PRODUCTS

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Damla TUNCER-BUDANUR

2016-04-01

Full Text Available Food additives used to preserve flavor or to enhance the taste and appearance of foods are also available in oral hygiene products. The aim of this review is to provide information concerning food additives in oral hygiene products and their adverse effects. A great many of food additives in oral hygiene products are potential allergens and they may lead to allergic reactions such as urticaria, contact dermatitis, rhinitis, and angioedema. Dental practitioners, as well as health care providers, must be aware of the possibility of allergic reactions due to food additives in oral hygiene products. Proper dosage levels, delivery vehicles, frequency, potential benefits, and adverse effects of oral health products should be explained completely to the patients. There is a necessity to raise the awareness among dental professionals on this subject and to develop a data gathering system for possible adverse reactions.

Determining S-1 dosage at hospitals prioritizing cancer chemotherapy

International Nuclear Information System (INIS)

Morimoto, Shigefumi; Kitada, Noriaki; Anami, Setsuko

2008-01-01

Although it is recommended that the standard S-1 dosage should be based on how large the body surface area is, an on-site setting of the appropriate dosage is often lower than the standard one, depending on the individual's condition and considering possible side effects and so, on. Here, we investigated usage conditions for S-1 as a part of field training for expert pharmacists at our hospital that performs total clinical treatments. Decreases in dosage per day for elderly patients were although the standard dosage is generally determined according to the amount of a patient's body surface. We conducted a retrospective survey with a total 90 patients by creating a tree-diagram to identify a reduction standard. It was found that the S-1 dosage was decreased when there were side effects, aggravation in performance status, decrease in kidney function, old age, combined injection chemotherapy, and a decrease in radiation therapy performance. The dosage decreases without such medical reasons were seen in only 4 of the 90 patients. At hospitals giving priority to chemotherapy, it became clear that appropriate treatment was promoted by decreasing. The individual target dosage on the basis of daily medical examination. (author)

Candida albicans septicemia in a premature infant successfully treated with oral fluconazole

DEFF Research Database (Denmark)

Bodé, S; Pedersen-Bjergaard, Lars; Hjelt, K

1992-01-01

A premature male infant, birth-weight 1460 g, was treated successfully for a Candida albicans septicemia with orally administered fluconazole for 20 days. Dosage was 5 mg/kg/day. No side effects were seen. Fluconazole may present a major progress in treatment of invasive C. albicans infections...

Intelligent system for improving dosage control

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Fabio Cosme Rodrigues dos Santos

2017-02-01

Full Text Available Coagulation is one of the most important processes in a drinking-water treatment plant, and it is applied to destabilize impurities in water for the subsequent flocculation stage. Several techniques are currently used in the water industry to determine the best dosage of the coagulant, such as the jar-test method, zeta potential measurements, artificial intelligence methods, comprising neural networks, fuzzy and expert systems, and the combination of the above-mentioned techniques to help operators and engineers in the water treatment process. Current paper presents an artificial neural network approach to evaluate optimum coagulant dosage for various scenarios in raw water quality, using parameters such as raw water color, raw water turbidity, clarified and filtered water turbidity and a calculated Dose Rate to provide the best performance in the filtration process. Another feature in current approach is the use of a backpropagation neural network method to estimate the best coagulant dosage simultaneously at two points of the water treatment plant. Simulation results were compared to the current dosage rate and showed that the proposed system may reduce costs of raw material in water treatment plant.

[Study on dosage form design for improving oral bioavailability of traditional Chinese medicines].

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Xia, Hai-Jian; Zhang, Zhen-Hai; Yao, Dong-Dong; Jia, Xiao-Bin

2013-09-01

Both chemical drugs and traditional Chinese medicines have the problem of low bioavailability. However, as traditional Chinese medicines are a multi-component complex, their dosage forms are required to be designed in line with their characteristics, in order to improve the bioavailability of traditional Chinese medicines. Traditional Chinese medicines are mostly prepared into pill, powder, paste, elixir and decoction, but with such drawbacks as high administration dose and poor efficacy. With the process of modernization of traditional Chinese medicines, new-type preparations have be developed and made outstanding achievements. However, they fail to make an organic integration between traditional Chinese medicine theories and modern preparation theories. Characteristics of traditional Chinese medicines are required to be taken into account during the development of traditional Chinese medicines. In the article, multi-component preparation technology was adopted to establish a multi-component drug release system of traditional Chinese medicines on the basis of multiple components of traditional Chinese medicines.

Enhancement of solubility and oral bioavailability of manidipine by formation of ternary solid dispersion with d-α-tocopherol polyethylene glycol 1000 succinate and copovidone.

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Chamsai, Benchawan; Limmatvapirat, Sontaya; Sungthongjeen, Srisagul; Sriamornsak, Pornsak

2017-12-01

Low bioavailability of oral manidipine (MDP) is due to its low water solubility. The objective of this study was to increase the solubility and bioavailability of MDP by fabricating ternary solid dispersion (tSD) with d-α-tocopherol polyethyleneglycol-1000-succinate and copovidone. In this study, solid ternary phase diagram was applied in order to check the homogeneity of tSD prepared by melting and solidifying with dry ice. The physicochemical properties of different formulations were determined by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and hot stage microscopy. Their solubility, dissolution, stability and bioavailability were also investigated. The results demonstrated that tSD obtained from ternary phase diagram divided into homogeneous and non-homogeneous regions. In the homogenous region, the transparent characteristics of tSD was observed and considered as a glass solution, which have a higher MDP solubility than that in non-homogenous region. The hot stage microscopy, DSC and PXRD confirmed that solid dispersion was formed in which MDP was molecularly dispersed in the carriers, especially in the homogenous region of phase diagram. FTIR analysis demonstrated strong hydrogen bonding between amine groups of MDP and carbonyl groups of copovidone, which supported a higher solubility and dissolution of tSD. The pharmacokinetic study in Wistar rats showed that the tSD had the greatest effect on oral bioavailability. Immediate hypotensive effect of tSD was also observed in vivo. The improvement of stability, dissolution and oral bioavailability of MDP could be achieved by using tSD technique.

Bioequivalence of 2 Formulations of Sildenafil Oral Soluble Film 100 mg and Sildenafil Citrate (Viagra) 100 mg Oral Tablets in Healthy Male Volunteers.

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Dadey, Eric

Sildenafil citrate tablets (VIAGRA; Pfizer Inc) have been used since 1998 as an oral therapy for the treatment of erectile dysfunction. However, in some cases, patients may have difficulty in swallowing tablets, and the need to use water to aid in the oral administration of the tablets has the potential to interrupt the sexual encounter, reduce spontaneity, and therefore decrease the quality of the experience. Two oral soluble film (OSF) formulations of sildenafil were developed using MonoSol Rx's proprietary PharmFilm technology. Both films were formulated to dissolve rapidly on the tongue, thereby releasing the drug into the oral cavity, whereupon it is swallowed without the use of water. From a patient perspective, it is anticipated that the film formulations of sildenafil citrate will provide a more compliant and discreet dosage form. The purpose of this clinical study was to compare the bioequivalence of the 2 sildenafil OSF 100 mg formulations (MonoSol Rx, LLC) with the sildenafil citrate 100 mg tablets. The design was a single-dose, randomized, open-label, 3-period, 6-sequence, 3-treatment, single-center, crossover study conducted in 18 healthy, nonsmoking male volunteers under fasting conditions, with each treatment period separated by a 7-day washout period. Plasma sildenafil concentrations were measured predose and then periodically to 24 hours after dosing. The 90% confidence intervals for plasma sildenafil AUC0-t, AUC0-∞, and Cmax for both sildenafil OSF formulations as compared with sildenafil citrate tablets were all within the 80%-125% range, indicating bioequivalence of both film formulations to sildenafil citrate tablets. Overall, the demonstrated bioequivalence coupled with the performance advantages of an OSF dosage form (ie, rapid dissolution in the mouth, can be taken without water, and can be dosed discreetly) suggest that the sildenafil OSF may provide an attractive alternative to sildenafil citrate oral tablets.

Clinical pharmacology of novel anticancer agents : Focus on oral formulations

NARCIS (Netherlands)

de Weger, V.A.

2017-01-01

The taxanes paclitaxel and docetaxel have a low oral bioavailability, as a result of poor water solubility and high first-pass effect. The water-solubility could be improved by the development of solid dispersion formulations for oral use. In this thesis it is shown that the combination of the solid

Evaluation of students' knowledge about paediatric dosage calculations.

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Özyazıcıoğlu, Nurcan; Aydın, Ayla İrem; Sürenler, Semra; Çinar, Hava Gökdere; Yılmaz, Dilek; Arkan, Burcu; Tunç, Gülseren Çıtak

2018-01-01

Medication errors are common and may jeopardize the patient safety. As paediatric dosages are calculated based on the child's age and weight, risk of error in dosage calculations is increasing. In paediatric patients, overdose drug prescribed regardless of the child's weight, age and clinical picture may lead to excessive toxicity and mortalities while low doses may delay the treatment. This study was carried out to evaluate the knowledge of nursing students about paediatric dosage calculations. This research, which is of retrospective type, covers a population consisting of all the 3rd grade students at the bachelor's degree in May, 2015 (148 students). Drug dose calculation questions in exam papers including 3 open ended questions on dosage calculation problems, addressing 5 variables were distributed to the students and their responses were evaluated by the researchers. In the evaluation of the data, figures and percentage distribution were calculated and Spearman correlation analysis was applied. Exam question on the dosage calculation based on child's age, which is the most common method in paediatrics, and which ensures right dosages and drug dilution was answered correctly by 87.1% of the students while 9.5% answered it wrong and 3.4% left it blank. 69.6% of the students was successful in finding the safe dose range, and 79.1% in finding the right ratio/proportion. 65.5% of the answers with regard to Ml/dzy calculation were correct. Moreover, student's four operation skills were assessed and 68.2% of the students were determined to have found the correct answer. When the relation among the questions on medication was examined, a significant relation (correlation) was determined between them. It is seen that in dosage calculations, the students failed mostly in calculating ml/dzy (decimal). This result means that as dosage calculations are based on decimal values, calculations may be ten times erroneous when the decimal point is placed wrongly. Moreover, it

A clinical evaluation of amlexanox oral adhesive pellicles in the treatment of recurrent aphthous stomatitis and comparison with amlexanox oral tablets: a randomized, placebo controlled, blinded, multicenter clinical trial

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Gao Feng

2009-05-01

Full Text Available Abstract Background Amlexanox has been developed as a 5 percent topical oral paste for the treatment of patients with recurrent aphthous stomatitis (RAS in most European countries. However, it is not yet available in China and has not been generally accepted in clinical treatment. The aim of this study was to explore the effectiveness of amlexanox oral adhesive pellicles in the treatment of minor recurrent aphthous ulcers, and compare the results with those of amlexanox oral adhesive tablets in order to analyse the difference between the two dosage forms of amlexanox. Methods We performed a randomized, blinded, placebo-controlled, parallel, multicenter clinical study. A total of 216 patients with minor recurrent aphthous ulcers (MiRAU were recruited and randomized to amlexanox pellicles or placebo pellicles. Pellicles were consecutively applied four times per day, for five days. The size and pain level of ulcers were measured and recorded on treatment days 0, 4 and 6. Finally, the results were compared with those of our previous 104 cases treated with amlexanox tablets. Results Amlexanox oral adhesive pellicles significantly reduced ulcer size (P= 0.017 for day 4, P=0.038 for day 6 and alleviated ulcer pain (P=0.021 for day 4, P=0.036 for day 6. No significant difference was observed in the treatment effectiveness between the pellicle and tablet form of amlexanox. Conclusions Amlexanox oral adhesive pellicles are as effective and safe as amlexanox oral adhesive tablets in the treatment of MiRAU for this Chinese cohort. However, pellicles seem to be more comfortable to use when compared with the dosage form of tablets. Therefore, in clinical practice, amlexanox oral adhesive pellicles may be a better choice for RAS patients. Trials registration Nederlands Trial Register NTR1727.

Safety of higher dosages of Viscum album L. in animals and humans - systematic review of immune changes and safety parameters

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Kiene Helmut

2011-08-01

Full Text Available Abstract Background Viscum album L extracts (VAE, mistletoe and isolated mistletoe lectins (ML have immunostimulating properties and a strong dose-dependent cytotoxic activity. They are frequently used in complementary cancer treatment, mainly to improve quality of life, but partly also to influence tumour growth, especially by injecting VAE locally and in high dosage. The question is raised whether these higher dosages can induce any harm or immunosuppressive effects. Methods Systematic review of all experiments and clinical studies investigating higher dosages of VAE in animals and humans (Viscum album > 1 mg in humans corresponding to > 0.02 mg/kg in animals or ML > 1 ng/kg and assessing immune parameters or infections or adverse drug reactions. Results 69 clinical studies and 48 animal experiments reported application of higher doses of VAE or ML and had assessed immune changes and/or harm. In these studies, Viscum album was applied in dosages up to 1500 mg in humans and 1400 mg/kg in animals, ML was applied up to 6.4 μg/kg in humans and in animals up to 14 μg/kg subcutaneously, 50 μg/kg nasally and 500 μg/kg orally. A variety of immune parameters showed fluctuating or rising outcomes, but no immunosuppressive effect. Side effects consisted mainly of dose-dependent flu-like symptoms (FLS, fever, local reactions at the injection site and various mild unspecific effects. Occasionally, allergic reactions were reported. After application of high doses of recombinant ML, reversible hepatotoxicity was observed in some cases. Conclusions Application of higher dosages of VAE or ML is not accompanied by immunosuppression; altogether VAE seems to exhibit low risk but should be monitored by clinicians when applied in high dosages.

The Importance of Superplastizer Dosage in the Mix Design of Lightweight Aggregate Concrete Reinforced With Plypropylene Fiber

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Shafigh Payam

2016-01-01

Full Text Available This paper reports the results of a study conducted to investigate the effect of superplasticizer (SP dosage on the slump, density, compressive strength and splitting tensile strength under different curing conditions of a lightweight aggregate concrete reinforced with polypropylene (PP fiber. The lightweight aggregate used in this study was oil palm shell, which is an agricultural solid waste, originating from the palm oil industry. The results indicated that an increase in superplasticizer increased the workability, however, all the mechanical properties declined significantly. The reduction in the 28-day compressive and splitting tensile strengths was about 14. This study showed that although additional SP can improve the workability of the concrete, it may have a negative effect on the other properties of concrete. Therefore, the SP dosage in concrete mixtures containing PP fiber should be limited to a certain amount.

Dosage sensitivity shapes the evolution of copy-number varied regions.

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Benjamin Schuster-Böckler

2010-03-01

Full Text Available Dosage sensitivity is an important evolutionary force which impacts on gene dispensability and duplicability. The newly available data on human copy-number variation (CNV allow an analysis of the most recent and ongoing evolution. Provided that heterozygous gene deletions and duplications actually change gene dosage, we expect to observe negative selection against CNVs encompassing dosage sensitive genes. In this study, we make use of several sources of population genetic data to identify selection on structural variations of dosage sensitive genes. We show that CNVs can directly affect expression levels of contained genes. We find that genes encoding members of protein complexes exhibit limited expression variation and overlap significantly with a manually derived set of dosage sensitive genes. We show that complexes and other dosage sensitive genes are underrepresented in CNV regions, with a particular bias against frequent variations and duplications. These results suggest that dosage sensitivity is a significant force of negative selection on regions of copy-number variation.

Effect of vitamin E on protein bound carbohydrate complexes in radiation treated oral squamous cell carcinoma patients

International Nuclear Information System (INIS)

Chitra, S.; Shyamala Devi, C.S.

2008-01-01

Serum glycoproteins were evaluated in oral squamous cell carcinoma patients treated with radiotherapy and also the effect of vitamin E was studied. Cell surface glycoconjugates are important parameters in the detection of malignancy. Thus, the objective of the present study is to evaluate the efficacy of vitamin E on glycoproteins in oral cavity cancer patients treated with radiotherapy. The study includes 26 age and sex matched normal healthy individuals and 26 patients with squamous cell carcinoma of oral cavity. These patients were divided into two groups, one for radiotherapy alone (at a dosage of 6000 cGy in five fractions per week for a period of six weeks) and the other for radiotherapy plus vitamin E supplementation (at a dosage of 400 IU/day of vitamin E) for the entire period of radiotherapy. Levels of hexose, hexosamine, fucose and sialic acid were increased in oral squamous cell carcinoma patients and a significant decrease was observed in radiation treated patients when compared to control. The levels of glycoconjugates were significantly decreased in radiation treated patients supplemented with vitamin E. This measurement may be useful in assessing disease progression and identifying patients resistant to therapy and a possible role of vitamin E on reduction in glycoconjugate levels of radiation treated oral squamous cell carcinoma patients. (author)

Sensitive, automatic method for the determination of diazepam and its five metabolites in human oral fluid by online solid-phase extraction and liquid chromatography with tandem mass spectrometry

DEFF Research Database (Denmark)

Jiang, Fengli; Rao, Yulan; Wang, Rong

2016-01-01

A novel and simple online solid-phase extraction liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous determination of diazepam and its five metabolites including nordazepam, oxazepam, temazepam, oxazepam glucuronide, and temazepam glucuronide...... in human oral fluid. Human oral fluid was obtained using the Salivette(®) collection device, and 100 μL of oral fluid samples were loaded onto HySphere Resin GP cartridge for extraction. Analytes were separated on a Waters Xterra C18 column and quantified by liquid chromatography with tandem mass...

Parental genome dosage imbalance deregulates imprinting in Arabidopsis.

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Pauline E Jullien

2010-03-01

Full Text Available In mammals and in plants, parental genome dosage imbalance deregulates embryo growth and might be involved in reproductive isolation between emerging new species. Increased dosage of maternal genomes represses growth while an increased dosage of paternal genomes has the opposite effect. These observations led to the discovery of imprinted genes, which are expressed by a single parental allele. It was further proposed in the frame of the parental conflict theory that parental genome imbalances are directly mirrored by antagonistic regulations of imprinted genes encoding maternal growth inhibitors and paternal growth enhancers. However these hypotheses were never tested directly. Here, we investigated the effect of parental genome imbalance on the expression of Arabidopsis imprinted genes FERTILIZATION INDEPENDENT SEED2 (FIS2 and FLOWERING WAGENINGEN (FWA controlled by DNA methylation, and MEDEA (MEA and PHERES1 (PHE1 controlled by histone methylation. Genome dosage imbalance deregulated the expression of FIS2 and PHE1 in an antagonistic manner. In addition increased dosage of inactive alleles caused a loss of imprinting of FIS2 and MEA. Although FIS2 controls histone methylation, which represses MEA and PHE1 expression, the changes of PHE1 and MEA expression could not be fully accounted for by the corresponding fluctuations of FIS2 expression. Our results show that parental genome dosage imbalance deregulates imprinting using mechanisms, which are independent from known regulators of imprinting. The complexity of the network of regulations between expressed and silenced alleles of imprinted genes activated in response to parental dosage imbalance does not support simple models derived from the parental conflict hypothesis.

Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals.

Science.gov (United States)

Rajabalaya, Rajan; Musa, Muhammad Nuh; Kifli, Nurolaini; David, Sheba R

2017-01-01

Liquid crystal (LC) dosage forms, particularly those using lipid-based lyotropic LCs (LLCs), have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations.

Determination of amphetamine-type stimulants in oral fluid by solid-phase microextraction and gas chromatography-mass spectrometry.

Science.gov (United States)

Souza, Daniele Z; Boehl, Paula O; Comiran, Eloisa; Mariotti, Kristiane C; Pechansky, Flavio; Duarte, Paulina C A V; De Boni, Raquel; Froehlich, Pedro E; Limberger, Renata P

2011-06-24

A method for the simultaneous identification and quantification of amphetamine (AMP), methamphetamine (MET), fenproporex (FEN), diethylpropion (DIE) and methylphenidate (MPH) in oral fluid collected with Quantisal™ device has been developed and validated. Thereunto, in-matrix propylchloroformate derivatization followed by direct immersion solid-phase microextraction and gas chromatography-mass spectrometry were employed. Deuterium labeled AMP was used as internal standard for all the stimulants and analysis was performed using the selected ion monitoring mode. The detector response was linear for the studied drugs in the concentration range of 2-256 ng mL(-1) (neat oral fluid), except for FEN, whereas the linear range was 4-256 ng mL(-1). The detection limits were 0.5 ng mL(-1) (MET), 1 ng mL(-1) (MPH) and 2 ng mL(-1) (DIE, AMP, FEN), respectively. Accuracy of quality control samples remained within 98.2-111.9% of the target concentrations, while precision has not exceeded 15% of the relative standard deviation. Recoveries with Quantisal™ device ranged from 77.2% to 112.1%. Also, the goodness-of-fit concerning the ordinary least squares model in the statistical inference of data has been tested through residual plotting and ANOVA. The validated method can be easily automated and then used for screening and confirmation of amphetamine-type stimulants in drivers' oral fluid. Copyright © 2011 Elsevier B.V. All rights reserved.

Simple and Inexpensive Methods Development for Determination of Venlafaxine Hydrochloride from Its Solid Dosage Forms by Visible Spectrophotometry

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K. Raghubabu

2012-01-01

Full Text Available Two simple, sensitive and cost effective visible spectrophotometric methods (M1 and M2 have been developed for the determination of venlafaxine hydrochloride from bulk and tablet dosage forms. The method M1 is based on the formation of green colored coordination complex by the drug with cobalt thiocyanate which is quantitatively extractable into nitro benzene with an absorption maximum of 626.4 nm. The method M2 involves internal salt formation of aconitic anhydride, dehydration product of citric acid [CIA] with acetic anhydride [Ac2O] to form colored chromogen with an absorption maximum of 561.2 nm. The calibration graph is linear over the concentration range of 10-50 µg/mL and 8-24 µg/mL for method M1 and M2 respectively. The proposed methods are applied to commercial available tablets and the results are statistically compared with those obtained by the reference method and validated by recovery studies. The results are found satisfactory and reproducible. These methods are applied successfully for the estimation of the venlafaxine hydrochloride in the presence of other ingredients that are usually present in dosage forms.

Solid lipid nanoparticles as oral delivery systems of phenolic compounds: Overcoming pharmacokinetic limitations for nutraceutical applications.

Science.gov (United States)

Nunes, Sara; Madureira, Ana Raquel; Campos, Débora; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Manuela; Reis, Flávio

2017-06-13

Drug delivery systems, accompanied by nanoparticle technology, have recently emerged as prominent solutions to improve the pharmacokinetic properties, namely bioavailability, of therapeutic and nutraceutical agents. Solid lipid nanoparticles (SLNs) have received much attention from researchers due to their potential to protect or improve drug properties. SLNs have been reported to be an alternative system to traditional carriers, such as emulsions, liposomes, and polymeric nanoparticles. Phenolic compounds are widespread in plant-derived foodstuffs and therefore abundant in our diet. Over the last decades, phenolic compounds have received considerable attention due to several health promoting properties, mostly related to their antioxidant activity, which can have important implications for health. However, most of these compounds have been associated with poor bioavailability being poorly absorbed, rapidly metabolized and eliminated, which compromises its biological and pharmacological benefits. This paper provides a systematic review of the use of SLNs as oral delivery systems of phenolic compounds, in order to overcome pharmacokinetic limitations of these compounds and improved nutraceutical potential. In vitro studies, as well as works describing topical and oral treatments will be revisited and discussed. The classification, synthesis, and clinical application of these nanomaterials will be also considered in this review article.

Matrix effect on leaching of Bisphenol A diglycidyl ether (BADGE) from epoxy resin based inner lacquer of aluminium tubes into semi-solid dosage forms.

Science.gov (United States)

Lipke, Uwe; Haverkamp, Jan Boris; Zapf, Thomas; Lipperheide, Cornelia

2016-04-01

To study the impact of different semi-solid dosage form components on the leaching of Bisphenol A (BPA) and Bisphenol A diglycidyl ether (BADGE) from the epoxy resin-based inner lacquer of aluminium tubes, the tubes were filled with different matrix preparations and stored at an elevated temperature. Despite compliance with the European Standards EN 15348 and EN 15766 on porosity and polymerisation of internal coatings of aluminium tubes, the commercially available tubes used in the study contained an increased amount of polymerisation residues, such as unbound BPA, BADGE and BADGE derivatives in the lacquer, as determined by acetonitrile extraction. Storage of Macrogol ointments in these tubes resulted in an almost quantitative migration of the unbound polymerisation residues from the coating into the ointment. In addition, due to alterations observed in the RP-HPLC chromatograms of the matrix spiked with BADGE and BADGE derivatives it is supposed that the leachates can react with formulation components. The contamination of the medicinal product by BPA, BADGE and BADGE derivatives can be precluded by using aluminium tubes with an internal lacquer with a low degree of unbound polymerisation residues. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Intercavitary implants dosage calculation

International Nuclear Information System (INIS)

Rehder, B.P.

The use of spacial geometry peculiar to each treatment for the attainment of intercavitary and intersticial implants dosage calculation is presented. The study is made in patients with intercavitary implants by applying a modified Manchester technique [pt

21 CFR 522.1660 - Oxytetracycline injectable dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline injectable dosage forms. 522.1660 Section 522.1660 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 522.1660 Oxytetracycline injectable dosage forms. ...

Radiation dosage

Energy Technology Data Exchange (ETDEWEB)

Finston, Roland [Health Physics, Stanford University, Stanford, CA (United States)

1986-07-01

Radiation dosage at Bikini Atoll is the result of current soil contamination, a relic of the nuclear weapons testing program of some 30 years ago. The principal contaminants today and some of their physical properties are listed: cesium-137, strontium-90, plutonium -239, 240 and americium-241. Cobalt-60 contributes less than 1 to the dose and is not considered significant. A resident of the atoll would accumulate radiation dose (rem) in two ways -- by exposure to radiation emanating from the ground and vegetation, and by exposure to radiation released in the spontaneous decay of radionuclides that have entered his body during the ingestion of locally grown foods. The latter process would account for some 90% of the dose; cesium-137 would be responsible for 0 90% of it. Since BARC's method of estimating dosage differs in some respects from that employed by the Lawrence Livermore National Laboratory (LLNL), (Ref.1, LLNL 1982) we are presenting our method in detail. The differences have two sources. First, the numbers used by BARC for the daily ingestion of radionuclides via the diet are higher than LLNL's. Second, BARC's calculation of dose from radionuclide intake utilizes the ICRP system. The net result is that BARC doses are consistently higher than LLNL doses, and in this respect are more conservative.

Radiation dosage

International Nuclear Information System (INIS)

Finston, Roland

1986-01-01

Radiation dosage at Bikini Atoll is the result of current soil contamination, a relic of the nuclear weapons testing program of some 30 years ago. The principal contaminants today and some of their physical properties are listed: cesium-137, strontium-90, plutonium -239, 240 and americium-241. Cobalt-60 contributes less than 1 to the dose and is not considered significant. A resident of the atoll would accumulate radiation dose (rem) in two ways -- by exposure to radiation emanating from the ground and vegetation, and by exposure to radiation released in the spontaneous decay of radionuclides that have entered his body during the ingestion of locally grown foods. The latter process would account for some 90% of the dose; cesium-137 would be responsible for 0 90% of it. Since BARC's method of estimating dosage differs in some respects from that employed by the Lawrence Livermore National Laboratory (LLNL), (Ref.1, LLNL 1982) we are presenting our method in detail. The differences have two sources. First, the numbers used by BARC for the daily ingestion of radionuclides via the diet are higher than LLNL's. Second, BARC's calculation of dose from radionuclide intake utilizes the ICRP system. The net result is that BARC doses are consistently higher than LLNL doses, and in this respect are more conservative

Development of microparticles for oral administration of the non-conventional radical scavenger IAC and testing in an inflammatory rat model.

Science.gov (United States)

Passerini, Nadia; Albertini, Beatrice; Sabatino, Marcello Di; Corace, Giuseppe; Luppi, Barbara; Canistro, Donatella; Vivarelli, Fabio; Cirillo, Silvia; Soleti, Antonio; Merizzi, Giulia; Paolini, Moreno

2016-10-15

The bis (1-hydroxy-2,2,6,6-tetramethyl-4-piperidinyl)-decandioate (IAC), is an innovative non- radical scavenger used with success in numerous disease models such as inflammation, neurological disorders, hepatitis and diabetes. The pharmacological treatments have been performed by the intraperitoneal route of administration, representing to date, the main limit for the drug use. The aim of this study was to develop a delivery system that allows the oral administration of IAC while maintaining its therapeutic efficacy. Solid Lipid Microparticles (SLMs) containing a theoretical 18% (w/w) of IAC have been produced by the spray congealing technology; three formulations have been tested (A, B and C) using different low melting point carriers (stearic acid, Compritol(®) HD5ATO and carnauba wax) alone or in combination. All IAC loaded SLMs exhibited a spherical shape, encapsulation efficiency higher than 94% and particle size suitable for the oral route. Administered per os at different dosages in an inflammation rat model, all SLMs demonstrated their efficacy in reducing oedema and alleviating pain, compared to the gold standards Indomethacin and Paracetamol. These results suggested that the SLMs are an efficacious delivery system for the oral administration of IAC, potentially useful for the treatment of others diseases related to an over production of free radicals. Copyright © 2016 Elsevier B.V. All rights reserved.

Comprehensive review on additives of topical dosage forms for drug delivery.

Science.gov (United States)

Garg, Tarun; Rath, Goutam; Goyal, Amit K

2015-12-01

Skin is the largest organ of the human body and plays the most important role in protecting against pathogen and foreign matter. Three important modes such as topical, regional and transdermal are widely used for delivery of various dosage forms. Among these modes, the topical dosage forms are preferred because it provides local therapeutic activity when applied to the skin or mucous membranes. Additives or pharmaceutical excipients (non-drug component of dosage form) are used as inactive ingredients in dosage form or tools for structuring dosage forms. The main use of topical dosage form additives are controling the extent of absorption, maintaining the viscosity, improving the stability as well as organoleptic property and increasing the bulk of the formulation. The overall goal of this article is to provide the clinician with information related to the topical dosage form additives and their current major applications against various diseases.

Radiation dosage of various CT-methods in lung diagnostics

International Nuclear Information System (INIS)

Heinz-Peer, G.; Weninger, F.; Nowotny, R.; Herold, C.J.

1996-01-01

Introduction of the computed tomography index CTDI and the multiple scan average dose (MSAD) has led to standardization of the dose description in CT examinations. Despite the use of these dose parameters, many different dosages are reported in the literature for different CT methods. In addition, there is still a wide range of radiation dosimetry results reported for conventional CT, helical CT, and HRCT used in chest examinations. The variations in dosage are mainly due to difference in factors affecting the dose, i.e. beam geometry, beam quality, scanner geometry ('generation'), and operating parameters. In addition, CT dosimetry instrumentation and methodology make a contribution to dosages. Recent studies calculating differences in factors affecting dosage and CT dosimetry and using similar operating parameters, show similar results in CT dosimetry for conventional and helical CT. On the other hand, dosages for HRCT were greatly reduced. This was mainly caused by narrow beam collimation and increasing section spacing. (orig.) [de

Drug delivery from the oral cavity: a focus on mucoadhesive buccal drug delivery systems.

Science.gov (United States)

Shinkar, Dattatraya Manohar; Dhake, Avinash Sridhar; Setty, Chitral Mallikarjuna

2012-01-01

Since the early 1980s the concept of mucoadhesion has gained considerable interest in pharmaceutical technology. The various advantages associated with these systems made buccal drug delivery as a novel route of drug administration. It prolongs the residence time of the dosage form at the site of application. These systems remain in close contact with the absorption tissue, the mucous membrane, and thus contribute to improved and/or better therapeutic performance of the drug and of both local and systemic effects. This review highlights the anatomy and structure of oral mucosa, mechanism and theories of mucoadhesion, factors affecting mucoadhesion, characteristics and properties of desired mucoadhesive polymers, various types of dosage forms, and general considerations in design of mucoadhesive buccal dosage forms, permeation enhancers, and evaluation methods. Over the past few decades the mucoadhesive buccal drug delivery system has received a great deal of attention to develop mucoadhesive dosage forms to enable the prolonged retention at the site of action, providing a controlled release of drug for improved therapeutic outcome. Mucoadhesive drug delivery gives facility to include a permeation enhancer/enzyme inhibitor or pHmodifier in the formulation and versatility in designing as multidirectional or unidirectional release systems for local and systemic action. Local delivery to tissues of the oral cavity has a number of applications, including treatment of local conditions such as periodontal disease, bacterial and fungal infections, and aphthous stomatitis and vesiculo bullous diseases. For the treatment of chronic diseases, the mucoadhesive buccal drug delivery system allows easily accessibility and is generally well-accepted for administeringdrugs by systemic action.

Hydraulic Modular Dosaging Systems for Machine Drives

Directory of Open Access Journals (Sweden)

A. J. Kotlobai

2005-01-01

Full Text Available The justified principle of making modular dosaging systems for positive-displacement multimotor hydraulic drives used in running gear and technological equipment of mobile construction, road and agricultural machines makes it possible to synchronize motion of running parts. The examples of the realization of modular dosaging systems and an algorithm of their operation are given in the paper.

Oral antimicrobials increase antimicrobial resistance in porcine E. coli--a systematic review.

Science.gov (United States)

Burow, E; Simoneit, C; Tenhagen, B-A; Käsbohrer, A

2014-03-01

Administration of antimicrobials to livestock increases the risk of antimicrobial resistance (AMR) in commensal bacteria. Antimicrobials in pig production are usually administered per pen via feed which implies treatment of sick alongside with healthy animals. The objective of this systematic literature review was to investigate the effect of orally administered antimicrobials on AMR in Escherichia coli of swine. Studies published in peer reviewed journals were retrieved from the international online databases ISI Web of Knowledge, PubMed, Scopus and the national electronic literature data base of Deutsches Institut für Medizinische Dokumentation und Information. The studies were assessed using the eligibility criteria English or German language, access to full paper version, defined treatment and control group (initial value or non-treatment) as well as administration and resistance testing of the same antimicrobial class. In the qualitative synthesis, only studies were included presenting the summary measures odds ratio or prevalence of resistance, the category of the applied antimicrobial and the dosage. An effect of the antimicrobial on AMR in E. coli was evaluated as an "increase", "no effect" or "decrease" if the odds or alternatively the prevalence ratio were >1.0, 1.0 or antimicrobial substance and dosage was missing in 4 and 5 of the 11 finally selected studies. The 36 identified trials were inhomogenous in usage and provision of information on sample size. Oral administration of antimicrobials increases the risk of AMR in E. coli from swine. There is however a lack of studies on the impact of dosage and longitudinal effects of treatment. The published studies have a number of issues concerning their scientific quality. More high quality research is needed to better address and quantifiy the effect of orally administered antimicrobials on AMR in swine. Copyright © 2014 Elsevier B.V. All rights reserved.

Development of clinical dosage forms for a poorly water-soluble drug II: formulation and characterization of a novel solid microemulsion preconcentrate system for oral delivery of a poorly water-soluble drug.

Science.gov (United States)

Li, Ping; Hynes, Sara R; Haefele, Thomas F; Pudipeddi, Madhu; Royce, Alan E; Serajuddin, Abu T M

2009-05-01

The solution of a poorly water-soluble drug in a liquid lipid-surfactant mixture, which served as a microemulsion preconcentrate, was converted into a solid form by incorporating it in a solid polyethylene glycol (PEG) matrix. The solid microemulsion preconcentrates thus formed consisted of Capmul PG8 (propylene glycol monocaprylate) as oil, Cremophor EL (polyoxyl 35 castor oil) as surfactant, and hydrophilic polymer PEG 3350 as solid matrix. The drug (aqueous solubility: 0.17 microg/mL at pH 1-8 and 25 degrees C) was dissolved in a melt of the mixture at 65-70 degrees C and then the hot solution was filled into hard gelatin capsules; the liquid gradually solidified upon cooling below 55 degrees C. The solid system was characterized by differential scanning calorimetry (DSC), scanning electron microscopy (SEM), confocal Raman microscopy (CRM), and the dispersion testing in water. It was confirmed that a solid microemulsion preconcentrate is a two-phase system, where clusters of crystalline PEG 3350 formed the solid structure (m.p. 55-60 degrees C) and the liquid microemulsion preconcentrate dispersed in between PEG 3350 crystals as a separate phase. The drug remained dissolved in the liquid phase. In vitro release testing showed that the preconcentrate dispersed readily in water forming a microemulsion with the drug dissolved in the oil particles (PEG 3350 did not interfere with the process of self-microemulsification.

Mydriatics release from solid and semi-solid ophthalmic formulations using different in vitro methods.

Science.gov (United States)

Pescina, Silvia; Macaluso, Claudio; Gioia, Gloria Antonia; Padula, Cristina; Santi, Patrizia; Nicoli, Sara

2017-09-01

The aim of the present paper was the development of semi-solid (hydrogels) and solid (film) ophthalmic formulations for the controlled release of two mydriatics: phenylephrine and tropicamide. The formulations - based on polyvinylalcohol and hyaluronic acid - were characterized, and release studies were performed with three different in vitro set-ups, i.e. Franz-type diffusion cell, vial method and inclined plane; for comparison, a solution and a commercial insert, both clinically used to induce mydriasis, were evaluated. Both gels and film allowed for a controlled release of drugs, appearing a useful alternative for mydriatics administration. However, the release kinetic was significantly influenced by the method used, highlighting the need for optimization and standardization of in vitro models for the evaluation of drug release from ophthalmic dosage forms.

Measurement of in-vivo dosage increase due to dental alloys during therapeutic irradiation of the mouth cavity

International Nuclear Information System (INIS)

Thilmann, C.; Mose, S.; Saran, F.; Schopohl, B.; Boettcher, H.D.

1995-01-01

The degree of dosage increase in the immediate surrounding of metallic dental materials was measured in an in-vivo study during therapeutic irradiation with 60 Co gamma rays in the area of mouth cavity of 11 patients. Measurements were carried out by thermoluminescent dosimetry at permamently fixed golden teeth and alloy specimens containing gold and palladium and amalgam. The following relative dodage values according to a simultanelusly measured reference value were measured at the surface of the different dental materials: 161% near fixed golden caps, 168% near the specimen containing gold in a high percentage, 133% near the specimen of palladium and 161% near the specimen of amalgam. The in vivo measured dosage increases due to metallic dental prosthesis are less than values obtained using back scatter arramgements for irradiating phantoms. Despite this, they could be of clinical relevance. Thus the usage of a mucous membrane protection during irradiation with 60 Co, as a means of preventing local lesions of the oral mucosa, due to dental alloys within the treatment volume remains inevitable. (orig.) [de

Surface modification of solid lipid nanoparticles for oral delivery of curcumin: Improvement of bioavailability through enhanced cellular uptake, and lymphatic uptake.

Science.gov (United States)

Baek, Jong-Suep; Cho, Cheong-Weon

2017-08-01

Curcumin has been reported to exhibit potent anticancer effects. However, poor solubility, bioavailability and stability of curcumin limit its in vivo efficacy for the cancer treatment. Solid lipid nanoparticles (SLN) are a promising delivery system for the enhancement of bioavailability of hydrophobic drugs. However, burst release of drug from SLN in acidic environment limits its usage as oral delivery system. Hence, we prepared N-carboxymethyl chitosan (NCC) coated curcumin-loaded SLN (NCC-SLN) to inhibit the rapid release of curcumin in acidic environment and enhance the bioavailability. The NCC-SLN exhibited suppressed burst release in simulated gastric fluid while sustained release was observed in simulated intestinal fluid. Furthermore, NCC-SLN exhibited increased cytotoxicity and cellular uptake on MCF-7 cells. The lymphatic uptake and oral bioavailability of NCC-SLN were found to be 6.3-fold and 9.5-fold higher than that of curcumin solution, respectively. These results suggest that NCC-SLN could be an efficient oral delivery system for curcumin. Copyright © 2017 Elsevier B.V. All rights reserved.

Food, physiology and drug delivery.

Science.gov (United States)

Varum, F J O; Hatton, G B; Basit, A W

2013-12-05

Gastrointestinal physiology is dynamic and complex at the best of times, and a multitude of known variables can affect the overall bioavailability of drugs delivered via the oral route. Yet while the influences of food and beverage intake as just two of these variables on oral drug delivery have been extensively documented in the wider literature, specific information on their effects remains sporadic, and is not so much contextually reviewed. Food co-ingestion with oral dosage forms can mediate several changes to drug bioavailability, yet the precise mechanisms underlying this have yet to be fully elucidated. Likewise, the often detrimental effects of alcohol (ethanol) on dosage form performance have been widely observed experimentally, but knowledge of which has only moderately impacted on clinical practice. Here, we attempt to piece together the available subject matter relating to the influences of both solid and liquid foodstuffs on the gastrointestinal milieu and the implications for oral drug delivery, with particular emphasis on the behaviour of modified-release dosage forms, formulation robustness and drug absorption. Providing better insight into these influences, and exemplifying cases where formulations have been developed or modified to circumvent their associated problems, can help to appropriately direct the design of future in vitro digestive modelling systems as well as oral dosage forms resilient to these effects. Moreover, this will help to better our understanding of the impact of food and alcohol intake on normal gut behaviour and function. Copyright © 2013 Elsevier B.V. All rights reserved.

Assessment of Veterinary Pharmaceutical Products Registered in ...

African Journals Online (AJOL)

Topical, intramammary, intrauterine and ophthalmic routes accounted for 4.7%, 3.3%, 1.0% and 0.1% of the registered products respectively. ... Dosage forms for oral administration included solids (53.4%) namely powders, tablets, boluses, freeze dried products, granules; liquids (46.3%) namely suspensions, solutions, ...

Validation of an In Vitro Bioaccessability Test Method for the Estimation of the Bioavailability of Arsenic from Soil and Sediment

Science.gov (United States)

2012-12-01

evaluate predictive performance following methods described in Malinowski et al. (1997). Acceptance criteria and control limits will be based on...69: 69–78. Malinowski , H., P. Marroum, V.R. Uppoor, et al. 1997. Draft guidance for industry extended release solid oral dosage forms. In: Young D

Relationship between xerostomia and psychotropic drugs in patients with schizophrenia: evaluation using an oral moisture meter.

Science.gov (United States)

Okamoto, A; Miyachi, H; Tanaka, K; Chikazu, D; Miyaoka, H

2016-12-01

Patients with schizophrenia are most commonly treated with antipsychotic medications, often with the addition of anxiolytics. This study used an oral moisture meter to evaluate xerostomia in patients with schizophrenia taking typical and atypical antipsychotics, anxiolytics and non-psychotropic medications. Patients diagnosed with schizophrenia according to ICD-10 criteria in the Department of Psychiatry, Kitasato University East, and affiliated hospitals were studied. All patients were on psychotropic medications. Patients with diseases associated with xerostomia, such as Sjögren's syndrome I, were excluded. A total of 127 patients were enrolled. Mean oral moisture was 27·81 ± 2·27% (normal, ≥30·0%). A significant association was observed between objective oral moisture and the subjective sense of dry mouth. Multivariate analysis revealed a negative correlation between the number of antipsychotics and, especially, anxiolytics, and the degree of oral moisture. Drug dosages themselves were not significantly correlated with dry mouth. These findings suggest that objective oral moisture measurements show decreased moisture in patients on these medications and that the degree of moisture shows a greater negative correlation with the number, as opposed to the dosages, of psychotropic drugs administered. When patients with schizophrenia visit a dental clinic, it is important for the dentist to accurately assess the degree of oral moisture and to determine the medications being taken. Based on these findings of the association of polypharmacy with xerostomia, dentists are encouraged to inform the psychiatrist of the need to actively manage patients' xerostomia. © 2016 John Wiley & Sons Ltd.

21 CFR 526.1696 - Penicillin intramammary dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin intramammary dosage forms. 526.1696 Section 526.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS INTRAMAMMARY DOSAGE FORMS § 526.1696 Penicillin...

Enhanced dissolution and oral bioavailability of valsartan solid dispersions prepared by a freeze-drying technique using hydrophilic polymers.

Science.gov (United States)

Xu, Wei-Juan; Xie, Hong-Juan; Cao, Qing-Ri; Shi, Li-Li; Cao, Yue; Zhu, Xiao-Yin; Cui, Jing-Hao

2016-01-01

This study aimed to improve the dissolution rate and oral bioavailability of valsartan (VAL), a poorly soluble drug using solid dispersions (SDs). The SDs were prepared by a freeze-drying technique with polyethylene glycol 6000 (PEG6000) and hydroxypropylmethylcellulose (HPMC 100KV) as hydrophilic polymers, sodium hydroxide (NaOH) as an alkalizer, and poloxamer 188 as a surfactant without using any organic solvents. In vitro dissolution rate and physicochemical properties of the SDs were characterized using the USP paddle method, differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and Fourier transform-infrared (FT-IR) spectroscopy, respectively. In addition, the oral bioavailability of SDs in rats was evaluated by using VAL (pure drug) as a reference. The dissolution rates of the SDs were significantly improved at pH 1.2 and pH 6.8 compared to those of the pure drug. The results from DSC, XRD showed that VAL was molecularly dispersed in the SDs as an amorphous form. The FT-IR results suggested that intermolecular hydrogen bonding had formed between VAL and its carriers. The SDs exhibited significantly higher values of AUC 0-24 h and Cmax in comparison with the pure drug. In conclusion, hydrophilic polymer-based SDs prepared by a freeze-drying technique can be a promising method to enhance dissolution rate and oral bioavailability of VAL.

The role of friction in perceived oral texture

NARCIS (Netherlands)

Wijk, de R.A.; Prinz, J.F.

2005-01-01

Instrumentally measured in vitro friction in semi-solid foods was related to oral texture sensations. Increased fat content resulted in lower sensations of roughness, higher sensations of creaminess, and lower friction, suggesting that lubrication is the mechanism by which fat affects oral texture

Calming effect of orally administered γ-aminobutyric acid in Shih Tzu dogs.

Science.gov (United States)

Uetake, Katsuji; Okumoto, Ayano; Tani, Noriko; Goto, Akihiro; Tanaka, Toshio

2012-12-01

The calming effects of γ-aminobutyric acid (GABA) by oral administration were investigated in four adult Shih Tzu dogs. Three dosage levels (1, 2 and 4 mg/kg body weight) and non-administration were tested by an increase and decrease method. Changes in activity (for 1.5 h) and urinary cortisol levels (pre-administration, 3 and 7 h later) of dogs were monitored after administration. Without reference to dosage level, the mean times spent standing (P = 0.06), sitting (P level was observed at 7 h after administration (P GABA exerts calming effects on dogs as well as humans. © 2012 The Authors. Animal Science Journal © 2012 Japanese Society of Animal Science.

Measurement of warfarin in the oral fluid of patients undergoing anticoagulant oral therapy.

Directory of Open Access Journals (Sweden)

Silvia Ghimenti

Full Text Available BACKGROUND: Patients on warfarin therapy undergo invasive and expensive checks for the coagulability of their blood. No information on coagulation levels is currently available between two controls. METHODOLOGY: A method was developed to determine warfarin in oral fluid by HPLC and fluorimetric detection. The chromatographic separation was performed at room temperature on a C-18 reversed-phase column, 65% PBS and 35% methanol mobile phase, flow rate 0.7 mL/min, injection volume 25 µL, excitation wavelength 310 nm, emission wavelength 400 nm. FINDINGS: The method was free from interference and matrix effect, linear in the range 0.2-100 ng/mL, with a detection limit of 0.2 ng/mL. Its coefficient of variation was <3% for intra-day measurements and <5% for inter-day measurements. The average concentration of warfarin in the oral fluid of 50 patients was 2.5±1.6 ng/mL (range 0.8-7.6 ng/mL. Dosage was not correlated to INR (r = -0.03, p = 0.85 but positively correlated to warfarin concentration in the oral fluid (r = 0.39, p = 0.006. The correlation between warfarin concentration and pH in the oral fluid (r = 0.37, p = 0.009 confirmed the importance of pH in regulating the drug transfer from blood. A correlation between warfarin concentration in the oral fluid and INR was only found in samples with pH values ≥7.2 (r = 0.84, p = 0.004. CONCLUSIONS: Warfarin diffuses from blood to oral fluid. The method allows to measure its concentration in this matrix and to analyze correlations with INR and other parameters.

Paper sludge (PS) to bioethanol: Evaluation of virgin and recycle mill sludge for low enzyme, high-solids fermentation.

Science.gov (United States)

Boshoff, Sonja; Gottumukkala, Lalitha Devi; van Rensburg, Eugéne; Görgens, Johann

2016-03-01

Paper sludge (PS) from the paper and pulp industry consists primarily of cellulose and ash and has significant potential for ethanol production. Thirty-seven PS samples from 11 South African paper and pulp mills exhibited large variation in chemical composition and resulting ethanol production. Simultaneous saccharification and fermentation (SSF) of PS in fed-batch culture was investigated at high solid loadings and low enzyme dosages. Water holding capacity and viscosity of the PS influenced ethanol production at elevated solid loadings of PS. High viscosity of PS from virgin pulp mills restricted the solid loading to 18% (w/w) at an enzyme dosage of 20 FPU/gram dry PS (gdPS), whereas an optimal solid loading of 27% (w/w) was achieved with corrugated recycle mill PS at 11 FPU/gdPS. Ethanol concentration and yield of virgin pulp and corrugated recycle PS were 34.2g/L at 66.9% and 45.5 g/L at 78.2%, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

Simultaneous saccharification and ethanol fermentation at high corn stover solids loading in a helical stirring bioreactor.

Science.gov (United States)

Zhang, Jian; Chu, Deqiang; Huang, Juan; Yu, Zhanchun; Dai, Gance; Bao, Jie

2010-03-01

The higher ethanol titer inevitably requires higher solids loading during the simultaneous enzymatic saccharification and fermentation (SSF) using lignocellulose as the feedstock. The mixing between the solid lignocellulose and the liquid enzyme is crucially important. In this study, a bioreactor with a novel helical impeller was designed and applied to the SSF operation of the steam explosion pretreated corn stover under different solids loadings and different enzyme dosages. The performances using the helical impeller and the common Rushton impeller were compared and analyzed by measuring rheological properties and the mixing energy consumption. The results showed that the new designed stirring system had better performances in the saccharification yield, ethanol titer, and energy cost than those of the Rushton impeller stirring. The mixing energy consumption under different solids loadings and enzyme dosages during SSF operation were analyzed and compared to the thermal energy in the ethanol produced. A balance for achieving the optimal energy cost between the increased mixing energy cost and the reduced distillation energy cost at the high solids loading should be made. The potentials of the new bioreactor were tested under various SSF conditions for obtaining optimal ethanol yield and titer. (c) 2009 Wiley Periodicals, Inc.

Lamellar crystalline self-assembly behaviour and solid lipid nanoparticles of a palmityl prodrug analogue of Capecitabine—A chemotherapy agent

Energy Technology Data Exchange (ETDEWEB)

Gong, Xiaojuan; Moghaddam, Minoo J.; Sagnella, Sharon M.; Conn, Charlotte E.; Danon, Stephen J.; Waddington, Lynne J.; Drummond, Calum J. [CSIRO/MSE

2014-09-24

An amphiphile prodrug, 5'-deoxy-5-fluoro-N⁴-(palmityloxycarbonyl) cytidine or 5'-deoxy-5-fluoro-N⁴-(hexadecanaloxycarbonyl) cytidine (5-FCPal), consisting of the same head group as the commercially available chemotherapeutic agent Capecitabine, linked to a palmityl hydrocarbon chain via a carbamate bond is reported. Thermal analysis of this prodrug indicates that it melts at ~115 °C followed quickly by degradation beginning at ~120 °C. The neat solid 5-FCPal amphiphile acquires a lamellar crystalline arrangement with a d-spacing of 28.6 ± 0.3 Å, indicating interdigitation of the hydrocarbon chains. Under aqueous conditions, solid 5-FCPal is non-swelling and no lyotropic liquid crystalline phase formation is observed. In order to assess the in vitro toxicity and in vivo efficacy in colloidal form, solid lipid nanoparticles (SLNs) with an average size of ~700 nm were produced via high pressure homogenization. The in vitro toxicity of the 5-FCPal SLNs against several different cancer and normal cell types was assessed over a 48 h period, and IC₅₀ values were comparable to those observed for Capecitabine. The in vivo efficacy of the 5-FCPal SLNs was then assessed against the highly aggressive mouse 4T1 breast cancer model. To do so, the prodrug SLNs were administered orally at 3 different dosages (0.1, 0.25, 0.5 mmol/mouse/day) and compared to Capecitabine delivered at the same dosages. After 21 days of receiving the treatments, the 0.5 mmol dose of 5-FCPal exhibited the smallest average tumour volume. Since 5-FCPal is activated in a similar manner to Capecitabine via a 3 step enzymatic pathway with the final step occurring preferentially at the tumour site, formulation of the prodrug into SLNs combines the advantage of selective, localized activation with the sustained release properties of nanostructured amphiphile self-assembly and multiple payload materials thereby potentially creating a more effective anticancer agent.

[Novel irradiation techniques in the treatment of solid tumours. Radiotherapy for metastases].

Science.gov (United States)

Mayer, Arpád; Póti, Zsuzsa

2014-02-23

Novel developments in percutaneous radiotherapy, such as positron emission tomography/computed tomography, adaptive radiation planning, intensity modulation radiotherapy and intensity modulated arc therapy (RapidArc), as well as the newer generation of image control (cone-beam computed tomography) and image guided radiotherapy ensure increased dosages of planning target volume and clinical target volume of solid tumours without damaging surrounding tissues and providing maximal protection. By raising the dosages of planned target volume and clinical target volume, these novel technical developments have created new indications in the treatment of solid tumours. With the aid of the cone-beam computed tomography and image guided radiotherapy the organ metastasis (lung, liver, spinal cord) and the primary tumour can be treated safety and effectively. Hypofractionation, dose escalation and the use of stereotactic devices can probably decrease radiation damage. The authors review the most common forms of evidence-based fractionation schemes used in irradiation therapy.

beta. -Amyloid gene dosage in Alzheimer's disease

Energy Technology Data Exchange (ETDEWEB)

Murdoch, G H; Manuelidis, L; Kim, J H; Manuelidis, E E

1988-01-11

The 4-5 kd amyloid ..beta..-peptide is a major constituent of the characteristic amyloid plaque of Alzheimer's disease. It has been reported that some cases of sporatic Alzheimer's disease are associated with at least a partial duplication of chromosome 21 containing the gene corresponding to the 695 residue precursor of this peptide. To contribute to an understanding of the frequency to such a duplication event in the overall Alzheimer's population, the authors have determined the gene dosage of the ..beta..-amyloid gene in this collection of cases. All cases had a clinical diagnosis of Alzheimer's confirmed neuropathologically. Each Alzheimer's case had an apparent normal diploid ..beta..-amyloid gene dosage, while control Down's cases had the expected triploid dosage. Thus partial duplication of chromosome 21 may be a rare finding in Alzheimer's disease. Similar conclusions were just reported in several studies of the Harvard Alzheimer collection.

21 CFR 524.1662 - Oxytetracycline hydrochloride ophthalmic and topical dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride ophthalmic and topical dosage forms. 524.1662 Section 524.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... DOSAGE FORM NEW ANIMAL DRUGS § 524.1662 Oxytetracycline hydrochloride ophthalmic and topical dosage forms. ...

ENROBAGES POLYMERIQUES DE FORMES SOLIDES: CARACTERISATION ET OPTIMISATION

OpenAIRE

Muschert , Susanne

2008-01-01

Aqueous polymer dispersions are commonly used in the pharmaceutical industry to coat oral dosage forms and to allow for controlled drug delivery. They offer major advantages compared to organic polymer solutions, such as reduced environmental concerns and toxicity risks. However, care must be taken that the films are stable during long term storage and that decreasing drug release rates due to further polymer particle coalescence are avoided. The idea of this work was to add an appropriate se...

The Impact of Wine Style and Sugar Addition in liqueur d’expedition (dosage Solutions on Traditional Method Sparkling Wine Composition

Directory of Open Access Journals (Sweden)

Belinda Kemp

2017-01-01

Full Text Available The purpose of this study was to investigate the effect of wine style and cane sugar addition in the liqueur d’expedition (dosage solution on volatile aroma compounds (VOCs in traditional method sparkling wine. There were 24 bottles of each treatment produced. Treatments were sparkling wine zero dosage (ZD; NV sparkling wine + sugar (BS; unoaked still Chardonnay wine + sugar (UC; Pinot noir 2009 sparkling wine + sugar (PN; Niagara produced Brandy + sugar (B and Icewine (IW. The control treatment in the sensory analysis was an oaked still Chardonnay wine + sugar (OC because the zero-dosage wine was not suitable for a difference test that compared wines with sugar to one without. Standard wine chemical parameters were analysed before disgorging and after liqueur d’expedition was added and included; pH, titratable acidity (TA g/L, alcohol (v/v %, residual sugar (RS g/L, free and total SO2 and total phenolics (A.U.. Volatile aroma compounds (VOCs analysed by Headspace Solid- Phase Micro-Extraction Gas Chromatography-Mass Spectrometry (HS-SPME-GC-MS included two alcohols, and six ethyl esters. ZD wines had the highest foam height and highest dissolved oxygen level. Sugar affected VOC concentrations in all treatments at five weeks post-disgorging, but by 15 weeks after liqueur d’expedition addition, the wine with added sugar had similar VOC concentrations to the ZD wines. The type of wines used in the dosage solutions had more influence on VOC concentrations than sugar addition.

Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches.

Science.gov (United States)

Madureira, Ana Raquel; Nunes, Sara; Campos, Débora A; Fernandes, João C; Marques, Cláudia; Zuzarte, Monica; Gullón, Beatriz; Rodríguez-Alcalá, Luís M; Calhau, Conceição; Sarmento, Bruno; Gomes, Ana Maria; Pintado, Maria Manuela; Reis, Flávio

2016-01-01

Rosmarinic acid (RA) possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe) delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL) were evaluated for cell (lymphocytes) viability, necrosis and apoptosis, and antioxidant/prooxidant effects upon DNA. Wistar rats were orally treated for 14 days with vehicle (control) and with Witepsol or Carnauba nanoparticles loaded with RA at 1 and 10 mg/kg body weight/d. Blood, urine, feces, and several tissues were collected for analysis. Free and loaded RA, at 0.15 mg/mL, presented a safe profile, while genotoxic potential was found for the higher dose (1.5 mg/mL), mainly by necrosis. Our data suggest that both types of nanoparticles are safe when loaded with moderate concentrations of RA, without in vitro genotoxicity and cytotoxicity and with an in vivo safety profile in rats orally treated, thus opening new avenues for use in nutraceutical applications.

21 CFR 522.1222 - Ketamine hydrochloride injectable dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Ketamine hydrochloride injectable dosage forms. 522.1222 Section 522.1222 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... ANIMAL DRUGS § 522.1222 Ketamine hydrochloride injectable dosage forms. ...

Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats.

Science.gov (United States)

Choi, Jia; Ryu, Su-Jung; Kim, Kui-Jin; Kim, Hyung-Min; Chung, Hee-Chul; Lee, Boo-Yong

2018-01-20

Gelidium elegans extract (GEE) is derived from a red alga from the Asia-Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD) rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted 5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL) for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

Investigation of contrast agent dosage for perfusion-weighted MRI

International Nuclear Information System (INIS)

Erb, G.; Benner, T.; Heiland, S.; Reith, W.; Sartor, K.; Forsting, M.

1997-01-01

Purpose: In this study we investigated, whether increasing the dosage of a paramagnetic contrast agent results in a stronger signal decrease in T 2 *-weighted perfusion sequences and therefore more meaningful parameter maps. Material and methods: In a prospective study bolus injection of gadolinium-DTPA was performed at dosages of 0.1, 0.2, and 0.3 mmol/kg body weight (BW) in 10 patients each. Before, during and after bolus injection 40 T 2 *-weighted images of a reference brain slice were acquired within 65.6 seconds on a 1.0 T clinical scanner and perfusion parameters were calculated. Results: Due to the limited signal decrease during bolus passage and the resulting low signal-difference-to-noise ratio (ΔS/N) no reliable differentiation of gray and white matter was possible at a contrast agent dosage of 0.1 mmol/kg BW. Only at higher dosages, both, signal decrease and ΔS/N were strong enough to allow differentiation of gray and white matter and to yield reliable parameter maps. Conclusion: For meaningful MR perfusion imaging at 1.0 T and with the given sequence a contrast agent dosage of at least 0.2 mmol/kg BW is necessary, if a 0.5-molar contrast agent is used. (orig.) [de

Drug delivery properties of macroporous polystyrene solid foams

OpenAIRE

Canal Barnils, Cristina; Aparicio, Rosa María; Vílchez, Alejandro; Esquena, Jordi; García-Celma, María José

2012-01-01

Purpose. Polymeric porous foams have been evaluated as possible new pharmaceutical dosage forms. Methods. These materials were obtained by polymerization in the continuous phase of highly concentrated emulsions prepared by the phase inversion temperature method. Their porosity, specific surface and surface topography were characterized, and the incorporation and release of active principles was studied using ketoprofen as model lipophilic molecule. Results. Solid foams with very h...

Near infrared spectroscopy in the development of solid dosage forms.

Science.gov (United States)

Räsänen, Eetu; Sandler, Niklas

2007-02-01

The use of near infrared (NIR) spectroscopy has rapidly grown partly due to demands of process analytical applications in the pharmaceutical industry. Furthermore, newest regulatory guidelines have advanced the increase of the use of NIR technologies. The non-destructive and non-invasive nature of measurements makes NIR a powerful tool in characterization of pharmaceutical solids. These benefits among others often make NIR advantageous over traditional analytical methods. However, in addition to NIR, a wide variety of other tools are naturally also available for analysis in pharmaceutical development and manufacturing, and those can often be more suitable for a given application. The versatility and rapidness of NIR will ensure its contribution to increased process understanding, better process control and improved quality of drug products. This review concentrates on the use of NIR spectroscopy from a process research perspective and highlights recent applications in the field.

Advances in simultaneous DSC-FTIR microspectroscopy for rapid solid-state chemical stability studies: some dipeptide drugs as examples.

Science.gov (United States)

Lin, Shan-Yang; Wang, Shun-Li

2012-04-01

The solid-state chemistry of drugs has seen growing importance in the pharmaceutical industry for the development of useful API (active pharmaceutical ingredients) of drugs and stable dosage forms. The stability of drugs in various solid dosage forms is an important issue because solid dosage forms are the most common pharmaceutical formulation in clinical use. In solid-state stability studies of drugs, an ideal accelerated method must not only be selected by different complicated methods, but must also detect the formation of degraded product. In this review article, an analytical technique combining differential scanning calorimetry and Fourier-transform infrared (DSC-FTIR) microspectroscopy simulates the accelerated stability test, and simultaneously detects the decomposed products in real time. The pharmaceutical dipeptides aspartame hemihydrate, lisinopril dihydrate, and enalapril maleate either with or without Eudragit E were used as testing examples. This one-step simultaneous DSC-FTIR technique for real-time detection of diketopiperazine (DKP) directly evidenced the dehydration process and DKP formation as an impurity common in pharmaceutical dipeptides. DKP formation in various dipeptides determined by different analytical methods had been collected and compiled. Although many analytical methods have been applied, the combined DSC-FTIR technique is an easy and fast analytical method which not only can simulate the accelerated drug stability testing but also at the same time enable to explore phase transformation as well as degradation due to thermal-related reactions. This technique offers quick and proper interpretations. Copyright © 2012 Elsevier B.V. All rights reserved.

Formulation and delivery strategies of ibuprofen: challenges and opportunities.

Science.gov (United States)

Irvine, Jake; Afrose, Afrina; Islam, Nazrul

2018-02-01

Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), is mostly administered orally and topically to relieve acute pain and fever. Due to its mode of action this drug may be useful in the treatment regimens of other, more chronic conditions, like cystic fibrosis. This drug is poorly soluble in aqueous media and thus the rate of dissolution from the currently available solid dosage forms is limited. This leads to poor bioavailability at high doses after oral administration, thereby increasing the risk of unwanted adverse effects. The poor solubility is a problem for developing injectable solution dosage forms. Because of its poor skin permeability, it is difficult to obtain an effective therapeutic concentration from topical preparations. This review aims to give a brief insight into the status of ibuprofen dosage forms and their limitations, particle/crystallization technologies for improving formulation strategies as well as suggesting its incorporation into the pulmonary drug delivery systems for achieving better therapeutic action at low dose.

A basic insight into the stability and manufacturing aspects of solid dispersions

Directory of Open Access Journals (Sweden)

Jishnu Vijay

2012-01-01

Full Text Available The development of a bioavailable dosage form is the most challenging task for the researchers. In the arena of advanced drug delivery systems, the solid dispersion techniques seem to be a promising system for the development of an optimized, bioavailable formulation of Class 2 drugs. The methods of formulation of solid dispersion have been summarized. This article is an effort to define a solid dispersion and its classification. The prospective of the stability of solid dispersion has also been discussed. Moreover, the major techniques that have been used so far such as the fusion/melting method, solvent evaporation method, hot melt extrusion method, supercritical fluid methods, have also been detailed.

[Pharmaceutical counseling of non-conventional dosage forms concerning the health-literacy and the patient adherence in public medication dispensing -Questionnaire surveys in Hungarian community pharmacies.

Science.gov (United States)

Somogyi, O; Zelko, R

Although the non-conventional dosage forms (e.g. modified release per oral systems or transdermal patches) have more significant advantages than other conventional dosage forms, the pa- tients have to apply them correctly in their home medicine using to reach the effective and safe therapy. A guideline of relevant application instructions contribute to development of an effective pharmaceutical counseling in community pharmacies. The counseling and advices can improve the patients' knowledge concerning application rules of different new dosage forms (health- literacy) with patient adherence. Finally it will result more effective and safer therapies. The aim of our Hungarian questionnaire surveys was to explore the patients' drug application habits or application errors and improve special verbal counseling of mentioned non-conventional dosage forms in community pharmacies. Understandable patient information leaflets were developed about application rules and besides the levels of patients' reading comprehension was evaluated in case of the leaflet of medicinal patches. The results show that a properly developed text is useful for the majority of patients but they need the verbal explanation as well, moreover there is a demand for the verbal counseling in community pharmacies. The most common application errors were explored and the most effective instructions or application rules were collected for the pharmacists and patients concerning the modified release tablets or capsules and transdermal patches.

Two Unusual Cases of Oral Lichen Planus Arising After Oral Squamous Cell Carcinoma: Can Oral Cancer Trigger Autoimmunity?

Science.gov (United States)

Gissi, Davide Bartolomeo; Asioli, Sofia; Gabusi, Andrea

2017-08-01

Autoimmune diseases occur when the immune system fails to recognize self-antigens expressed on the body's own cells and attacks them. Oral lichen planus (OLP) is a chronic autoimmune mucocutaneous disease of the oral cavity characterized by white/red lesions. Considered a potentially malignant disorder, OLP evolution into oral squamous cell carcinoma (OSCC) is still a matter of debate. While chronic autoimmune inflammation is considered a potential risk factor for malignant transformation in many solid tumors, the opposite idea that cancer may trigger autoimmune responses remains controversial. We describe 2 patients who developed lesions clinically suggestive of OLP with histological evidence of lichenoid infiltration some time after OSCC removal, even in areas far from the neoplastic site. Neither patient had OLP before the diagnosis of OSCC, or reported exposure to OLP-associated etiologic factors, and neither. experienced tumor recurrence during follow-up. Our findings suggest that oral cancer remission may be linked to OLP development, but further studies are necessary to unveil the underlying mechanisms and possible prognostic implications.

Attitude and perception of patients and health care practitioners toward oral sustained release dosage forms in Palestine.

Science.gov (United States)

Zaid, Abdel Naser

2010-10-01

To evaluate the knowledge of health professionals in Palestine regarding the advantages of sustained release dosage forms (SRDFs) over conventional therapy. Data were gathered from a questionnaire that was handed out to community pharmacists, physicians and patients. Pharmaceutical industry decision makers were enrolled in this study. Data were analyzed using the SPSS. Pharmacists (92.9%) and 89.2% of physicians thought that SRDFs improve patient compliance. 81.5% of pharmacists and 77% of physicians were in agreement regarding the capacity of SRDFs to maintain therapeutic activity during night. In this study, 81.5% of pharmacists and 81% of physicians believed that SRDFs provide further advantage with psychiatric patients who forget to take their medications. Pharmacists (63.1%) and only 63.5% of physicians believed that SRDFs yield a time saving for nurses who use SRDFs in hospital. Only 45.3% of physicians and 43.4% of pharmacists thought that SRDFs result in cost saving due to better disease management. Pharmacists (95.2%) and 95.9% of physicians agreed that SRDFs could be the right choice for faith patient's who must take their medication during the month of Ramadan. Pharmacists (66.7%) and 50.7% of physicians recognize that SRDFs may be unsafe if they are improperly formulated. Bad swallowing was also recognized as inconveniences of SRDFs by 67.9% of pharmacists and 57.3% of physicians. Given the above advantages, 75% of patients showed economical problems regarding the cost of the single course therapy of SRDFs and 100% of interviewed patients were enthusiastic about the advantage of SRDFs during Ramadan. The advantages of SRDFs are not completely understood by Palestinian health professionals. Pharmaceutical industries should pay more attention to the development and advertising of SRDFs due to the valuable advantages of these dosage forms.

Dosage of boron traces in graphite, uranium and beryllium oxide; Dosage de traces de bore dans le graphite, l'uranium et l'oxyde de beryllium

Energy Technology Data Exchange (ETDEWEB)

Coursier, J [Ecole Nationale Superieure de Physique et Chimie Industrielles, 75 - Paris (France); Hure, J; Platzer, R [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

1955-07-01

The problem of the dosage of the boron in the materials serving to the construction of nuclear reactors arises of the following way: to determine to about 0,1 ppm close to the quantities of boron of the order of tenth ppm. We have chosen the colorimetric analysis with curcumin as method of dosage. To reach the indicated contents, it is necessary to do a previous separation of the boron and the materials of basis, either by extraction of tetraphenylarsonium fluoborate in the case of the boron dosage in uranium and the beryllium oxide, either by the use of a cations exchanger resin of in the case of graphite. (M.B.) [French] Le probleme du dosage du bore dans les materiaux servant a la construction de reacteurs nucleaires se pose de la facon suivante: determiner a environ 0,1 ppm pres des quantites de bore de l'ordre de quelques dixiemes de ppm. Nous avons choisit la colorimetrie a la curcumine comme methode de dosage. Pour atteindre les teneurs indiquees, il est necessaire d'effectuer une separation prealable du bore et des materiaux de base, soit par extraction du fluoborate de tetraphenylarsonium dans le cas du dosage de bore dans l'uranium et l'oxyde de beryllium, soit par l'utilisation d'une resine echangeuse de cations dans le cas du graphite. (M.B.)

Dosage compensation of serine-4 transfer RNA in Drosophila melanogaster

International Nuclear Information System (INIS)

Birchler, J.A.; Owenby, R.K.; Jacobson, K.B.

1982-01-01

A dosage series of the X chromosome site for serine-4 transfer RNA consisting of one of three copies in females and one to two in males was constructed to test whether transfer RNA expression is governed by dosage compensation. A dosage effect on the level of the serine-4 isoacceptor was observed in both females and males when the structural locus was varied. However, in males, each dose had a relatively greater expression so the normal one dose was slightly greater than the total female value and the duplicated male had the highest relative expression of all the types examined. Serine-4 levels in males and females from an isogenic Oregon-R stock were similar. Thus the transfer RNA levels conform to the expectations of dosage compensation

Formulating a poorly water soluble drug into an oral solution suitable for paediatric patients; lorazepam as a model drug

NARCIS (Netherlands)

A.C. Van Der Vossen (Anna C.); I. Van Der Velde (Iris); O. Smeets (Oscar); Postma, D.J.; Eckhardt, M.; A. Vermes (Andras); B.C.P. Koch (Birgit C. P.); A.G. Vulto (Arnold); L.M. Hanff (Lidwien)

2017-01-01

textabstractIntroduction Many drugs are unavailable in suitable oral paediatric dosage forms, and pharmacists often have to compound drugs to provide paediatric patients with an acceptable formulation in the right dose. Liquid formulations offer the advantage of dosing flexibility and ease of

Perioperative effects of oral midazolam premedication in children undergoing skin laser treatment. A double-blinded randomized placebo-controlled trial

NARCIS (Netherlands)

Shoroghi, Mehrdad; Arbabi, Shahriyar; Farahbakhsh, Farshid; Sheikhvatan, Mehrdad; Abbasi, Ali

2011-01-01

Purpose: To investigate and compare the efficacy of oral midazolam with two different dosages in orange juice on perioperative hemodynamics and behavioral changes in children who underwent skin laser treatment in an academic educational Hospital. Methods: Ninety children, candidates for skin laser

Dried, irradiated sewage solids as supplemental feed for cattle

International Nuclear Information System (INIS)

Smith, G.S.; Kiesling, H.E.; Ray, E.E.; Orcasberro, R.; Trujillo, P.; Herbel, C.H.; Sivinski, J.S.

1980-01-01

Sewage solids were collected as 'primary settled solids' and then dried and gamma-irradiated (using 60 Co or 177 Cs) to absorbed dosage of about one magarad to minimize viable parasites and pathogenic organisms. Nutrient composition and bioassays suggested prospective usage as supplemental feed for ruminants. In a large-scale experiment, beef cows grazing poor-quality rangeland forage during late gestation-early lactation were given either no supplemental feed or cottonseed meal or experimental supplement comprised of 62% sewage solids. Supplements were provided for 13 weeks until rangeland forage quality improved seasonably. Supplemental cottenseed meal for cows improved weaning weights of calves by about 11% over unsupplemented controls; whereas, supplement with 62% sewage solids improved calf weaning weights by about 7%. Hazards or risks to animals or to human health appear to be slight when sewage solids of this type are fed as supplemental feeds to cattle in production programs of this type. (Auth.)

Evolution of vertebrate sex chromosomes and dosage compensation.

Science.gov (United States)

Graves, Jennifer A Marshall

2016-01-01

Differentiated sex chromosomes in mammals and other vertebrates evolved independently but in strikingly similar ways. Vertebrates with differentiated sex chromosomes share the problems of the unequal expression of the genes borne on sex chromosomes, both between the sexes and with respect to autosomes. Dosage compensation of genes on sex chromosomes is surprisingly variable - and can even be absent - in different vertebrate groups. Systems that compensate for different gene dosages include a wide range of global, regional and gene-by-gene processes that differ in their extent and their molecular mechanisms. However, many elements of these control systems are similar across distant phylogenetic divisions and show parallels to other gene silencing systems. These dosage systems cannot be identical by descent but were probably constructed from elements of ancient silencing mechanisms that are ubiquitous among vertebrates and shared throughout eukaryotes.

Evaluation of insecticides in different dosages to control cicadas in parica plantations

Directory of Open Access Journals (Sweden)

Odineila Martins Monteiro

2014-07-01

Full Text Available This study aimed to determine the more efficient and economically viable dosage of chemical insecticide to control Quesada gigas (Hemiptera: Cicadidae nymphs in parica plantations. Three dosages of three products (carbofuran, imidacloprid and thiamethoxam were tested based on the maximum recommended dosage for the control of cicadas in coffee plants and applied in total area. The dosage of one kilogram of a commercial product based in thiamethoxam per hectare was more efficient economically and environmentally to control nymphs of Q. gigas in parica plantations.

[Oral complications of chemotherapy of malignant neoplasms].

Science.gov (United States)

Obralić, N; Tahmiscija, H; Kobaslija, S; Beslija, S

1999-01-01

Function and integrity disorders of the oral cavity fall into the most frequent complication of the chemotherapy of leucemias, malignant lymphomas and solid tumors. Complications associated with cancer chemotherapy can be direct ones, resulting from the toxic action of antineoplastic agents on the proliferative lining of the mouth, or indirect, as a result of myelosuppression and immunosuppression. The most frequent oral complications associated with cancer chemotherapy are mucositis, infection and bleeding. The principles of prevention and management of oral complications during cancer chemotherapy are considered in this paper.

21 CFR 206.10 - Code imprint required.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Code imprint required. 206.10 Section 206.10 Food...: GENERAL IMPRINTING OF SOLID ORAL DOSAGE FORM DRUG PRODUCTS FOR HUMAN USE § 206.10 Code imprint required... imprint that, in conjunction with the product's size, shape, and color, permits the unique identification...

21 CFR 522.1696 - Penicillin G procaine implantation and injectable dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Penicillin G procaine implantation and injectable dosage forms. 522.1696 Section 522.1696 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... DOSAGE FORM NEW ANIMAL DRUGS § 522.1696 Penicillin G procaine implantation and injectable dosage forms. ...

Prednisone raw material characterization and formulation development

Directory of Open Access Journals (Sweden)

Leonardo Henrique Toehwé

2018-01-01

Full Text Available ABSTRACT Solid dosage forms for oral use, particularly tablets, are the most highly used dosage forms in therapy because they are easily administered, have high productivity and relatively low cost and provide a more stable drug to form a semi-solid net. Numerous parameters influence the quality of the final dosage form. In this study, the dissolution profile of 20-mg prednisone tablets bioequivalent to the reference product and three test formulations were evaluated using stability testing. During the study, prednisone tablets and the active pharmaceutical ingredient (API prednisone from two different manufacturers were characterized with respect to their physical and physicochemical properties. The results showed that the dissolution profiles of the test batches and the reference product did not retain pharmaceutical equivalence throughout all the stability study. Notably, both samples of API prednisone were of the same crystal form, and any phase transition that occurred during the study could not be attributed to dissolution variation during stability.

[A PhD completed. Trauma to the gingiva by oral hygiene aids and oral piercings].

Science.gov (United States)

Hennequin-Hoenderdos, N L; Slot, D E; van der Weijden, G A

2017-12-01

Maintaining healthy teeth and soft oral tissue is important. Clinical research has shown manual toothbrushes with end-rounded filaments to cause significantly less gingival abrasions than those without end-rounding. Tapered filaments are an alternative to end-rounded filaments, but there is no solid evidence for their effectiveness. For the interdental spaces that the toothbrush doesn't reach, the use of special oral hygiene aids is advised. Clinical studies of gingivitis patients have shown that both interdental brushes and plastic-rubber bristles reduce gingivitis after 4 weeks of use. Plastic-rubber bristles result in a significant improvement in the tendency for interdental bleeding compared with interdental brushes, and they cause less abrasion of the gingiva. Other factors that can potentially traumatise soft and hard oral tissue are oral piercings. Wearing oral piercings is not without risk. Tongue and lip piercings are associated with the risk of gingival recession, and tongue piercings are associated with tooth fractures. To prevent the risk of complications, patients should be discouraged from wearing oral piercings.

Comparison of three different types of cilostazol-loaded solid dispersion: Physicochemical characterization and pharmacokinetics in rats.

Science.gov (United States)

Mustapha, Omer; Kim, Kyung Soo; Shafique, Shumaila; Kim, Dong Shik; Jin, Sung Giu; Seo, Youn Gee; Youn, Yu Seok; Oh, Kyung Taek; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon

2017-06-01

The aim of this research was to compare three different types of cilostazol-loaded solid dispersion system including solvent-evaporated, solvent-wetted and surface-attached solid dispersion. The effect of polymers and surfactants on the aqueous solubility of cilostazol was investigated, leading to the selection of polyvinylpyrrolidone (PVP) and sodium lauryl sulphate (SLS). Employing a spray-drying technique, numerous surface-attached, solvent-evaporated and solvent-wetted solid dispersions were prepared with various amounts PVP and SLS using water, 90% ethanol and acetone, respectively. Their physicochemical properties, solubility, dissolution and oral bioavailability in rats were assessed compared to the drug powder. Among each solid dispersion system tested, the surface-attached, solvent-evaporated and solvent-wetted solid dispersions composed of cilostazol, PVP and SLS at weight ratios of 3.0 : 0.75 : 1.5, 3.0 : 3.0 : 1.5 and 3.0 : 3.0 : 1.5, respectively, provided the highest drug solubility and dissolution. The solvent-evaporated solid dispersion gave homogeneous and very small spherical particles, in which the drug was changed to an amorphous state. In the solvent-wetted solid dispersion, the amorphous drug was attached to the polymer surface. Conversely, in the surface-attached solid dispersion, the carriers were adhered onto the surface of the unchanged crystalline drug. The solubility, dissolution and oral bioavailability were significantly increased in the order of solvent-evaporated>solvent-wetted>surface-attached>drug powder. Thus, the type of solid dispersion considerably affected the physicochemical properties, aqueous solubility and oral bioavailability. Furthermore, the cilostazol-loaded solvent-evaporated solid dispersion with the highest oral bioavailability would be actively recommended as a practical oral pharmaceutical product. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation and evaluation of diclofenac sodium orally disintegrating tablets

Directory of Open Access Journals (Sweden)

Iancu Valeriu

2016-06-01

Full Text Available Orally disintegrating tablets (ODTs are dosage forms which disintegrate in mouth within seconds without need of water. This type of quality in dosage form can be attained by addition of different varieties of excipients. Pharmaburst™ 500 is a co-processed excipient system which allows rapid disintegration and low adhesion to punches. The aim of the present study was to develop and evaluate 25 mg diclofenac sodium ODTs (orodispersible tablets batches by direct compression method at different compression forces 10 kN (F1 and 20 kN (F2 and directly compressible excipients used in different ratio (Avicel PH 102, magnesium stearate and coprocessed excipient Pharmaburst™ 500, 70% and 80% w/w. The obtained batches were analyzed for appearance, tablet thickness, uniformity of weight, hardness, friability, disintegration time, and non-compendial methods (wetting time. Co-processed Pharmaburst™ 500 excipient 70% used for sodium diclofenac ODT obtaining determined good results for quality control tests evaluation.

Solubility enhancement of BCS Class II drug by solid phospholipid dispersions: Spray drying versus freeze-drying.

Science.gov (United States)

Fong, Sophia Yui Kau; Ibisogly, Asiye; Bauer-Brandl, Annette

2015-12-30

The poor aqueous solubility of BCS Class II drugs represents a major challenge for oral dosage form development. Using celecoxib (CXB) as model drug, the current study adopted a novel solid phospholipid nanoparticle (SPLN) approach and compared the effect of two commonly used industrial manufacturing methods, spray- and freeze-drying, on the solubility and dissolution enhancement of CXB. CXB was formulated with Phospholipoid E80 (PL) and trehalose at different CXB:PL:trehalose ratios, of which 1:10:16 was the optimal formulation. Spherical amorphous SPLNs with average diameters <1μm were produced by spray-drying; while amorphous 'matrix'-like structures of solid PL dispersion with larger particle sizes were prepared by freeze-drying. Formulations from both methods significantly enhanced the dissolution rates, apparent solubility, and molecularly dissolved concentration of CXB in phosphate buffer (PBS, pH 6.5) and in biorelevant fasted state simulated intestinal fluid (FaSSIF, pH 6.5) (p<0.05). While similar dissolution rates were found, the spray-dried SPLNs had a larger enhancement in apparent solubility (29- to 132-fold) as well as molecular solubility (18-fold) of CXB at equilibrium (p<0.05). The strong capability of the spray-dried SPLNs to attain 'true' supersaturation state makes them a promising approach for bioavailability enhancement of poorly soluble drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Automatic identification and normalization of dosage forms in drug monographs

Science.gov (United States)

2012-01-01

Background Each day, millions of health consumers seek drug-related information on the Web. Despite some efforts in linking related resources, drug information is largely scattered in a wide variety of websites of different quality and credibility. Methods As a step toward providing users with integrated access to multiple trustworthy drug resources, we aim to develop a method capable of identifying drug's dosage form information in addition to drug name recognition. We developed rules and patterns for identifying dosage forms from different sections of full-text drug monographs, and subsequently normalized them to standardized RxNorm dosage forms. Results Our method represents a significant improvement compared with a baseline lookup approach, achieving overall macro-averaged Precision of 80%, Recall of 98%, and F-Measure of 85%. Conclusions We successfully developed an automatic approach for drug dosage form identification, which is critical for building links between different drug-related resources. PMID:22336431

Single, 14-Day, and 13-Week Repeated Dose Toxicity Studies of Daily Oral Gelidium elegans Extract Administration to Rats

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Jia Choi

2018-01-01

Full Text Available Gelidium elegans extract (GEE is derived from a red alga from the Asia–Pacific region, which has antioxidant, anti-adipogenic, and anti-hyperglycemic effects. However, detailed studies of the toxicology of GEE have not been performed. We evaluated the single oral dose toxicity of GEE in male and female Sprague-Dawley (CD rats. GEE did not cause deaths or have toxic effects at dosages of 5000 mg/kg/day, although compound-colored stools and diarrhea were observed in both sexes, which lasted <2 days. Therefore, the LD50 of GEE is likely to be >5000 mg/kg. We next evaluated the repeated oral dose toxicity of GEE in CD rats over 14 days and 13 weeks. GEE did not induce any significant toxicological changes in either sex at 2000 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects, in terms of clinical signs, mortality, body mass, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy, organ masses, or histopathology, at dosages of 500, 1000, or 2000 mg/kg/day. The no observed adverse effect level (NOAEL for GEE is thus likely to be >2000 mg/kg/day, and no pathology was identified in potential target organs. Therefore, this study indicates that repeated oral dosing with GEE is safe in CD rats.

Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals

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Rajabalaya R

2017-02-01

Full Text Available Rajan Rajabalaya, Muhammad Nuh Musa, Nurolaini Kifli, Sheba R David PAPRSB Institute of Health Sciences, Universiti Brunei Darussalam, Brunei Darussalam Abstract: Liquid crystal (LC dosage forms, particularly those using lipid-based lyotropic LCs (LLCs, have generated considerable interest as potential drug delivery systems. LCs have the physical properties of liquids but retain some of the structural characteristics of crystalline solids. They are compatible with hydrophobic and hydrophilic compounds of many different classes and can protect even biologicals and nucleic acids from degradation. This review, focused on research conducted over the past 5 years, discusses the structural evaluation of LCs and their effects in drug formulations. The structural classification of LLCs into lamellar, hexagonal and micellar cubic phases is described. The structures of these phases are influenced by the addition of surfactants, which include a variety of nontoxic, biodegradable lipids; these also enhance drug solubility. LLC structure influences drug localization, particle size and viscosity, which, in turn, determine drug delivery properties. Through several specific examples, we describe the applications of LLCs in oral and topical drug formulations, the latter including transdermal and ocular delivery. In oral LLC formulations, micelle compositions and the resulting LLC structures can determine drug solubilization and stability as well as intestinal transport and absorption. Similarly, in topical LLC formulations, composition can influence whether the drug is retained in the skin or delivered transdermally. Owing to their enhancement of drug stability and promotion of controlled drug delivery, LLCs are becoming increasingly popular in pharmaceutical formulations. Keywords: liquid crystal, drug delivery, controlled release, lyotropic, surfactants, drug localization

Evaluation of the effect of torsemide on warfarin dosage requirements.

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Lai, Sophia; Momper, Jeremiah D; Yam, Felix K

2017-08-01

Background According to drug interaction databases, torsemide may potentiate the effects of warfarin. Evidence for this drug-drug interaction, however, is conflicting and the clinical significance is unknown. Objective The aim of this study is to evaluate the impact of torsemide initiation on warfarin dosage requirements. Setting This study was conducted at the Veterans Affairs Healthcare System in San Diego, California. Method A retrospective cohort study was conducted using Veterans Affairs data from patients who were converted from bumetanide to torsemide between March 2014 and July 2014. Patients were also prescribed and taking warfarin during the observation period. Warfarin dosage requirements were evaluated to determine if any changes occurred within the first 3 months of starting torsemide. Main outcome measure The primary outcome was the average weekly warfarin dose before and after torsemide initiation. Results Eighteen patients met study inclusion criteria. The weekly warfarin dose before and after initiation of torsemide was not significantly different (34 ± 15 and 34 ± 13 mg, p > 0.05). Of those eighteen patients, only two experienced elevations in INR that required a decrease in warfarin dosage after torsemide initiation. Between those two patients, dosage reductions ranged from 5.3 to 18%. Conclusion These results indicated that most patients did not require any warfarin dosage adjustments after torsemide was initiated. The potential for interaction, however, still exists. While empiric warfarin dosage adjustments are not recommended when initiating torsemide, increased monitoring is warranted to minimize the risk of adverse effects.

Improved water and sodium absorption from oral rehydration solutions based on rice syrup in a rat model of osmotic diarrhea.

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Wapnir, R A; Litov, R E; Zdanowicz, M M; Lifshitz, F

1991-04-01

Rice syrup solids, rice protein, and casein hydrolysate were added to experimental oral rehydration solutions in various combinations and tested in a rat intestinal perfusion system. Chronic osmotic diarrhea was induced in juvenile rats by supplying the cathartic agents, magnesium citrate and phenolphthalein, in their drinking water for 1 week. The experimental oral rehydration solutions were compared with standard oral rehydration solutions containing 20 gm/L or 30 gm/L of glucose and with each other to determine if there were significant differences in net water, sodium, or potassium absorption. An oral rehydration solution containing 30 gm/L of rice syrup solids had a net water absorption rate significantly higher than that of the standard 20 gm/L glucose-based oral rehydration solution (2.1 +/- 0.62 versus 1.5 +/- 0.48 microliters/[min x cm], p less than 0.05). Casein hydrolysate did not significantly affect net water absorption. However, combinations of 30 gm/L rice syrup solids and 5 gm/L casein hydrolysate significantly increased (p less than 0.05) net sodium and potassium absorption compared with the 20 gm/L glucose-based oral rehydration solution but not versus rice syrup solids alone. Oral rehydration solutions containing 30 gm/L rice syrup solids plus 5 gm/L rice protein, and 30 gm/L rice syrup solids plus 5 gm/L casein hydrolysate, had net water absorption rates significantly higher than the rate of a 30 gm/L glucose-based oral rehydration solution (2.5 +/- 0.36 and 2.4 +/- 0.38, respectively, versus 0.87 +/- 0.40 microliters/[min x cm], p less than 0.05). Rice protein and casein hydrolysate, however, did not significantly affect net water, sodium, or potassium absorption when added to rice protein glucose-based oral rehydration solutions. An inverse correlation between osmolality and net water absorption was observed (r = -0.653, p less than 0.02). The data suggest that substitution of rice syrup solids for glucose in oral rehydration solutions will

Evidenced Based Approach for a Definition of Defined Daily Dosages of Antibiotics Used in German Pig Production

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Lothar Kreienbrock

2018-02-01

Full Text Available The use of antibiotics in veterinary medicine and a resulting development of antimicrobial resistance is a topic of major concern. Especially for primary care, evidence is needed to guarantee the efficacy of anti­biotic drugs in future. For this, the correct dosage is an essential measure to prevent antibiotic resistance. Because veterinarians used practice differs from the manufacturer’s recommendations, data is needed to describe evidence-based defined daily doses for animals (DDDA.In 2011 data was collected on the usage of antibiotics in farm animals in conjunction with the Vet­CAb-study (Veterinary consumption of antibiotics in Germany (see vetcab-s.de, van Rennings et al., 2015. Since then, data is continuously collected on the kind of antibiotics, the number of doses, number of animals treated and treatment frequencies. For this presentation the antibiotic usage in 2011 of 500 German pig farms totalling 18,150 treatment courses were recorded and analysed with regard to their dosage. The used daily dosage (UDD was calculated from the amount of the drug used and a defined standard weight for the four different age groups in pig production: sows (200kg, piglets (4kg, weaners (15kg and fattening pigs (50 kg.Apart from the UDD the expertise of pharmacologists was also taken into account to determine a DDDA for each antibiotic. This definition of DDDA is pinpointed by the recommendation of the EMA and has to be determined for each drug in combination with animal species and the form of application.The study showed that in pig production, the antibiotic groups tetracycline and ß-lactams are mainly used. More than 90% of all treatments are given orally. For tetracycline the manufacturers recommend a dose of approximately 80 mg / kg orally in pigs. The DDDAs determined from expert opinions are around 50mg/ kg. In the present study with 500 analysed pig farms the average UDD was 39.6 mg / kg. Previous stud­ies in Germany identified an

Thermal and Isothermal Methods in Development of Sustained Release Dosage Forms of Ketorolac Tromethamine

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Dimple Chopra

2008-01-01

Full Text Available Differential scanning calorimetry (DSC is a rapid and convenient and conclusive method of screening drug-polymer blend during preformulation studies as it allows polymer incompatibility to be established instantaneously. Various batches of matrix tablets of ketorolac tromethamine (KTM with a series of compatible polymers were prepared. Batches of tablets which gave desired sustained release profile were subjected to stability testing according to ICH guidelines. The analysis for drug content was done using high performance liquid chromatography (HPLC method. The results revealed that there was no statistically significant change in drug content after storage of matrix tablets at elevated temperature of 40°C and 75% relative humidity. From our study we conclude that with careful selection of different polymers and their combinations, a stable sustained release oral dosage form of ketorolac tromethamine can be achieved.

Children's medicines in Tanzania: a national survey of administration practices and preferences.

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Adams, Lisa V; Craig, Sienna R; Mmbaga, Elia John; Naburi, Helga; Lahey, Timothy; Nutt, Cameron T; Kisenge, Rodrick; Noel, Gary J; Spielberg, Stephen P

2013-01-01

The dearth of age-appropriate formulations of many medicines for children poses a major challenge to pediatric therapeutic practice, adherence, and health care delivery worldwide. We provide information on current administration practices of pediatric medicines and describe key stakeholder preferences for new formulation characteristics. We surveyed children aged 6-12 years, parents/caregivers over age 18 with children under age 12, and healthcare workers in 10 regions of Tanzania to determine current pediatric medicine prescription and administration practices as well as preferences for new formulations. Analyses were stratified by setting, pediatric age group, parent/caregiver education, and healthcare worker cadre. Complete data were available for 206 children, 202 parents/caregivers, and 202 healthcare workers. Swallowing oral solid dosage forms whole or crushing/dissolving them and mixing with water were the two most frequently reported methods of administration. Children frequently reported disliking medication taste, and many had vomited doses. Healthcare workers reported medicine availability most significantly influences prescribing practices. Most parents/caregivers and children prefer sweet-tasting medicine. Parents/caregivers and healthcare workers prefer oral liquid dosage forms for young children, and had similar thresholds for the maximum number of oral solid dosage forms children at different ages can take. There are many impediments to acceptable and accurate administration of medicines to children. Current practices are associated with poor tolerability and the potential for under- or over-dosing. Children, parents/caregivers, and healthcare workers in Tanzania have clear preferences for tastes and formulations, which should inform the development, manufacturing, and marketing of pediatric medications for resource-limited settings.

Stress free oral medication in captive cervids

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G.M. Das

2009-09-01

Full Text Available Efficacy of oral administration of fenbendazole was studied against gastrointestinal helminthes in captive Cheetal (Axis axis at Hisar Deer Park from November 2006- January 2007. A novel method of administration of oral medication that included acclimatizing cheetal to feed individually from specific containers and providing drugs in feed after habituation was developed. Efficacy of fenbendazole was assessed by egg per gram EPG count of faecal sample on day 11 and 19 post 1st treatment and 4 days after 2nd treatment i.e. on 22nd day and compared with pre-treatment counts. Fenbendazole was efficacious against Strongyles sp., Strongyloides sp., Ascaris sp., Trichuris sp. and Moniezia sp. and significantly reduced the mean EPG of faeces, decreasing p< 0.01 after provision of drug at doses of 7.5 mg/kg body weight. The method was efficacious and provided adequate dosage to individual animals irrespective of their social hierarchy.

A Report of Two Cases of Solid Facial Edema in Acne

OpenAIRE

Kuhn-R?gnier, Sarah; Mangana, Joanna; Kerl, Katrin; Kamarachev, Jivko; French, Lars E.; Cozzio, Antonio; Navarini, Alexander A.

2017-01-01

Introduction Solid facial edema (SFE) is a rare complication of acne vulgaris. To examine the clinical features of acne patients with solid facial edema, and to give an overview on the outcome of previous topical and systemic treatments in the cases so far published. Methods We report two cases from Switzerland, both young men with initially papulopustular acne resistant to topical retinoids. Results Both cases responded to oral isotretinoin, in one case combined with oral steroids. Our cases...

Delivery of bioactive peptides and proteins across oral (buccal) mucosa.

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Senel, S; Kremer, M; Nagy, K; Squier, C

2001-06-01

The identification of an increasing array of highly potent, endogenous peptide and protein factors termed cytokines, that can be efficiently synthesized using recombinant DNA technology, offers exciting new approaches for drug therapy. However, the physico-chemical and biological properties of these agents impose limitations in formulation and development of optimum drug delivery systems as well as on the routes of delivery. Oral mucosa, including the lining of the cheek (buccal mucosa), floor of mouth and underside of tongue (sublingual mucosa) and gingival mucosa, has received much attention in the last decade because it offers excellent accessibility, is not easily traumatized and avoids degradation of proteins and peptides that occurs as a result of oral administration, gastrointestinal absorption and first-pass hepatic metabolism. Peptide absorption occurs across oral mucosa by passive diffusion and it is unlikely that there is a carrier-mediated transport mechanism. The principal pathway is probably via the intercellular route where the major permeability barrier is represented by organized array of neutral lipids in the superficial layers of the epithelium. The relative role of aqueous as opposed to the lipid pathway in drug transport is still under investigation; penetration is not necessarily enhanced by simply increasing lipophilicity, for other effects, such as charge and molecular size, also play an important role in absorption of peptide and protein drugs. Depending on the pharmacodynamics of the peptides, various oral mucosal delivery systems can be designed. Delivery of peptide/protein drugs by conventional means such as solutions has some limitations. The possibility of excluding a major part of drug from absorption by involuntary swallowing and the continuous dilution due to salivary flow limits a controlled release. However these limitations can be overcome by adhesive dosage forms such as gels, films, tablets, and patches. They can localize the

Application of DBNPA dosage for biofouling control in spiral wound membrane systems

KAUST Repository

Siddiqui, Amber

2017-05-30

Biocides may be used to control biofouling in spiral-wound reverse osmosis (RO) and nanofiltration (NF) systems. The objective of this study was to investigate the effect of biocide 2,2-dibromo-3-ni-trilopropionamide (DBNPA) dosage on biofouling control. Preventive biofouling control was studied applying a continuous dosage of substrate (0.5 mg/L) and DBNPA (1 mg/L). Curative biofouling control was studied on pre-grown biofilms, once again applying a continuous dosage of substrate (0.5 mg acetate C/L) and DBNPA (1 and 20 mg/L). Biofouling studies were performed in membrane fouling simulators (MFSs) supplied with biodegradable substrate and DBNPA. The pressure drop was monitored in time and at the end of the study, the accumulated biomass in MFS was quantified by adenosine triphosphate (ATP) and total organic carbon (TOC) analysis. Continuous dosage of DBNPA (1 mg/L) prevented pressure drop increase and biofilm accumulation in the MFSs during a run time of 7 d, showing that biofouling can be managed by preventive DBNPA dosage. For biofouled systems, continuous dosage of DBNPA (1 and 20 mg/L) inactivated the accumulated biomass but did not restore the original pressure drop and did not remove the accumulated inactive cells and extracellular polymeric substances (EPS), indicating DBNPA dosage is not suitable for curative biofouling control.

Cefuroxime axetil solid dispersions prepared using solution enhanced dispersion by supercritical fluids.

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Jun, Seoung Wook; Kim, Min-Soo; Jo, Guk Hyun; Lee, Sibeum; Woo, Jong Soo; Park, Jeong-Sook; Hwang, Sung-Joo

2005-12-01

Cefuroxime axetil (CA) solid dispersions with HPMC 2910/PVP K-30 were prepared using solution enhanced dispersion by supercritical fluids (SEDS) in an effort to increase the dissolution rate of poorly water-soluble drugs. Their physicochemical properties in solid state were characterized by differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectrometry (FT-IR) and scanning electron microscopy. No endothermic and characteristic diffraction peaks corresponding to CA were observed for the solid dispersions in DSC and PXRD. FTIR analysis demonstrated the presence of intermolecular hydrogen bonds between CA and HPMC 2910/PVP K-30 in solid dispersions, resulting in the formation of amorphous or non-crystalline CA. Dissolution studies indicated that the dissolution rates were remarkably increased in solid dispersions compared with those in the physical mixture and drug alone. In conclusion, an amorphous or non-crystalline CA solid dispersion prepared using SEDS could be very useful for the formulation of solid dosage forms.

Rationale and design of the oral HEMe iron polypeptide Against Treatment with Oral Controlled Release Iron Tablets trial for the correction of anaemia in peritoneal dialysis patients (HEMATOCRIT trial

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Isbel Nicole M

2009-07-01

Full Text Available Abstract Background The main hypothesis of this study is that oral heme iron polypeptide (HIP; Proferrin® ES administration will more effectively augment iron stores in erythropoietic stimulatory agent (ESA-treated peritoneal dialysis (PD patients than conventional oral iron supplementation (Ferrogradumet®. Methods Inclusion criteria are peritoneal dialysis patients treated with darbepoietin alpha (DPO; Aranesp®, Amgen for ≥ 1 month. Patients will be randomized 1:1 to receive either slow-release ferrous sulphate (1 tablet twice daily; control or HIP (1 tablet twice daily for a period of 6 months. The study will follow an open-label design but outcome assessors will be blinded to study treatment. During the 6-month study period, haemoglobin levels will be measured monthly and iron studies (including transferring saturation [TSAT] measurements will be performed bi-monthly. The primary outcome measure will be the difference in TSAT levels between the 2 groups at the end of the 6 month study period, adjusted for baseline values using analysis of covariance (ANCOVA. Secondary outcome measures will include serum ferritin concentration, haemoglobin level, DPO dosage, Key's index (DPO dosage divided by haemoglobin concentration, and occurrence of adverse events (especially gastrointestinal adverse events. Discussion This investigator-initiated multicentre study has been designed to provide evidence to help nephrologists and their peritoneal dialysis patients determine whether HIP administration more effectively augments iron stores in ESP-treated PD patients than conventional oral iron supplementation. Trial Registration Australia New Zealand Clinical Trials Registry number ACTRN12609000432213.

Effectiveness of motivational interviewing at improving oral health: a systematic review

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Andreia Morales Cascaes

2014-02-01

Full Text Available OBJECTIVE : To analyze the effectiveness of motivational interviewing (MI at improving oral health behaviors (oral hygiene habits, sugar consumption, dental services utilization or use of fluoride and dental clinical outcomes (dental plaque, dental caries and periodontal status. METHODS : A systematic search of PubMed, LILACS, SciELO, PsyINFO, Cochrane and Google Scholar bibliographic databases was conducted looking for intervention studies that investigated MI as the main approach to improving the oral health outcomes investigated. RESULTS : Of the 78 articles found, ten met the inclusion criteria, all based on randomized controlled trials. Most studies (n = 8 assessed multiple outcomes. Five interventions assessed the impact of MI on oral health behaviors and nine on clinical outcomes (three on dental caries, six on dental plaque, four on gingivitis and three on periodontal pockets. Better quality of evidence was provided by studies that investigated dental caries, which also had the largest population samples. The evidence of the effect of MI on improving oral health outcomes is conflicting. Four studies reported positive effects of MI on oral health outcomes whereas another four showed null effect. In two interventions, the actual difference between groups was not reported or able to be recalculated. CONCLUSIONS : We found inconclusive effectiveness for most oral health outcomes. We need more and better designed and reported interventions to fully assess the impact of MI on oral health and understand the appropriate dosage for the counseling interventions.

Oral Delivery of Probiotics in Poultry Using pH-Sensitive Tablets.

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Jiang, Tao; Li, Hui-Shan; Han, Geon Goo; Singh, Bijay; Kang, Sang-Kee; Bok, Jin-Duck; Kim, Dae-Duk; Hong, Zhong-Shan; Choi, Yun-Jaie; Cho, Chong-Su

2017-04-28

As alternatives to antibiotics in livestocks, probiotics have been used, although most of them in the form of liquid or semisolid formulations, which show low cell viability after oral administration. Therefore, suitable dry dosage forms should be developed for livestocks to protect probiotics against the low pH in the stomach such that the products have higher probiotics survivability. Here, in order to develop a dry dosage forms of probiotics for poultry, we used hydroxypropyl methylcellulose phthalate 55 (HPMCP 55) as a tablet-forming matrix to develop probiotics in a tablet form for poultry. Here, we made three different kinds of probiotics-loaded tablet under different compression forces and investigated their characteristics based on their survivability, morphology, disintegration time, and kinetics in simulated gastrointestinal fluid. The results indicated that the probiotics formulated in the tablets displayed higher survival rates in acidic gastric conditions than probiotics in solution. Rapid release of the probiotics from the tablets occurred in simulated intestinal fluid because of fast swelling of the tablets in neutral pH. As a matrix of tablet, HPMCP 55 provided good viability of probiotics after 6 months under refrigeration. Moreover, after oral administration of probiotics-loaded tablets to chicken, more viable probiotics were observed, than with solution type, through several digestive areas of chicken by the tablets.

Drug delivery properties of macroporous polystyrene solid foams.

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Canal, Cristina; Aparicio, Rosa Maria; Vilchez, Alejandro; Esquena, Jordi; García-Celma, Maria José

2012-01-01

Polymeric porous foams have been evaluated as possible new pharmaceutical dosage forms. These materials were obtained by polymerization in the continuous phase of highly concentrated emulsions prepared by the phase inversion temperature method. Their porosity, specific surface and surface topography were characterized, and the incorporation and release of active principles was studied using ketoprofen as model lipophilic molecule. Solid foams with very high pore volume, mainly inside macropores, were obtained by this method. The pore morphology of the materials was characterized, and very rough topography was observed, which contributed to their nearly superhydrophobic properties. These solid foams could be used as delivery systems for active principles with pharmaceutical interest, and in the present work ketoprofen was used as a model lipophilic molecule. Drug incorporation and release was studied from solid foam disks, using different concentrations of the loading solutions, achieving a delayed release with short lag-time.

Controlled release systems containing solid dispersions: strategies and mechanisms.

Science.gov (United States)

Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Park, Jun Bom; Lee, Beom-Jin

2011-10-01

In addition to a number of highly soluble drugs, most new chemical entities under development are poorly water-soluble drugs generally characterized by an insufficient dissolution rate and a small absorption window, leading to the low bioavailability. Controlled-release (CR) formulations have several potential advantages over conventional dosage forms, such as providing a uniform and prolonged therapeutic effect to improve patient compliance, reducing the frequency of dosing, minimizing the number of side effects, and reducing the strength of the required dose while increasing the effectiveness of the drug. Solid dispersions (SD) can be used to enhance the dissolution rate of poorly water-soluble drugs and to sustain the drug release by choosing an appropriate carrier. Thus, a CR-SD comprises both functions of SD and CR for poorly water-soluble drugs. Such CR dosage forms containing SD provide an immediately available dose for an immediate action followed by a gradual and continuous release of subsequent doses to maintain the plasma concentration of poorly water-soluble drugs over an extended period of time. This review aims to summarize all currently known aspects of controlled release systems containing solid dispersions, focusing on the preparation methods, mechanisms of action and characterization of physicochemical properties of the system.

First-in-Human Clinical Trial of Oral ONC201 in Patients with Refractory Solid Tumors.

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Stein, Mark N; Bertino, Joseph R; Kaufman, Howard L; Mayer, Tina; Moss, Rebecca; Silk, Ann; Chan, Nancy; Malhotra, Jyoti; Rodriguez, Lorna; Aisner, Joseph; Aiken, Robert D; Haffty, Bruce G; DiPaola, Robert S; Saunders, Tracie; Zloza, Andrew; Damare, Sherri; Beckett, Yasmeen; Yu, Bangning; Najmi, Saltanat; Gabel, Christian; Dickerson, Siobhan; Zheng, Ling; El-Deiry, Wafik S; Allen, Joshua E; Stogniew, Martin; Oster, Wolfgang; Mehnert, Janice M

2017-08-01

Purpose: ONC201 is a small-molecule selective antagonist of the G protein-coupled receptor DRD2 that is the founding member of the imipridone class of compounds. A first-in-human phase I study of ONC201 was conducted to determine its recommended phase II dose (RP2D). Experimental Design: This open-label study treated 10 patients during dose escalation with histologically confirmed advanced solid tumors. Patients received ONC201 orally once every 3 weeks, defined as one cycle, at doses from 125 to 625 mg using an accelerated titration design. An additional 18 patients were treated at the RP2D in an expansion phase to collect additional safety, pharmacokinetic, and pharmacodynamic information. Results: No grade >1 drug-related adverse events occurred, and the RP2D was defined as 625 mg. Pharmacokinetic analysis revealed a C max of 1.5 to 7.5 μg/mL (∼3.9-19.4 μmol/L), mean half-life of 11.3 hours, and mean AUC of 37.7 h·μg/L. Pharmacodynamic assays demonstrated induction of caspase-cleaved keratin 18 and prolactin as serum biomarkers of apoptosis and DRD2 antagonism, respectively. No objective responses by RECIST were achieved; however, radiographic regression of several individual metastatic lesions was observed along with prolonged stable disease (>9 cycles) in prostate and endometrial cancer patients. Conclusions: ONC201 is a selective DRD2 antagonist that is well tolerated, achieves micromolar plasma concentrations, and is biologically active in advanced cancer patients when orally administered at 625 mg every 3 weeks. Clin Cancer Res; 23(15); 4163-9. ©2017 AACR . ©2017 American Association for Cancer Research.

Dosage compensation and demasculinization of X chromosomes in Drosophila.

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Bachtrog, Doris; Toda, Nicholas R T; Lockton, Steven

2010-08-24

The X chromosome of Drosophila shows a deficiency of genes with male-biased expression, whereas mammalian X chromosomes are enriched for spermatogenesis genes expressed premeiosis and multicopy testis genes. Meiotic X-inactivation and sexual antagonism can only partly account for these patterns. Here, we show that dosage compensation (DC) in Drosophila may contribute substantially to the depletion of male genes on the X. To equalize expression between X-linked and autosomal genes in the two sexes, male Drosophila hypertranscribe their single X, whereas female mammals silence one of their two X chromosomes. We combine fine-scale mapping data of dosage compensated regions with genome-wide expression profiles and show that most male-biased genes on the D. melanogaster X are located outside dosage compensated regions. Additionally, X-linked genes that have newly acquired male-biased expression in D. melanogaster are less likely to be dosage compensated, and parental X-linked genes that gave rise to an autosomal male-biased retrocopy are more likely located within compensated regions. This suggests that DC contributes to the observed demasculinization of X chromosomes in Drosophila, both by limiting the emergence of male-biased expression patterns of existing X genes, and by contributing to gene trafficking of male genes off the X. Copyright 2010 Elsevier Ltd. All rights reserved.

Pharmaceutical optimization of lipid-based dosage forms for the improvement of taste-masking, chemical stability and solubilizing capacity of phenobarbital.

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Monteagudo, Ezequiel; Langenheim, Mariana; Salerno, Claudia; Buontempo, Fabián; Bregni, Carlos; Carlucci, Adriana

2014-06-01

Microemulsions (MEs) and self-emulsifying drug delivery systems (SEEDS) containing phenobarbital (Phe) were developed to improve its chemical stability, solubilizing capacity and taste-masking in oral liquid dosage forms. Cremophor® RH40 and Labrasol® were used as surfactants for the screening of ME regions, Capmul® MCM L, Captex® 355, Imwitor® 408, Myglyol® 840 and Isopropyl myristate were the oil phases assayed; Transcutol® P, Polyethylene-glycol 400, glycerol, Propylene-glycol and ethanol the cosurfactants. Phe stability assay was carried out (20:4:20:56% and 20:4:35:41% (w/w); surfactant:oily phase:cosurfactant:water) for both surfactants; only one containing ethanol showed significant dismissing in its drug content. Solubility capacity for these selected formulations were also evaluated, an amount between 17 and 58 mg/mL of Phe could be loaded. At last, an optimized ME formulation with Cremophor® RH40 20%, Capmul® MCM L 4%, PEG 400 35% and sucralose 2% (w/w) was chosen in order to optimize taste-masking using an electronic tongue. Strawberry along with banana and tutti-frutti flavors plus mint flavor proved to be the best ones. Labrasol-based pre-concentrates were tested for (micro)emulsifying properties; all of them resulted to behave as SEDDS. In summary, a rationale experimental design conducted to an optimized ME for Phe oral pediatric administration which was able to load 5-fold times the currently used dose (4 mg/mL), with no sign of physical or chemical instability and with improved taste; SEDDS for capsule filling were also obtained. The biopharmaceutical advantages described for these dosage forms encourage furthering in vivo evaluation.

Novel solid self-emulsifying drug delivery system of coenzyme Q₁₀ with improved photochemical and pharmacokinetic behaviors.

Science.gov (United States)

Onoue, Satomi; Uchida, Atushi; Kuriyama, Kazuki; Nakamura, Tatsuya; Seto, Yoshiki; Kato, Masashi; Hatanaka, Junya; Tanaka, Toshiyuki; Miyoshi, Hiroyuki; Yamada, Shizuo

2012-08-15

The present study was undertaken to develop a solid self-emulsifying drug delivery system of coenzyme Q(10) (CoQ(10)/s-SEDDS) with high photostability and oral bioavailability. The CoQ(10)/s-SEDDS was prepared by spray-drying an emulsion preconcentrate containing CoQ(10), medium-chain triglyceride, sucrose ester of fatty acid, and hydroxypropyl cellulose, and its physicochemical, photochemical, and pharmacokinetic properties were evaluated. The CoQ(10)/s-SEDDS powder with a diameter of ca. 15 μm was obtained by spray-drying, in which the CoQ(10) was mostly amorphized. The CoQ(10)/s-SEDDS exhibited immediate self-emulsification when introduced to aqueous media under gentle agitation, forming uniform fine droplets with a mean diameter of ca. 280 nm. There was marked generation of reactive oxygen species, in particular superoxide, from CoQ(10) exposed to simulated sunlight (250W/m(2)), suggesting potent photoreactivity. Nano-emulsified solution of CoQ(10) under light exposure underwent photodegradation with 22-fold higher degradation kinetics than crystalline CoQ(10), although the CoQ(10)/s-SEDDS was less photoreactive. After the oral administration of CoQ(10)/s-SEDDS (100 mg-CoQ(10)/kg) in rats, enhanced exposure of CoQ(10) was observed with increases in both C(max) and AUC of ca. 5-fold in comparison with those of orally administered crystalline CoQ(10). From the improved physicochemical and pharmacokinetic data, the s-SEDDS approach upon spray-drying might be a suitable dosage option for enhancing nutraceutical and pharmaceutical values of CoQ(10). Copyright © 2012 Elsevier B.V. All rights reserved.

The shaping and functional consequences of the dosage effect landscape in multiple myeloma.

Science.gov (United States)

Samur, Mehmet K; Shah, Parantu K; Wang, Xujun; Minvielle, Stéphane; Magrangeas, Florence; Avet-Loiseau, Hervé; Munshi, Nikhil C; Li, Cheng

2013-10-02

Multiple myeloma (MM) is a malignant proliferation of plasma B cells. Based on recurrent aneuploidy such as copy number alterations (CNAs), myeloma is divided into two subtypes with different CNA patterns and patient survival outcomes. How aneuploidy events arise, and whether they contribute to cancer cell evolution are actively studied. The large amount of transcriptomic changes resultant of CNAs (dosage effect) pose big challenges for identifying functional consequences of CNAs in myeloma in terms of specific driver genes and pathways. In this study, we hypothesize that gene-wise dosage effect varies as a result from complex regulatory networks that translate the impact of CNAs to gene expression, and studying this variation can provide insights into functional effects of CNAs. We propose gene-wise dosage effect score and genome-wide karyotype plot as tools to measure and visualize concordant copy number and expression changes across cancer samples. We find that dosage effect in myeloma is widespread yet variable, and it is correlated with gene expression level and CNA frequencies in different chromosomes. Our analysis suggests that despite the enrichment of differentially expressed genes between hyperdiploid MM and non-hyperdiploid MM in the trisomy chromosomes, the chromosomal proportion of dosage sensitive genes is higher in the non-trisomy chromosomes. Dosage-sensitive genes are enriched by genes with protein translation and localization functions, and dosage resistant genes are enriched by apoptosis genes. These results point to future studies on differential dosage sensitivity and resistance of pro- and anti-proliferation pathways and their variation across patients as therapeutic targets and prognosis markers. Our findings support the hypothesis that recurrent CNAs in myeloma are selected by their functional consequences. The novel dosage effect score defined in this work will facilitate integration of copy number and expression data for identifying driver

Midazolam intravenous conscious sedation in oral surgery. A retrospective study of 372 cases.

Science.gov (United States)

Runes, J; Ström, C

1996-01-01

In 1987 the Swedish Dental Act was amended to allow Swedish dentists who have undergone a specific accreditation course to administer intra-venous sedation. Midazolam is a benzodiazepin derivate with express sedative and hypnotic qualities, powerful amnesia, a short half-life time and few secondary effects. From 1989-1994 midazolam intravenous conscious sedation (ICS) was administered in 372 cases in the Department of Oral and Maxillofacial Surgery, County Hospital, Falun. This study presents data on the 298 patients. Although surgical removal of impacted wisdom teeth predominated, implant surgery, reduction of fractures and correction of anomalies were also carried out. Supplementary sedative premedication was rarely used. Most patients were treated under local anaesthesia. The mean dosage was 10.45 mg (range 1.25-40 mg). Mean dosage/kg was 0.15 mg (range 0.03-0.50 mg). The average duration of anaesthesia was 50 minutes. The average recovery time was 94 minutes. Three hundred and sixty-nine of 372 planned treatments were completed. No serious complications occurred. The patients were co-operative during surgery and were satisfied with the treatment. Compared with full anaesthesia this method required less resources and is a valuable complement in management of anxious patients undergoing oral surgery.

Doubled dosage of sofosbuviris expected for inhibiting Zika virus infection

Institute of Scientific and Technical Information of China (English)

Somsri Wiwanitkit; Viroj Wiwanitkit

2017-01-01

Sofosbuvir is a new antiviral drug that has been recommended for management of hepatitis C virus (HCV) for a few years. New researches support that sofosbuvir might be useful for the management of Zika virus infection. Based on the pharmacological activity, inhibiting the HCV RNA-dependent RNA polymerase (RdRp or NS5 protein), sofosbuvir is proposed for its effectiveness against Zika virus infection. Here, the authors used a mathematical modelling theoretical approach to predict the expected dosage of sofosbuvir for inhibiting Zika virus infection. Based on the modeling study, if sofosbuvir is assigned for management of Zika virus infection, doubled dosage of the present dosage for hepatitis C management is recommended.

Dosage of boron traces in graphite, uranium and beryllium oxide

International Nuclear Information System (INIS)

Coursier, J.; Hure, J.; Platzer, R.

1955-01-01

The problem of the dosage of the boron in the materials serving to the construction of nuclear reactors arises of the following way: to determine to about 0,1 ppm close to the quantities of boron of the order of tenth ppm. We have chosen the colorimetric analysis with curcumin as method of dosage. To reach the indicated contents, it is necessary to do a previous separation of the boron and the materials of basis, either by extraction of tetraphenylarsonium fluoborate in the case of the boron dosage in uranium and the beryllium oxide, either by the use of a cations exchanger resin of in the case of graphite. (M.B.) [fr

Applicability of UV laser-induced solid-state fluorescence spectroscopy for characterization of solid dosage forms.

Science.gov (United States)

Woltmann, Eva; Meyer, Hans; Weigel, Diana; Pritzke, Heinz; Posch, Tjorben N; Kler, Pablo A; Schürmann, Klaus; Roscher, Jörg; Huhn, Carolin

2014-10-01

High production output of solid pharmaceutical formulations requires fast methods to ensure their quality. Likewise, fast analytical procedures are required in forensic sciences, for example at customs, to substantiate an initial suspicion. We here present the design and the optimization of an instrumental setup for rapid and non-invasive characterization of tablets by laser-induced fluorescence spectroscopy (with a UV-laser (λ ex = 266 nm) as excitation source) in reflection geometry. The setup was first validated with regard to repeatability, bleaching phenomena, and sensitivity. The effect on the spectra by the physical and chemical properties of the samples, e.g. their hardness, homogeneity, chemical composition, and granule grain size of the uncompressed material, using a series of tablets, manufactured in accordance with design of experiments, was investigated. Investigation of tablets with regard to homogeneity, especially, is extremely important in pharmaceutical production processes. We demonstrate that multiplicative scatter correction is an appropriate tool for data preprocessing of fluorescence spectra. Tablets with different physical and chemical characteristics can be discriminated well from their fluorescence spectra by subjecting the results to principal component analysis.

Solid lipid nanoparticles of amphotericin B (AmbiOnp): in vitro and in vivo assessment towards safe and effective oral treatment module.

Science.gov (United States)

Chaudhari, Manisha B; Desai, Preshita P; Patel, Pratikkumar A; Patravale, Vandana B

2016-08-01

Amphotericin B, a gold standard broad spectrum antibiotic used in treatment of systemic fungal infections and visceral leishmaniasis, though is effective parenterally offers severe nephrotoxicity whereas the oral delivery is reported to give very meager oral bioavailability. Thus, to alleviate the toxicity and to improve oral bioavailability, an effective oral delivery approach in the form of solid lipid nanoparticles of amphotericin B (AmbiOnp) was reported earlier by our group. In this investigation, we report the predominant formation of nontoxic superaggregated form of amphotericin B, resulting from the probe sonication-assisted nanoprecipitation technique. The developed formulation was further confirmed to retain this nontoxic form and was found to be stable over the varied gastrointestinal conditions. Further, in vitro antifungal activity of AmbiOnp against Candida albicans showed minimum inhibitory concentration value of 7.812 μg/mL attributed to controlled release of drug from nanoparticulate matrix. In vivo pharmacokinetic studies revealed a relative bioavailability of AmbiOnp to be 1.05-fold with a Cmax of 1109.31 ± 104.79 ng/mL at the end of 24 h which was comparable to Cmax of 1417.49 ± 85.52 ng/mL achieved with that of marketed formulation (Fungizone®) given intravenously establishing efficacy of AmbiOnp. In vivo biodistribution studies indicated very low levels of Amphotericin B in kidneys when given as AmbiOnp as compared to that of marketed formulation proving its safety and was further corroborated by renal toxicity studies. Further, the formulations were found to be stable under refrigeration condition over a period of 3 months.

Anti-m antibody in solid tumors-two case reports.

Science.gov (United States)

Soni, Shiv Kumar; Goyal, Hari; Sood, S K; Setia, Rasika

2014-09-01

Anti-M antibodies are usually of IgM, appear as cold agglutinins and are clinically insignificant. We are reporting two cases of anti-M in cases of solid tumors where the anti-M caused discrepancy in blood grouping, reacted in coombs phase of crossmatching. Anti-M in first case showed dosage effect. These antibodies can be clinical significant when detected in coombs phase, making M antigen negative coombs compatible unit transfusion imperative.

Brand versus generic dispensing trend for ciprofloxacin 500 mg, levofloxacin 500 mg, and moxifloxacin 400 mg (oral dosage forms) among pharmacies of Karachi, Pakistan.

Science.gov (United States)

Zehra, Fatima; Naqvi, Atta Abbas; Tasneem, Sumbul; Ahmad, Rizwan; Ahmad, Niyaz; Shamsi, Adnan Zia; Asghar, Naqiya Ali; Khan, Ghufran Ullah

2017-01-01

Pakistan spends 0.7% of its gross domestic product on health. The public sector health-care system provides services to 22% of population thus paving the way for a dominant private sector. Patients in Pakistan mostly pay their medical expenses directly, and 64% of the health expenditures are borne by the household. Expenditure on medicine constitutes 43% of the total household expenditure. A quantitative cross-sectional study was conducted in Karachi, Pakistan, for a month. It was aimed at gathering response from different pharmacies to understand the brand versus generic dispensing trend of ciprofloxacin 500 mg, levofloxacin 500 mg, and moxifloxacin 400 mg oral dosage forms. The study employed convenience sampling and used a survey checklist. The data gathered was entered in SPSS version 22. The mean price per tablet for ciprofloxacin brand and generic was reported at Pakistani Rupees (PKR) 48.44 and PKR 26.85, respectively. The trend for dispensing ciprofloxacin highlighted a split in the market between brand (51%) and generic (49%). For levofloxacin brand and generic, the price per tablet was reported at PKR 36.50 and PKR 36.15 respectively, and despite same price, the market was dominated by generic levofloxacin (92%). Due to a price difference between brand and generic moxifloxacin, i.e., PKR 129.44 and PKR 71.91, respectively, the market was mostly occupied by the generic form (75%). Pricing mechanism must be revisited, and the authorities should take stern actions against any illegitimate price hike. The surging burden of drug expenditure on poorer sections of the society must be addressed by the government on an urgent basis.

TaS2 nanosheet-based room-temperature dosage meter for nitric oxide

Directory of Open Access Journals (Sweden)

Qiyuan He

2014-09-01

Full Text Available A miniature dosage meter for toxic gas is developed based on TaS2 nanosheets, which is capable of indicating the toxic dosage of trace level NO at room temperature. The TaS2 film-based chemiresistor shows an irreversible current response against the exposure of NO. The unique non-recovery characteristic makes the TaS2 film-based device an ideal indicator of total dosage of chronicle exposure.

Absolute Oral Bioavailability of Creatine Monohydrate in Rats: Debunking a Myth.

Science.gov (United States)

Alraddadi, Eman A; Lillico, Ryan; Vennerstrom, Jonathan L; Lakowski, Ted M; Miller, Donald W

2018-03-08

Creatine is an ergogenic compound used by athletes to enhance performance. Supplementation with creatine monohydrate (CM) has been suggested for musculoskeletal and neurological disorders. Until now, little is known about its pharmacokinetic profile. Our objective was to determine the oral bioavailability of CM and the influence of dose on oral absorption. Rats were dosed orally with low dose (10 mg/kg) or high dose (70 mg/kg) 13 C-labeled CM. Blood samples were removed at various time points. Muscle and brain tissue were collected at the conclusion of the study. Plasma and tissue levels of 13 C-labeled creatine were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Physiologically based pharmacokinetic (PBPK) models of CM were built using GastroPlus™. These models were used to predict the plasma concentration-time profiles of creatine hydrochloride (CHCL), which has improved aqueous solubility compared to CM. Absolute oral bioavailability for low dose CM was 53% while high dose CM was only 16%. The simulated C max of 70 mg/kg CHCL was around 35 μg/mL compared to 14 μg/mL for CM with a predicted oral bioavailability of 66% with CHCL compared to 17% with CM. Our results suggest that the oral bioavailability of CM is less than complete and subject to dose and that further examination of improved dosage formulations of creatine is warranted.

A brief history of dosage compensation

Indian Academy of Sciences (India)

depression of X-linked gene activity in the female, as well as by hyperexpression of the ... to the Harvey lecture, Muller had presented important ideas relative to dosage ... at Columbia. I do recall a talk by the popular physical anthro- pologist ...

Improved protocol and data analysis for accelerated shelf-life estimation of solid dosage forms.

Science.gov (United States)

Waterman, Kenneth C; Carella, Anthony J; Gumkowski, Michael J; Lukulay, Patrick; MacDonald, Bruce C; Roy, Michael C; Shamblin, Sheri L

2007-04-01

To propose and test a new accelerated aging protocol for solid-state, small molecule pharmaceuticals which provides faster predictions for drug substance and drug product shelf-life. The concept of an isoconversion paradigm, where times in different temperature and humidity-controlled stability chambers are set to provide a critical degradant level, is introduced for solid-state pharmaceuticals. Reliable estimates for temperature and relative humidity effects are handled using a humidity-corrected Arrhenius equation, where temperature and relative humidity are assumed to be orthogonal. Imprecision is incorporated into a Monte-Carlo simulation to propagate the variations inherent in the experiment. In early development phases, greater imprecision in predictions is tolerated to allow faster screening with reduced sampling. Early development data are then used to design appropriate test conditions for more reliable later stability estimations. Examples are reported showing that predicted shelf-life values for lower temperatures and different relative humidities are consistent with the measured shelf-life values at those conditions. The new protocols and analyses provide accurate and precise shelf-life estimations in a reduced time from current state of the art.

Pavor nocturnus: a complication of single daily tricyclic or neuroleptic dosage.

Science.gov (United States)

Flemenbaum, A

1976-05-01

The author tested the hypothesis that a single bedtime dosage schedule of tricyclic or neuroleptic medication produces increased frequency of night terrors by administering a questionnaire to 30 medical patients who were not receiving such medications and 100 psychiatric patients on either multiple- or single-dosage schedules. Psychiatric patients on multiple-dosage schedules reported no more frightening dreams than the medical patients, whereas almost three-fourths of those receiving single bedtime doses had frightening dreams, a significant difference from the medical sample. This preliminary report is presented to call attention to the possible undesirable effects of a single dose schedule.

[The effect of biyuanshu oral liquid on the formation of Pseudomonas aeruginosa biofilms in vitro].

Science.gov (United States)

Liu, Xiang; Chen, Haihong; Wang, Shengqing

2012-07-01

To observe the effect of biyuanshu oral liquid on the formation of pseudomonas aeruginosa biofilms in vitro. Pseudomonas aeruginosa biofilm was established by plate culture and detected by Scanning electron microscopy and AgNO3 staining. After treated with different dosages of biyuanshu oral liquid and erythromycin, the pseudomonas aeruginosa biofilms were observed by AgNO3 staining and the number of viable bacteria were measured by serial dilution. The pseudomonas aeruginosa biofilms could be detected by SEM at the seventh culture day and it was consistent with the detection of AgNO3 staining. The biyuanshu oral liquid and erythromycin have the effect on inhibiting the formation of pseudomonas aeruginosa biofilms. But with the already formed pseudomonas aeruginosa biofilms the inhibition was not significant. The serial dilution method showed that the viable counts of bacteria of biyuanshu oral liquid and erythromycin treated groups were significantly lower than those untreated groups (P formation of pseudomonas aeruginosa biofilms in vitro.

21 CFR 522.1662 - Oxytetracycline hydrochloride implantation or injectable dosage forms.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Oxytetracycline hydrochloride implantation or injectable dosage forms. 522.1662 Section 522.1662 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1662 Oxytetracycline hydrochloride implantation or injectable...

Tetraphenylimidodiphosphinate as solid phase extractant for preconcentrative separation of thorium from aqueous solution

International Nuclear Information System (INIS)

Na Liu; Yanfei Wang; Chuhua He

2016-01-01

A simple and reliable method for solid phase extraction of thorium using tetraphenylimidodiphosphinate is presented. The solid phase extraction process was optimized at equilibrium time 3 h, pH = 4.5, initial concentration 30 mg L -1 and extractant dosage 0.01 g with 98.95 % of removal efficiency and 29.68 mg g -1 of adsorption capacity. The interfering ions experiments indicated that it had almost no effect on thorium adsorption. Kinetics data follow the pseudo-first-order model and equilibrium data agreed with the Langmuir isotherm model very well. FT-IR analysis indicated that imino group and phosphoryl acted as the significant roles in the solid phase extraction process. (author)

A systematic review of the use of dosage form manipulation to obtain required doses to inform use of manipulation in paediatric practice.

Science.gov (United States)

Richey, Roberta H; Hughes, Clare; Craig, Jean V; Shah, Utpal U; Ford, James L; Barker, Catrin E; Peak, Matthew; Nunn, Anthony J; Turner, Mark A

2017-02-25

This study sought to determine whether there is an evidence base for drug manipulation to obtain the required dose, a common feature of paediatric clinical practice. A systematic review of the data sources, PubMed, EMBASE, CINAHL, IPA and the Cochrane database of systematic reviews, was used. Studies that considered the dose accuracy of manipulated medicines of any dosage form, evidence of safety or harm, bioavailability, patient experience, tolerability, contamination and comparison of methods of manipulation were included. Case studies and letters were excluded. Fifty studies were eligible for inclusion, 49 of which involved tablets being cut, split, crushed or dispersed. The remaining one study involved the manipulation of suppositories of one drug. No eligible studies concerning manipulation of oral capsules or liquids, rectal enemas, nebuliser solutions, injections or transdermal patches were identified. Twenty four of the tablet studies considered dose accuracy using weight and/or drug content. In studies that considered weight using adapted pharmacopoeial specifications, the percentage of halved tablets meeting these specifications ranged from 30% to 100%. Eighteen studies investigated bioavailability, pharmacokinetics or clinical outcomes following manipulations which included nine delayed or modified release formulations. In each of these nine studies the entirety of the dosage form was administered. Only one of the 18 studies was identified where drugs were manipulated to obtain a proportion of the dosage form, and that proportion administered. The five studies that considered patient perception found that having to manipulate the tablets did not have a negative impact on adherence. Of the 49 studies only two studies reported investigating children. This review yielded limited evidence to support manipulation of medicines for children. The results cannot be extrapolated between dosage forms, methods of manipulation or between different brands of the same

Sodium Lauryl Sulfate Competitively Interacts with HPMC-AS and Consequently Reduces Oral Bioavailability of Posaconazole/HPMC-AS Amorphous Solid Dispersion.

Science.gov (United States)

Chen, Yuejie; Wang, Shujing; Wang, Shan; Liu, Chengyu; Su, Ching; Hageman, Michael; Hussain, Munir; Haskell, Roy; Stefanski, Kevin; Qian, Feng

2016-08-01

Sodium lauryl sulfate (SLS), as an effective surfactant, is often used as a solubilizer and/or wetting agent in various dosage forms for the purpose of improving the solubility and dissolution of lipophilic, poorly water-soluble drugs. This study aims to understand the impact of SLS on the solution behavior and bioavailability of hypromellose acetate succinate (HPMC-AS)-based posaconazole (PSZ) ASDs, and to identify the underlying mechanisms governing the optimal oral bioavailability of ASDs when surfactants such as SLS are used in combination. Fluorescence spectroscopy and optical microscopy showed that "oil-out" or "liquid-liquid phase separation (LLPS)" occurred in the supersaturated PSZ solution once drug concentration surpassed ∼12 μg/mL, which caused the formation of drug-rich oily droplets with initial size of ∼300-400 nm. Although FT-IR study demonstrated the existence of specific interactions between PSZ and HPMC-AS in the solid state, predissolved HPMC-AS was unable to delay LLPS of the supersaturated PSZ solution and PSZ-rich amorphous precipitates with ∼16-18% HPMC-AS were formed within 10 min. The coprecipitated HPMC-AS was found to be able to significantly delay the crystallization of PSZ in the PSZ-rich amorphous phase from less than 10 min to more than 4 h, yet coexistent SLS was able to negate this crystallization inhibition effect of HPMC-AS in the PSZ-rich amorphous precipitates and cause fast PSZ crystallization within 30 min. 2D-NOESY and the CMC/CAC results demonstrated that SLS could assemble around HPMC-AS and competitively interact with HPMC-AS in the solution, thus prevent HPMC-AS from acting as an effective crystallization inhibitor. In a crossover dog PK study, this finding was found to be correlating well with the in vivo bioavailability of PSZ ASDs formulated with or without SLS. The SLS containing PSZ ASD formulation demonstrated an in vivo bioavailability ∼30% of that without SLS, despite the apparently better in vitro

Influence of Mycotoxin Binders on the Oral Bioavailability of Doxycycline in Pigs.

Science.gov (United States)

De Mil, Thomas; Devreese, Mathias; De Saeger, Sarah; Eeckhout, Mia; De Backer, Patrick; Croubels, Siska

2016-03-16

Mycotoxin binders are feed additives that aim to adsorb mycotoxins in the gastrointestinal tract of animals, making them unavailable for systemic absorption. The antimicrobial drug doxycycline (DOX) is often used in pigs and is administered through feed or drinking water; hence, DOX can come in contact with mycotoxin binders in the gastrointestinal tract. This paper describes the effect of four mycotoxin binders on the absorption of orally administered DOX in pigs. Two experiments were conducted: The first used a setup with bolus administration to fasted pigs at two different dosages of mycotoxin binder. In the second experiment, DOX and the binders were mixed in the feed at dosages recommended by the manufacturers (= field conditions). Interactions are possible between some of the mycotoxin binders dosed at 10 g/kg feed but not at 2 g/kg feed. When applying field conditions, no influences were seen on the plasma concentrations of DOX.

Biopharmaceutical evaluation of transnasal, sublingual, and buccal disk dosage forms of butorphanol.

Science.gov (United States)

Shyu, W C; Mayol, R F; Pfeffer, M; Pittman, K A; Gammans, R E; Barbhaiya, R H

1993-07-01

A series of three-way crossover randomized studies were conducted to evaluate the absolute bioavailability of butorphanol, a potent agonist-antagonist analgesic, from transnasal, sublingual, and buccal disk formulations in order to identify a practical alternative to oral administration. In each study, healthy male volunteers received 2 mg doses of butorphanol tartrate intravenously and either transnasally, sublingually or buccally. Serial blood samples were collected over 12 h and butorphanol plasma concentrations were determined by radioimmunoassay. The plasma concentration data were subjected to non-compartmental pharmacokinetic analysis. The elimination half-life of butorphanol was about 3-5 h and was independent of the route of administration. Absorption of butorphanol following transnasal administration was faster than that observed following sublingual or buccal administration. Mean absolute bioavailabilities of sublingual tablet and buccal disk formulation were only 19 per cent and 29 per cent, respectively, but for transnasal administration the value rose significantly, to 70 per cent. Based on the results of these studies, transnasal dosage form of butorphanol was selected for further clinical trials of treatment of moderate to severe pain.

Stability of pyrimethamine in a liquid dosage formulation stored for three months.

Science.gov (United States)

Nahata, M C; Morosco, R S; Hipple, T F

1997-12-01

The stability of pyrimethamine in a liquid dosage formulation stored for up to three months was studies. Commercially available 25-mg pyrimethamine tablets were crushed with a mortar and pestle and mixed with a 1:1 mixture of Simple Syrup, NF, and 1% methylcellulose to yield a suspension with a pyrimethamine concentration of 2 mg/mL. The suspension was poured into 10 amber plastic and 10 amber glass prescription bottles; 5 plastic and 5 glass bottles were stored at 4 degrees C, and the remaining bottles were kept at 25 degrees C. Samples were collected at intervals up to 91 days and tested for pyrimethamine concentration by stability-indicating high-performance liquid chromatography. Pyrimethamine remained stable throughout the three-month study period under all conditions. At 4 degrees C, pyrimethamine concentrations remained above 96% of the initial concentration; at 25 degrees C, pyrimethamine concentrations remained above 91%. No substantial changes in pH were observed. Pyrimethamine was stable for at least 91 days in an oral suspension stored in plastic or glass prescription bottles at 4 or 25 degrees C.

Candesartan cilexetil loaded nanodelivery systems for improved oral bioavailability.

Science.gov (United States)

Dudhipala, Narendar; Veerabrahma, Kishan

2017-02-01

Candesartan cilexetil (CC), an antihypertensive drug, has low oral bioavailability due to poor solubility and hepatic first-pass metabolism. These are major limitations in oral delivery of CC. Several approaches are known to reduce the problems of solubility and improve the bioavailability of CC. Among various approaches, nanotechnology-based delivery of CC has potential to overcome the challenges associated with the oral administration. This review focuses on various nano-based delivery systems available and tried for improving the aqueous solubility, dissolution and consequently bioavailability of CC upon oral administration. Of all, solid lipid nanoparticles appear to be promising delivery system, based on current reported results, for delivery of CC, as this system improved the oral bioavailability and possessed prolonged pharmacodynamic effect.

Children's medicines in Tanzania: a national survey of administration practices and preferences.

Directory of Open Access Journals (Sweden)

Lisa V Adams

Full Text Available OBJECTIVE: The dearth of age-appropriate formulations of many medicines for children poses a major challenge to pediatric therapeutic practice, adherence, and health care delivery worldwide. We provide information on current administration practices of pediatric medicines and describe key stakeholder preferences for new formulation characteristics. PATIENTS AND METHODS: We surveyed children aged 6-12 years, parents/caregivers over age 18 with children under age 12, and healthcare workers in 10 regions of Tanzania to determine current pediatric medicine prescription and administration practices as well as preferences for new formulations. Analyses were stratified by setting, pediatric age group, parent/caregiver education, and healthcare worker cadre. RESULTS: Complete data were available for 206 children, 202 parents/caregivers, and 202 healthcare workers. Swallowing oral solid dosage forms whole or crushing/dissolving them and mixing with water were the two most frequently reported methods of administration. Children frequently reported disliking medication taste, and many had vomited doses. Healthcare workers reported medicine availability most significantly influences prescribing practices. Most parents/caregivers and children prefer sweet-tasting medicine. Parents/caregivers and healthcare workers prefer oral liquid dosage forms for young children, and had similar thresholds for the maximum number of oral solid dosage forms children at different ages can take. CONCLUSIONS: There are many impediments to acceptable and accurate administration of medicines to children. Current practices are associated with poor tolerability and the potential for under- or over-dosing. Children, parents/caregivers, and healthcare workers in Tanzania have clear preferences for tastes and formulations, which should inform the development, manufacturing, and marketing of pediatric medications for resource-limited settings.

Synthesis and properties of hydroxy acrylic resin with high solid content

Science.gov (United States)

Yu, Zhen; Hu, Mingguang; Cui, Han; Xiao, Jijun

2017-10-01

Manufacturers of automotive repair finishes are tending to reduce more and more the level of volatile organic compounds in their paints in order to comply with increasingly strict environmental legislation. A high solid hydroxy acrylic resin was synthesised using CARDURA E10 and a type of hydroxyacrylic acid resin, its' acid value, hydroxylvalue, viscosity, structure, morphology was measured and film-forming properties after curing were characterised. The results show that the addition of CARDURA E10 in the copolymer composition significantly reduced the viscosity of the polymer system, improved the solid content of the resin and the physical properties of the coating. The hydroxyl acrylate resin with solid content of 90% and excellent comprehensive performance were successfully prepared by controlling the initiator dosage, polymerization temperature and monomer ratio.

Two Oral Midazolam Preparations in Pediatric Dental Patients: A Prospective Randomised Clinical Trial

OpenAIRE

Katayoun Salem; Shaqayegh Kamranzadeh; Maryam Kousha; Shahnaz Shaeghi; Fatemeh AbdollahGorgi

2015-01-01

Pharmacological sedation is an alternative behavior management strategy in pediatric dentistry. The aim of this study was to compare the behavioral and physiologic effects of “commercially midazolam syrup” versus “orally administered IV midazolam dosage form (extemporaneous midazolam (EF))” in uncooperative pediatric dental patients. Eighty-eight children between 4 to 7 years of age received 0.2–0.5 mg/kg midazolam in this parallel trial. Physiologic parameters were recorded at baseline and e...

Permeability enhancers dramatically increase zanamivir absolute bioavailability in rats: implications for an orally bioavailable influenza treatment.

Directory of Open Access Journals (Sweden)

Eric H Holmes

Full Text Available We have demonstrated that simple formulations composed of the parent drug in combination with generally regarded as safe (GRAS permeability enhancers are capable of dramatically increasing the absolute bioavailability of zanamivir. This has the advantage of not requiring modification of the drug structure to promote absorption, thus reducing the regulatory challenges involved in conversion of an inhaled to oral route of administration of an approved drug. Absolute bioavailability increases of up to 24-fold were observed when Capmul MCM L8 (composed of mono- and diglycerides of caprylic/capric acids in glycerol was mixed with 1.5 mg of zanamivir and administered intraduodenally to rats. Rapid uptake (t(max of 5 min and a C(max of over 7200 ng/mL was achieved. Variation of the drug load or amount of enhancer demonstrated a generally linear variation in absorption, indicating an ability to optimize a formulation for a desired outcome such as a targeted C(max for enzyme saturation. No absorption enhancement was observed when the enhancer was given 2 hr prior to drug administration, indicating, in combination with the observed tmax, that absorption enhancement is temporary. This property is significant and aligns well with therapeutic applications to limit undesirable drug-drug interactions, potentially due to the presence of other poorly absorbed polar drugs. These results suggest that optimal human oral dosage forms of zanamivir should be enteric-coated gelcaps or softgels for intraduodenal release. There continues to be a strong need and market for multiple neuraminidase inhibitors for influenza treatment. Creation of orally available formulations of inhibitor drugs that are currently administered intravenously or by inhalation would provide a significant improvement in treatment of influenza. The very simple GRAS formulation components and anticipated dosage forms would require low manufacturing costs and yield enhanced convenience. These results

Development of polymer film dosage forms of lidocaine for buccal administration. I. Penetration rate and release rate.

Science.gov (United States)

Okamoto, H; Taguchi, H; Iida, K; Danjo, K

2001-12-13

We examined the penetration rate of lidocaine (LC) through excised oral mucosa from hamster cheek pouch and the in vitro release rate of LC from film dosage forms with hydroxypropylcellulose (HPC) as a film base. Addition of glycyrrhizic acid (GL) to the HPC films increased the LC release rate almost GL-content-dependently, while an optimum GL content was observed for the LC penetration rate. No LC penetration was observed from an acidic aqueous solution (pH 3.4) of LC, suggesting only unionized LC can substantially penetrate through the mucosa. A significant relationship between the penetration rate of LC and the release rate of unionized LC was found, suggesting that the in vitro dissolution study is a useful tool to predict the penetration rate taking the unionized drug fraction into consideration.

Carboxymethyl starch mucoadhesive microspheres as gastroretentive dosage form.

Science.gov (United States)

Lemieux, Marc; Gosselin, Patrick; Mateescu, Mircea Alexandru

2015-12-30

Carboxymethyl starch microspheres (CMS-MS) were produced from carboxymethyl starch powder (CMS-P) with a degree of substitution (DS) from 0.1 to 1.5 in order to investigate the influence of DS on physicochemical, drug release and mucoadhesion properties as well as interactions with gastrointestinal tract (GIT) epithelial barrier models. Placebo and furosemide loaded CMS-MS were obtained by emulsion-crosslinking with sodium trimetaphosphate (STMP). DS had an impact on increasing equilibrium water uptake and modulating drug release properties of the CMS-MS according to the surrounding pH. The transepithelial electrical resistance (TEER) of NCI-N87 gastric cell monolayers was not influenced in presence of CMS-MS, whereas that of Caco-2 intestinal cell monolayers decreased with increasing DS but recovered initial values at about 15h post-treatment. CMS-MS with increasing DS also enhanced furosemide permeability across both NCI-N87 and Caco-2 monolayers at pH gradients from 3.0 to 7.4. Mucoadhesion of CMS-MS on gastric mucosa (acidic condition) increased with the DS up to 55% for a DS of 1.0 but decreased on neutral intestinal mucosa to less than 10% with DS of 0.1. The drug release, permeability enhancement and mucoadhesive properties of the CMS-MS suggest CMS-MS with DS between 0.6 and 1.0 as suitable excipient for gastroretentive oral delivery dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

Short-time, high-dosage penicillin infusion therapy of syphilis

DEFF Research Database (Denmark)

Lomholt, Hans; Poulsen, Asmus; Brandrup, Flemming

2003-01-01

The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G intraven......The optimal dosage and duration of penicillin treatment for the various stages of syphilis are not known. We present data on 20 patients with syphilis (primary, secondary or latent) treated with high-dose, short-time penicillin infusion therapy. Patients were given 10 MIU of penicillin G...

Safety, pharmacokinetics, and antitumor properties of anlotinib, an oral multi-target tyrosine kinase inhibitor, in patients with advanced refractory solid tumors

Directory of Open Access Journals (Sweden)

Yongkun Sun

2016-10-01

Full Text Available Abstract Background Anlotinib is a novel multi-target tyrosine kinase inhibitor that is designed to primarily inhibit VEGFR2/3, FGFR1-4, PDGFR α/β, c-Kit, and Ret. We aimed to evaluate the safety, pharmacokinetics, and antitumor activity of anlotinib in patients with advanced refractory solid tumors. Methods Anlotinib (5–16 mg was orally administered in patients with solid tumor once a day on two schedules: (1 four consecutive weeks (4/0 or (2 2-week on/1-week off (2/1. Pharmacokinetic sampling was performed in all patients. Twenty-one patients were further enrolled in an expanded cohort study on the recommended dose and schedule. Preliminary tumor response was also assessed. Results On the 4/0 schedule, dose-limiting toxicity (DLT was grade 3 hypertension at 10 mg. On the 2/1 schedule, DLT was grade 3 hypertension and grade 3 fatigue at 16 mg. Pharmacokinetic assessment indicated that anlotinib had long elimination half-lives and significant accumulation during multiple oral doses. The 2/1 schedule was selected, with 12 mg once daily as the maximum tolerated dose for the expanding study. Twenty of the 21 patients (with colon adenocarcinoma, non-small cell lung cancer, renal clear cell cancer, medullary thyroid carcinoma, and soft tissue sarcoma were assessable for antitumor activity of anlotinib: 3 patients had partial response, 14 patients had stable disease including 12 tumor burden shrinkage, and 3 had disease progression. The main serious adverse effects were hypertension, triglyceride elevation, hand-foot skin reaction, and lipase elevation. Conclusions At the dose of 12 mg once daily at the 2/1 schedule, anlotinib displayed manageable toxicity, long circulation, and broad-spectrum antitumor potential, justifying the conduct of further studies.

Sample preparation composite and replicate strategy case studies for assay of solid oral drug products.

Science.gov (United States)

Nickerson, Beverly; Harrington, Brent; Li, Fasheng; Guo, Michele Xuemei

2017-11-30

Drug product assay is one of several tests required for new drug products to ensure the quality of the product at release and throughout the life cycle of the product. Drug product assay testing is typically performed by preparing a composite sample of multiple dosage units to obtain an assay value representative of the batch. In some cases replicate composite samples may be prepared and the reportable assay value is the average value of all the replicates. In previously published work by Harrington et al. (2014) [5], a sample preparation composite and replicate strategy for assay was developed to provide a systematic approach which accounts for variability due to the analytical method and dosage form with a standard error of the potency assay criteria based on compendia and regulatory requirements. In this work, this sample preparation composite and replicate strategy for assay is applied to several case studies to demonstrate the utility of this approach and its application at various stages of pharmaceutical drug product development. Copyright © 2017 Elsevier B.V. All rights reserved.

Genetic basis for dosage sensitivity in Arabidopsis thaliana.

Directory of Open Access Journals (Sweden)

Isabelle M Henry

2007-04-01

Full Text Available Aneuploidy, the relative excess or deficiency of specific chromosome types, results in gene dosage imbalance. Plants can produce viable and fertile aneuploid individuals, while most animal aneuploids are inviable or developmentally abnormal. The swarms of aneuploid progeny produced by Arabidopsis triploids constitute an excellent model to investigate the mechanisms governing dosage sensitivity and aneuploid syndromes. Indeed, genotype alters the frequency of aneuploid types within these swarms. Recombinant inbred lines that were derived from a triploid hybrid segregated into diploid and tetraploid individuals. In these recombinant inbred lines, a single locus, which we call SENSITIVE TO DOSAGE IMBALANCE (SDI, exhibited segregation distortion in the tetraploid subpopulation only. Recent progress in quantitative genotyping now allows molecular karyotyping and genetic analysis of aneuploid populations. In this study, we investigated the causes of the ploidy-specific distortion at SDI. Allele frequency was distorted in the aneuploid swarms produced by the triploid hybrid. We developed a simple quantitative measure for aneuploidy lethality and using this measure demonstrated that distortion was greatest in the aneuploids facing the strongest viability selection. When triploids were crossed to euploids, the progeny, which lack severe aneuploids, exhibited no distortion at SDI. Genetic characterization of SDI in the aneuploid swarm identified a mechanism governing aneuploid survival, perhaps by buffering the effects of dosage imbalance. As such, SDI could increase the likelihood of retaining genomic rearrangements such as segmental duplications. Additionally, in species where triploids are fertile, aneuploid survival would facilitate gene flow between diploid and tetraploid populations via a triploid bridge and prevent polyploid speciation. Our results demonstrate that positional cloning of loci affecting traits in populations containing ploidy and

Enhanced systemic exposure of saquinavir via the concomitant use of curcumin-loaded solid dispersion in rats.

Science.gov (United States)

Kim, Su-A; Kim, Sung-Whan; Choi, Hoo-Kyun; Han, Hyo-Kyung

2013-08-16

The present study aimed to evaluate the effect of curcumin-loaded solid dispersion on the pharmacokinetics of saquinavir in rats. Solid dispersion (SD) formulation was prepared with Solutol® HS15 to improve the solubility and bioavailability of curcumin. Subsequently, its inhibition effect on P-gp mediated cellular efflux was examined by using NCI/ADR-RES cells overexpressing P-gp. Compared to the untreated curcumin, SD formulation enhanced the cellular uptake of rhodamine-123, a P-gp substrate by approximately 3 folds in NCI/ADR-RES cells. The oral and intravenous pharmacokinetics of saquinavir were also determined in rats with/without curcumin in the different formulations. Compared to the control given saquinavir alone, curcumin-loaded solid dispersion significantly (p<0.05) increased the oral exposure of saquinavir in rats, while it did not affect the intravenous pharmacokinetics of saquinavir. The AUC and Cmax of oral saquinavir increased by 3.8- and 2.7-folds, respectively in the presence of curcumin-loaded solid dispersion. In contrast, the untreated curcumin did not affect the oral pharmacokinetics of saquinavir. These results suggest that SD formulation of curcumin should be effective to improve the in vivo effectiveness of curcumin as an absorption enhancer, leading to the improved oral exposure of saquinavir. Copyright © 2013 Elsevier B.V. All rights reserved.

Design of ANFIS Structures and GMDH Type-Neural Network for Prediction of Optimum Coagulant Dosage in Water Treatment Process Case Study: Great Water Treatment Plant in Guilan Province

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Allahyar Daghbandan

2015-11-01

Full Text Available Given the increasing importance of surface water bodies as supply sources of drinking water and regarding the requirement for using different chemicals at various stages of water treatment processes, it is essential to investigate coagulant consumption in water treatment plants. Determination of the required dosage of coagulants used in the coagulation and flocculation unit is one of the most important decisions in water treatment operations. For this purpose, the jar test is generally used to determine the type and concentration of suitable coagulants in a water treatment plant. However, the test is rather time-consuming and unreliable due to the inaccurate results it yields. Instead, intelligent methods can be employed to overcome this shortcoming of the jar test. In this study, experimental data were collected over the period from 2011 to 2012 and further refined for study. Two non-linear models based on adaptive neuro-fuzzy inference system (ANFIS and GMDH-type neural networks were then developed and experimental results were used to determine the optimum poly-aluminium chloride dosage for use at Guilan water treatment plant. The effects of input parameters including temperature, pH, turbidity, suspended solids, electrical conductivity, and color were investigated on coagulant dosage. The ANFIS model was found to outperform the GMDH model in predicting the required poly-aluminium chloride dosage.

Usefulness and safety of early against delayed oral intake after appendectomy

International Nuclear Information System (INIS)

Sheikh, I.A.; Taj, R.U.

2015-01-01

Objective: To evaluate the usefulness and safety of early versus late oral intake after appendectomy. Study Design: Randomized clinical trial. Place and Duration of Study: Combined Military Hospital Multan from August 2008 to February 2009. Material and Methods: One hundred patients with uncomplicated acute appendicitis, undergoing appendectomy under general anesthesia were included in the study and randomly divided into two equal groups. Early oral intake group (group A) was allowed fluids, when patients were out of effects of general anesthesia. Delayed fed (group B) was started oral fluids, on appearance of normal bowel sounds or passage of flatus. Low residue solid diet was started, after tolerance of oral fluids, in both groups. Results: Early oral intake resulted in start of solid diet earlier by average 9 hours; these patients had normal bowel sounds, and passed flatus, earlier, after 4 hours and 5 hours as compared to late feeding group. Six (12%) patients had mild ileus in early fed group whereas 4(8%) patients in delayed fed group had mild ileus. Thirty eight (76%) early fed patients were very satisfied, as compared to 29 (58%) delayed fed patients. The hospital stay was prolonged by 2 days in delayed fed group. Conclusion: Early oral feeding implemented after appendectomy is safe and effective, with a shortened hospital stay as the primary benefit in patients after appendectomy. (author)

Safety profile of solid lipid nanoparticles loaded with rosmarinic acid for oral use: in vitro and animal approaches

Directory of Open Access Journals (Sweden)

Madureira AR

2016-08-01

Full Text Available Ana Raquel Madureira,1 Sara Nunes,2 Débora A Campos,1 João C Fernandes,2 Cláudia Marques,3 Monica Zuzarte,2 Beatriz Gullón,1 Luís M Rodríguez-Alcalá,1 Conceição Calhau,3,4 Bruno Sarmento,5–7 Ana Maria Gomes,1 Maria Manuela Pintado,1 Flávio Reis2 1Catholic University of Portugal, CBQF – Center for Biotechnology and Fine Chemistry – Associate Laboratory, Faculty of Biotechnology, Porto, Portugal; 2Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences (IBILI, Faculty of Medicine, and CNC.IBILI Consortium, University of Coimbra, Coimbra, Portugal; 3Department of Biochemistry, Faculty of Medicine, University of Porto, Porto, Portugal; 4Center for Health Technology and Services Research (CINTESIS, Porto, Portugal; 5Department of Pharmaceutical Sciences, Institute of Health Sciences-North, CESPU, Gandra, Portugal; 6“I3S” Instituto de Investigação e Inovação em Saúde, University of Porto, Porto, Portugal; 7INEB, Institute of Biomedical Engineering, University of Porto, Porto, Portugal Abstract: Rosmarinic acid (RA possesses several protective bioactivities that have attracted increasing interest by nutraceutical/pharmaceutical industries. Considering the reduced bioavailability after oral use, effective (and safe delivery systems are crucial to protect RA from gastrointestinal degradation. This study aims to characterize the safety profile of solid lipid nanoparticles produced with Witepsol and Carnauba waxes and loaded with RA, using in vitro and in vivo approaches, focused on genotoxicity and cytotoxicity assays, redox status markers, hematological and biochemical profile, liver and kidney function, gut bacterial microbiota, and fecal fatty acids composition. Free RA and sage extract, empty nanoparticles, or nanoparticles loaded with RA or sage extract (0.15 and 1.5 mg/mL were evaluated for cell (lymphocytes viability, necrosis and apoptosis, and antioxidant

Solid dispersion of dutasteride using the solvent evaporation method: Approaches to improve dissolution rate and oral bioavailability in rats.

Science.gov (United States)

Choi, Jin-Seok; Lee, Sang-Eun; Jang, Woo Suk; Byeon, Jong Chan; Park, Jeong-Sook

2018-09-01

The aim of this study was to develop a dutasteride (DUT) solid dispersion (SD) using hydrophilic substances to enhance its dissolution (%) and oral bioavailability in rats. DUT-SD formulations were prepared with various co-polymers using a solvent evaporation method. The physical properties of DUT-SD formulations were confirmed using field emission scanning electron microscopy (FE-SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and attenuated total reflectance Fourier transform infrared (ATR-FT-IR) spectroscopy. The toxicity and oral bioavailability of DUT-SD formulations were evaluated. Tocopheryl polyethylene glycol-1000-succinate (TPGS) was chosen as the solubilizer; and methylene chloride, and Aerosil® 200 or microcrystalline cellulose (MCC) were chosen as the solvent and carrier, respectively, based on a solubility test and pre-dissolution study. The dissolution levels of DUT-SD formulations were 86.3 ± 2.3% (F15) and 95.1 ± 1.9% (F16) after 1 h, which were higher than those of the commercial product, i.e., Avodart® (75.8 ± 1.5%) in 0.1 N HCl containing 1% (w/v) sodium lauryl sulfate (SLS). The F16 formulation was found to be stable, after assessing its dissolution (%) and drug content (%) for 6 months. The DUT-SD formulations resulted in relative bioavailability (BA) values of 126.4% (F15) and 132.1% (F16), which were enhanced compared to that of Avodart®. Dissolution (%) and relative BA values were both increased by hydrogen interaction between TPGS and DUT. This study might contribute to a new formulation (powder) whose oral bioavailability is greater than that of Avodart® (soft capsule), which could facilitate to the use of the SD system during the production process. Copyright © 2018 Elsevier B.V. All rights reserved.

Administered activity of Tc-99m MDP for bone scintigraphy, standard or individual dosage?

International Nuclear Information System (INIS)

Vestergren, E.; Gretarsdottir, J.; Jacobsson, L.

2002-01-01

Background and Aim: Adult patients are generally, irrespective of size, given the same amount of activity for a certain type of nuclear medicine examination, a standard dosage. Identical image quality is essential when comparing different patient studies. The aim of this study is to evaluate different dosage methods for Tc-99m-MDP bone scintigraphy and to investigate whether individual dosage will decrease the variations in image quality between different patients. Material and Methods: 100 consecutive adult patients (aged between 40 and 89 years) undergoing whole body bone scintigraphy were studied. Eight patients were excluded from the study because of abnormal high uptake in the areas of interest. The patient weight and height were registered. The activity in the syringes was measured before and after the injection of about 600 MBq Tc-99m MDP. Scanning was performed, with a dual head gamma camera (Maxxus or Millennium VG, General Electric) equipped with a high-resolution collimator, at approximately 4 hours (mean 3.8 h) post-injection. Regions of interest (ROI) were drawn over the lumbar spine (posterior view), the right femur (anterior view) and also soft tissue background regions for each area. The total counts, maximum counts/pixel and number of pixels in the ROIs were registered. The maximum number of counts/pixel (background-subtracted), SPINEmax and FEMURmax were chosen as the image quality parameters. For each patient, SPINEmax and FEMURmax where recalculated to the number that would have been obtained with standard dosage (exactly 600 MBq), and dosage proportional to body weight, body surface area and body height. All values were corrected to a scanning time 3.8 h after injection. Results: Both with a standard activity dosage and a dosage proportional to body height, SPINEmax decreases with increasing body weight. Dosage proportional to body weight gives increasing values of SPINEmax with increasing body weight. Dosage proportional to body surface area

Porosity measurement of solid pharmaceutical dosage forms by gamma-ray transmission

International Nuclear Information System (INIS)

Martins de Oliveira, Jose; Andreo Filho, Newton; Vinicius Chaud, Marco; Angiolucci, Tatiana; Aranha, Norberto; Germano Martins, Antonio Cesar

2010-01-01

The aim of the present work is the determination of porosity in tablets by using the gamma-ray transmission technique. Tablet dissolution depends on some inherent characteristics of the manufacturing process, such as compression force, tablet volume, density and porosity, nature of excipients, preparation methods and its physical-chemical properties. Porosity is a measure of empty spaces in a material and can be determined by various techniques. In this paper, we propose the use of a gamma-ray transmission technique to obtain the porosity of experimental formulation of tablets. The results of porosity were compared with those obtained by using conventional methodology (density and mercury intrusion). The experimental setup for gamma-ray transmission consists of a gamma-ray source of 241 Am (photons of 59.6 keV and an activity of 3.7x10 9 Bq), an NaI(Tl) scintillation detector, collimators and a standard gamma-ray spectrometry electronics. Our results suggest that the gamma-ray transmission technique is a powerful tool for non-destructive porosity quantification of solid pharmaceutical forms and presents smaller errors than those obtained with conventional methodologies.

[Preparation of Oenothera biennis Oil Solid Lipid Nanoparticles Based on Microemulsion Technique].

Science.gov (United States)

Piao, Lin-mei; Jin, Yong; Cui, Yan-lin; Yin, Shou-yu

2015-06-01

To study the preparation of Oenothera biennis oil solid lipid nanoparticles and its quality evaluation. The solid lipid nanoparticles were prepared by microemulsion technique. The optimum condition was performed based on the orthogonal design to examine the entrapment efficiency, the mean diameter of the particles and so on. The optimal preparation of Oenothera biennis oil solid lipid nanoparticles was as follows: Oenothera biennis dosage 300 mg, glycerol monostearate-Oenothera biennis (2: 3), Oenothera biennis -RH/40/PEG-400 (1: 2), RH-40/PEG-400 (1: 2). The resulting nanoparticles average encapsulation efficiency was (89.89 ± 0.71)%, the average particle size was 44.43 ± 0.08 nm, and the Zeta potential was 64.72 ± 1.24 mV. The preparation process is simple, stable and feasible.

Fenproporex and amphetamine pharmacokinetics in oral fluid after controlled oral administration of fenproporex.

Science.gov (United States)

Comiran, Eloisa; Souza, Daniele Zago; Boehl, Paula Otero; Cássia Mariotti, Kristiane de; Pechansky, Flavio; Duarte, Paulina do Carmo Arruda Vieira; De Boni, Raquel Brandini; Fröehlich, Pedro Eduardo; Limberger, Renata Pereira

2012-10-01

Fenproporex hydrochloride (FEN) is an anorectic drug used in the treatment of obesity, and its major metabolite is amphetamine (AMP), another central nervous system stimulant. The concentration versus time profile of FEN and its metabolite AMP has been described in classic biological matrices such as plasma and urine; however, there are no reports of such data in oral fluid. The aim of this study is to describe the pharmacokinetics of FEN and AMP in oral fluid after intake of FEN. Twenty-five milligrams of FEN (1 capsule of Desobesi-m) was orally administered to 6 male volunteers, and oral fluid samples were collected with a Quantisal device during 24.00 hours after drug ingestion. These samples were submitted to solid-phase microextraction before analysis by gas chromatography-mass spectrometry in the selected-ion-monitoring mode, using deuterium-labeled AMP as internal standard. After FEN administration, both analytes could be detected in oral fluid of all volunteers with an initial detection time varying from 0.50 to 1.00 hour. FEN peak concentrations occurred between 1.00 and 1.50 hours after administration and were between 70.7 and 227.5 μg/L. For AMP, peak concentration occurred between 1.50 and 4.00 hours, reaching 33.0-150.9 μg/L. The authors observed that oral administration of FEN resulted in significant amounts of FEN and AMP in oral fluid, showing that oral fluid could be a biological matrix suitable for pharmacokinetic studies for both analytes. Using a compartmental approach, FEN data were best fitted by 1-compartment model with first-order input and output, whereas AMP followed a 2-compartment model with first-order input and output.

A step toward development of printable dosage forms for poorly soluble drugs

DEFF Research Database (Denmark)

Raijada, Dharaben Kaushikkumar; Genina, Natalja; Fors, Daniela

2013-01-01

The purpose of this study was to formulate printable dosage forms for a poorly soluble drug (piroxicam; PRX) and to gain understanding of critical parameters to be considered during development of such dosage forms. Liquid formulations of PRX were printed on edible paper using piezoelectric inkjet...

Maths anxiety and medication dosage calculation errors: A scoping review.

Science.gov (United States)

Williams, Brett; Davis, Samantha

2016-09-01

A student's accuracy on drug calculation tests may be influenced by maths anxiety, which can impede one's ability to understand and complete mathematic problems. It is important for healthcare students to overcome this barrier when calculating drug dosages in order to avoid administering the incorrect dose to a patient when in the clinical setting. The aim of this study was to examine the effects of maths anxiety on healthcare students' ability to accurately calculate drug dosages by performing a scoping review of the existing literature. This review utilised a six-stage methodology using the following databases; CINAHL, Embase, Medline, Scopus, PsycINFO, Google Scholar, Trip database (http://www.tripdatabase.com/) and Grey Literature report (http://www.greylit.org/). After an initial title/abstract review of relevant papers, and then full text review of the remaining papers, six articles were selected for inclusion in this study. Of the six articles included, there were three experimental studies, two quantitative studies and one mixed method study. All studies addressed nursing students and the presence of maths anxiety. No relevant studies from other disciplines were identified in the existing literature. Three studies took place in the U.S, the remainder in Canada, Australia and United Kingdom. Upon analysis of these studies, four factors including maths anxiety were identified as having an influence on a student's drug dosage calculation abilities. Ultimately, the results from this review suggest more research is required in nursing and other relevant healthcare disciplines regarding the effects of maths anxiety on drug dosage calculations. This additional knowledge will be important to further inform development of strategies to decrease the potentially serious effects of errors in drug dosage calculation to patient safety. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lyophilized sponges loaded with curcumin solid lipid nanoparticles for buccal delivery: Development and characterization.

Science.gov (United States)

Hazzah, Heba A; Farid, Ragwa M; Nasra, Maha M A; El-Massik, Magda A; Abdallah, Ossama Y

2015-08-15

This study aimed to prepare and evaluate mucoadhesive sponges as dosage forms for delivering solid lipid nanoparticles. For this purpose curcumin (Cur) was formulated as solid nanoparticles (SLN) using Gelucire 50/13, and polaxomer 407. The prepared CurSLN dispersion was thickened with different mucoadhesive polymers. Different concentrations of glycerol, and mannitol of range (0.25-20%), and (0-1%), respectively were also examined. The formed gel was poured into oblong molds and freeze dried to form mucoadhesive sponge to be applied to the buccal mucosa. The prepared sponges were evaluated for their, in-vivo residence time, in-vitro and in-vivo drug release, and hydration capacity. Surface morphology for the different sponges were examined using SEM. TEM was also carried out for sponge fragments previously dispersed into water. Infrared spectroscopy was conducted to investigate interaction between used ingredients. The results showed that the CurSLN loaded HPMC, and Polycarbophil sponges showed 4, and 15 h in-vivo residence time, respectively, providing a considerable amount of curcumin into saliva. The incorporation of glycerol and mannitol at concentration of 1% provided elegant and flexible sponges. The SEM showed that the deposition of CurSLN differed according to the type of polymer used. TEM confirmed the integrity of liberated CurSLN from sponges. IR spectra showed an interaction between HPMC and poloxamer 407, which affected its behavior as a gelling agent. The obtained results provide an efficient approach for delivering solid lipid nanoparticles in a solid dosage form keeping the nanoparticle characters and integrity. Copyright © 2015 Elsevier B.V. All rights reserved.

Antioxidant status in oral subchronic toxicity of fipronil and fluoride co-exposure in buffalo calves.

Science.gov (United States)

Gill, Kamalpreet Kaur; Dumka, Vinod Kumar

2016-02-01

The effects of fipronil and fluoride co-exposure were investigated on antioxidant status of buffalo calves. A total of 24 healthy male buffalo calves divided into 4 groups were treated for 98 consecutive days. Group I, receiving no treatment, served as the control. Animals of groups II and III were orally administered with fipronil at the dosage of 0.5 mg/kg/day and sodium fluoride (NaF) at the dosage of 6.67 mg/kg/day, respectively, for 98 days. Group IV was coadministered with fipronil and NaF at the same dosages as groups II and III. Administration of fipronil alone produced significant elevation in lipid peroxidation (LPO) and decrease in the levels of nonenzymatic antioxidant glutathione (GSH). However, it did not produce any significant effect on the activities of enzymatic antioxidants including glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD). NaF exposure led to enhanced oxidative stress as shown by significant increase in the LPO and SOD activities while GPx and CAT activities and GSH levels were significantly decreased. Co-exposure to fipronil and NaF showed additive effects on LPO, GPx activity, and GSH levels. © The Author(s) 2013.

Dissolution rate enhancement of repaglinide by solid dispersion

African Journals Online (AJOL)

Keywords: Diabetes, Solid dispersion, Repaglinide, Solubility, Dissolution, Burst release. Tropical Journal of ... high lipophilicity (logP = 3.97) and relatively low oral bioavailability (56 .... II drug, i.e., low soluble and high permeable in nature. As.

Exhaled breath and oral cavity VOCs as potential biomarkers in oral cancer patients.

Science.gov (United States)

Bouza, M; Gonzalez-Soto, J; Pereiro, R; de Vicente, J C; Sanz-Medel, A

2017-03-01

Corporal mechanisms attributed to cancer, such as oxidative stress or the action of cytochrome P450 enzymes, seem to be responsible for the generation of a variety of volatile organic compounds (VOCs) that could be used as non-invasive diagnosis biomarkers. The present work presents an attempt to use VOCs from exhaled breath and oral cavity air as biomarkers for oral squamous cell carcinoma (OSCC) patients. A total of 52 breath samples were collected (in 3 L Tedlar bags) from 26 OSCC patients and 26 cancer-free controls. The samples were analyzed using solid-phase microextraction followed by gas chromatography-mass spectrometry detection. Different statistical strategies (e.g., Icoshift, SIMCA, LDA, etc) were used to classify the analytical data. Results revealed that compounds such as undecane, dodecane, decanal, benzaldehyde, 3,7-dimethyl undecane, 4,5-dimethyl nonane, 1-octene, and hexadecane had relevance as possible biomarkers for OSCC. LDA classification with these compounds showed well-defined clusters for patients and controls (non-smokers and smokers). In addition to breath analysis, preliminary studies were carried out to evaluate the possibility of lesion-surrounded air (analyzed OSCC tumors are in the oral cavity) as a source of biomarkers. The oral cavity location of the squamous cell carcinoma tumors constitutes an opportunity to non-invasively collect the air surrounding the lesion. Small quantities (20 ml) of air collected in the oral cavity were analyzed using the above methodology. Results showed that aldehydes present in the oral cavity might constitute potential OSCC biomarkers.

Conscious Sedation Efficacy of 0.3 and 0.5 mg/kg Oral Midazolam for Three to Six Year-Old Uncooperative Children Undergoing Dental Treatment: A Clinical Trial

Directory of Open Access Journals (Sweden)

Masoud Fallahinejad Ghajari

2016-10-01

Full Text Available Objectives: Midazolam with variable dosages has been used to induce sedation in pediatric dentistry. The aim of this study was to compare the efficacy of two dosages of oral midazolam for conscious sedation of children undergoing dental treatment.Materials and Methods: In this randomized crossover double blind clinical trial, 20 healthy children (ASA I aged three to six years with negative or definitely negative Frankl behavioral rating scale were evaluated. Half of the children received 0.5mg/kg oral midazolam plus 1mg/kg hydroxyzine (A orally in the first session and 0.3mg/kg oral midazolam plus 1mg/kg hydroxyzine (B in the next session. The other half received the drugs on a reverse order. Sedation degree by Houpt sedation rating scale, heart rate and level of SpO2 were assessed at the beginning and after 15 and 30 minutes. The data were analyzed using SPSS 19 and Wilcoxon Signed Rank and McNemar’s tests.Results: The results showed that although administration of 0.5mg/kg oral midazolam was slightly superior to 0.3mg/kg oral midazolam in terms of sedation efficacy, the differences were not significant (P>0.05. The difference in treatment success was not significant either (P>0.05. Heart rate, oxygen saturation (SpO2 and respiratory rate were within the normal range and did not show a significant change (P>0.05.Conclusions: The overall success rate of the two drug combinations namely 0.5mg/kg oral midazolam plus hydroxyzine and 0.3mg/kg oral midazolam plus hydroxyzine was not significantly different for management of pediatric patients.Keywords: Conscious Sedation; Pediatric Dentistry; Midazolam; Hydroxyzine

Efficacy, tolerability, and pharmacokinetics of oxcarbazepine oral loading in patients with epilepsy.

Science.gov (United States)

Kim, Dong Wook; Gu, Nami; Jang, In-Jin; Chu, Kon; Yu, Kyung-Sang; Cho, Joo-Youn; Yoon, Seo Hyun; Kim, Hwa Suk; Oh, Jeeyoung; Lee, Sang Kun

2012-01-01

The rapid achievement of effective levels of antiepileptic drugs (AEDs) is required in patients with epilepsy who have a higher risk of seizures, and oral loading of AEDs may be an important consideration in these patients. We performed the present study to investigate the efficacy and tolerability of oral loading of oxcarbazepine in patients with recurrent seizures, or after temporary discontinuation of AEDs for diagnostic or presurgical evaluation of epilepsy. Forty adult patients were studied and oxcarbazepine was administered orally at a single loading dosage of 30 mg/kg. The plasma levels of oxcarbazepine and its active metabolite, 10,11-dihydro-10-hydroxy-carbazepine (monohydroxy derivative, MHD), were measured, and clinical assessment of adverse events was performed at 2, 4, 6, 8, 10, 12, 16, and 24 h after oral loading of oxcarbazepine. Approximately two-thirds of patients reached effective levels of MHD 2 h after receiving the oral loading, and all patients reached effective levels 4 h after oxcarbazepine administration. Most patients maintained therapeutic MHD levels for at least 16 h. Almost half of the patients experienced adverse events, but all were mild to moderate in severity and resolved spontaneously within 24 h. Our study shows that oral loading of oxcarbazepine is an effective and well-tolerated method for rapidly achieving therapeutic levels of MHD in patients with epilepsy, and is a useful option in selected patients with recurrent seizures, or after temporary discontinuation of AEDs. Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

Low-dosage helical CT applications for chest medical checkup and lung cancer screening

International Nuclear Information System (INIS)

Wang Ping; Cui Fa; Liang Huanqing; Zheng Minfei

2005-01-01

Objective: A discussion on low-dosage helical CT applications on chest medical checkup and lung cancer screening. Methods: On the 100 chest medical check up with three different of protocols, including standard-dosage (the tube current was 230 mAs) were compared with low-dose (tube current was 50 mAs or 30 mAs). Results: Low-dosage helical CT scan provides excellent images. In 100 chest medical checkup, 39 nodules or masses were revealed, enlarged lymph node was noted in 1 case; emphysema or bullae was demonstrated in 3 segments; thickening of bronchial wall was shown in 2 cases; and localized pleural thickening was found in 1 case. Conclusion: In chest checkup or lung cancer screening low-dosage helical CT (tube current 30 mAs) will not only guarantee image quality but also reduce the radiation dose during the examination. (authors)

Enhancement of Solubility of Lamotrigine by Solid Dispersion and Development of Orally Disintegrating Tablets Using 32 Full Factorial Design

Directory of Open Access Journals (Sweden)

Jatinderpal Singh

2015-01-01

Full Text Available Present investigation deals with the preparation and evaluation of orally disintegrating tablets (ODTs of lamotrigine using β-cyclodextrin and PVP-K30 as polymers for the preparation of solid dispersion which help in enhancement of aqueous solubility of this BCS CLASS-II drug and sodium starch glycolate (SSG and crospovidone as a superdisintegrating agent, to reduce disintegration time. The ODTs were prepared by direct compression method. Nine formulations were developed with different ratios of superdisintegrating agents. All the formulations were evaluated for disintegration time, weight variation, hardness, friability, drug content uniformity, wetting time, and in vitro drug release study. In vitro drug release study was performed using United States Pharmacopoeia (USP type 2 dissolution test apparatus employing paddle stirrer at 50 rpm using 900 mL of 0.1 N HCl maintained at 37°C ± 0.5°C as the dissolution medium. On the basis of evaluation parameters formulations were prepared using β-CD 1 : 1 solid dispersion. Then 32 full factorial design was applied using SSG and crospovidone in different ratios suggested by using design expert 8.0.7.1 and optimized formulation was prepared using amount of SSG and crospovidone as suggested by the software. The optimized formulation prepared had disintegrating time of 15 s, wetting time of 24 s, and % friability of 0.55.

On Strategies of Improving Junior High School Students' Oral English Ability

Institute of Scientific and Technical Information of China (English)

罗茜

2015-01-01

With the increasingly frequent international exchanges,English,as an international language,has been attached greater importance.The oral English ability of junior high school students plays an indispensable role in their everyday study and social interaction,and it is the present junior school study that can lay a solid foundation for their future study and life. Therefore,to comprehensively improve their oral English ability is in urgent need and of paramount significance.This paper focuses on analyzing the external and internal factors influencing the cultivation of junior high school students' oral English ability,and put forwards the corresponding cultivating strategies of the oral English ability of junior high school students.

On Strategies of Improving Junior High School Students’ Oral English Ability

Institute of Scientific and Technical Information of China (English)

罗茜

2015-01-01

With the increasingly frequent international exchanges,English,as an international language,has been attached greater importance.The oral English ability of junior high school students plays an indispensable role in their everyday study and social interaction,and it is the present junior school study that can lay a solid foundation for their future study and life.Therefore,to comprehensively improve their oral English ability is in urgent need and of paramount significance.This paper focuses on analyzing the external and internal factors influencing the cultivation of junior high school students’oral English ability,and put forwards the corresponding cultivating strategies of the oral English ability of junior high school students.

Oral administration of antimicrobials increase antimicrobial resistance in E. coli from chicken--a systematic review.

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Simoneit, C; Burow, E; Tenhagen, B-A; Käsbohrer, A

2015-01-01

Antimicrobials play an important role in animal and human health care. It was the aim of this systematic review to assess the effects of oral administration of antimicrobials on the development of antimicrobial resistance (AMR) in Escherichia coli (E. coli) from chickens. Moreover, the effects of the administration of more than one antimicrobial and of different dosages were studied. Literature was searched in November 2012 from the electronic databases ISI Web of Science, PubMed, Scopus and a national literature database (DIMDI) as well as the database ProQuest LLC. The search was updated in March 2014. Original studies describing a treatment (A) and a control group of either non-treatment (C) or initial value (0) and determining AMR in E. coli at different sample points (SP) were included. The literature search resulted in 35 full text articles on the topic, seven (20%) of which contained sufficient information on the administered antimicrobial and the impact of treatment on AMR. Most papers described the use of more than one antimicrobial, several dosages, controls (non-treatment or pre-treatment) and measured AMR at different SPs leading to a total of 227 SPs on the impact of the use of antimicrobials on AMR in chickens. 74% of the SPs (168/227) described a higher AMR-rate in E. coli from treated animals than from controls. After the administration of a single antimicrobial, AMR increased at 72% of the SPs. Administration of more than one antimicrobial increased AMR at 82% of the SPs. Higher dosages were associated with similar or higher AMR rates. The limited number of studies for each antimicrobial agent and the high variability in the resistance effect call for more well designed studies on the impact of oral administration on AMR development and spread. Copyright © 2014 Elsevier B.V. All rights reserved.

Microstructure, texture and oral processing: New ways to reduce sugar and salt in foods

NARCIS (Netherlands)

Stieger, M.A.; Velde, van de F.

2013-01-01

Food oral processing as the bridge between food texture, microstructure and sensory perception has gained enormous interest in the last decade. This review provides an overview of the role of the microstructure of soft- and semi-solid foods in food oral processing and sensory perception. Phase

Dosage-based parameters for characterization of puff dispersion results.

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Berbekar, Eva; Harms, Frank; Leitl, Bernd

2015-01-01

A set of parameters is introduced to characterize the dispersion of puff releases based on the measured dosage. These parameters are the dosage, peak concentration, arrival time, peak time, leaving time, ascent time, descent time and duration. Dimensionless numbers for the scaling of the parameters are derived from dimensional analysis. The dimensionless numbers are tested and confirmed based on a statistically representative wind tunnel dataset. The measurements were carried out in a 1:300 scale model of the Central Business District in Oklahoma City. Additionally, the effect of the release duration on the puff parameters is investigated. Copyright © 2014 Elsevier B.V. All rights reserved.

Spectrophotometric Determination of Trimipramine in Tablet Dosage ...

African Journals Online (AJOL)

Purpose: To develop and validate simple, rapid and sensitive spectrophotometric procedures for determination of trimipramine in tablet dosage form. Methods: The methods were based on the interaction of trimipramine as n-electron donor with the ο-acceptor, iodine and various π-acceptors, namely: chloranil (CH), ...

X chromosome dosage compensation via enhanced transcriptional elongation in Drosophila.

Science.gov (United States)

Larschan, Erica; Bishop, Eric P; Kharchenko, Peter V; Core, Leighton J; Lis, John T; Park, Peter J; Kuroda, Mitzi I

2011-03-03

The evolution of sex chromosomes has resulted in numerous species in which females inherit two X chromosomes but males have a single X, thus requiring dosage compensation. MSL (Male-specific lethal) complex increases transcription on the single X chromosome of Drosophila males to equalize expression of X-linked genes between the sexes. The biochemical mechanisms used for dosage compensation must function over a wide dynamic range of transcription levels and differential expression patterns. It has been proposed that the MSL complex regulates transcriptional elongation to control dosage compensation, a model subsequently supported by mapping of the MSL complex and MSL-dependent histone 4 lysine 16 acetylation to the bodies of X-linked genes in males, with a bias towards 3' ends. However, experimental analysis of MSL function at the mechanistic level has been challenging owing to the small magnitude of the chromosome-wide effect and the lack of an in vitro system for biochemical analysis. Here we use global run-on sequencing (GRO-seq) to examine the specific effect of the MSL complex on RNA Polymerase II (RNAP II) on a genome-wide level. Results indicate that the MSL complex enhances transcription by facilitating the progression of RNAP II across the bodies of active X-linked genes. Improving transcriptional output downstream of typical gene-specific controls may explain how dosage compensation can be imposed on the diverse set of genes along an entire chromosome.

Determination of dasatinib in the tablet dosage form by ultra high performance liquid chromatography, capillary zone electrophoresis, and sequential injection analysis.

Science.gov (United States)

Gonzalez, Aroa Garcia; Taraba, Lukáš; Hraníček, Jakub; Kozlík, Petr; Coufal, Pavel

2017-01-01

Dasatinib is a novel oral prescription drug proposed for treating adult patients with chronic myeloid leukemia. Three analytical methods, namely ultra high performance liquid chromatography, capillary zone electrophoresis, and sequential injection analysis, were developed, validated, and compared for determination of the drug in the tablet dosage form. The total analysis time of optimized ultra high performance liquid chromatography and capillary zone electrophoresis methods was 2.0 and 2.2 min, respectively. Direct ultraviolet detection with detection wavelength of 322 nm was employed in both cases. The optimized sequential injection analysis method was based on spectrophotometric detection of dasatinib after a simple colorimetric reaction with folin ciocalteau reagent forming a blue-colored complex with an absorbance maximum at 745 nm. The total analysis time was 2.5 min. The ultra high performance liquid chromatography method provided the lowest detection and quantitation limits and the most precise and accurate results. All three newly developed methods were demonstrated to be specific, linear, sensitive, precise, and accurate, providing results satisfactorily meeting the requirements of the pharmaceutical industry, and can be employed for the routine determination of the active pharmaceutical ingredient in the tablet dosage form. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Managing the oral side-effects of medications used to treat multiple sclerosis.

Science.gov (United States)

Cockburn, N; Pateman, K; Taing, M W; Pradhan, A; Ford, P J

2017-09-01

Many medications used to manage multiple sclerosis (MS) affect oral health. This review aimed to identify the oral side-effects of the current drugs recommended in Australia to treat MS and make dental practitioners aware of the range of symptoms. The Australian Therapeutic Guidelines and the Australian Medicines Handbook were searched for medications used to treat MS. For each medication, the generic name, class, route of administration, dosage and drug company reported side-effects were extracted from the online Monthly Index of Medical Specialties (MIMs) database. Meyler's Side-effect of Drugs Encyclopaedia was used to identify any additional oral adverse reactions to medications used to treat MS. Fourteen drugs were identified for the treatment of MS progression and 13 drugs for the treatment of MS symptoms. For these medications, 18 oral side-effects were documented: xerostomia was the most common, followed by dysgeusia, dysphagia, mouth ulceration and sinusitis. Anticholinergic drugs caused xerostomia while immunosuppressants resulted in more infection-related side-effects. Dental practitioners should be aware of the range of symptoms likely to be reported by this population. Clinicians are encouraged to continue providing dental care for their patients who develop MS and refer complex cases to specialists. © 2017 Australian Dental Association.

Single oral dose toxicity test of platycodin d, a saponin from platycodin radix in mice.

Science.gov (United States)

Lee, Won-Ho; Gam, Cheol-Ou; Ku, Sae-Kwang; Choi, Seong-Hun

2011-12-01

The object of this study was to evaluate the single oral dose toxicity of platycodin D, a saponin from the root of Platycodon grandiflorum in male and female mice. Platycodin D was administered to female and male mice as an oral dose of 2000, 1000, 500, 250 and 125 mg/kg (body wt.). Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after treatment, upon necropsy, organ weight and histopathology of 14 principle organs were examined. As the results, no platycodin D treatment related mortalities, clinical signs, changes on the body and organ weights, gross and histopathological observations against 14 principle organs were detected up to 2000 mg/kg in both female and male mice. Therefore, LD50 (50% lethal dose) and approximate LD of playtcodin D after single oral treatment in female and male mice were considered over 2000 mg/kg - the limited dosages recommended by KFDA Guidelines [2009-116, 2009], respectively.

Dosage-dependent non-linear effect of L-dopa on human motor cortex plasticity.

Science.gov (United States)

Monte-Silva, Katia; Liebetanz, David; Grundey, Jessica; Paulus, Walter; Nitsche, Michael A

2010-09-15

The neuromodulator dopamine affects learning and memory formation and their likely physiological correlates, long-term depression and potentiation, in animals and humans. It is known from animal experiments that dopamine exerts a dosage-dependent, inverted U-shaped effect on these functions. However, this has not been explored in humans so far. In order to reveal a non-linear dose-dependent effect of dopamine on cortical plasticity in humans, we explored the impact of 25, 100 and 200 mg of L-dopa on transcranial direct current (tDCS)-induced plasticity in twelve healthy human subjects. The primary motor cortex served as a model system, and plasticity was monitored by motor evoked potential amplitudes elicited by transcranial magnetic stimulation. As compared to placebo medication, low and high dosages of L-dopa abolished facilitatory as well as inhibitory plasticity, whereas the medium dosage prolonged inhibitory plasticity, and turned facilitatory plasticity into inhibition. Thus the results show clear non-linear, dosage-dependent effects of dopamine on both facilitatory and inhibitory plasticity, and support the assumption of the importance of a specific dosage of dopamine optimally suited to improve plasticity. This might be important for the therapeutic application of dopaminergic agents, especially for rehabilitative purposes, and explain some opposing results in former studies.

Efficacy of Plantago major, chlorhexidine 0.12% and sodium bicarbonate 5% solution in the treatment of oral mucositis in cancer patients with solid tumour: A feasibility randomised triple-blind phase III clinical trial.

Science.gov (United States)

Cabrera-Jaime, Sandra; Martínez, Cristina; Ferro-García, Tarsila; Giner-Boya, Pilar; Icart-Isern, Teresa; Estrada-Masllorens, Joan M; Fernández-Ortega, Paz

2018-02-01

Oral mucositis is one of the most common adverse effects of chemotherapy and radiotherapy. The aim of this study was to compare the efficacy of Plantago major extract versus chlorhexidine 0.12% versus sodium bicarbonate 5% in the symptomatic treatment of chemotherapy-induced oral mucositis in solid tumour cancer patients. Multicentre randomised controlled trial estimated sample of 45 solid tumour patients with grade II-III mucositis. The participants were randomised to one of three treatments, consisting of sodium bicarbonate 5% aqueous solution together with: an additional dose of sodium bicarbonate 5% aqueous solution, Plantago major extract, or chlorhexidine 0.12%. The primary outcomes were severity of mucositis, pain intensity, oral intake capacity and quality of life. The independent variable was treatment group, and confounders included sociodemographic data, neutrophil count, chemotherapy drug and dose received. Of the 50 patients enrolled, 68% (n = 34) achieved grade 0 mucositis (none), with those using the double sodium bicarbonate rinse healing in five days on average (95% CI 3.9, 6.5) versus seven days (95% CI 5.3, 9,0) for the chlorhexidine group and seven days (95% CI 5.3, 8.5) for the Plantago major group. The pain experienced by the participants lessened over the 14 days of treatment, but differences in pain intensity between the three groups did not show statistical significance (p = 0.762). Healing time was shorter with the double sodium bicarbonate solution compared to the other two rinses, but the differences were not significant. Our results suggest it may be time to reconsider the use of Plantago major extract in the management of oral mucositis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Human metabolism and excretion kinetics of the fragrance lysmeral after a single oral dosage.

Science.gov (United States)

Scherer, Max; Koch, Holger M; Schütze, Andre; Pluym, Nikola; Krnac, Dusan; Gilch, Gerhard; Leibold, Edgar; Scherer, Gerhard

2017-03-01

2-(4-tert-Butylbenzyl)propionaldehyde, also known as lysmeral, lilial or lily-aldehyde (CAS No 80-54-6) is a synthetic fragrance used in a variety of consumer products like perfumes, after shave lotions, cosmetics and others. Due to its broad application, lysmeral was selected for the development of a biomonitoring method for the general population within the frame of the cooperation project of the Federal Ministry for the Environment (BMUB) and the German Chemical Industry Association (VCI). The project also comprises the identification of suitable biomarkers of exposure in human urine as well as basic toxicokinetic data after defined, experimental exposure. For this purpose, 5 healthy subjects were orally dosed once with 5.26mg lysmeral. Urine was collected immediately before and for 48h after administration of the fragrance. The lysmeral metabolites lysmerol, lysmerylic acid, hydroxylated lysmerylic acid and 4-tert-butylbenzoic acid (TBBA) were determined in all urine samples by a newly developed UPLC-MS/MS (ultra-high pressure liquid chromatography combined with tandem mass spectrometry) method. Peak excretion for all metabolites occurred between 2 and 5h after oral application, with the primary metabolites (lysmerol and lysmerylic acid) being excreted about 1h earlier than the secondary metabolites (hydroxylated lysmerylic acid and TBBA). More than 90% of all measured lysmeral metabolites were excreted after 12h, with the renal excretion being virtually complete after 48h. After this time period, TBBA, lysmerol, lysmerylic acid and hydroxyl-lysmerylic acid represent on average 14.3, 1.82, 0.20 and 0.16%, respectively, of the dose administered. In total, the 4 metabolites determined represent about 16.5% of the dose. With the conversion factors derived from the controlled human study, we estimated median exposure doses for lysmeral in a group of 40 human volunteers from the general population of approximately 140-220μg per day. In conclusion, the lysmeral

Effect of an interactive voice response system on oral anticoagulant management.

Science.gov (United States)

Oake, Natalie; van Walraven, Carl; Rodger, Marc A; Forster, Alan J

2009-04-28

Monitoring oral anticoagulants is logistically challenging for both patients and medical staff. We evaluated the effect of adding an interactive voice response system to computerized decision support for oral anticoagulant management. We developed an interactive voice response system to communicate to patients the results of international normalized ratio testing and their dosage schedules for anticoagulation therapy. The system also reminded patients of upcoming and missed appointments for blood tests. We recruited patients whose anticoagulation control was stable after at least 3 months of warfarin therapy. We prospectively examined clinical data and outcomes for these patients for an intervention period of at least 3 months. We also collected retrospective data for each patient for the 3 months before study enrolment. We recruited 226 patients between Nov. 23, 2006, and Aug. 1, 2007. The mean duration of the intervention period (prospective data collection) was 4.2 months. Anticoagulation control was similar for the periods during and preceding the intervention (mean time within the therapeutic range 80.3%, 95% confidence interval [CI] 77.5% to 83.1% v. 79.9%, 95% CI 77.3% to 82.6%). The interactive voice response system delivered 1211 (77.8%) of 1557 scheduled dosage messages, with no further input required from clinic staff. The most common reason for clinic staff having to deliver the remaining messages (accounting for 143 [9.2%] of all messages) was an international normalized ratio that was excessively high or low, (i.e., 0.5 or more outside the therapeutic range). When given the option, 76.6% of patients (164/214) chose to continue with the interactive voice response system for management of their anticoagulation after the study was completed. The system reduced staff workload for monitoring anticoagulation therapy by 48 min/wk, a 33% reduction from the baseline of 2.4 hours. Interactive voice response systems have a potential role in improving the

[Evaluation of N2O inhalation and oral midazolam conscious sedation in pediatric dentistry of children with intellectual disability].

Science.gov (United States)

Tian, Xiao-hua; Yang, Yan-zhong; Li, Xiao-feng

2015-06-01

To evaluate the effect of N2O inhalation and oral midazolam sedation on uncooperative patients with intellectual disability in pediatric dentistry. N2O inhalation (35%-50%) and oral midazolam conscious sedation (dosages range: 0.50-0.75 mg/kg) were applied to 67 uncooperative pediatric patients with intellectual disability in outpatient department. The patients were divided into 2 groups: group A (N2O inhalation conscious sedation) and group B(oral midazolam conscious sedation).Treatment results and safety were statistically analyzed by Chi-square test with SPSSl3.0 software package. The mean success rate was 70%. The success rate in group B (75%) was higher than group A (67%). The overall incidence of adverse reactions was 13%(9/67). The adverse reaction rate in group B (25%) was significantly higher than group A (5%, P<0.05). N2O inhalation and oral midazolam conscious sedation are effective and safe in pediatric dental uncooperative patients with intellectual disability.

High-performance liquid chromatographic analysis of methadone hydrochloride oral solution.

Science.gov (United States)

Beasley, T H; Ziegler, H W

1977-12-01

A direct and rapid high-performance liquid chromatographic assay for methadone hydrochloride in a flavored oral solution dosage form is described. A syrup sample, one part diluted with three parts of water, is introduced onto a column packed with octadecylsilane bonded on 10 micrometer porous silica gel (reversed phase). A formic acid-ammonium formate-buffered mobile phase is linear programmed with acetonitrile. The absorbance is monitored continuously at 280 or 254 nm, using a flow-through, UV, double-beam photometer. An aqueous methadone hydrochloride solution is used for external standardization. The relative standard deviation was not more than 1.0%. Drug recovery from a syrup base was better than 99.8%.

Solid self-nanoemulsifying drug delivery systems for oral delivery of polypeptide-k: Formulation, optimization, in-vitro and in-vivo antidiabetic evaluation.

Science.gov (United States)

Garg, Varun; Kaur, Puneet; Singh, Sachin Kumar; Kumar, Bimlesh; Bawa, Palak; Gulati, Monica; Yadav, Ankit Kumar

2017-11-15

Development of self-nanoemulsifying drug delivery systems (SNEDDS) of polypeptide-k (PPK) is reported with the aim to achieve its oral delivery. Box-Behnken design (BBD) was adopted to develop and optimize the composition of SNEDDS. Oleoyl polyoxyl-6 glycerides (A), Tween 80 (B), and diethylene glycol monoethyl ether (C) were used as oil, surfactant and co-surfactant, respectively as independent variables. The effect of variation in their composition was observed on the mean droplet size (y1), polydispersity index (PDI) (y2), % drug loading (y3) and zeta potential (y4). As per the optimal design, seventeen SNEDDS prototypes were prepared. The optimized composition of SNEDDS formulation was 25% v/v Oleoyl polyoxyl-6 glycerides, 37% v/v Tween 80, 38% v/v diethylene glycol monoethyl ether, and 3% w/v PPK. The optimized formulation revealed values of y1, y2, y3, and y4 as 31.89nm, 0.16, 73.15%, and -15.65mV, respectively. Further the optimized liquid SNEDDS were solidified through spray drying using various hydrophilic and hydrophobic carriers. Among the various carriers, Aerosil 200 was found to provide desirable flow, compression, disintegration and dissolution properties. Both, liquid and solid-SNEDDS have shown release of >90% within 10min. The formulation was found stable with change in pH, dilution, temperature variation and freeze thaw cycles in terms of droplet size, zeta potential, drug precipitation and phase separation. Crystalline PPK was observed in amorphous state in solid SNEDDS when characterized through DSC and PXRD studies. The biochemical, hematological and histopathological results of streptozotocin induced diabetic rats shown promising antidiabetic potential of PPK loaded in SNEDDS at its both the doses (i.e. 400mg/kg and 800mg/kg) as compared to its naïve form at both the doses. The study revealed successful formulation of SNEDDS for oral delivery of PPK. Copyright © 2017 Elsevier B.V. All rights reserved.

Interventions for preventing oral mucositis in patients with cancer receiving treatment: oral cryotherapy.

Science.gov (United States)

Riley, Philip; Glenny, Anne-Marie; Worthington, Helen V; Littlewood, Anne; Clarkson, Jan E; McCabe, Martin G

2015-12-23

where feasible. For dichotomous outcomes, we reported risk ratios (RR) and 95% confidence intervals (CI). For continuous outcomes, we reported mean differences (MD) and 95% CIs. We pooled similar studies in random-effects meta-analyses. We reported adverse effects in a narrative format. We included 14 RCTs analysing 1280 participants. The vast majority of participants did not receive radiotherapy to the head and neck, so this review primarily assesses prevention of chemotherapy-induced oral mucositis. All studies were at high risk of bias. The following results are for the main comparison: oral cryotherapy versus control (standard care or no treatment). Adults receiving fluorouracil-based (5FU) chemotherapy for solid cancersOral cryotherapy probably reduces oral mucositis of any severity (RR 0.61, 95% CI 0.52 to 0.72, 5 studies, 444 analysed, moderate quality evidence). In a population where 728 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 444 (95% CI 379 to 524). The number needed to treat to benefit one additional person (NNTB), i.e. to prevent them from developing oral mucositis, is 4 people (95% CI 3 to 5).The results were similar for moderate to severe oral mucositis (RR 0.52, 95% CI 0.41 to 0.65, 5 studies, 444 analysed, moderate quality evidence). NNTB 4 (95% CI 4 to 6).Severe oral mucositis is probably reduced (RR 0.40, 95% CI 0.27 to 0.61, 5 studies, 444 analysed, moderate quality evidence). Where 300 per 1000 would develop severe oral mucositis, oral cryotherapy would reduce this to 120 (95% CI 81 to 183), NNTB 6 (95% CI 5 to 9). Adults receiving high-dose melphalan-based chemotherapy before haematopoietic stem cell transplantation (HSCT)Oral cryotherapy may reduce oral mucositis of any severity (RR 0.59, 95% CI 0.35 to 1.01, 5 studies, 270 analysed, low quality evidence). Where 824 per 1000 would develop oral mucositis, oral cryotherapy would reduce this to 486 (95% CI reduced to 289 to increased to 833). The NNTB is 3

Efficacy of nystatin for the treatment of oral candidiasis: a systematic review and meta-analysis

Directory of Open Access Journals (Sweden)

Lyu X

2016-03-01

Full Text Available Xin Lyu, Chen Zhao, Zhi-min Yan, Hong HuaDepartment of Oral Medicine, Peking University School and Hospital of Stomatology, Beijing, People’s Republic of ChinaObjective: To systematically review and assess the efficacy, different treatment protocols (formulation, dosage, and duration, and safety of nystatin for treating oral candidiasis.Methods: Four electronic databases were searched for trials published in English till July 1, 2015. Randomized controlled trials comparing nystatin with other antifungal therapies or a placebo were included. Clinical and/or mycological cure was the outcome evaluation. A meta-analysis or descriptive study on the efficacy, treatment protocols, and safety of nystatin was conducted.Results: The meta-analysis showed that nystatin pastille was significantly superior to placebo in treating denture stomatitis. Nystatin suspension was not superior to fluconazole in treating oral candidiasis in infants, children, or HIV/AIDS patients. The descriptive investigations showed that administration of nystatin suspension and pastilles in combination for 2 weeks might achieve a higher clinical and mycological cure rate, and using the nystatin pastilles alone might have a higher mycological cure rate, when compared with using nystatin suspensions alone. Nystatin pastilles at a dose of 400,000 IU resulted in a significantly higher mycological cure rate than that administrated at a dose of 200,000 IU. Furthermore, treatment with nystatin pastilles for 4 weeks seemed to have better clinical efficacy than treatment for 2 weeks. Descriptive safety assessment showed that poor taste and gastrointestinal adverse reaction are the most common adverse effects of nystatin.Conclusion: Nystatin pastille was significantly superior to placebo in treating denture stomatitis, while nystatin suspension was not superior to fluconazole in treating oral candidiasis in infants, children, or HIV/AIDS patients. Indirect evidence from a descriptive study

Accelerated in-vitro release testing methods for extended-release parenteral dosage forms.

Science.gov (United States)

Shen, Jie; Burgess, Diane J

2012-07-01

This review highlights current methods and strategies for accelerated in-vitro drug release testing of extended-release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in-situ depot-forming systems and implants. Extended-release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, 'real-time' in-vitro release tests for these dosage forms are often run over a long time period. Accelerated in-vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in-vitro release methods using United States Pharmacopeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended-release parenteral dosage forms, along with the accelerated in-vitro release testing methods currently employed are discussed. Accelerated in-vitro release testing methods with good discriminatory ability are critical for quality control of extended-release parenteral products. Methods that can be used in the development of in-vitro-in-vivo correlation (IVIVC) are desirable; however, for complex parenteral products this may not always be achievable. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Accelerated in vitro release testing methods for extended release parenteral dosage forms

Science.gov (United States)

Shen, Jie; Burgess, Diane J.

2012-01-01

Objectives This review highlights current methods and strategies for accelerated in vitro drug release testing of extended release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in situ depot-forming systems, and implants. Key findings Extended release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, “real-time” in vitro release tests for these dosage forms are often run over a long time period. Accelerated in vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in vitro release methods using United States Pharmacopoeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended release parenteral dosage forms, along with the accelerated in vitro release testing methods currently employed are discussed. Conclusions Accelerated in vitro release testing methods with good discriminatory ability are critical for quality control of extended release parenteral products. Methods that can be used in the development of in vitro-in vivo correlation (IVIVC) are desirable, however for complex parenteral products this may not always be achievable. PMID:22686344

The effect of different dosage regimens of tranexamic acid on blood loss in bimaxillary osteotomy: a randomized, double-blind, placebo-controlled study.

Science.gov (United States)

Apipan, B; Rummasak, D; Narainthonsaenee, T

2018-05-01

The purpose of this study was to compare the effects of three dosage regimens of intravenous tranexamic acid and normal saline placebo on blood loss and the requirement for transfusion during bimaxillary osteotomy. A prospective, randomized, double-blind, placebo-controlled study was performed. Eighty patients scheduled for elective bimaxillary osteotomy were divided into four groups: a placebo group and three groups receiving a single dose of tranexamic acid 10, 15, or 20mg/kg body weight after the induction of anaesthesia. Demographic data, the anaesthetic time, the operative time, and the experience of the surgical team were similar in the four groups. Patients receiving placebo had increased blood loss compared to those receiving tranexamic acid. No significant difference in blood loss was found among those who received 10, 15, or 20mg/kg body weight of tranexamic acid. There was no significant difference in transfusion requirement, amount of 24-h postoperative vacuum drainage, length of hospital stay, or complications among the four groups. Prophylactic tranexamic acid decreased bleeding during bimaxillary osteotomy. Of the three dosages of tranexamic acid studied, the most efficacious and cost-effective dose to reduce bleeding was 10mg/kg body weight. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Endotoxin dosage in sepsis

Directory of Open Access Journals (Sweden)

Vincenzo Rondinelli

2012-03-01

Full Text Available Introduction. Endotoxin, a component of the cell wall of Gram-negative bacteria is a major contributor to the pathogenesis of septic shock and multiple organ failure (MOF. Its entry into the bloodstream stimulates monocytes/macrophages which once activated produce and release cytokines, nitric oxide and other mediators that induce systemic inflammation, endothelial damage, organ dysfunction, hypotension (shock and MOF.The aim of this study is to evaluate the usefulness of a quantitative test for the dosage of endotoxin to determine the risk of severe Gram-negative sepsis. Materials and methods. In the period January 2009 - June 2011 we performed 897 tests for 765 patients, mostly coming from the emergency room and intensive care, of which 328 (43% women (mean age 53 and 437 (57% male (mean age 49. Fifty-nine patients, no statistically significant difference in sex, were monitored by an average of two determinations of EA.All patients had procalcitonin values significantly altered.The kit used was EAA (Endotoxin Activity Assay Estor Company, Milan, which has three ranges of endotoxin activity (EA: low risk of sepsis if <0.40 units, medium if between 0.40 and 0.59; high if 0.60. Results. 78 out of 765 patients (10% had a low risk, 447 (58% a medium risk and 240 (32% a high risk.The dosage of EA, combined with that of procalcitonin, has allowed a more targeted antibiotic therapy. Six patients in serious clinical conditions were treated by direct hemoperfusion with Toraymyxin, a device comprising a housing containing a fiber polypropylene and polystyrene with surface-bound polymyxin B, an antibiotic that removes bacterial endotoxins from the blood. Conclusions.The test is useful in risk stratification as well as Gram negative sepsis, to set and monitor targeted therapies, also based on the neutralization of endotoxin.

Intrathecal baclofen in multiple sclerosis and spinal cord injury: complications and long-term dosage evolution.

Science.gov (United States)

Draulans, Nathalie; Vermeersch, Kristof; Degraeuwe, Bart; Meurrens, Tom; Peers, Koen; Nuttin, Bart; Kiekens, Carlotte

2013-12-01

To investigate the long-term dosage evolution and complication rate of intrathecal baclofen use in multiple sclerosis and spinal cord injury patients, based on a large population with a long follow-up. Retrospective data analysis. Academic hospital. Patients with multiple sclerosis (n = 81) or spinal cord injury (n = 49) having an intrathecal baclofen pump implanted at the University Hospitals Leuven between 1988 and 2009. Medical records review of included patients in August 2010. Complications linked to intrathecal baclofen therapy. Daily baclofen dosage after 3 and 6 months, and yearly thereafter. Data on dosage evolution were analysed using a mixed-effect linear model. In 130 patients with a mean follow-up of 63 months, comprising 797 pump years, 104 complications were recorded. This corresponds to a complication rate of 0.011 per month, equally divided among both groups. Seventy-eight of these complications were catheter related. The mean dosage of baclofen stabilizes two years after implantation at 323 µg/day in the multiple sclerosis population. In spinal cord injury patients the daily dose only stabilizes after five years at a significantly higher dosage (504 µg/day). No significant increase in dosage is seen in the long term. In multiple sclerosis and spinal cord injury patients, intrathecal baclofen therapy has a complication rate of 1% per month. Complications are mainly due to catheter-related problems (74%). The intrathecal baclofen dosage stabilizes in the long term, indicating that long-term tolerance, defined as progressive diminution of the susceptibility to the effects of a drug, is not present.

Spectrophotometric Determination of Cilostazol in Tablet Dosage Form

African Journals Online (AJOL)

Purpose: To develop simple, rapid and selective spectrophotometric methods for the determination of cilostazol in tablet dosage form. Methods: Cilostazol was dissolved in 50 % methanol and its absorbance was scanned by ultraviolet (UV) spectrophotometry. Both linear regression equation and standard absorptivity were ...

A novel accelerated oxidative stability screening method for pharmaceutical solids.

Science.gov (United States)

Zhu, Donghua Alan; Zhang, Geoff G Z; George, Karen L S T; Zhou, Deliang

2011-08-01

Despite the fact that oxidation is the second most frequent degradation pathway for pharmaceuticals, means of evaluating the oxidative stability of pharmaceutical solids, especially effective stress testing, are still lacking. This paper describes a novel experimental method for peroxide-mediated oxidative stress testing on pharmaceutical solids. The method utilizes urea-hydrogen peroxide, a molecular complex that undergoes solid-state decomposition and releases hydrogen peroxide vapor at elevated temperatures (e.g., 30°C), as a source of peroxide. The experimental setting for this method is simple, convenient, and can be operated routinely in most laboratories. The fundamental parameter of the system, that is, hydrogen peroxide vapor pressure, was determined using a modified spectrophotometric method. The feasibility and utility of the proposed method in solid form selection have been demonstrated using various solid forms of ephedrine. No degradation was detected for ephedrine hydrochloride after exposure to the hydrogen peroxide vapor for 2 weeks, whereas both anhydrate and hemihydrate free base forms degraded rapidly under the test conditions. In addition, both the anhydrate and the hemihydrate free base degraded faster when exposed to hydrogen peroxide vapor at 30°C under dry condition than at 30°C/75% relative humidity (RH). A new degradation product was also observed under the drier condition. The proposed method provides more relevant screening conditions for solid dosage forms, and is useful in selecting optimal solid form(s), determining potential degradation products, and formulation screening during development. Copyright © 2011 Wiley-Liss, Inc.

Inventory of oral anticancer agents : Pharmaceutical formulation aspects with focus on the solid dispersion technique

NARCIS (Netherlands)

Sawicki, E.; Schellens, J. H M; Beijnen, J. H.; Nuijen, B.

2016-01-01

Dissolution from the pharmaceutical formulation is a prerequisite for complete and consistent absorption of any orally administered drug, including anticancer agents (oncolytics). Poor dissolution of an oncolytic can result in low oral bioavailability, high variability in blood concentrations and

Optimizing the dosage of stabilizing chemical

OpenAIRE

Harjula, Tomi

2013-01-01

A chemical company provides chemical treatment at customer mill in paper industry. This thesis work was done to determine the optimum dosage of stabilizing chemical. The theoretical framework explains the basics of paper brightness and bleaching and how these topics are connected to each other. The knowledge gained is very valuable and can possibly be used in the future in other similar applications as well. This thesis work contains confidential back ground information. Key ...

INVESTIGATION OF THE PHARMACO-TECHNOLOGICAL PROPERTIES OF SOLID DISPERSIONS OF THIOCTIC ACID, OBTAINED BY MICRONIZATION

Directory of Open Access Journals (Sweden)

Kovalevska, I. V.

2018-04-01

Full Text Available Introduction. Thioctic acid is used in the treatment of diseases that are characterized by lack of mitochondrial activity, which is responsible for the formation of free radicals. Widespread use of thioctic acid is due to the chemical structure. The thioctic acid exhibits biological activity in both hydrophilic and hydrophobic environments. Thioctic acid is an enzyme cofactor and a powerful antioxidant, it regulates the transcription of numerous genes, participates in regulation of glucose and lipid metabolism, increases insulin sensitivity, and forms complexes with heavy metals. Thioctic acid has a high pharmacological potential, which is confirmed by the evidence base of clinical trials. An analysis of the literature on the oral use of thioctic acid indicates that solid dosage forms can be used for long-term therapy. This route of administration is limited by factors such as reduced solubility in acidic environments and enzymatic degradation. For this reason, the search for various compositions of auxiliary substances and methods of obtaining drugs is an urgent task of pharmaceutical technology. Material & methods. Objects of study were solid dispersions of thioctic acid (SDTA on the basis of cellulose derivatives: microcrystalline (MCC, HPMC (hydroxypropyl methylcellulose and polyvinylpyrrolidone (PVP as compared to thioctic acid (TA. The samples were made by solid phase method using micronization in a laboratory shredder at a ratio of 1: 1. Pharmacological and technological parameters were determined according to generally accepted methods. Results & discussion. In appearance the resulting mixtures had lemon color, without inclusions and the formation of conglomerates, with homogeneous sized particles According to the pharmaco-technological studies, the samples do not have a satisfactory flowability. The values of the Carr index and the ratio of Hausner make it possible to conclude that there is a large force of cohesion between the

Liquid and solid self-microemulsifying drug delivery systems for improving the oral bioavailability of andrographolide from a crude extract of Andrographis paniculata.

Science.gov (United States)

Sermkaew, Namfa; Ketjinda, Wichan; Boonme, Prapaporn; Phadoongsombut, Narubodee; Wiwattanapatapee, Ruedeekorn

2013-11-20

The purpose of this study was to develop self-microemulsifying formulations of an Andrographis paniculata extract in liquid and pellet forms for an improved oral delivery of andrographolide. The optimized liquid self-microemulsifying drug delivery system (SMEDDS) was composed of A. paniculata extract (11.1%), Capryol 90 (40%), Cremophor RH 40 (40%) and Labrasol (8.9%). This liquid SMEDDS was further adsorbed onto colloidal silicon dioxide and microcrystalline cellulose, and converted to SMEDDS pellets by the extrusion/spheronization technique. The microemulsion droplet sizes of the liquid and pellet formulations after dilution with water were in the range of 23.4 and 30.3 nm. The in vitro release of andrographolide from the liquid SMEDDS and SMEDDS pellets was 97.64% (SD 1.97%) and 97.74% (SD 3.36%) within 15 min, respectively while the release from the initial extract was only 10%. The oral absorption of andrographolide was determined in rabbits. The C(max) value of andrographolide from the A. paniculata extract liquid SMEDDS and SMEDDS pellet formulations (equivalent to 17.5mg/kg of andrographolide) was 6-fold and 5-fold greater than the value from the initial extract in aqueous suspension (equivalent to 35 mg/kg of andrographolide), respectively. In addition, the AUC(0-12h) was increased 15-fold by the liquid SMEDDS and 13-fold by the SMEDDS pellets compared to the extract in aqueous suspension, respectively. The results clearly indicated that the liquid and solid SMEDDS could be effectively used to improve the dissolution and oral bioavailability that would also enable a reduction in the dose of the poorly water soluble A. paniculata extract. Copyright © 2013 Elsevier B.V. All rights reserved.

Development and characterization of a gastroretentive dosage form composed of chitosan and hydroxyethyl cellulose for alendronate

Directory of Open Access Journals (Sweden)

Chen YC

2013-12-01

Full Text Available Ying-Chen Chen,1,* Hsiu-O Ho,1,* Chiao-Chi Chiu,1 Ming-Thau Sheu1,2 1School of Pharmacy, College of Pharmacy, Taipei Medical University, 2Clinical Research Center and Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan*These authors contributed equally to this workAbstract: In this study, alendronate, the most commonly used biphosphonate for treating osteoporosis, was formulated as gastroretentive dosage form (GRDF tablets to enhance its oral bioavailability. GRDF tablets were characterized with the effects of different molecular weights (MWs of chitosan (CS and hydroxyethyl cellulose (HEC at various ratios on swelling, floating, and physical integrity. The CS component was formed using various acids: acetic, lactic, malic, succinic, and citric, and a high viscosity grade of HEC was selected. The results demonstrated that the swelling ratios of the formulations comprising high MW CS were lower than those of low or medium MW CS when salts were formed with any countering acids except for acetic acid. The decreasing ranking of the swelling rates was: CS-citrate > CS-malate > CS-lactate > CS-succinate > CS-acetate. A negative correlation was found between the pKa of the respective countering acid and the swelling rate. The swelling rate was promoted if an acidic salt of CS with a lower water content was incorporated, while it became slower when tablet hardness was higher or the compression force to form tablets was increased. Although HEC did not contribute to swelling or floating, it played a role in maintaining structural integrity. A prolonged dissolution profile of alendronate GRDF tablets developed in this study was observed.Keywords: gastroretentive dosage form, chitosan, hydrogel, hydroxyethyl cellulose, swelling, alendronate

Methotrexate Dosage Reduction Upon Adalimumab Initiation: Clinical and Ultrasonographic Outcomes from the Randomized Noninferiority MUSICA Trial.

Science.gov (United States)

Kaeley, Gurjit S; Evangelisto, Amy M; Nishio, Midori J; Goss, Sandra L; Liu, Shufang; Kalabic, Jasmina; Kupper, Hartmut

2016-08-01

To examine the clinical and ultrasonographic (US) outcomes of reducing methotrexate (MTX) dosage upon initiating adalimumab (ADA) in MTX-inadequate responders with moderately to severely active rheumatoid arthritis (RA). MUSICA (NCT01185288) was a double-blind, randomized, parallel-arm study of 309 patients with RA receiving MTX ≥ 15 mg/week for ≥ 12 weeks before screening. Patients were randomized to high dosage (20 mg/week) or low dosage (7.5 mg/week) MTX; all patients received 40 mg open-label ADA every other week for 24 weeks. The primary endpoint was Week 24 mean 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) to test for noninferiority of low-dosage MTX using a 15% margin. US images were scored using a 10-joint semiquantitative system incorporating OMERACT definitions for pathology, assessing synovial hypertrophy, vascularity, and bony erosions. Rapid improvement in clinical indices was observed in both groups after addition of ADA. The difference in mean DAS28-CRP (0.37, 95% CI 0.07-0.66) comparing low-dosage (4.12, 95% CI 3.88-4.34) versus high-dosage MTX (3.75, 95% CI 3.52-3.97) was statistically significant and non-inferiority was not met. Statistically significant differences were not detected for most clinical, functional, and US outcomes. Pharmacokinetic and safety profiles were similar. In MUSICA, Week 24 mean DAS28-CRP, the primary endpoint, did not meet non-inferiority for the low-dosage MTX group. Although the differences between the 2 MTX dosage groups were small, our study findings did not support routine MTX reduction in MTX inadequate responders initiating ADA.

Measurement of the lowest dosage of phenobarbital that can produce drug discrimination in rats

Science.gov (United States)

Overton, Donald A.; Stanwood, Gregg D.; Patel, Bhavesh N.; Pragada, Sreenivasa R.; Gordon, M. Kathleen

2009-01-01

Rationale Accurate measurement of the threshold dosage of phenobarbital that can produce drug discrimination (DD) may improve our understanding of the mechanisms and properties of such discrimination. Objectives Compare three methods for determining the threshold dosage for phenobarbital (D) versus no drug (N) DD. Methods Rats learned a D versus N DD in 2-lever operant training chambers. A titration scheme was employed to increase or decrease dosage at the end of each 18-day block of sessions depending on whether the rat had achieved criterion accuracy during the sessions just completed. Three criterion rules were employed, all based on average percent drug lever responses during initial links of the last 6 D and 6 N sessions of a block. The criteria were: D%>66 and N%50 and N%33. Two squads of rats were trained, one immediately after the other. Results All rats discriminated drug versus no drug. In most rats, dosage decreased to low levels and then oscillated near the minimum level required to maintain criterion performance. The lowest discriminated dosage significantly differed under the three criterion rules. The squad that was trained 2nd may have benefited by partially duplicating the lever choices of the previous squad. Conclusions The lowest discriminated dosage is influenced by the criterion of discriminative control that is employed, and is higher than the absolute threshold at which discrimination entirely disappears. Threshold estimations closer to absolute threshold can be obtained when criteria are employed that are permissive, and that allow rats to maintain lever preferences. PMID:19082992

A REVIEW ON SOLID DISPERSION: A DISSOLUTION ENHANCEMENT TECHNIQUE

OpenAIRE

Ingle U.S.; Gaikwad P.D.; Bankar V.H.; Pawar S.P.

2011-01-01

The enhancement of the oral bioavailability is currently one of the greatest challenges in the development of poorly water soluble drugs. To increase the dissolution and hence the bioavaibility it is important to increase the solubility of the poorly water soluble drugs. One of the possible ways to overcome this limitation is the use of solid dispersion technology. This article contains the different methods and mechanism used in the solid dispersion technology also overlooks the various carr...

[Post-marketing re-evaluation about usage and dosage of Chinese medicine based on human population pharmacokinetics].

Science.gov (United States)

Jiang, Junjie; Xie, Yanming

2011-10-01

The usage and dosage of Chinese patent medicine are determined by rigorous evaluation which include four clinical trail stages: I, II, III. But the usage and dosage of Chinese patent medicine are lacked re-evaluation after marketing. And this lead to unchanging or fixed of the usage and dosage of Chinese patent medicine instead of different quantity based on different situations in individual patients. The situation of Chinese patent medicine used in clinical application is far away from the idea of the "Treatment based on syndrome differentiation" in traditional Chinese medicine and personalized therapy. Human population pharmacokinetics provides data support to the personalized therapy in clinical application, and achieved the postmarking reevaluating of the usage and dosage of Chinese patent medicine. This paper briefly introduced the present situation, significance and the application of human population pharmacokinetics about re-evaluation of the usage and dosage of Chinese patent medicine after marketing.

Life cycle assessment of selective non-catalytic reduction (SNCR) of nitrous oxides in a full-scale municipal solid waste incinerator

DEFF Research Database (Denmark)

Møller, Jacob; Munk, Bjarne; Crillesen, Kim

2011-01-01

Selective non-catalytic reduction (SNCR) of nitrous oxides in a full-scale municipal solid waste incinerator was investigated using LCA. The relationship between NOx-cleaning and ammonia dosage was measured at the plant. Un-reacted ammonia – the ammonia slip – leaving the flue-gas cleaning system......-cleaning efficiency, the fate of the ammonia slip as well as the environmental impact from ammonia production, the potential acidification and nutrient enrichment from NOx-cleaning was calculated as a function of ammonia dosage. Since the exact fate of the ammonia slip could not be measured directly, a number...... of scenarios were set up ranging from “best case” with no ammonia from the slip ending up in the environment to “worst case” where all the ammonia slip eventually ended up in the environment and contributed to environmental pollution. In the “best case” scenario the highest ammonia dosage was most beneficial...

Boxing and mixed martial arts: preliminary traumatic neuromechanical injury risk analyses from laboratory impact dosage data.

Science.gov (United States)

Bartsch, Adam J; Benzel, Edward C; Miele, Vincent J; Morr, Douglas R; Prakash, Vikas

2012-05-01

In spite of ample literature pointing to rotational and combined impact dosage being key contributors to head and neck injury, boxing and mixed martial arts (MMA) padding is still designed to primarily reduce cranium linear acceleration. The objects of this study were to quantify preliminary linear and rotational head impact dosage for selected boxing and MMA padding in response to hook punches; compute theoretical skull, brain, and neck injury risk metrics; and statistically compare the protective effect of various glove and head padding conditions. An instrumented Hybrid III 50th percentile anthropomorphic test device (ATD) was struck in 54 pendulum impacts replicating hook punches at low (27-29 J) and high (54-58 J) energy. Five padding combinations were examined: unpadded (control), MMA glove-unpadded head, boxing glove-unpadded head, unpadded pendulum-boxing headgear, and boxing glove-boxing headgear. A total of 17 injury risk parameters were measured or calculated. All padding conditions reduced linear impact dosage. Other parameters significantly decreased, significantly increased, or were unaffected depending on padding condition. Of real-world conditions (MMA glove-bare head, boxing glove-bare head, and boxing glove-headgear), the boxing glove-headgear condition showed the most meaningful reduction in most of the parameters. In equivalent impacts, the MMA glove-bare head condition induced higher rotational dosage than the boxing glove-bare head condition. Finite element analysis indicated a risk of brain strain injury in spite of significant reduction of linear impact dosage. In the replicated hook punch impacts, all padding conditions reduced linear but not rotational impact dosage. Head and neck dosage theoretically accumulates fastest in MMA and boxing bouts without use of protective headgear. The boxing glove-headgear condition provided the best overall reduction in impact dosage. More work is needed to develop improved protective padding to minimize

Oral transmucosal delivery of naratriptan.

Science.gov (United States)

Sattar, Mohammed; Lane, Majella E

2016-11-30

Naratriptan (NAR) is currently used as the hydrochloride salt (NAR.HCl) for the treatment of migraine and is available in tablet dosage forms for oral administration. Buccal drug delivery offers a number of advantages compared with conventional oral delivery including rapid absorption, avoidance of first pass metabolism and improved patient compliance. We have previously prepared and characterised the base form of NAR and shown that it has more favourable properties for buccal delivery compared with NAR.HCl. This study describes the design and evaluation of a range of formulations for oral transmucosal delivery of NAR base. Permeation studies were conducted using excised porcine buccal tissue mounted in Franz cells. Of the neat solvents examined, Transcutol ® P (TC) showed the greatest enhancement effects and was the vehicle in which NAR was most soluble. The mechanisms by which TC might promote permeation were further probed using binary systems containing TC with either buffer or Miglyol 812 ® (MG). Mass balance studies were also conducted for these systems. The permeation of TC as well as NAR was also monitored for TC:MG formulations. Overall, TC appears to promote enhanced membrane permeation of NAR because of its rapid uptake into the buccal tissue. Synergistic enhancement of buccal permeation was observed when TC was combined with MG and this is attributed to the increased thermodynamic activity of NAR in these formulations. Significantly enhanced permeation of NAR was achieved for TC:MG and this was also associated with less TC remaining on the tissue or in the tissue at the end of the experiment. To our knowledge this is the first report where both enhancer and active have been monitored in buccal permeation studies. The findings underline the importance of understanding the fate of vehicle components for rational formulation design of buccal delivery systems. Copyright © 2016 Elsevier B.V. All rights reserved.

[Influence of tendencies toward depression, neurosis and psychosomatic disorders on oral symptoms].

Science.gov (United States)

Sasaki, Emi

2005-12-01

This study revealed that the tendencies towards depression, neurosis, and psychosomatic disorders have effects on oral symptoms. The total number of subjects was 102. The subjects were divided into two groups using the SDS (Self-rating Depression Scale): a control group of 66 subjects with an SDS value of less than 40, and a group of 36 subjects having depression tendencies with an SDS value of over 50. Most of the subjects in the depression tendency group showed symptoms of neurosis and psychosomatic disorders as well. The two groups were compared on the basis of their psychological characteristics, dosages of medicine taken, esthesis of mouth dryness, glossalgia, salivary flow rate, oral wettability, existence of dental cavities, and condition of the oral mucosa. No xerostomia at the mucobuccal fold was observed in the depression tendency group. However, there was an evident decrease of the resting salivary flow rate and the wettability of proglossis. It is considered that such a decrease resulted in an increase in the symptoms derived from xerostomia or esthesis of mouth dryness. The number of conservable but untreated dental cavities in the depression tendency group was larger than that in the control group with a significant difference, suggesting that both oral self-care and dental care management tended to be inadequate in the depression tendency group.

Evaluation of the impact of sodium lauryl sulfate source variability on solid oral dosage form development.

Science.gov (United States)

Qiang, Dongmei; Gunn, Jocelyn A; Schultz, Leon; Li, Z Jane

2010-12-01

The objective of this study was to investigate the effects of sodium lauryl sulfate (SLS) from different sources on solubilization/wetting, granulation process, and tablet dissolution of BILR 355 and the potential causes. The particle size distribution, morphology, and thermal behaviors of two pharmaceutical grades of SLS from Spectrum and Cognis were characterized. The surface tension and drug solubility in SLS solutions were measured. The BILR 355 tablets were prepared by a wet granulation process and the dissolution was evaluated. The critical micelle concentration was lower for Spectrum SLS, which resulted in a higher BILR 355 solubility. During wet granulation, less water was required to reach the same end point using Spectrum than Cognis SLS. In general, BILR 355 tablets prepared with Spectrum SLS showed a higher dissolution than the tablets containing Cognis SLS. Micronization of SLS achieved the same improved tablet dissolution as micronized active pharmaceutical ingredient. The observed differences in wetting and solubilization were likely due to the different impurity levels in SLS from two sources. This study demonstrated that SLS from different sources could have significant impact on wet granulation process and dissolution. Therefore, it is critical to evaluate SLS properties from different suppliers, and then identify optimal formulation and process parameters to ensure robustness of drug product manufacture process and performance.

Gamma sterilization of cefotaxime sodium in the solid state

International Nuclear Information System (INIS)

Kattan, M.; Aladawi, M. A.; Hammoudeh, A.; Albaroudi, H.

2010-08-01

To investigate the effect of gamma irradiation on the solid state of Cefotaxime sodium salt (C 1 8H 1 6N 8 Na 2 O 7 S 3 ) as a member of the third generation of cephalosporin. Solid Cefotaxime as a pharmaceutical dosage was exposed to doses of 0, 5, 10, 15, 20, 25, and 50 kGy in 60 Co package irradiator. Physical and chemical characteristics of Cefotaxime sodium have been investigated by using UV (Ultra Violet) and IR (Infra Red) spectroscopic, pH, solubility and DSC (Deferential Scanning Calorimetric) methods. The biological activity of Cefotaxime sodium was investigated using Escherichia coli ATCC 25922 as a strain of bacteria. The obtained results indicated that gamma irradiation have no effect on physical and chemical characteristics of Cefotaxime sodium, No significant differences were found between irradiated and non-irradiated samples in the biological activity of Cefotaxime sodium on E. Coli. (Author)

The impact of supersaturation level for oral absorption of BCS class IIb drugs, dipyridamole and ketoconazole, using in vivo predictive dissolution system: Gastrointestinal Simulator (GIS).

Science.gov (United States)

Tsume, Yasuhiro; Matsui, Kazuki; Searls, Amanda L; Takeuchi, Susumu; Amidon, Gregory E; Sun, Duxin; Amidon, Gordon L

2017-05-01

The development of formulations and the assessment of oral drug absorption for Biopharmaceutical Classification System (BCS) class IIb drugs is often a difficult issue due to the potential for supersaturation and precipitation in the gastrointestinal (GI) tract. The physiological environment in the GI tract largely influences in vivo drug dissolution rates of those drugs. Thus, those physiological factors should be incorporated into the in vitro system to better assess in vivo performance of BCS class IIb drugs. In order to predict oral bioperformance, an in vitro dissolution system with multiple compartments incorporating physiologically relevant factors would be expected to more accurately predict in vivo phenomena than a one-compartment dissolution system like USP Apparatus 2 because, for example, the pH change occurring in the human GI tract can be better replicated in a multi-compartmental platform. The Gastrointestinal Simulator (GIS) consists of three compartments, the gastric, duodenal and jejunal chambers, and is a practical in vitro dissolution apparatus to predict in vivo dissolution for oral dosage forms. This system can demonstrate supersaturation and precipitation and, therefore, has the potential to predict in vivo bioperformance of oral dosage forms where this phenomenon may occur. In this report, in vitro studies were performed with dipyridamole and ketoconazole to evaluate the precipitation rates and the relationship between the supersaturation levels and oral absorption of BCS class II weak base drugs. To evaluate the impact of observed supersaturation levels on oral absorption, a study utilizing the GIS in combination with mouse intestinal infusion was conducted. Supersaturation levels observed in the GIS enhanced dipyridamole and ketoconazole absorption in mouse, and a good correlation between their supersaturation levels and their concentration in plasma was observed. The GIS, therefore, appears to represent in vivo dissolution phenomena and

Volcanic ash dosage calculator: A proof-of-concept tool to support aviation stakeholders during ash events

Science.gov (United States)

Dacre, H.; Prata, A.; Shine, K. P.; Irvine, E.

2017-12-01

The volcanic ash clouds produced by Icelandic volcano Eyjafjallajökull in April/May 2010 resulted in `no fly zones' which paralysed European aircraft activity and cost the airline industry an estimated £1.1 billion. In response to the crisis, the Civil Aviation Authority (CAA), in collaboration with Rolls Royce, produced the `safe-to-fly' chart. As ash concentrations are the primary output of dispersion model forecasts, the chart was designed to illustrate how engine damage progresses as a function of ash concentration. Concentration thresholds were subsequently derived based on previous ash encounters. Research scientists and aircraft manufactures have since recognised the importance of volcanic ash dosages; the accumulated concentration over time. Dosages are an improvement to concentrations as they can be used to identify pernicious situations where ash concentrations are acceptably low but the exposure time is long enough to cause damage to aircraft engines. Here we present a proof-of-concept volcanic ash dosage calculator; an innovative, web-based research tool, developed in close collaboration with operators and regulators, which utilises interactive data visualisation to communicate the uncertainty inherent in dispersion model simulations and subsequent dosage calculations. To calculate dosages, we use NAME (Numerical Atmospheric-dispersion Modelling Environment) to simulate several Icelandic eruption scenarios, which result in tephra dispersal across the North Atlantic, UK and Europe. Ash encounters are simulated based on flight-optimal routes derived from aircraft routing software. Key outputs of the calculator include: the along-flight dosage, exposure time and peak concentration. The design of the tool allows users to explore the key areas of uncertainty in the dosage calculation and to visualise how this changes as the planned flight path is varied. We expect that this research will result in better informed decisions from key stakeholders during

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

Directory of Open Access Journals (Sweden)

Tapan Kumar Giri

2012-12-01

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

Video fluoroscopic techniques for the study of Oral Food Processing

Science.gov (United States)

Matsuo, Koichiro; Palmer, Jeffrey B.

2016-01-01

Food oral processing and pharyngeal food passage cannot be observed directly from the outside of the body without instrumental methods. Videofluoroscopy (x-ray video recording) reveals the movement of oropharyngeal anatomical structures in two dimensions. By adding a radiopaque contrast medium, the motion and shape of the food bolus can be also visualized, providing critical information about the mechanisms of eating, drinking, and swallowing. For quantitative analysis of the kinematics of oral food processing, radiopaque markers are attached to the teeth, tongue or soft palate. This approach permits kinematic analysis with a variety of textures and consistencies, both solid and liquid. Fundamental mechanisms of food oral processing are clearly observed with videofluoroscopy in lateral and anteroposterior projections. PMID:27213138

Use of a screening method to determine excipients which optimize the extent and stability of supersaturated drug solutions and application of this system to solid formulation design.

Science.gov (United States)

Vandecruys, Roger; Peeters, Jef; Verreck, Geert; Brewster, Marcus E

2007-09-05

Assessing the effect of excipients on the ability to attain and maintain supersaturation of drug-based solution may provide useful information for the design of solid formulations. Judicious selection of materials that affect either the extent or stability of supersaturating drug delivery systems may be enabling for poorly soluble drug candidates or other difficult-to-formulate compounds. The technique suggested herein is aimed at providing a screening protocol to allow preliminary assessment of these factors based on small to moderate amounts of drug substance. A series of excipients were selected that may, by various mechanisms, affect supersaturation including pharmaceutical polymers such as HMPC and PVP, surfactants such as Polysorbate 20, Cremophor RH40 and TPGS and hydrophilic cyclodextrins such as HPbetaCD. Using a co-solvent based method and 25 drug candidates, the data suggested, on the whole, that the surfactants and the selected cyclodextrin seemed to best augment the extent of supersaturation but had variable benefits as stabilizers, while the pharmaceutical polymers had useful effect on supersaturation stability but were less helpful in increasing the extent of supersaturation. Using these data, a group of simple solid dosage forms were prepared and tested in the dog for one of the drug candidates. Excipients that gave the best extent and stability for the formed supersaturated solution in the screening assay also gave the highest oral bioavailability in the dog.

Digital and conventional radiology techniques: comparison of dosage and costs

International Nuclear Information System (INIS)

Arranza, L.; Albornoz, C. de

1996-01-01

To compare the radiation dosage and costs in conventional and digital technologies. The study dealt with transverse sections. The dosage applied with conventional technology was measured in 254 patients who intertwined 402 explorations of 6 anatomic regions in 4 Radiodiagnostic Services. The dosage applied with digital technology was measured in 57 patients who underwent 95 explorations of the same anatomic region in one Radiodiagnostic Service. The costs of the 6 types of conventional and digital explorations performed were calculated for two Radiodiagnostic Service. The doses administered (mGy) using convectional/digital technology were as follows: chest PA 0.2/0.1; chest LAT 0.7/0.3; breast CC 7.0/8.4; breast LAT 7.0/7.8; breast OB 7.0/10.5; cervical spine AP 9.6/9.0; cervical spine LAT 21.9/29.6; pelvis AP 7.3/7.1; plain abdominal 6.5/2.2. The costs incurred (1992 pesetas) with the convectional/digital technologies: chest AP and LAT 1,393/2,973; portable chest 2,027/3,714; mammography 2,357/3,486; phlebography 12,718/14,023; hysterosalpingography 4,876/6,701; bone scientigraphy 1,633/2,839. Compared with conventional technology, digital imaging reduces the radiation doses received by the patients, except in the case of mammography. The costs associated with the use of digital technology are greater than those incurred with conventional technology, mainly due to the costs of amortization. the use of digital technology is more justified when: 1) it is very necessary to reduce the dosage; 2) studies of chest and abdomen predominant; 3) the volume of utilization is high; 4) staff management is flexible , and 5) the cost of purchasing the equipment is lower. (Author) 10 refs

Minimum effective dosages of anti-TNF in rheumatoid arthritis: a cross-sectional study.

Science.gov (United States)

de la Torre, Inmaculada; Valor, Lara; Nieto, Juan Carlos; Montoro, María; Carreño, Luis

2014-01-01

To evaluate the modified dosages of anti-TNF in controlling disease activity in rheumatoid arthritis (RA) measured by DAS28-ESR. Cross-sectional study: RA patients treated with etanercept (ETN), adalimumab (ADA) or infliximab (IFX), at standard or modified doses. dosage, concomitant disease modifying drugs (DMARDs), DAS28-ESR. 195 RA patients included (79% women, mean age 58.1 years): ETN=81, ADA=56, IFX=58. Mean disease duration and time to first biological treatment was higher in IFX group (P=.01). Patients distribution by dosage: standard: ETN (72.8%), ADA (69.6%), IFX (27.6%); escalated: IFX (69%), ADA (5.4%), ETN (0%); reduced: ETN (27.1%), ADA (25%), IFX (3.4%). Concomitant DMARDs use was lower in ETN (58.2%) than ADA (66.07%) and IFX (79.31%). Higher proportion of responders (DAS28 ≤3.2) in ADA (65.3%) and ETN (61.7%) than IFX (48.3%). RA clinical control can be preserved with modified anti-TNF dosages. Controlled prospective studies should be performed to define when therapy can be tailored and for which patients. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Continuous intravenous infusion of ampicillin and gentamicin during parenteral nutrition to 36 newborn infants using a dosage schedule

DEFF Research Database (Denmark)

Colding, H; Møller, S; Andersen, G E

1984-01-01

Ampicillin and gentamicin were given continuously i.v. to 36 newborn infants using a dosage schedule and the results were compared with those obtained in an earlier study including 88 infants who received individually calculated dosages. With the dosage schedule the variation in the serum concent...

3D printing of high drug loaded dosage forms using thermoplastic polyurethanes.

Science.gov (United States)

Verstraete, G; Samaro, A; Grymonpré, W; Vanhoorne, V; Van Snick, B; Boone, M N; Hellemans, T; Van Hoorebeke, L; Remon, J P; Vervaet, C

2018-01-30

It was the aim of this study to develop high drug loaded (>30%, w/w), thermoplastic polyurethane (TPU)-based dosage forms via fused deposition modelling (FDM). Model drugs with different particle size and aqueous solubility were pre-processed in combination with diverse TPU grades via hot melt extrusion (HME) into filaments with a diameter of 1.75 ± 0.05 mm. Subsequently, TPU-based filaments which featured acceptable quality attributes (i.e. consistent filament diameter, smooth surface morphology and good mechanical properties) were printed into tablets. The sustained release potential of the 3D printed dosage forms was tested in vitro. Moreover, the impact of printing parameters on the in vitro drug release was investigated. TPU-based filaments could be loaded with 60% (w/w) fine drug powder without observing severe shark skinning or inconsistent filament diameter. During 3D printing experiments, HME filaments based on hard TPU grades were successfully converted into personalized dosage forms containing a high concentration of crystalline drug (up to 60%, w/w). In vitro release kinetics were mainly affected by the matrix composition and tablet infill degree. Therefore, this study clearly demonstrated that TPU-based FDM feedstock material offers a lot of formulation freedom for the development of personalized dosage forms. Copyright © 2017 Elsevier B.V. All rights reserved.

Dronabinol oral solution in the management of anorexia and weight loss in AIDS and cancer.

Science.gov (United States)

Badowski, Melissa E; Yanful, Paa Kwesi

2018-01-01

The true incidence of anorexia secondary to human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and cancer is not well classified owing to the fact that there is a lack of standardized definitions and recent clinical data in these settings. Dronabinol, or Δ-9-tetrahydrocannabinol, is a synthetic molecule that closely mimics the action of Cannabis sativa L., a naturally occurring compound activated in the central nervous system by cannabinoid receptors. Dronabinol exerts its effects by directly acting on the vomiting and appetite control centers in the brain, which in turn increases appetite and prevents vomiting. In the USA, dronabinol is currently available in two dosage formulations - oral capsule and oral solution. While the oral capsule was initially approved by the US Food and Drug Administration in 1985, the recent approval of the oral solution in 2016 presents an "easy-to-swallow" alternative for patients using or intending to use dronabinol. Dronabinol is indicated in adult patients with HIV/AIDS for the treatment of anorexia and weight loss. However, there is no approved indication in the setting of cancer-related anorexia and weight loss. This review aims at presenting available data on the use of oral dronabinol in the management of anorexia and weight loss in HIV/AIDS and cancer, as well as characterizing and highlighting the pharmacotherapeutic considerations of the newest formulation of dronabinol.

Polymer nanocomposite particles of S-nitrosoglutathione: A suitable formulation for protection and sustained oral delivery.

Science.gov (United States)

Wu, Wen; Gaucher, Caroline; Fries, Isabelle; Hu, Xian-Ming; Maincent, Philippe; Sapin-Minet, Anne

2015-11-10

S-nitrosoglutathione (GSNO) is a nitric oxide (NO) donor with therapeutic potential for cardiovascular disease treatment. Chronic oral treatment with GSNO is limited by high drug sensitivity to the environment and limited oral bioavailability, requiring the development of delivery systems able to sustain NO release. The present work describes new platforms based on polymer nanocomposite particles for the delivery of GSNO. Five types of optimized nanocomposite particles have been developed (three based on chitosan, two based on alginate sodium). Those nanocomposite particles encapsulate GSNO with high efficiency from 64% to 70% and an average size of 13 to 61 μm compatible with oral delivery. Sustained release of GSNO in vitro was achieved. Indeed, chitosan nanocomposites discharged their payload within 24h; whereas alginate nanocomposites released GSNO more slowly (10% of GSNO was still remaining in the dosage form after 24h). Their cytocompatibility toward intestinal Caco-2 cells (MTT assay) was acceptable (IC50: 6.07 ± 0.07-9.46 ± 0.08 mg/mL), demonstrating their suitability as oral delivery systems for GSNO. These delivery systems presented efficient GSNO loading and sustained release as well as cytocompatibility, showing their promise as a means of improving the oral bioavailability of GSNO and as a potential new treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

Monitoring of multiple solid-state transformations at tablet surfaces using multi-series near-infrared hyperspectral imaging and multivariate curve resolution

DEFF Research Database (Denmark)

Alexandrino, Guilherme L; Khorasani, Milad Rouhi; Amigo Rubio, Jose Manuel

2015-01-01

The assessment of the solid-state stability of active pharmaceutical ingredient (API) and/or excipients in solid dosage forms during manufacturing and storage is mandatory for safeguarding quality of the final products. In this work, the solid-state transformations in tablets prepared as blends...... of piroxicam monohydrate (API), polyvinylpyrrolidone and the lactose forms monohydrate or anhydrate were studied when the tablets were exposed to the 23-120°C range. Multi-series near-infrared hyperspectral images were obtained from the surface of each sample for unveiling the local evolution of the solid......-state transformations. The preprocessed spectra from the images (dataset) were arranged in augmented matrices, according to the composition of the tablets, and the profile of the overlapped compounds (relative concentration) along the solid-state transformations in the pixels was resolved by using multivariate curve...

Prevalence and trends of cellulosics in pharmaceutical dosage forms.

Science.gov (United States)

Mastropietro, David J; Omidian, Hossein

2013-02-01

Many studies have shown that cellulose derivatives (cellulosics) can provide various benefits when used in virtually all types of dosage forms. Nevertheless, the popularity of their use in approved drug products is rather unknown. This research reports the current prevalence and trends of use for 15 common cellulosics in prescription drug products. The cellulosics were powdered and microcrystalline cellulose (MCC), ethyl cellulose, hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), hypromellose (HPMC), HPMC phthalate, HPMC acetate succinate, cellulose acetate (CA), CA phthalate, sodium (Na) and calcium (Ca) carboxymethylcellulose (CMC), croscarmellose sodium (XCMCNa), methyl cellulose, and low substituted HPC. The number of brand drug products utilizing each cellulosics was determined using the online drug index Rxlist. A total of 607 brand products were identified having one or more of the cellulosics as an active or inactive ingredient. An array of various dosage forms was identified and revealed HPMC and MCC to be the most utilized cellulosics in all products followed by XCMCNa and HPC. Many products contained two or more cellulosics in the formulation (42% containing two, 23% containing three, and 4% containing 4-5). The largest combination occurrence was HPMC with MCC. The use of certain cellulosics within different dosage form types was found to contain specific trends. All injectables utilized only CMCNa, and the same with all ophthalmic solutions utilizing HPMC, and otic suspensions utilizing HEC. Popularity and trends regarding cellulosics use may occur based on many factors including functionality, safety, availability, stability, and ease of manufacturing.

Upgrade of deep bed filtration with activated carbon dosage for compact micropollutant removal from wastewater in technical scale.

Science.gov (United States)

Löwenberg, Jonas; Zenker, Armin; Krahnstöver, Thérèse; Boehler, Marc; Baggenstos, Martin; Koch, Gerhard; Wintgens, Thomas

2016-05-01

The removal of micropollutants from drinking and wastewater by powdered activated carbon (PAC) adsorption has received considerable attention in research over the past decade with various separation options having been investigated. With Switzerland as the first country in the world having adopted a new legislation, which forces about 100 wastewater treatment plants to be upgraded for the removal of organic micropollutants from municipal wastewater, the topic has reached practical relevance. In this study, the process combination of powdered activated carbon (PAC) adsorption and deep bed filtration (DBF) for advanced municipal wastewater treatment was investigated over an extended period exceeding one year of operation in technical scale. The study aimed to determine optimum process conditions to achieve sufficient micropollutant removal in agreement with the new Swiss Water Ordinance under most economic process design. It was shown that the addition of PAC and Fe(3+) as combined coagulation and flocculation agent improved effluent water quality with respect to dissolved organic pollutants as well as total suspended solids (TSS), turbidity and PO4-P concentration in comparison to a DBF operated without the addition of PAC and Fe(3+). Sufficient micropollutant (MP) removal of around 80% was achieved at PAC dosages of 10 mg/L revealing that PAC retained in the filter bed maintained considerable adsorption capacity. In the investigated process combination the contact reactor serves for adsorption as well as for flocculation and allowed for small hydraulic retention times of minimum 10 min while maintaining sufficient MP removal. The flocculation of two different PAC types was shown to be fully concluded after 10-15 min, which determined the flocculation reactor size while both PAC types proved suitable for the application in combination with DBF and showed no significant differences in MP removal. Finally, the capping of PAC dosage during rain water periods, which

Manufacturing Amorphous Solid Dispersions with a Tailored Amount of Crystallized API for Biopharmaceutical Testing.

Science.gov (United States)

Theil, Frank; Milsmann, Johanna; Anantharaman, Sankaran; van Lishaut, Holger

2018-05-07

The preparation of an amorphous solid dispersion (ASD) by dissolving a poorly water-soluble active pharmaceutical ingredient (API) in a polymer matrix can improve the bioavailability by orders of magnitude. Crystallization of the API in the ASD, though, is an inherent threat for bioavailability. Commonly, the impact of crystalline API on the drug release of the dosage form is studied with samples containing spiked crystallinity. These spiked samples possess implicit differences compared to native crystalline samples, regarding size and spatial distribution of the crystals as well as their molecular environment. In this study, we demonstrate that it is possible to grow defined amounts of crystalline API in solid dosage forms, which enables us to study the biopharmaceutical impact of actual crystallization. For this purpose, we studied the crystal growth in fenofibrate tablets over time under an elevated moisture using transmission Raman spectroscopy (TRS). As a nondestructive method to assess API crystallinity in ASD formulations, TRS enables the monitoring of crystal growth in individual dosage forms. Once the kinetic trace of the crystal growth for a certain environmental condition is determined, this method can be used to produce samples with defined amounts of crystallized API. To investigate the biopharmaceutical impact of crystallized API, non-QC dissolution methods were used, designed to identify differences between the various amounts of crystalline materials present. The drug release in the samples manufactured in this fashion was compared to that of samples with spiked crystallinity. In this study, we present for the first time a method for targeted crystallization of amorphous tablets to simulate crystallized ASDs. This methodology is a valuable tool to generate model systems for biopharmaceutical studies on the impact of crystallinity on the bioavailability.

Dried, irradiated sewage solids as supplemental feed for cattle

Energy Technology Data Exchange (ETDEWEB)

Smith, G.S.; Kiesling, H.E.; Ray, E.E.; Orcasberro, R.; Trujillo, P.; Herbel, C.H.

1979-01-01

Sewage solids were collected as primary settled solids and then dried and gamma-irradiated (using /sup 60/Co or /sup 137/Cs) to absorbed dosage of about one megarad to minimize viable parasites and pathogenic organisms. Nutrient composition and bioassays with rumen microbes suggested prospective usage as supplemental feed for ruminants. Short-term experiments with sheep and then with cattle further suggested that usage of nutrients could be beneficial and that accumulation of heavy metals was not excessive. A longer-term feeding trial with cattle fed sewage solids as 20% of diet for 68 days demonstrated that tissue uptake of elements such as Cu, Fe and Pb was measurably increased, but not sufficient to exceed ranges considered normal. Likewise, of 22 refractory organic compounds having toxicological interest, only a few were detectible in adipose tissue and none of these exceeded levels that have been reported in tissues from cattle produced conventionally. In a large-scale experiment, beef cows grazing poor-quality rangeland forage during late gestation-early lactation were given either no spplemental feed or cottonseed meal or experimental supplement comprised of 62% sewage solids. Supplements were provided for 13 weeks until rangeland forage quality improved seasonably. Supplemental cottonseed meal for cows improved weaning weights of calves by about 11% over unsupplemented controls; whereas, supplement with 62% sewage solids improved calf weaning weights by about 7%. Hazards or risks to animals or to human health appear to be slight when sewage solids of this type are fed as supplemental feeds to cattle in production programs of this type.

Development of novel cilostazol-loaded solid SNEDDS using a SPG membrane emulsification technique: Physicochemical characterization and in vivo evaluation.

Science.gov (United States)

Mustapha, Omer; Kim, Kyung Soo; Shafique, Shumaila; Kim, Dong Shik; Jin, Sung Giu; Seo, Youn Gee; Youn, Yu Seok; Oh, Kyung Taek; Lee, Beom-Jin; Park, Young Joon; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon

2017-02-01

The objective of this study was to develop a novel solid self-nanoemulsifying drug delivery system (SNEDDS) using a membrane emulsification technique involving Shirasu porous glass (SPG) which produced very small and uniform emulsion droplets, resulting in enhanced solubility, dissolution and oral bioavailability of poorly water-soluble cilostazol. The effects of carriers on the drug solubility were assessed, and pseudo-ternary phase diagrams were plotted. Among the liquid SNEDDS formulations tested, the liquid SNEDDS composed of peceol (oil), Tween 20 (surfactant) and Labrasol (cosurfactant) at a weight ratio of 15/55/30, produced the smallest emulsion droplet size. The cilostazol-loaded liquid SNEDDS formulation was suspended in the distilled water and subjected to SPG membrane emulsification. Calcium silicate was added as a solid carrier in this liquid SNEDDS, completely suspended and spray-dried, leading to the production of a cilostazol-loaded solid SNEDDS. The emulsion droplet size, solubility and dissolution of the emulsified solid SNEDDS were assessed as compared to the solid SNEDDS prepared without emulsification. Moreover, the physicochemical characteristics and pharmacokinetics in rats were evaluated with the emulsified solid SNEDDS. The emulsified solid SNEDDS provided significantly smaller and more uniform nanoemulsions than did the non-emulsified solid SNEDDS. The emulsified solid SNEDDS showed significantly higher drug solubility and dissolution as compared to the non-emulsified solid SNEDDS. The crystalline drug in it was converted into the amorphous state. Moreover, in rats, it gave significantly higher initial plasma concentrations and AUC compared to the drug powder, suggesting its improved oral bioavailability of cilostazol. Thus, this novel solid SNEDDS developed using a membrane emulsification technique represents a potentially powerful oral delivery system for cilostazol. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel technology to prepare oral formulations for preclinical safety studies.

Science.gov (United States)

Niwa, Toshiyuki; Hashimoto, Naofumi

2008-02-28

A novel method to prepare oral formulations, normally suspended dosage form, for preclinical safety studies in animals has been developed using a rotation/revolution mixer. Small hard balls made of zirconia were added to the mixing process to evaluate effectiveness in making a high quality suspension. The driving with balls loaded in the cylindrical container (vessel) of the mixer was quite efficient in dispersing and milling the particles of the active pharmaceutical ingredient (API) in an aqueous medium. The API powder and a small amount of oral aqueous medium (vehicle) were successfully mixed by the spinning motion of the balls in the vessel as though the paste-like suspension was kneaded with a mortar and pestle. It was found that the milled suspension with the mean size of 10-20microm could be prepared, in addition finer milling of less than 10microm could be achieved by selecting the material of vessel. Optimum driving conditions including mixing time, size and quantity of balls, and the standard operational procedure was established using compounds varying in physicochemical properties. The particle size and quantitative analysis by HPLC showed that the resultant suspension was well-milled and highly homogeneous with the nearly intended concentration of API. The proposed method established by this experiment could be applied to the actual safety studies in the real preparation scale of oral suspension.

Radiation exposure to nuclear medicine technologists from administering I-131 therapy dosages

International Nuclear Information System (INIS)

Chaudakshetrin, P.; Pusuwan, P.; Sritongkul, N.; Tuntawiroon, M.

2007-01-01

Full text: Therapeutic doses of I-131 for treatment of thyroid cancer are administered orally in liquid or capsule form. During the last few years, a total number of patients loaded in our isolation ward increased from 4 to 10 patients per week. When considering radiation safety precautions for attending technologists, it is preferable to use the dose in capsules. The purpose of this study is to compare radiation exposure to nuclear medicine technologists from administering I-131 therapy dosages in capsules and in liquid form in a closed system. Materials and Methods: Three year radiation exposure to technologists during I-131 administration was analyzed. From January 2004 to June 2005 dose administration was in liquid form (n=263) and from July 2005 to February 2007 in capsules (n=541). Radiation dose assessment was performed with an electronic personal dosimeter (PDM 112). The dose rate in μSv and time spent per patient were recorded. Results: Dose received per patient when I-131 was given in a liquid was 3.50 ± 1.67 μSv and 1.17 ± 0.66 μSv when given in capsules. Compared with the use of a liquid, capsules significantly reduced radiation dose to technologists by 66% (P < 0.001). These doses received depended not only on the administered activity but also on the time, distance and shielding. Time spent per patient, including a brief visit before the time of dosing to explain the procedure and answer questions was reduced slightly from 4.4 ± 2.2 to 3.7 ± 1.8 minutes (P < 0.01). These correspond to a reduction in a yearly dose to 1 technologist by 40%, from 0.63 mSv to 0.38 mSv from dosing to 175 and 325 patients respectively. Conclusions: The measured doses clearly showed that handling of I-131 therapy dosages either in a liquid form or capsules are not the major contributors to the technologist's radiation exposure in routine clinical practice. However, one has to be cautious and follow good work practice to avoid risk of radiation exposure and radioiodine

The effect of dosages of microbial consortia formulation and synthetic fertilizer on the growth and yield of field-grown chili

Science.gov (United States)

Istifadah, N.; Sapta, D.; Krestini, H.; Natalie, B.; Suryatmana, P.; Nurbaity, A.; Hidersah, R.

2018-03-01

Chili (Capsicum annuum, L) is one of important horticultural crop in Indonesia. Formulation of microbial consortia containing Bacillus subtilis, Pseudomonas sp., Azotobacter chroococcum and Trichoderma harzianum has been developed. This study evaluated the effects of dosage of the microbial formulation combined with NPK fertilizer on growth and yield of chili plants in the field experiment. The experiment was arranged in completely randomized design of factorial, in which the first factor was dosage of formulation (0, 2.5, 5.0, 7.5, 10 g per plant) and the second factor was NPK fertilizer dosage (0, 25, 50 and 75% of the standard dosage). The treatments were replicated three times. For application, the formulation was mixed with chicken manure 1:10 (w/v). The results showed that application of microbial formulation solely improved the chili growth. There was interaction between dosages of the microbial formulation and NPK fertilizer in improving plant height, nitrogen availability and the chili yield, while there was no interaction between those dosages in improving the root length. Combination between microbial formulation at the dosage of 5.0-7.5 g per plant combined with NPK fertilizer with the dosage 50 or 75% of the standard dosage support relatively better growth and the chili yield.

Medical Management of Oral Lichen Planus: A Systematic Review

Science.gov (United States)

Chokshi, Krunal; Desai, Sachin; Malu, Rahul; Chokshi, Achala

2016-01-01

Introduction Oral Lichen Planus (OLP) is a chronic inflammatory, T-cell-mediated autoimmune oral mucosal disease with unclear aetiology. The clinical management of OLP poses considerable difficulties to the oral physician. Aim The aim was to assess the efficacy of any form of intervention used to medically manage OLP. Materials and Methods We searched and analysed the following databases (from January 1990 to December 2014):- Cochrane Oral Health Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE. All Randomised Controlled Trials (RCTs) for the medical management of OLP which compared active treatment with placebo or between active treatments were considered in this systematic review. Participants of any age, gender or race having symptomatic OLP (including mixed forms), unconnected to any identifiable cause (e.g. lichenoid drug reactions) and confirmed by histopathology have been included. Interventions of all types, including topical treatments or systemic drugs of variable dosage, duration & frequency of delivery have been considered. All the trials identified were appraised by five review authors and the data for all the trials were synthesised using specifically designed data extraction form. Binary data has been presented as risk ratios (RR) with 95% confidence intervals (CI) and continuous data as mean differences (MD) with 95% CIs. Results A total of 35 RCTs were included in this systematic review on medical management of OLP. No strong evidence suggesting superiority of any specific intervention in reducing pain and clinical signs of OLP were shown by the RCTs included here. Conclusion Future RCTs on a larger scale, adopting standardized outcome assessing parameters should be considered. PMID:27042598

Histomorphological study of submandibulary glands of rats submitted to low dosage of X-radiation

International Nuclear Information System (INIS)

Navarro, Claudia Maria; Onofre, Mirian Aparecida; Chan, Carolina; Cordeiro, Rita de Cassis Loiola; Raveli, Dirceu Barnabe

1996-01-01

The minimal dosage of X-ray that is likely to induce cellular alterations is unknown and there are just a few reports with low dosage in odontologic literature. The authors developed a histomorphological analysis of the submandibulary glands of rat that received low dosage of X radiation. The body of the animals was covered with a lead lamin leaving the cervical area uncovered. The submandibular glands were exposed to 1,80 Gy of X-radiation in a single dose. After 24, 48, 72 hours, 7, 14 and 21 days the glands were excised, fixed and prepared for analysis in light microscopy. Mild degenerative changes and nuclear pleomorfism, mainly on the first three experimental periods were observed. (author)

A Report of Two Cases of Solid Facial Edema in Acne.

Science.gov (United States)

Kuhn-Régnier, Sarah; Mangana, Joanna; Kerl, Katrin; Kamarachev, Jivko; French, Lars E; Cozzio, Antonio; Navarini, Alexander A

2017-03-01

Solid facial edema (SFE) is a rare complication of acne vulgaris. To examine the clinical features of acne patients with solid facial edema, and to give an overview on the outcome of previous topical and systemic treatments in the cases so far published. We report two cases from Switzerland, both young men with initially papulopustular acne resistant to topical retinoids. Both cases responded to oral isotretinoin, in one case combined with oral steroids. Our cases show a strikingly similar clinical appearance to the cases described by Connelly and Winkelmann in 1985 (Connelly MG, Winkelmann RK. Solid facial edema as a complication of acne vulgaris. Arch Dermatol. 1985;121(1):87), as well as to cases of Morbihan's disease that occurs as a rare complication of rosacea. Even 30 years after, the cause of the edema remains unknown. In two of the original four cases, a potential triggering factor was identified such as facial trauma or insect bites; however, our two patients did not report such occurrencies. The rare cases of solid facial edema in both acne and rosacea might hold the key to understanding the specific inflammatory pattern that creates both persisting inflammation and disturbed fluid homeostasis which can occur as a slightly different presentation in dermatomyositis, angioedema, Heerfordt's syndrome and other conditions.

Estimated Effect of Epoetin Dosage on Survival among Elderly Hemodialysis Patients in the United States

OpenAIRE

Zhang, Yi; Thamer, Mae; Cotter, Dennis; Kaufman, James; Hernán, Miguel A.

2009-01-01

Background and objectives: The common finding that low achieved hemoglobin in observational studies and high target hemoglobin in randomized trials each were associated with increased mortality and high epoetin dosage has suggested the possibility that high epoetin dosage might explain the increased mortality risk.

Solid Lipid Particles for Oral Delivery of Peptide and Protein Drugs II - The Digestion of Trilaurin Protects Desmopressin from Proteolytic Degradation

DEFF Research Database (Denmark)

Christophersen, Philip Carsten; Zhang, Long; Müllertz, Anette

2014-01-01

, which is the same rank order as the lipid degradation rate. A reverse rank order was found for the protection of desmopressin from enzymatic degradation due to spatial separation of desmopressin from the protease. TG12 accelerated the release of desmopressin from all lipid particles when added as either...... and protease was determined. Trilaurin (TG12), trimyristin (TG14), tripalmitin (TG16), and tristearin (TG18) were used as lipid excipients to produce solid lipid microparticles. RESULTS: In the presence of lipase, the rate of drug release from different lipid particles was in the order of TG14 > TG16 > TG18...... drug-free microparticles to the lipolysis medium or incorporated in TG16 particles. Additionally, TG12 particles protected desmopressin from degradation when present in the lipolysis medium with the other lipid microparticles. CONCLUSIONS: TG12 is a very interesting lipid for oral lipid formulations...

Hyperintense acute reperfusion marker is associated with higher contrast agent dosage in acute ischaemic stroke

Energy Technology Data Exchange (ETDEWEB)

Ostwaldt, Ann-Christin; Schaefer, Tabea; Villringer, Kersten; Fiebach, Jochen B. [Charite Universitaetsmedizin Berlin, Academic Neuroradiology, Center for Stroke Research Berlin (CSB), Berlin (Germany); Rozanski, Michal; Ebinger, Martin [Charite Universitaetsmedizin Berlin, Academic Neuroradiology, Center for Stroke Research Berlin (CSB), Berlin (Germany); Charite Universitaetsmedizin, Department of Neurology, Berlin (Germany); Jungehuelsing, Gerhard J. [Stiftung des Buergerlichen Rechts, Juedisches Krankenhaus Berlin, Berlin (Germany)

2015-11-15

The hyperintense acute reperfusion marker (HARM) on fluid-attenuated inversion recovery (FLAIR) images is associated with blood-brain barrier (BBB) permeability changes. The aim of this study was to examine the influence of contrast agent dosage on HARM incidence in acute ischaemic stroke patients. We prospectively included 529 acute ischaemic stroke patients (204 females, median age 71 years). Patients underwent a first stroke-MRI within 24 hours from symptom onset and had a follow-up on day 2. The contrast agent Gadobutrol was administered to the patients for perfusion imaging or MR angiography. The total dosage was calculated as ml/kg body weight and ranged between 0.04 and 0.31 mmol/kg on the first examination. The incidence of HARM was evaluated on day 2 FLAIR images. HARM was detected in 97 patients (18.3 %). HARM incidence increased significantly with increasing dosages of Gadobutrol. Also, HARM positive patients were significantly older. HARM was not an independent predictor of worse clinical outcome, and we did not find an association with increase risk of haemorrhagic transformation. A higher dosage of Gadobutrol in acute stroke patients on initial MRI is associated with increased HARM incidence on follow-up. MRI studies on BBB should therefore standardize contrast agent dosages. (orig.)

Adrenal Insufficiency under Standard Dosage of Glucocorticoid Replacement after Unilateral Adrenalectomy for Cushing’s Syndrome

Directory of Open Access Journals (Sweden)

Kentaro Fujii

2016-01-01

Full Text Available Glucocorticoid replacement is needed for patients after adrenal surgery for Cushing’s syndrome; however, the adequate dosage is not easily determined. The patient was a 62-year-old woman who has had hypertension for 5 years and presented with heart failure due to hypertrophic cardiomyopathy. She consulted with us because of general fatigue, facial edema, and muscle weakness and was diagnosed with Cushing’s syndrome. A laparoscopic left adrenalectomy was performed, standard dosage of postoperative replacement was administered, and she was discharged with 30 mg/day of hydrocortisone (cortisol. However, she suffered from loss of appetite and was transferred to an emergency unit with the symptoms of adrenal insufficiency on postoperative day 15. After initial hydrocortisone replacement with 200 mg/day, the dosage was gradually decreased during hospitalization; however, reduction of hydrocortisone dosage lower than 60 mg/day was difficult because of nausea and fatigue. Her circadian cortisol profile after hydrocortisone administration showed delayed and lowered peaks, which suggested that hydrocortisone absorption in the intestine was impaired. Therefore, complicated heart failure may have led to the adrenal insufficiency in the patient. In such cases, we should consider postoperative administration of more than the standard dosage of hydrocortisone to avoid adrenal insufficiency after surgery for Cushing’s syndrome.

Dosage Parameters in Pediatric Outcome Studies Reported in 9 Peer-Reviewed Occupational Therapy Journals from 2008 to 2014: A Content Analysis

Science.gov (United States)

Gee, Bryan M.; Lloyd, Kimberly; Devine, Nancy; Tyrrell, Erin; Evans, Trisha; Hill, Rebekah; Dineen, Stacee; Magalogo, Kristin

2016-01-01

Occupational therapists determine the dosage when establishing the plan of care for their pediatric clients. A content analysis was conducted using 123 pediatric occupational therapy outcomes studies from 9 scholarly international occupational therapy journals. The parameters of dosage were calculated using descriptive statistics in order to obtain a representation of dosage available within the current collage of pediatric occupational therapy outcomes studies. The results revealed that most studies reported portions of dosage parameters within the published studies. The average findings for the subcomponents related to dosage were session length (minutes) M = 58.7, duration of plan of care (weeks) M = 12.1, session frequency (per week) M = 3.4, and total hours of therapy (hours) M = 18.1. This first attempt at describing and calculating dosage related to pediatric occupational therapy practice indicates that evidence is lacking within the published literature to adequately guide OT dosage decisions. Further research related to dosage in pediatric occupational therapy practice is needed. PMID:26949547

Self-Micro Emulsifying Drug Delivery Systems: a Strategy to Improve Oral Bioavailability

Directory of Open Access Journals (Sweden)

Vijay K. Sharma

Full Text Available Aim: Oral route has always been the favorite route of drug administration in many diseases and till today it is the first way investigated in the development of new dosage forms. The major problem in oral drug formulations is low and erratic bioavailability, which mainly results from poor aqueous solubility, thereby pose problems in their formulation. For the therapeutic delivery of lipophilic active moieties (BCS class II drugs, lipid based formulations are inviting increasing attention. Methods: To that aim, from the web sites of PubMed, HCAplus, Thomson, and Registry were used as the main sources to perform the search for the most significant research articles published on the subject. The information was then carefully analyzed, highlighting the most important results in the formulation and development of self-micro emulsifying drug delivery systems as well as its therapeutic activity. Results: Self-emulsifying drug delivery system (SMEDDS has gained more attention due to enhanced oral bio-availability enabling reduction in dose, more consistent temporal profiles of drug absorption, selective targeting of drug(s toward specific absorption window in GIT, and protection of drug(s from the unreceptive environment in gut. Conclusions: This article gives a complete overview of SMEDDS as a promising approach to effectively deal with the problem of poorly soluble molecules.

The characteristics of novel dosage forms

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Milić-Aškrabić Jela

2003-01-01

Full Text Available The objective of pharmaceutical-technological development is to find a procedure of transforming an active substance (a drug into a drug dosage form which is not only acceptable for application, but also enables the active substance to be released following administration, pursuant to therapy objectives. The aim is that the concentration of the active substance in the action location rapidly reaches a therapeutic level and maintains an approximately constant level in the course of a particular time, according to the established therapeutic goal. The primary objective is to present the active ingredient (drug in the form and concentration/quantity that enables the corresponding therapeutic response, i.e. to control the site and rate of medicinal substance release from the drug, as well as the rate at which it reaches the membranes and surfaces to which it is absorbed, while applying a common method of administration. The procedures used to achieve this goal are becoming highly complex and demanding and are aiming at sophisticated drug delivery systems and functional packaging material. Development from the existing drug molecule, through the conventional drug dosage form, to a new system of drug "delivery" (novel delivery system, can improve the drug (active substance characteristics significantly in view of compliance (acceptability by the patient, safety and efficiency. The paper presents an overview of the most important examples of pharmaceutical forms with controlled release and advanced drug "carriers".

Dosage of DTPA administration by inhalation

International Nuclear Information System (INIS)

Koizumi, Akira; Fukuda, Satoshi; Yamada, Yuji; Iida, Haruzo; Shimo, Michikuni

2000-01-01

The administration of DTPA by inhalation was examined as an emergency medical treatment. In order to estimate the practical dosage to the human, an accurate model of the human air way was connected to a anesthetizer and respiration was simulated. Ca-DTPA, aerosolized by an ultra-sonic nebulizer, was administered by inhalation to the model. For the experiments, the respiratory volume (tidal volume) and the respiration rate was 12 per minute. Irrigation water from the model of larynx and mouth, and the air filter were collected and measured by chelate titration in order to determine the quantity of aerosolized DTPA and the amount deposited on the trachea and lang. The results indicated that the quantity of aerosolized DTPA varied with dilution of the DTPA solution in a ample. It was found that a 3 time dilution was the most practical and that 73 mg of DTPA per minute could be aerosolized. Furthermore, the results indicated that 46% of the aerosolized DTPA was taken in through inhalation and that 26% of DTPA was deposited in the trachea and lung. These results suggest that in practical application in the emergency medical treatment, 15 minutes of inhalation could delivered to approximately 500 mg of DTPA, and 130 mg could be delivered to the trachea and lung. It is considered that these quantity are enough amount to increase the effects of radioactive nuclides from the body, comparing with the recommended dosage for injection administration. (author)

Dosage of strontium 90 in human bone ashes; Dosage du strontium 90 sans les cendres d'os humain

Energy Technology Data Exchange (ETDEWEB)

Patti, F; Jeanmaire, L [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

1964-07-01

The determination of {sup 90}Sr in bones by dosage of its daughter product {sup 90}Y is a 4-step process: 1) elimination of the phosphate ions by precipitation of the Ca and Sr as oxalate in the presence of acid; 2) reduction in the calcium concentration to a suitable level by the addition of a known volume of nitric acid (a single precipitation is sufficient), the precipitation yield of the strontium nitrate is checked by the measurement of the amount of {sup 85}Sr added as tracer; 3) purification by a yttrium hydroxide precipitation; 4) extraction at equilibrium of the {sup 90}Y which is counted to give the concentration. By using 50 gm of ash it is possible to detect about 0.1 pCi of {sup 90}Sr per gram of calcium. The advantages of this technique: -) treatment of a large quantity of bone ash -) the use of a small volume of nitric acid (less than 2 ml/g of ash, and -) the various operations present no difficulty. (authors) [French] Determination du Sr dans les os par dosage de son produit de filiation {sup 90}Y. Principe du dosage: 1 - Eliminer les ions phosphates par precipitation du calcium et du strontium sous forme d'oxalate en milieu acide. 2 - Reduire la concentration en calcium a un niveau convenable par addition d'un volume determine d'acide nitrique (une seule precipitation est necessaire). Le rendement de precipitation du nitrate de strontium est controle par la mesure de {sup 85}Sr ajoute comme traceur. 3 - Purifier par une precipitation d'hydroxyde d'yttrium. 4 - Extraire a l'equilibre l'{sup 90}Y qui eat compte pour determiner le {sup 90}Sr. En traitant 50 g de cendre, il est possible de deceler de l'ordre de 0,1 pCi de {sup 90}Sr par gramme de calcium. Les 3 avantages de cette technique: 1 - traitement d'une quantite importante de cendres d'os, 2 - emploi d'un faible volume d'acide nitrique (moins de 2 ml/g de cendres), et 3 - les diverses operations ne presentent aucune difficulte.

The impact of combined oral contraceptives on ocular tissues: a review of ocular effects

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Marilita M. Moschos

2017-10-01

Full Text Available The aim of this manuscript is to review the action and adverse effects of combined oral contraceptives (COCs on ocular tissues. The percentage of unwanted pregnancies and the subsequent abortions make contraception crucial worldwide. Over 100 million women around the world use common contraceptive methods, including intrauterine devices, combined estrogen and progestin oral contraceptives, as well as progestin only preparations (oral contraceptives, implants or injections. COCs are widely used for contraception, but they are also indicated in menorrhagia, endometriosis, acne and hirsutism, fibroid uterus and premenstrual syndrome. However, they have been associated with high rates of cardiovascular events, venous thromboembolic disease, ischemic strokes and breast cancer. The incidence of COCs-related ocular complications is estimated to be 1 in 230 000, including dry eye symptoms, corneal edema, lens opacities and retinal neuro-ophthalmologic or vascular complications. We may infer that the serious ocular complications of COCs can be prevented by eliminating the estrogen dosage and choosing third-generation progestins. In any case, doctors should take into consideration the systemic and ocular history of the patients before selecting any method of contraception.

Development and Evaluation of Liquid and Solid Self-Emulsifying Drug Delivery Systems for Atorvastatin

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Anna Czajkowska-Kośnik

2015-11-01

Full Text Available The objective of this work was to design and characterize liquid and solid self-emulsifying drug delivery systems (SEDDS for poorly soluble atorvastatin. To optimize the composition of liquid atorvastatin-SEDDS, solubility tests, pseudoternary phase diagrams, emulsification studies and other in vitro examinations (thermodynamic stability, droplet size and zeta potential analysis were performed. Due to the disadvantages of liquid SEDDS (few choices for dosage forms, low stability and portability during the manufacturing process, attempts were also made to obtain solid SEDDS. Solid SEDDS were successfully obtained using the spray drying technique from two optimized liquid formulations, CF3 and OF2. Despite liquid SEDDS formulation, CF3 was characterized by lower turbidity, higher percentage transmittance and better self-emulsifying properties, and based on the in vitro dissolution study it can be concluded that better solubilization properties were exhibited by solid formulation OF2. Overall, the studies demonstrated the possibility of formulating liquid and solid SEEDS as promising carriers of atorvastatin. SEDDS, with their unique solubilization properties, provide the opportunity to deliver lipophilic drugs to the gastrointestinal tract in a solubilized state, avoiding dissolution—a restricting factor in absorption rate of BCS Class 2 drugs, including atorvastatin.

Disposition Kinetics and Optimal Dosage of Ciprofloxacin in Healthy Domestic Ruminant Species

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Ijaz Javed

2009-01-01

Full Text Available The purpose of this experimental study was to determine the disposition kinetics and optimal dosages of ciprofloxacin in healthy domestic ruminant species including adult female buffalo, cow, sheep and goat. The drug was given as a single intramuscular dose of 5 mg/kg. The plasma concentrations of the drug were determined with HPLC and pharmacokinetic variables were determined. The biological half-life (t1/2 β was longer in cows (3.25 ± 0.46 h followed by intermediate values in buffaloes (3.05 ± 0.20 h and sheep (2.93 ± 0.45 h and shorter in goats (2.62 ± 0.39 h. The volume of distribution (Vd in buffaloes was 1.09 ± 0.06 l/kg, cows 1.24 ± 0.16 l/kg, sheep 2.89 ± 0.30 l/kg and goats 3.76 ± 0.92 l/kg. Total body clearance (ClB expressed in l/h/kg was minimum in buffaloes 0.25 ± 0.02 followed by values in cows 0.31 ± 0.02 and sheep 0.75 ± 0.04 and maximum in goats 1.09 ± 0.11. An optimal dosage regimen for 12-h interval consisted of 5.17, 5.62, 6.54 and 6.10 mg/kg body weight as priming and 4.84, 5.37, 6.26 and 5.91 mg/kg body weight as maintenance intramuscular dose in buffalo, cow, sheep and goat, respectively. The manufacturers of ciprofloxacin have claimed 5 mg/kg dose to be repeated after 24 h. However, the investigated dosage regimen may be repeated after 12 h to maintain MIC at the end of the dosage interval. Therefore, it is imperative that an optimal dosage regimen be based on the disposition kinetics data determined in the species and environment in which a drug is to be employed clinically.

Blood glucose and liver function in dogs administered a xylitol drinking water additive at zero, one and five times dosage rates

Directory of Open Access Journals (Sweden)

James M.G. Anthony

2011-05-01

Full Text Available A study was designed to determine the safety of a drinking water additive that reduces plaque and calculus in dogs, and contains xylitol as an active ingredient. The randomized, double-blind, placebo-controlled study was performed in 15 crossbred dogs that were randomly divided into three groups and had their drinking water treated for 14 days with either: i a commercial health care product (BreathaLyser Plus at the recommended dosage, ii an experimental health care product (BreathaLyser Plus containing five times the amount of xylitol, or iii a placebo of purified water with a colour additive. Results demonstrated that the continuous administration of a commercial, drinking water, oral health product containing xylitol, at one and five times the normal inclusion rate, does not cause hypoglycemia or alter liver function in dogs.

3D printing of a wearable personalized oral delivery device: A first-in-human study

Science.gov (United States)

Brambilla, Davide

2018-01-01

Despite the burgeoning interest in three-dimensional (3D) printing for the manufacture of customizable oral dosage formulations, a U.S. Food and Drug Administration–approved tablet notwithstanding, the full potential of 3D printing in pharmaceutical sciences has not been realized. In particular, 3D-printed drug-eluting devices offer the possibility for personalization in terms of shape, size, and architecture, but their clinical applications have remained relatively unexplored. We used 3D printing to manufacture a tailored oral drug delivery device with customizable design and tunable release rates in the form of a mouthguard and, subsequently, evaluated the performance of this system in the native setting in a first-in-human study. Our proof-of-concept work demonstrates the immense potential of 3D printing as a platform for the development and translation of next-generation drug delivery devices for personalized therapy. PMID:29750201

Solid Phospholipid Dispersions for Oral Delivery of Poorly Soluble Drugs

DEFF Research Database (Denmark)

Fong, Sophia Yui Kau; Martins, Susana A. M.; Brandl, Martin

2016-01-01

Celecoxib (CXB) is a Biopharmaceutical Classification System class II drug in which its oral bioavailability is limited by poor aqueous solubility. Although a range of formulations aiming to increase the solubility of CXB have been developed, it is not completely understood, whether (1) an increase...... the importance of evaluating both, solubility and permeability, and the use of biorelevant medium for testing the candidate-enabling performance of liposomal formulations. Mechanisms at molecular level that may explain the effect of PL formulations on the permeability of CXB are also discussed....

ACE-it: a tool for genome-wide integration of gene dosage and RNA expression data

NARCIS (Netherlands)

van Wieringen, W.N.; Belien, J.A.M.; Vosse, S.; Achame, E.M.; Ylstra, B.

2006-01-01

Summary: We describe a tool, called ACE-it (Array CGH Expression integration tool). ACE-it links the chromosomal position of the gene dosage measured by array CGH to the genes measured by the expression array. ACE-it uses this link to statistically test whether gene dosage affects RNA expression. ©

Thermodynamics of water-solid interactions in crystalline and amorphous pharmaceutical materials.

Science.gov (United States)

Sacchetti, Mark

2014-09-01

Pharmaceutical materials, crystalline and amorphous, sorb water from the atmosphere, which affects critical factors in the development of drugs, such as the selection of drug substance crystal form, compatibility with excipients, dosage form selection, packaging, and product shelf-life. It is common practice to quantify the amount of water that a material sorbs at a given relative humidity (RH), but the results alone provide minimal to no physicochemical insight into water-solid interactions, without which pharmaceutical scientists cannot develop an understanding of their materials, so as to anticipate and circumvent potential problems. This research was conducted to advance the science of pharmaceutical materials by examining the thermodynamics of solids with sorbed water. The compounds studied include nonhygroscopic drugs, a channel hydrate drug, a stoichiometric hydrate excipient, and an amorphous excipient. The water sorption isotherms were measured over a range of temperature to extract the partial molar enthalpy and entropy of sorbed water as well as the same quantities for some of the solids. It was found that water-solid interactions spanned a range of energy and entropy as a function of RH, which was unique to the solid, and which could be valuable in identifying batch-to-batch differences and effects of processing in material performance. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Gene dosage compensation calibrates four regulatory RNAs to control Vibrio cholerae quorum sensing

DEFF Research Database (Denmark)

Svenningsen, Sine L; Tu, Kimberly C; Bassler, Bonnie L

2009-01-01

the quorum regulatory RNAs 1-4 (Qrr1-4). The four Qrr sRNAs are functionally redundant. That is, expression of any one of them is sufficient for wild-type quorum-sensing behaviour. Here, we show that the combined action of two feedback loops, one involving the sRNA-activator LuxO and one involving the sRNA......Quorum sensing is a mechanism of cell-to-cell communication that allows bacteria to coordinately regulate gene expression in response to changes in cell-population density. At the core of the Vibrio cholerae quorum-sensing signal transduction pathway reside four homologous small RNAs (sRNAs), named......-target HapR, promotes gene dosage compensation between the four qrr genes. Gene dosage compensation adjusts the total Qrr1-4 sRNA pool and provides the molecular mechanism underlying sRNA redundancy. The dosage compensation mechanism is exquisitely sensitive to small perturbations in Qrr levels. Precisely...

Magnetic solid-phase extraction based on mesoporous silica-coated magnetic nanoparticles for analysis of oral antidiabetic drugs in human plasma

Energy Technology Data Exchange (ETDEWEB)

Souza, Karynne Cristina de; Andrade, Gracielle Ferreira [Centro de Desenvolvimento da Tecnologia Nuclear, CDTN/CNEN, Rua Professor Mário Werneck, s/n. Campus Universitário, Belo Horizonte, MG CEP 30.123-970 (Brazil); Vasconcelos, Ingrid; Oliveira Viana, Iara Maíra de; Fernandes, Christian [Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Martins Barros de Sousa, Edésia, E-mail: sousaem@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear, CDTN/CNEN, Rua Professor Mário Werneck, s/n. Campus Universitário, Belo Horizonte, MG CEP 30.123-970 (Brazil)

2014-07-01

In the present work, magnetic nanoparticles embedded into mesoporous silica were prepared in two steps: first, magnetite was synthesized by oxidation–precipitation method, and next, the magnetic nanoparticles were coated with mesoporous silica by using nonionic block copolymer surfactants as structure-directing agents. The mesoporous SiO{sub 2}-coated Fe{sub 3}O{sub 4} samples were functionalized using octadecyltrimethoxysilane as silanizing agent. The pure and functionalized silica nanoparticles were physicochemically and morphologically characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), N{sub 2} adsorption, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The resultant magnetic silica nanoparticles were applied as sorbents for magnetic solid-phase extraction (MSPE) of oral antidiabetic drugs in human plasma. Our results revealed that the magnetite nanoparticles were completely coated by well-ordered mesoporous silica with free pores and stable pore walls, and that the structural and magnetic properties of the Fe{sub 3}O{sub 4} nanoparticles were preserved in the applied synthesis route. Indeed, the sorbent material was capable of extracting the antidiabetic drugs from human plasma, being useful for the sample preparation in biological matrices. - Highlights: • SBA-15/Fe{sub 3}O{sub 4} was synthesized and functionalized with octadecyltrimethoxysilane. • Magnetite nanoparticles were completely coated by well-ordered mesoporous silica. • The samples were used as sorbent for magnetic solid-phase extraction (MSPE). • The sorbent material was capable of extracting drugs from human plasma. • The extraction ability makes the material a candidate to be employed as MSPE.

[The most effective dosage in the administration of PGF2-alpha for interruption of pregnancy during the 2d trimester].

Science.gov (United States)

Herczeg, J; Szontágh, F

1974-06-23

Artificial interruption of pregnancy contains too many risks from the 12th week of pregnancy. The authors have been working at finding the most suitable and effective dosage of prostaglandin for the interruption of pregnancy during the 2nd trimester. The new dosage experimented was 25 mg of prostaglandin F2alpha, followed by another 25 mg 6 hours later. The clinical efficiency of this dosage was tested. This procedures was used in 45 cases. The efficiency of the method was compared to the efficiency of the previously used dosage, which was 25 mg of prostaglandin F2alpha, followed by 25 mg 24 hours later. The new dosage was evaluated 91% efficient, while the previous dosage was found to be 75% efficient. The side effects were rated as acceptable by the patients. There was no case of infection. Two undeniable advantages were found with this new dosage: the duration of the actual procedure is considerably reduced, and the method appears to be much safer. The authors conclude that this new procedure offers numerous clinical advantages.

Study on image quality and dosage comparison of F/S system and DR system

International Nuclear Information System (INIS)

Kim, Sun Chil; Jung, Jae Eun

2003-01-01

Currently, many hospital are hastening to introduce digital radiography systems. This is a direct result of the intentions to improve medical services and to digitalized radiology information systems, and is also leading to the improvement of medical imaging technology. Throughout F/S system's long history, many people have researched the image quality and dosage concerning these systems, and as a result, huge improvements in the dosage of patients were possible. Similarly, I believe that DR systems need the same kind of effort. Of course, decreases in dosage that ignore image quality are unthinkable. The results of experiments conducted by five hospitals during a period of 3 months brought to us the conclusions listed below. Based on the comparison and analysis of the exposure control of F/S systems and DR systems, DR systems generally showed higher exposure control for parts of the phantom that became thicker, and the exposure control improved rapidly as the thickness increased. DR systems still proved to be somewhat deficient in resolution measurements compared to existing F/S systems. The image processing part of DR systems contributed much to these result. Under conditions used clinically, the dosage measurements of DR systems were generally higher regardless of region. According to the evaluation of image quality, DR systems showed a higher degree of satisfaction as the thickness of the region became thinner. As mentioned above and based on the mutual relationship experiments between the dosage and image quality of F/S systems and DR systems, research to increase the satisfaction of DR systems must be considered

Enzymatic lignocellulose hydrolysis: Improved cellulase productivity by insoluble solids recycling

Science.gov (United States)

2013-01-01

Background It is necessary to develop efficient methods to produce renewable fuels from lignocellulosic biomass. One of the main challenges to the industrialization of lignocellulose conversion processes is the large amount of cellulase enzymes used for the hydrolysis of cellulose. One method for decreasing the amount of enzyme used is to recycle the enzymes. In this study, the recycle of enzymes associated with the insoluble solid fraction after the enzymatic hydrolysis of cellulose was investigated for pretreated corn stover under a variety of recycling conditions. Results It was found that a significant amount of cellulase activity could be recovered by recycling the insoluble biomass fraction, and the enzyme dosage could be decreased by 30% to achieve the same glucose yields under the most favorable conditions. Enzyme productivity (g glucose produced/g enzyme applied) increased between 30 and 50% by the recycling, depending on the reaction conditions. While increasing the amount of solids recycled increased process performance, the methods applicability was limited by its positive correlation with increasing total solids concentrations, reaction volumes, and lignin content of the insoluble residue. However, increasing amounts of lignin rich residue during the recycle did not negatively impact glucose yields. Conclusions To take advantage of this effect, the amount of solids recycled should be maximized, based on a given processes ability to deal with higher solids concentrations and volumes. Recycling of enzymes by recycling the insoluble solids fraction was thus shown to be an effective method to decrease enzyme usage, and research should be continued for its industrial application. PMID:23336604

Enzymatic lignocellulose hydrolysis: Improved cellulase productivity by insoluble solids recycling

Directory of Open Access Journals (Sweden)

Weiss Noah

2013-01-01

Full Text Available Abstract Background It is necessary to develop efficient methods to produce renewable fuels from lignocellulosic biomass. One of the main challenges to the industrialization of lignocellulose conversion processes is the large amount of cellulase enzymes used for the hydrolysis of cellulose. One method for decreasing the amount of enzyme used is to recycle the enzymes. In this study, the recycle of enzymes associated with the insoluble solid fraction after the enzymatic hydrolysis of cellulose was investigated for pretreated corn stover under a variety of recycling conditions. Results It was found that a significant amount of cellulase activity could be recovered by recycling the insoluble biomass fraction, and the enzyme dosage could be decreased by 30% to achieve the same glucose yields under the most favorable conditions. Enzyme productivity (g glucose produced/g enzyme applied increased between 30 and 50% by the recycling, depending on the reaction conditions. While increasing the amount of solids recycled increased process performance, the methods applicability was limited by its positive correlation with increasing total solids concentrations, reaction volumes, and lignin content of the insoluble residue. However, increasing amounts of lignin rich residue during the recycle did not negatively impact glucose yields. Conclusions To take advantage of this effect, the amount of solids recycled should be maximized, based on a given processes ability to deal with higher solids concentrations and volumes. Recycling of enzymes by recycling the insoluble solids fraction was thus shown to be an effective method to decrease enzyme usage, and research should be continued for its industrial application.

Gonadal dosage during hip dysplasia radiography in the dog.

Science.gov (United States)

Wood, A K; Reynolds, K M; Leith, I S; Burns, P A

1977-01-01

Thermoluminescent dosemeters were used to estimate gonadal dosage during hip dysplasia radiography of labrador retriever dogs. The mean radiation dose to the unshielded testes was 100 millirad (mrad) and the estimated dose to the shielded testes was 9 mrad. It was considered unnecessary to shield the ovaries.

Comparative pharmacokinetics of oxytetracycline in blunt-snout bream (Megalobrama amblycephala) with single and multiple-dose oral administration.

Science.gov (United States)

Li, Ru-Qin; Ren, Yu-Wei; Li, Jing; Huang, Can; Shao, Jun-Hui; Chen, Xiao-Xuan; Wu, Zhi-Xin

2015-06-01

Research into the pharmacokinetics and residue elimination of oxytetracycline (OTC) is important both to determine the optimal dosage regimens and to establish a safe withdrawal time in fish. A depletion study is presented here for OTC in Megalobrama amblycephala with a single-dose (100 mg/kg) and multiple-dose (100 mg/kg for five consecutive days) oral administration. The study was conducted at 25 °C. As a result, a one-compartment model was developed. For the single dose, the absorption half-life was 5.79, 9.40, 6.96, and 8.06 h in the plasma, liver, kidney, and muscle, respectively. However, the absorption half-life was 3.62, 7.33, 4.59, and 6.02 h with multiple-dose oral administration. The elimination half-time in the plasma, liver, kidney, and muscle was 58.63, 126.43, 65.1, and 58.85 h when M. amblycephala was treated with a single dose. However, the elimination half-time changed to 91.75, 214.87, 126.22, and 135.84 h with multiple-dose oral administration.

Gamma ray dosage and mutation breeding in St. Augustinegrass

International Nuclear Information System (INIS)

Busey, P.

1980-01-01

Stolon pieces of St. Augustinegrass [Stenotaphrum secundatum (Walt.) Kuntze] were irradiated with gamma rays in an attempt to cause mutations. A practical dosage for most genotypes was 4,500 rads. This dosage caused considerable (50%) growth retardation and a mean survival of about 40% of single-node cuttings. However, Bitterblue and another accession were entirely killed at 4,000 rads. At 4,500 rads, up to 7% recognizable mutants of accession FA-243 were obtained. This proportion resulted when irradiated cuttings were propagated clonally and observed for 1.5 years in replicated microplots. In addition to morphological variants, a chimeral anthocyanin change was noticed. From this chimera arose a stable genotype with green stolons and white stigmas, whereas the source genotype (FA-243) had red stolons and purple stigmas. Associated reduction in fertility from 56 to 0.6% suggested that the mutation arose as a small chromosome deletion. Mutation breeding is effective in improving St. Augustinegrass when easily recognizable variants are needed

Absorption of macronutrients by cassava in different harvest dates and dosages of nitrogen

Directory of Open Access Journals (Sweden)

Nádia Souza dos Santos

Full Text Available A field experiment was carried out in 2010-2011 crop years in the experimental area of the Centro de Ciências Agrárias of the Universidade Federal de Roraima, in Boa Vista, Roraima, Brazil. This study aimed to evaluate the effect of nitrogen availability on the concentrations of N, P, K, Ca, Mg and S in cassava, cultivar Aciolina, in different harvest times. A randomized block design was used in split-plot, with four replications. Dosages of N in cover were applied randomly on the plots (0, 30, 60, 150 and 330 kg ha-1, and in the subplot the harvest dates 120, 150, 180, 210, 240, 270 and 300 days after emergence (DAE. The vegetal material was collected, ground and then underwent an analysis for determination of nutrients concentrations in the leaves (N, P, K, Ca Mg and S. The harvest dates and dosages of N affect the nutrient concentrations in the cassava leaves, cv. Aciolina. The macronutrients dosage in the leaves, 120 DAE, is a good indicator of the nutritional status of the cassava plant. The dosage of 150 kg ha-1 of N raises the tubers roots per plant. The sequence of the macronutrients concentration in the leaves of the cassava, cv. Aciolina is N>Ca>K>Mg>P>S.

Pharmaceutical cocrystals: a novel approach for oral bioavailability enhancement of drugs.

Science.gov (United States)

Chadha, Renu; Saini, Anupam; Arora, Poonam; Bhandari, Swati

2012-01-01

Solid dosage forms are by far the preferred drug delivery systems. However, these often face the problem of poor and erratic bioavailability during the drug development process. Numerous formulation strategies for drug delivery are currently under development, among which the solid forms such as polymorphs, solvates, salts, and cocrystals have been considered to be the most important for improving dissolution rate and bioavailability. Cocrystallization is a fairly new approach in pharmaceutical industry that can improve the solubility and, consequently, the bioactivity of the active pharmaceutical ingredient (API) without compromising its structural integrity. Pharmaceutical cocrystals have found their place in drug delivery, primarily due to their ability to produce alternative, viable solid forms when a more standard approach of salt and polymorph formation fails to deliver the desired objectives. Over the past few years, a number of papers have been published focusing on a broad range of subjects, from traditional crystal engineering to structure-property relationships of cocrystals. The present review, however, illustrates how the cocrystalline forms of APIs have improved their in vitro dissolution rate and in vivo bioavailability, often correlating well with their improved solubility as well.

Kinetics of Enzymatic High-Solid Hydrolysis of Lignocellulosic Biomass Studied by Calorimetry

DEFF Research Database (Denmark)

Olsen, Søren Nymand; Rasmussen, Erik Lumby; McFarland, K.C.

2011-01-01

analysis of the interrelationships of enzyme load and the rate, time, and extent of the reaction. The results suggest that the hydrolysis rate of pretreated corn stover is limited initially by available attack points on the substrate surface (conversion) but becomes proportional to enzyme dosage......Enzymatic hydrolysis of high-solid biomass (>10% w/w dry mass) has become increasingly important as a key step in the production of second-generation bioethanol. To this end, development of quantitative real-time assays is desirable both for empirical optimization and for detailed kinetic analysis...... rate with a detection limit of about 500 pmol glucose s−1. Hence, calorimetry is shown to be a highly sensitive real-time method, applicable for high solids, and independent on the complexity of the substrate. Dose–response experiments with a typical cellulase cocktail enabled a multidimensional...

Characterisation of lung tumour under dosage for interpretation of clinical trial data

International Nuclear Information System (INIS)

Taylor, M.L.; Dunn, L.; Franich, R.D.; Kron, T.; Height, F.

2010-01-01

Full text: It is well known that the periphery of lung tumours is under-dosed in radiotherapy as a result of electronic disequilibrium at the interface of lung and tumour tissue. Clinical trials often employ dose calculation algorithms which poorly approximate the dose to peripheral regions of tumour volumes. The aim of this study was to develop a set of systematic under-dosage estimates corresponding to various clinical parameters. High resolution Monte Carlo radiation transport calculations were undertaken for a systematic set of generic lung tumours irradiated with an external photon beam. Varied parameters include beam energy, field size, tumour size and distance to chest wall. Calculations were undertaken using both EGSnrc and GEAI T4. A 'Dose Reduction Factor' is defined which describes the dose to the peripheral 'shell' 01 the tumour, as relevant for multiple-field and arc therapy. For a 6 MV beam, under-dosage is typically between 2 and 5% for the different arrangements investigated, and for a 15 MV beam it is between 5 and 8% (relative to the central dose). Good agreement between EGSnrc and GEANT4 was demonstrated. Comparisons with pencil beam convolution calculations indicate that the treatment planning system does not identify this under-dosage. A systematic set of data has been obtained that characterises the extent of peripheral under-dosage in lung tumours for the retrospective evaluation of clinical trial data. The data presented i: also informative for clinics using less sophisticated planning algorithms, particularly when dose is being prescribed to covering isodoses. (author)

Formulation and evaluation of tablet dosage form of Hunteria ...