Search results for "excipients"
showing 10 items of 56 documents
Biowaiver monograph for immediate-release solid oral dosage forms: fluconazole.
2014
Literature data pertaining to the decision to allow a waiver of in vivo bioequivalence (BE) testing requirements for the approval of immediate release (IR) solid oral dosage forms containing fluconazole as the only active pharmaceutical ingredient (API) are reviewed. The decision is based on solubility, dissolution, permeability, therapeutic index, pharmacokinetic parameters, pharmacodynamic properties, and other relevant data. BE/bioavailability (BA) problems and drug-excipients interaction data were also reviewed and taken into consideration. According to the biopharmaceutics classification system (BCS), fluconazole in polymorphic forms II and III is a BCS class I drug and has a wide ther…
Biowaiver Monographs for Immediate-Release Solid Oral Dosage Forms: Nifedipine
2015
Literature data relevant to the biopharmaceutical properties of the active pharmaceutical ingredient (API) nifedipine are reviewed to evaluate whether a waiver of in vivo bioequivalence (BE) testing of immediate-release (IR) dosage forms formulated as tablets and soft gelatin capsules is warranted. Nifedipine's solubility and permeability, its therapeutic use and index, pharmacokinetics, food drug interactions, and any reported BE/bioavailability problems were all taken into consideration. Solubility and BA data indicate conclusively that nifedipine is a class II substance of biopharmaceutics classification system (BCS) and that the formulation of drug product plays a key role on the dissol…
Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Metformin Hydrochloride.
2021
Abstract Data are examined regarding possible waiver of in vivo bioequivalence testing (i.e. biowaiver) for approval of metformin hydrochloride (metformin) immediate-release solid oral dosage forms. Data include metformin's Biopharmaceutics Classification System (BCS) properties, including potential excipient interactions. Metformin is a prototypical transporter-mediated drug and is highly soluble, but only 50% of an orally administered dose is absorbed from the gut. Therefore, metformin is a BCS Class III substance. A BCS-based approval approach for major changes to marketed products and new generics is admissible if test and reference dosage forms have the identical active pharmaceutical …
Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Carbamazepine.
2020
Abstract Literature relevant to assessing whether BCS-based biowaivers can be applied to immediate release (IR) solid oral dosage forms containing carbamazepine as the single active pharmaceutical ingredient are reviewed. Carbamazepine, which is used for the prophylactic therapy of epilepsy, is a non-ionizable drug that cannot be considered “highly soluble” across the range of pH values usually encountered in the upper gastrointestinal tract. Furthermore, evidence in the open literature suggests that carbamazepine is a BCS Class 2 drug. Nevertheless, the oral absolute bioavailability of carbamazepine lies between 70 and 78% and both in vivo and in vitro data support the classification of ca…
Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Cephalexin Monohydrate.
2019
Literature data and results of experimental studies relevant to the decision to allow waiver of bioequivalence studies in humans for the approval of immediate release solid oral dosage forms containing cephalexin monohydrate are presented. Solubility studies were performed in accordance with the current biowaiver guidelines of the Food and Drug Administration, World Health Organization and European Medicines Agency, taking the degradation at some pH values into consideration. Together with solubility and permeability data for cephalexin monohydrate from the literature, it was demonstrated to be a Biopharmaceutics Classification System Class 1 drug. The pharmacokinetic behavior, results of b…
Etenzamīda kokristāli ar karbonskābēm: saderības ar palīgvielām noteikšana
2017
Darbā noteikta etenzamīda–fumārskābes un etenzamīda–4-hidroksibenzoskābes kokristālu saderība ar dažādām palīgvielām. Kokristālu saderība ar palīgvielām tika noteikta, izmantojot diferenciālās skenējošās kalorimetrijas, pulvera rentgendifraktometrijas un Furjē transformācijas infrasarkanās spektrometrijas analīzes metodes.
Effects of different cellulose derivatives on drug release mechanism studied at a preformulation stage
2003
As a matter of fact, in vitro dissolution is well known to be the method of choice for the pharmaceutical industry to develop effective medicines. However, many experiments must be performed all along a new product life and they represent an overcharge of work for researchers. The purpose of this paper was to assess the relevance of new parameters obtained during preformulation stage by Nuclear Magnetic Resonance (NMR) experiments to better understand drug release mechanism. This study was carried out with three cellulose derivatives currently used as carrier matrices (Microcrystalline cellulose (MCC), Hydroxypropylmethyl cellulose (HPMC) and Ethyl cellulose (EC)). Granules and tablets were…
Dissolution and dissolution/permeation experiments for predicting systemic exposure following oral administration of the BCS class II drug clarithrom…
2017
In order to save time and resources in early drug development, in vitro methods that correctly predict the formulation effect on oral drug absorption are necessary. The aim of this study was to 1) evaluate various BCS class II drug formulations with in vitro methods and in vivo in order to 2) determine which in vitro method best correlates with the in vivo results. Clarithromycin served as model compound in formulations with different particle sizes and content of excipients. The performed in vitro experiments were dissolution and dissolution/permeation experiments across two types of membrane, Caco-2 cells and excised rat intestinal sheets. The in vivo study was performed in rats. The oral…
Buccal Delivery of Methimazole as an Alternative Means for Improvement of Drug Bioavailability: Permeation Studies and Matrix System Design
2012
The aim of this study was to investigate the potential for systemic administration of Methimazole (MMI) through the buccal mucosa as an alternative route for drug delivery. Considering that the most important restriction in buccal drug delivery could be the low permeability of the mucosa, the ability of MMI to cross the mucosal barrier was assessed. Permeation of MMI through porcine buccal mucosa was investigated ex vivo using Franz type diffusion cells, buffer solution simulating saliva or natural human saliva as donor phase. The collected data suggested that buccal mucosa does not hinder MMI diffusion and the drug crosses the membrane (J(s) = 0.068 mg cm(-2) h(-1) and K(p) = 0.065 cm h(-1…
The effects of three absorption-modifying critical excipients on the in vivo intestinal absorption of six model compounds in rats and dogs.
2018
Pharmaceutical excipients that may affect gastrointestinal (GI) drug absorption are called critical pharmaceutical excipients, or absorption-modifying excipients (AMEs) if they act by altering the integrity of the intestinal epithelial cell membrane. Some of these excipients increase intestinal permeability, and subsequently the absorption and bioavailability of the drug. This could have implications for both the assessment of bioequivalence and the efficacy of the absorption-enhancing drug delivery system. The absorption-enhancing effects of AMEs with different mechanisms (chitosan, sodium caprate, sodium dodecyl sulfate (SDS)) have previously been evaluated in the rat single-pass intestin…