Abstract:
:The dependency of metformin in vivo disposition on the rate and extent of dissolution was studied. The analysis includes the use of fundamental principles of drug input, permeability, and intestinal transit time within the framework of a compartmental absorption transit model to predict key pharmacokinetic (PK) parameters and then compare the results to clinical data. The simulations show that the maximum plasma concentration (C(max) ) and area under the curve (AUC) are not significantly affected when 100% of drug is released within 2 h of oral dosing, which was confirmed with corresponding human PK data. Furthermore, in vitro dissolution profiles measured in aqueous buffers at pH values of 1.2, 4.5, and 6.8 were slower than in vivo release profiles generated by deconvolution of metformin products that were bioequivalent. On the basis of this work, formulations of metformin that release 100% in vitro in a time period equal to or less than two hours are indicated to be bioequivalent. The use of modeling offers a mechanistic-based approach for demonstrating acceptable bioperformance for metformin formulations without having to resort to in vivo bioequivalence studies and may be more robust than statistical comparison of in vitro release profiles. This work further provides a strategy for considering Biopharmaceutics Classification System (BCS) Class 3 compounds to be included under biowaiver guidelines as for BCS Class 1 compounds.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Crison JR,Timmins P,Keung A,Upreti VV,Boulton DW,Scheer BJdoi
10.1002/jps.23063subject
Has Abstractpub_date
2012-05-01 00:00:00pages
1773-82issue
5eissn
0022-3549issn
1520-6017pii
S0022-3549(15)31604-Xjournal_volume
101pub_type
杂志文章abstract::Responses from the second Product Quality Research Institute (PQRI) Blend Uniformity Working Group (BUWG) survey of industry have been reanalyzed to identify potential links between formulation and processing variables and the measured uniformity of blends and unit dosage forms. As expected, the variability of the ble...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1002/jps.23426
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abstract::The effect of the oral dosing volume (DV) on both gastric emptying and intestinal absorption was examined by analyzing the gastrointestinal disposition of a model solute, L-glucose, in rats. The amount of 14C-labeled L-glucose in the gastric and intestinal contents of sacrificed rats was measured at various times afte...
journal_title:Journal of pharmaceutical sciences
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doi:10.1002/jps.2600840417
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abstract::Drug transporters expressed in liver and kidney play a critical role in the elimination of a wide range of drugs and xenobiotics and inhibition of these transporters may therefore cause clinically significant drug-drug interactions (DDIs). Currently, in vitro transporter inhibition data are used to assess the risk tha...
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abstract::The interaction of cyclosporin A (CsA) with dimethyl-alpha- and -beta-cyclodextrins (DM-alpha-CyD and DM-beta-CyD) was investigated by the solubility method, electrospray ionization mass spectrometry (ESI-MS) and 1H-nuclear magnetic resonance spectroscopy (1H NMR). The extremely low solubility (1.9 x 10(-5) M at 25 de...
journal_title:Journal of pharmaceutical sciences
pub_type: 杂志文章
doi:10.1021/js980284+
更新日期:1999-01-01 00:00:00
abstract::Protein higher order structure (HOS) is an essential quality attribute to ensure protein stability and proper biological function. Protein HOS characterization is performed during comparability assessments for product consistency as well as during forced degradation studies for structural alteration upon stress. Circu...
journal_title:Journal of pharmaceutical sciences
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abstract::A simple and sensitive method is reported for the quantitative determination of the bronchodilator tulobuterol in human serum. Tulobuterol and an internal standard were extracted from alkalinized serum with ether and then back-extracted into dilute hydrochloric acid. After alkalinization and extraction of the aqueous ...
journal_title:Journal of pharmaceutical sciences
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doi:10.1002/jps.2600720526
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abstract::4-Fluoroisoleucine was produced by ammonolysis of 2-bromo-4-fluoro-3-methylpentanoic acid, which resulted from the bromofluorination of 4-methyl-2-pentenoic acid. It did not inhibit Plasmodium berghei in mice at 640 mg/kg and was not toxic to the animals. The fluoroamino acid inhibited Aspergillus niger, Trichoderma v...
journal_title:Journal of pharmaceutical sciences
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abstract::Systemic administration of drugs is ineffective in the treatment of central nervous system disorders because of the blood-brain barrier. Nasal administration has been suggested as an alternative administration route as drugs absorbed in the olfactory epithelium bypass the blood-brain barrier and reach the brain within...
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journal_title:Journal of pharmaceutical sciences
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abstract::Single-dose oral administration of a commercial polychlorinated biphenyl product containing 54% chlorine provided data with which to plot the time course of total polychlorinated biphenyl and individual components in the blood of swine and sheep. Pharmacokinetic parameters describing absorption from the gut and elimin...
journal_title:Journal of pharmaceutical sciences
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abstract::Three novel series of 4-oxoquinazoline derivatives were prepared and evaluated as potential antimicrobial agents. Evaluation of the antimicrobial activity of a variety of 4-substituted-1-thiosemicarbazides, 3,4-disubstituted thiazolines, and 3-substituted-5-thiazolidones reveals that the majority possess significant i...
journal_title:Journal of pharmaceutical sciences
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abstract::The silicon phthalocyanine Pc 4 is a second-generation photosensitizer that has several properties superior to other photosensitizers currently approved by the FDA, and it has shown significant promise for photodynamic therapy (PDT) in several cancer cells in vitro and model tumor systems in vivo. However, because of ...
journal_title:Journal of pharmaceutical sciences
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journal_title:Journal of pharmaceutical sciences
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abstract::The influences of 1-ethyl-, 1-butyl-, 1-hexyl-, and 1-octyl-2-pyrrolidone in their saline solutions on the transport of beta-estradiol, corticosterone, and hydrocortisone across hairless mouse skin under in vitro conditions have been investigated by the physical model approach. The experimental data were interpreted w...
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journal_title:Journal of pharmaceutical sciences
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abstract::The conditions of sorption of penicillins and cephalosporins on nonionic macroporous copolymers of styrenedivinylbenzene were evaluated. By increasing the methanol concentration in the eluent, the sorption decreased. Salts exerted little influence on sorption. However, pH exerted a remarkable effect on sorption, and t...
journal_title:Journal of pharmaceutical sciences
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journal_title:Journal of pharmaceutical sciences
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journal_title:Journal of pharmaceutical sciences
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abstract::In this study, we attempted to improve the oral absorption of ceftriaxone (CTX) by using an absorption carrier and the CTX complex together. After the CTX-Ca-carrageenan gel complex was prepared, several kinds of compounds (Capmul MCM C10, Gelucire 44/14, glycyrrhizin) were screened as potential oral enhancers for our...
journal_title:Journal of pharmaceutical sciences
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