An Investigation into the Importance of “Very Rapid Dissolution” Criteria for Drug Bioequivalence Demonstration using Gastrointestinal Simulation Technology
Journal Title: The AAPS Journal - Year 2009, Vol 11, Issue 2
Abstract
The Biopharmaceutics Classification System (BCS) is based on the mechanistic assumptions that the rate and extent of oral drug absorption are governed by drug solubility, intestinal permeability, and dissolution rate from the dosage form administered. One of the goals of BCS is to identify classes of drugs for which bioequivalence may be established based solely on the in vitro dissolution data, i.e., which would be eligible for biowaiver. On the basis of BCS, currently, the biowaiver concept is adopted and recommended for immediate release of drug products containing highly soluble and highly permeable compounds (BCS class 1 drugs). Dissolution testing properties are proposed to be more stringent: very rapid dissolution is demanded when generic drug application is submitted with the exemption of in vivo bioequivalence study. In the present paper, Gastrointestinal Simulation Technology has been applied in order to evaluate the potential for different in vitro drug dissolution kinetics to influence dosage forms in vivo behavior and the relevance of “very rapid dissolution” criteria to be met (i.e., more than 85% of dose dissolved in 15 min).
Authors and Affiliations
Ivan Kovačevi, Jelena Parojči, Marija Tubi-Grozdanis, Peter Langguth
Keywords
Related Articles
- EP ID EP681470
- DOI 10.1208/s12248-009-9114-3
- Views 91
- Downloads 0
Glycylsarcosine uptake in rabbit renal brush border membrane vesicles isolated from outer cortex or outer medulla: Evidence for heterogeneous distribution of oligopeptide transporters
Studies were initially performed in rabbit brush border membrane vesicles (BBMV) prepared from whole cortex plus outer medulla. In these studies using combined tissues, two distinct peptide/H+ transport systems were foun...
Critical Variables Associated with Nonbiodegradable Osmotically Controlled Implants
Osmotically controlled implants yield precise zero-order drug delivery kinetics and are utilized in a number of applications. The implants deliver drugs for extended periods (weeks to years) and exhibit good in vivo/in v...
Effect of Ethanol on Opioid Drug Permeability Through Caco-2 Cell Monolayers
Ethanol significantly increased the permeability of oxycodone, oxymorphone and atenolol in a concentration-dependent (1–5%) manner. The permeability of hydromorphone and metoprolol were not altered by ethanol. Th...
Comparative Performance of Cell Life Span and Cell Transit Models for Describing Erythropoietic Drug Effects
The online version of this article (doi:10.1208/s12248-011-9302-9) contains supplementary material, which is available to authorized users.
Biodegradable intraprostatic doxorubicin implants
Systemic chemotherapy is not effective in the treatment of prostate-confined cancer. We developed biodegradable, doxorubicin-loaded cylinders for intraprostatic implantation and evaluated the feasibility of using regiona...