Limitations of Some Commonly Described Practices in Drug Dissolution Testing and Suggestions to Address These

摘要

Dissolution tests are employed to establish the quality of drug products, mostly tablets and capsules, based on in vitro drug release characteristics of these products. In reality, a dissolution test may be considered as a simple extraction step in a vessel with a stirrer. Most of the commonly used apparatuses in this regard are known as paddle and basket apparatuses, in which a round bottom vessel (1 L) containing a stirrer referred to as paddle (an inverted T-shaped bar) or small wired cage (known as basket), respectively, are used. These apparatuses are very well recognized and used around the world with the acceptance of regulatory and standard setting organizations. Detailed descriptions about these apparatuses may be found in any of the most commonly followed pharmacopeias such as United States Pharmacopeia (USP) [1].As noted above, drug dissolution testing is a relatively simple technique, however, serious concerns and problems are often reported in the literature about it [2-5]. These reported problems often relate to: (1) failing of the performance evaluations of the apparatuses (calibration) and/or products; (2) lack of establishing the link between in vitro dissolution results and in vivo results, commonly referred to as in vitro-in vivo correlations or IVIVC; (3) lack of objectivity in setting or selecting experimental conditions for product evaluations (4) setting unreasonably wide tolerances based on complex and convoluted rationales. These wide spread concerns result in frustrations, within both regulatory and manufacturing environments, where objectivity and reliability of an analytical technique is of critical importance for establishing the standards for the assessment of quality of the drug products.