Experiences with USP Apparatus 4 Calibration

Abstract

Introduction This paper is a summary of results presented for the system suitability test of the flow through cell apparatus presented at a series of conferences starting with FIP’s Dissolution Workshop in Frankfurt, Germany, November 14, 1996, in particular the contribution “Collaborative Studies on Calibration—”The Flow-Through Cell”; J.Kramer, E. Wirbitzki. Under the chairmanship of Martin Siewert the “Dissolution Working Group”of FIP,now called “FIP Working Group 4”, performed two collaborative studies examining the use of USP Calibrator Tablets for apparatus suitability testing of USP Apparatus 4. Two basic principles are applied for in vitro dissolution testing:the “stirred beaker”methods and the “flow through” procedures. The “stirred beaker”methods place the dosage unit in a fixed volume in a vessel and the stirring provides mechanical agitation. The rotating basket and the paddle devices (Apparatus 1 and 2 of the USP) are simple,robust and adequately standardized. Another advantage of these two devices is that they can be easily automated,which is important for routine investigations. Therefore,the use of these devices is recommended in various guidelines as the first choice for the in vitro dissolution testing of immediate release dosage forms. Nevertheless,some difficulties may arise when a pH change/media change during investigation is desired,or when poorly soluble drugs are to be investigated. Furthermore,the hydrodynamics in the paddle apparatus are very complex and vary with site of the dosage form in the vessel. These variations may significantly affect the drug dissolution,should the dosage form position in the vessel vary due to sticking or floating. Another system is the reciprocating cylinder device (Apparatus type 3 of USP), the design of which is based on the disintegration tester as an alternative to the basket and paddle apparatus. Finally; with the “flow through cell” apparatus (Apparatus type 4 of the USP) the dosage unit is continuously flushed with a stream of fluid, simultaneously providing the medium and the mechanical agitation to facilitate dissolution of the drug. The flow through cell apparatus is designed for the dissolution testing of poorly soluble drug products, powders, granules and some special dosage forms such as lipidbased suppositories or implants. All of these dissolution devices are described in the Pharmacopeias, including the USP and the European, British, International,and Japanese Pharmacopeia. In order to obtain meaningful dissolution data and to yield reproducible