Dissolution Study of Active Pharmaceutical Ingredients Using the Flow Through Apparatus Usp 4

Introduction Dissolution is a critical parameter of pharmaceutical dosage forms. It is well recognized that in vitro dissolution testing,whether in development or in circulation, is relied upon to screen formulations during development and to ensure batch-to-batch quality control. In the USA and in Europe,more than 30 years of research have been devoted to characterizing the biopharmaceutical properties of drug products. Several guidelines have been published and all pharmacopoeias include a description of dissolution testing (1,2,3,4). During drug development, in vitro dissolution testing is an important tool in the evaluation of the best formulation and also in the understanding of possible risks related to specific gastrointestinal environment,dose dumping,food effects on bioavailability and interaction with other drugs. Today, dissolution studies are the most frequently used tools in the development,characterization and utilization processes of controlled release formulations. Dissolution is the process by which a solid solute with relatively low solubility enters into a solution in the presence of solvent (5). Dissolution rate may be defined as the amount of active ingredient in a solid dosage form dissolved in unit time under standardized conditions of liquid/solid interface,temperature,and media composition. A discriminative dissolution method has to be developed to exhibit different results when the manufacture or composition of a product changes.The dissolution method should be sensitive to variations that can have an impact on the in vivo performance of the dosage form. Among the different variations such as process,equipment,or materials,the characterization of the active pharmaceutical ingredient (API) is of prime importance.The crystal form of the API,its particle size distribution and its surface area are critical. Examining the dissolution rate can help consolidate this valuable information. Among the different in vitro systems available for API testing,the flow through system (USP Method 4) offers the best characteristics. It has been employed for many years in the testing of different dosage forms such as tablets and capsules. It is the method of choice for extended release and poorly soluble products. Using the specific powder cell, it is possible to characterize a drug substance with respect to its rate of dissolution. The aim of this work was to compare and characterize the biopharmaceutical properties of different batches of pharAbstract The flow through system has been employed for many years in the testing of different dosage forms such as tablets and capsules. The flow through cell is the method of choice for extended release and poorly soluble products. Thanks to the specific powder cell it is possible to characterize a drug substance with respect to its rate of dissolution. The aim of this work was to compare the biopharmaceutical properties of different batches of a drug substance using the dissolution rate determined using the flow through apparatus. The apparatus consists of a reservoir of dissolution medium,a pump that forces the dissolution medium upwards through the flow through cell and a cell specifically designed for powders,mounted vertically with a filter system preventing escape of undissolved particles. In the flow through method the test sample is located in a small-volume cell through which solvent passes at a temperature of 37 °C. Five batches of theophylline with a mean diameter of 128 μm to 673 μm and two batches of acetylsalicylic acid,either fine particles or needles,were studied. The experiment was conducted using six cells in an open system. Through the results obtained,the relationship between particle size distribution and dissolution rate has been verified. The rate of dissolution is faster for drug with low particle size and a higher surface area. The experimental parameters such as flow rate have been studied and optimized. The overall results demonstrate that it is possible to characterize the biopharmaceutical qualities of active pharmaceutical ingredients using the flow through cell. The method is reliable,reproducible and discriminating. It can easily be used to compare drugs with different particle size distributions.