Case Study IV: Enteric Coated Sustained Release Pellets in Hard Gelatin Capsules
IriSys was requested to expeditiously and aggressively develop for the U.S. market a product that had been tested outside the U.S. The compound had been originally formulated using spray-coated pellets encapsulated in hard gelatin capsules. The critical performance characteristics were determined by two separate in-vitro dissolution tests. One test was performed in a pH 1.2 dissolution medium, the other in a pH 6.8 dissolution medium. Protection from drug release at pH 1.2 and a specific controlled release profile at pH 6.8 were the targets. Development included transfer of the formulation and manufacturing process and duplication of the in vitro release profile of the original drug product. IriSys was among several contractors who were considered for the development program, IriSys was selected because of the ability to meet the aggressive timeline. IriSys conducted a development program to determine the feasibility of transferring the manufacturing process with the goal of enabling the generation of approximately 5 kg of clinical trial materials for a Phase 2A human clinical study. Two different equipment configurations were used in the program. First, preliminary development lots were produced using a Glatt fluid bed system to determine minimally acceptable processing conditions and maximum batch size. Then, a coating pan was used to produce development lots which after evaluation met dissolution requirements. Clinical trial materials were subsequently manufactured. Stability study testing demonstrated that the clinical trial materials were as stable as the original drug product. The aggressive timeline was met to reproduce a formulation and manufacturing process that required ingenuity and experience.
