A Comparison of Dissolution Testing on Lipid Soft Gelatin Capsules Using USP Apparatus 2 and Apparatus 4

Introduction Soft gelatin capsule (SGC) formulations are becoming more popular in recent years (1,2). These formulations can mask odors and unpleasant tastes,and are easy to swallow. They are suitable for encapsulation of lipid solutions,suspensions,or paste-like formulations,making them a useful option when formulating poorly water-soluble drugs. Due to the unique properties of SGC formulations,there exist many challenges to development of a good dissolution method. Generally,the drug is dissolved or suspended in oil before encapsulation. During dissolution,the oil may form a layer above the aqueous medium. In addition,oil droplets may become suspended in the medium. The existence of the lipid phase may hinder the release of the drug,and the oil layer or oil droplets may cause sampling problems. Furthermore,poor aqueous solubility of the drug may cause slow or incomplete dissolution. Initially,solubility studies on the drug substance were carried out resulting in a selection of suitable dissolution media. Dissolution experiments were tried using USP Apparatus 1,2,and 4. Since the dissolution rate was too slow using USP Apparatus 1,only Apparatus 2 and 4 were selected for further method development. During the method development,the sampling problems when using USP Apparatus 2 had to be resolved and a suitable flow cell chosen for Apparatus 4. Once these changes were made,dissolution profiles were obtained using both apparatuses for the two SGC formulations. The results were analyzed and compared.