Development of an im mold purposely devised for an oral pulsatile-release capsular device

Injection molding (IM) was recently proposed as the manufacturing technique for the preparation of an oral capsular device (Chronocap™) based on hydroxypropyl cellulose (HPC) and intended for pulsatile and/or colonic delivery. By employing a prototype mold, it was possible to obtain capsules able to impart a lag phase to the release of a model drug, both in vitro and in vivo, the duration of which was dependent on the shell thickness and composition [1,2]. As some technical limitations were encountered with respect to the mold, manufacturing process and molded items, the aim of the present work was the development of a novel mold to enhance the industrial scalability of the Chronocap™ pulsatile delivery device. Preliminarily, a formulation was selected composed of HPC (Klucel® LF) plasticized with polyethylene glycol 1500, and the relevant thermal, rheological and mechanical characteristics were in-depth evaluated. The need for a plasticizer was confirmed and its amount was related to the IM processability and mechanical stability of the molded items. Moreover, potential risks connected with the operating temperatures and heating time of the material were highlighted. Based on the results obtained, some changes were introduced into the press (e.g. reduced diameters of the piston and nozzle) and a novel mold was designed with several improved features (e.g. hot runner and consistent/reduced flow length in all directions). After adjusting the process parameters a fully automated manufacturing process was achieved with a cycle time reduced to about 5 s and no need for lubricants. The capsular devices prepared demonstrated good technological properties and improved reproducibility of the shell thickness, mechanical properties as well as release performance. [1] A. Gazzaniga et al., AAPS PharmSciTech 12, 295-303, 2011; [2] A. Gazzaniga et al., 38th CRS annual meeting & exposition July 30 - August 3, National Harbor, Maryland.