Injection molded gastroresistant capsular containers

Purpose To explore the possibility of preparing by injection molding (IM) a gastroresistant capsular shell based on hydroxypropyl methylcellulose acetate succinate (HPMCAS) for the development of dosage forms alternative to enteric coated ones. Methods A bench-top micromolding machine (BabyPlast 6/10P, Cronoplast S.L.; Rambaldi S.r.l., I) was used equipped with different molds (disk- or capsular-shaped; nominal thickness 200-1000 µm or 300-900 µm, respectively). HPMCAS was co-grinded with the plasticizer polyethylene glycol (PEG 1500) in a blade mill; blends containing release modifiers (Kollicoat® IR; Explotab® CLV) were prepared by mixing in turbula for 20’. Molded items were checked for weight, thickness, shape changes over time and gastric resistant performance (Dissolution test for delayed-release dosage forms, Method B, USP 34, apparatus 2). Results The processability conditions of the selected thermoplastic polymer and the need for a plasticizer in order to modulate the glassy and fragile nature of molded items was initially disclosed. The encouraging results achieved, using PEG 1500 as the plasticizer, also highlighted some critical issues related to the opening time of the device after the pH change as well as its physical and mechanical stability (shrinkage/warpage phenomena). Therefore, an in-depth formulation study was performed taking into consideration the addition of release modifiers potentially able to affect the dissolution/disintegration rate of the capsule shell at intestinal pH values. Capsular devices containing soluble (polyvinyl alcohol-polyethylene glycol graft copolymer) and/or superdisintegrant (sodium starch glycolate) adjuvants could be manufactured, and a promising performance was obtained considering both the gastric resistance in pH 1.2 medium and the break-up in pH 6.8 that take place within the first hour of the test. Conclusion The overall results demonstrated the feasibility by IM of a gastroresistant container and pointed out the objectives, in terms of composition and shape (dimension and thickness), to be pursued in the following development step.