Industrial Manufacture of Enteric Hard Capsules Using Novel Formulations Based on Hypromellose Phthalate/Gelatin and Investigation of Pantoprazole Release.

Abstract

Capsules are popular oral dosage forms because of their ease of production. They are widespread pharmaceutical products. Hard capsules are preferred dosage forms for new medicines undergoing clinical tests because they do not require expansive formulation development. Functional capsules with built-in gastroresistance, aside from the traditional hard-gelatin or cellulose-based vegetarian capsules, would be beneficial. In this research, the effect of polyethylene glycol-4000 (PEG-4000) was investigated on the formulation of uncoated enteric hard capsules based on hypromellose phthalate (HPMCPh) and gelatin. Three different formulations based on HPMCPh, gelatin, and PEG-4000 were tested to achieve the optimal formulation for the industrial production of hard enteric capsules with desired physicochemical and enteric properties. The results reveal that the capsules containing HPMCPh, gelatin, and PEG-4000 (F1) are stable in the stomach environment (pH = 1.2) for 120 min, and during this time, no release happens. The outcomes also demonstrate that PEG-4000 blocks the pores and improves enteric hard capsule formulation. In this research, we present a specific procedure for manufacturing uncoated enteric hard capsules on an industrial scale that does not require an extra coating step for the first time. The industrial-scale validated process can considerably reduce the cost of manufacturing standard enteric-coated dosage forms.