Stabilization of Hard Gelatin Capsule Shells Filled with Polyethylene Glycol Matrices

Abstract

The purpose of this study was to evaluate the effects of various stabilizers on the dissolution stability of liquid-filled capsule dosage forms containing a potent drug dissolved in polyethylene glycols. A systematic dissolution slowdown was observed in gelatin capsule formulations without a stabilizer and was exaggerated under stress storage conditions. This slowdown is attributed to cross-linking of the gelatin shells. Addition of butylated hydroxyanisole (BHA) delayed the onset of gelatin cross-linking, and a combination of BHA with water added to this formulation effectively prevented product dissolution slowdown. For similar formulations filled into hypromellose capsule shells, no dissolution slowdown was observed, even in the absence of stabilizers.

Keywords:

• stabilizers
• dissolution
• cross-linking
• gelatin
• polyethylene glycol
• hypromellose