Hard capsule shells with an inherent delayed release action are useful for oral administration of active ingredients, which are acid-labile and/or enzymatically degradable in the gastric environment, without the need of film coating. The objective of this study was to fabricate delayed release hard capsule shells by the dip coating method. The film coating formulations comprised blends of zein and methacrylic acid copolymer (Eudragit® L100-55), with and without the addition of the plasticizer, polyethylene glycol 1000. The rheology parameters (loss modulus (G'), storage modulus (G") and loss tangent (tan δ, G"/G')) of the film coating solution were measured to investigate the processability. Central composite design was used to investigate the main, interaction and quadratic effects of the proportion of methacrylic acid copolymer, solid content of the film formers and level of polyethylene glycol 1000 on the capsule wall thickness and mechanical strength. Multiple response optimization was further conducted, and the design space was established. The in vitro drug release in simulated gastric and intestinal fluids of three different formulations in the design space was compared. The results showed that the tan δ value after the gelation point should be < 0.9 in order to form a thin and sturdy capsule shell. The gelation time and viscosity of the coating solution were related to the thickness of the capsule shell. The study showed that drug release from the capsule with a specified thickness and mechanical strength can be modulated by varying the ratio of zein to methacrylic acid copolymer. The delayed drug release profile was achieved through the capsule shell fabricated from zein to methacrylic acid copolymer at the ratios of 75:25 and 83.2:16.8, with 10% polyethylene glycol 1000.
Keywords: Central composite design; Delayed release; Hard capsule shells; Methacrylic acid copolymer; Rheology; Zein.
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