Context: The success of the development of controlled release, multilayered, multiparticulate dosage form of a high-dose, highly-soluble drug is dependent upon proper material and processing choices.
Objective: To develop a controlled release dosage form of diltiazem hydrochloride using active layering and coating.
Methods: Active layering was achieved by spraying a drug solution onto sugar cores using polyvinyl alcohol - polyethylene glycol as a binder. Layered pellets with highest loading and lowest binder content were coated using aqueous dispersions of polyvinyl acetate (PVAc). The effects of the plasticizer and curing on drug release were evaluated.
Results and discussion: The binder level had no effect on the process efficiency. Drug release from PVAc-coated pellets was slowed by increasing PVAc level. Plasticization slowed drug release in comparison to nonplasticized formulations. Curing affected drug release of nonplasticized formulations only. Protection against humidity was essential in stabilizing drug release under stability study conditions.
Conclusion: Materials and process used were suitable to face the challenge posed by the high dose of the water-soluble drug on the success of the formulation. The effects of the plasticizer, curing and ability of packaging to protect against elevated humidity on the performance of the studied system should be considered in development.