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  • Application of active layering and coating techniques in the development of a multiparticulate, controlled release dosage form of a high-dose, highly soluble drug.

Application of active layering and coating techniques in the development of a multiparticulate, controlled release dosage form of a high-dose, highly soluble drug.

Pharmaceutical development and technology (2013-06-19)
Haitham Ahmad, Ismail Khalifeh, Bashar Alkhalidi, Khaled Aiedeh, Hatim S Alkhatib
ABSTRACT

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. To develop a controlled release dosage form of diltiazem hydrochloride using active layering and coating. 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. 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. 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
(+)-cis-Diltiazem hydrochloride, ≥99% (HPLC)
Sigma-Aldrich
Poly(vinyl acetate), average Mw ~100,000 by GPC, beads
Sigma-Aldrich
Poly(vinyl acetate), average Mw ~500,000 by GPC
Sigma-Aldrich
Kollicoat® SR 30 D, 28.5-31.5% solids basis
Diltiazem for system suitability, European Pharmacopoeia (EP) Reference Standard
Diltiazem hydrochloride, European Pharmacopoeia (EP) Reference Standard
Supelco
Diltiazem hydrochloride solution, 1.0 mg/mL in acetonitrile (as free base), ampule of 1 mL, certified reference material, Cerilliant®
USP
Diltiazem hydrochloride, United States Pharmacopeia (USP) Reference Standard
Poly(vinyl acetate), European Pharmacopoeia (EP) Reference Standard