Application of Factorial Design in the Premixing Operation of Diltiazem Timed-Release Pellets
Department of Pharmaceutics, CL Baid Metha College of Pharmacy, 1Formulation Research and Development, Fourrts India Laboratories Private Limited, Thoraipakkam, Tamil Nadu 600097, 2Department of Pharmacology, National Institute of Siddha, Tambaram, Tamil Nadu 600047, Chennai, India
Department of Pharmaceutics, CL Baid Metha College of Pharmacy, Thoraipakkam, Tamil Nadu 600097, India
The purpose of this study was to prepare diltiazem timed-release pellets using non pareil seeds. An important step in the preparation of timed-release multiparticulate dosage forms was to mix a pilot mixture composed of various polymers or waxes with different concentration. By using the three-factor and twolevel factorial design for the pilot mixing process, the mixing can be distinguished technically than the trial and error method. Core, non pareil seeds prepared by using a sugar solution. A fluidized bed processor was used to coat diltiazem on to the non pareil seeds. Hydroxypropyl methylcellulose E15 was used as coatings for non pareil seeds, with various percentage (10 %, 20 % and 30 %) in two levels (16.66 % and 33.33 %). According to the design matrix, pilot mixing was carried out for in vitro dissolution studies and optimized batches were prepared for masterblend and mixture based on the results. The Pareto chart supported the analysis of variance results for the model simplification and eliminating non-significant terms (p>0.05). The optimal process variable selected for optimizing the diltiazem timed-release pellets formulation was set to be pilot mix I=24.9 %, pilot mix II=16.6 % and pilot mix III=16.6 %. The optimized formula showed that half-life period was 2.361±0.243 h and shelf-life period was 6.875 h.