Pharmaceutical Technology Europe - November 2012 - (Page 7)

Applying Quality by Design for Extended Release Hydrophilic Matrix Tablets Quality by design (QbD) is a systematic approach to designing and developing pharmaceutical formulations and manufacturing processes to ensure predefined product quality. In the case of hydrophilic matrix tablets, it is important to consider potential variability in material attributes of the rate-controlling polymer in addition to variability in the API properties and processing conditions. This proactive and enhanced understanding supports efficient pharmaceutical product development. This study examines the effect and interaction of variations in hypromellose physicochemical properties on powder flow, the physical attributes of tablets, and in vitro drug-release profiles from two model formulations of extendedrelease (ER) hydrophilic matrix tablets using QbD principles. This article presents a QbD approach to determine the effect of material attributes on both the physical properties and in vitro drug-release performance of the matrix tablets. The excipient hypromellose United States Pharmacopeia (USP) substitution type 2208 (Methocel K15M Premium CR, Dow Chemical) was used as the rate-controlling polymer for two case studies with a soluble drug (propranolol hydrochloride [HCl]) and slightly soluble drug (theophylline). Normal variation of Methocel material attributes (apparent viscosity, percent hydroxylpropoxyl (HP) substitution, and particle size) was studied at polymer concentrations of 15% w/w and 30% w/w. The study demonstrated consistent physical properties for direct-compression blends and subsequent tablet cores, irrespective of the Methocel concentration or drug included. In vitro drug release, however, showed greater sensitivity to materialattribute variability at lower polymer concentration. to the elimination of production rejects and recalls due to quality issues. Before FDA introduced QbD into the chemistry, manufacturing, and controls (CMC) review process in 2004, the amount of product waste due to manufacturing mistakes was reported to be as high as 50%. PTE The importance of QbD QbD means designing and developing formulations and manufacturing processes to ensure predefined product quality. Building quality into drug products by design also benefits developers. Successful first-cycle approval, reduction of postapproval changes, and the potential of realtime release could offset initial investment associated with QbD implementation. Importantly, enhanced understanding of the product and manufacturing process also can lead An extended version of this article is available at: PharmTech.com/Robertson Ian A. Robertson, PhD, is global quality-by-design manager, Colorcon Ltd., UK. Sandip B. Tiwari, PhD, is regional technical manager at Colorcon Asia Pvt. Ltd. Tim D. Cabelka, PhD, is senior product research specialist at Dow Chemical. 2 EXTRACTABLES & LEACHABLES 9 ALZHEIMER’S DISEASE 5 NEWS 10 BLOGS 7 QUALITY BY DESIGN 11 TECHNOLOGY 8 BIOSIMILAR mAbS 12 STAFF http://www.PharmTech.com/Robertson

Table of Contents for the Digital Edition of Pharmaceutical Technology Europe - November 2012

Pharmaceutical Technology Europe - November 2012
Contents
Cover Story: Examining the Growing Challenge of Extractables & Leachables: An Industry Roundtable
News Bites
Applying Quality by Design for Extended-Release Hydrophilic Matrix Tablets
EU Sets Guidelines for Biosimilar Monoclonal Antibodies
Will Europe Discourage the Launch of New Alzheimer’s Drugs?
Blogs: Roche Under Investigation; Q3 Financial Reports
Top IT Technologies

Pharmaceutical Technology Europe - November 2012