Integrated Application of Quality-by-Design Principles to Drug Product Development: A Case Study of Brivanib Alaninate Film-Coated Tablets.

Modern drug product development is expected to follow quality-by-design (QbD) paradigm. At the same time, although there are several issue-specific examples in the literature that demonstrate the application of QbD principles, a holistic demonstration of the application of QbD principles to drug product development and control strategy, is lacking. This article provides an integrated case study on the systematic application of QbD to product development and demonstrates the implementation of QbD concepts in the different aspects of product and process design for brivanib alaninate film-coated tablets.

Comprehensive determination of extractables from five different brands of stoppers used for injectable products.

Five commonly used stopper formulations were tested for extractables using three different vehicles (pH 3 citrate buffer with 20% w/v sulfobutylether-beta-cyclodextrin, pH 8 phosphate buffer and 50/50 v/v polyoxyethylated castor oil/dehydrated alcohol). The stoppers, made from butyl and halobutyl rubbers, coated and uncoated with proprietary films, were stored in contact with each vehicle for up to 6 months at 40 degrees C/75% relative humidity (RH) or for up to 24 months at 25 degrees C/60% RH. Samples were analyzed for the presence of extractables using inductively coupled plasma-atomic emission spectroscopy, ion chromatography, high-performance liquid chromatography, and gas chromatography.