Control strategy definition for a drug product continuous wet granulation process: Industrial case study.

This paper describes the specific control strategy of the commercial manufacturing process of an immediate release tablet formulation based on continuous twin-screw wet granulation. This control strategy has been defined by a multidisciplinary team using an enhanced approach, in alignment with the quality by design principles. During process development, experiments have been performed according to multivariate designs first to identify critical material attributes and critical process parameters and then, to define process conditions generating a product having the required quality.

Preparation of poly(N-isopropylacrylamide) copolymers and preliminary assessment of their acute and subacute toxicity in mice.

A subacute toxicity study was conducted to evaluate the oral toxicity profile of poly(N-isopropylacrylamide) (PNIPAAm) derivatives. These thermoresponsive polymers may have several potential pharmaceutical applications such as ingredient for oral solid dosage form. A preliminary acute oral toxicity study was performed with one of the polymer (PNIPAAm-co-NVA) at a unique dose of 4000 mg/kg body weight administered to six male and six female mice, to determine the dosage for further evaluation.

Poly(N-isopropylacrylamide) copolymers for constant temperature controlled drug delivery.

In the course of the development of a new drug delivery concept, four thermosensitive copolymers of poly(N-isopropylacrylamide) (PNIPAAm), with phase transition temperature slightly higher than 37 degrees C, were synthesised and used as time-controlled drug delivery agents. For this purpose, compression-coated tablets coated with the thermosensitive copolymers and containing Na2SO4 were prepared and in vitro dissolution tests were performed at constant physiological temperature, the lag time before drug release being controlled by the amount of Na2SO4 incorporated into the form. Due to the salting out effect, the lag time was increased by up to 80-90% for PNIPAAm-co-NVA and PNIPAAm-co-MVA coated tablets.

Surfactant induced drug delivery based on the use of thermosensitive polymers.

A novel approach of controlled drug delivery using thermosensitive polymers is developed in this paper. The drug release occurs at physiological temperature, at which the polymer is normally not soluble, and no medium temperature changes are required to bring about the delivery. For this purpose benefit is taken from the specific binding properties of some anionic surfactants and poly(N-isopropylacrylamide) (PNIPAAm) in order to modify the dissolution properties of PNIPAAm and of a copolymer with N-vinyl-acetamide (NVA), and so to induce the release of a drug contained in compression coated tablets.

Multiplex gene expression analysis for high-throughput drug discovery: screening and analysis of compounds affecting genes overexpressed in cancer cells.

Drug discovery strategies are needed that can rapidly exploit multiple therapeutic targets associated with the complex gene expression changes that characterize a polygenic disease such as cancer. We report a new cell-based high-throughput technology for screening chemical libraries against several potential cancer target genes in parallel. Multiplex gene expression (MGE) analysis provides direct and quantitative measurement of multiple endogenous mRNAs using a multiplexed detection system coupled to reverse transcription-PCR.