Best practices for the development, scale-up, and post-approval change control of IR and MR dosage forms in the current quality-by-design paradigm.

In this whitepaper, the Manufacturing Technical Committee of the Product Quality Research Institute provides information on the common, best practices in use today in the development of high-quality chemistry, manufacturing and controls documentation. Important topics reviewed include International Conference on Harmonization, in vitro-in vivo correlation considerations, quality-by-design approaches, process analytical technologies and current scale-up, and process control and validation practices. It is the hope and intent that this whitepaper will engender expanded dialog on this important subject by the pharmaceutical industry and its regulatory bodies.

A novel method for estimating solid fraction of roller-compacted ribbons.

A simple method has been developed to estimate solid fraction or relative density of compacts using the weight of ribbons produced during roller compaction. The method provides an alternative to the commonly used dimensional measurement, especially for formulations not amenable to forming quality ribbons. Surface texture of the compaction rolls has been taken into consideration in our mathematical treatment along with correction for ribbon relaxation.

Cocrystal formation during cogrinding and storage is mediated by amorphous phase.

Purpose: The purpose of this work was to investigate the mechanisms of cocrystal formation during cogrinding and storage of solid reactants, and to establish the effects of water by cogrinding with hydrated form of reactants and varying RH conditions during storage.

Methods: The hydrogen bonded 1:1 carbamazepine-saccharin cocrystal (CBZ-SAC) was used as a model compound. Cogrinding of solid reactants was studied under ambient and cryogenic conditions.

Characterization of poly(ethylene oxide) as a drug carrier in hot-melt extrusion.

Poly(ethylene oxide) (PEO) as a drug carrier in hot-melt extrusion was studied by using a model drug, nifedipine, in a twin-screw extruder. Binary mixtures of PEO and nifedipine have been shown to be amenable to hot-melting at a temperature as low as 70 degrees C, well below nifedipine's melting point (172 degrees C). Hot-stage microscopy provided visual evidence that nifedipine can form a miscible dispersion with PEO at 120 degrees C.

Temperature/Humidity sensitivity of sustained-release formulations containing Kollidon SR.

The effects of temperature and humidity on tablets containing Kollidon SR have been evaluated using diphenhydramine HCl as a model drug. Exposure of tablets to ICH accelerated stability condition (40 degrees C/75%RH) in an open dish resulted in rapid increases in tablet hardness, accompahied by step-wise decreases in dissolution rate. Such a change can be observed as fast as an hour upon exposure.

Drug release from Kollicoat SR 30D-coated nonpareil beads: evaluation of coating level, plasticizer type, and curing condition.

A newly available polyvinylacetate aqueous dispersion, Kollicoat SR 30D, was evaluated with respect to its ability to modulate the in vitro release of a highly water-soluble model compound (diphenhydramine hydrochloride) from nonpareil-based systems. Kollicoat SR 30D premixed with a selected plasticizer (10% wt/wt propylene glycol, 2.5% triethyl citrate, or 2.