Enhanced Understanding of Pharmaceutical Materials Through Advanced Characterisation and Analysis.

The impact of pharmaceutical materials properties on drug product quality and manufacturability is well recognised by the industry. An ongoing effort across industry and academia, the Manufacturing Classification System consortium, aims to gather the existing body of knowledge in a common framework to provide guidance on selection of appropriate manufacturing technologies for a given drug and/or guide optimization of the physical properties of the drug to facilitate manufacturing requirements for a given processing route. Simultaneously, material scientists endeavour to develop characterisation methods such as size, shape, surface area, density, flow and compactibility that enable a stronger understanding of materials powder properties.

Development of a material sparing bulk density test comparable to a standard USP method for use in early development of API's.

Bulk density can be a key indicator of performance, and may influence choice of formulation route of materials in pharmaceutical development. During early development, the cost of API's can be expensive and the availability of material for powder property analysis is limited. The aim of this work was to investigate a suitable small-scale, low material requirement, bulk density test which would provide comparable data to the recommended large volume USP test.

Imaging dehydration kinetics of a channel hydrate form of the HIV-1 attachment inhibitor prodrug BMS-663068.

An analysis of the free acid form of the HIV-1 attachment inhibitor prodrug BMS-663068-01 revealed a reversible moisture sorption event in the 42%-46% relative humidity (RH) range. An existing single-crystal analysis indicated that these observations were due to the formation of a nonstoichiometric channel hydrate. This effect was reproducible on repeated cycles, suggesting that the material's structural integrity was not compromised because of the interconversion process.

Investigating the applicability of inverse gas chromatography to binary powdered systems: an application of surface heterogeneity profiles to understanding preferential probe-surface interactions.

The aim of this study was to investigate the applicability of surface energy characterization tools such as inverse gas chromatography for the analysis of binary systems. Drug substance was coated with two grades of silicon dioxide and the surface energy characteristics determined using a surface energy analyser. The results demonstrated that the measured dispersive surface energy of such intermediate samples were as a consequence of probe interactions with both constituent components, however, the degree and order of interaction with each species was related to surface energy heterogeneity and surface availability.

Formulation and process design for a solid dosage form containing a spray-dried amorphous dispersion of ibipinabant.

Amorphous forms of poorly soluble drugs are more frequently being incorporated into solid dispersions for administration and extensive research has led to a reasonable understanding of how these dispersions, although still kinetically unstable, improve stability relative to the pure amorphous form. There remains however a paucity of literature describing the effects on such solid dispersions of subsequent processing into solid dosage forms such as tablets. This paper addresses this area by looking at the effects of the addition of common excipients and different manufacturing routes on the stability of a spray-dried dispersion (SDD) of the cannabinoid CB-1 antagonist, ibipinabant.

The use of artificial neural networks for the selection of the most appropriate formulation and processing variables in order to predict the in vitro dissolution of sustained release minitablets.

The objective of this work was to apply artificial neural networks (ANNs) to examine the relative importance of various factors, both formulation and process, governing the in-vitro dissolution from enteric-coated sustained release (SR) minitablets. Input feature selection (IFS) algorithms were used in order to give an estimate of the relative importance of the various formulation and processing variables in determining minitablet dissolution rate. Both forward and backward stepwise algorithms were used as well as genetic algorithms.