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Objectives With poorly soluble drug candidates emerging in the drug discovery pipeline, the importance of the solid dispersion formulation approach is increasing. This strategy includes complete removal of drug crystallinity, and molecular dispersion of the poorly soluble compound in a hydrophilic polymeric carrier. The potential of this technique to increase oral absorption and hence bioavailability is enormous. Nevertheless, some issues have to be considered regarding thermodynamic instability, as well in supersaturated solutions that are formed upon dissolution as in the solid state. Key findings After a brief discussion on the historical background of solid dispersions and their current role in formulation, an overview will be given on the physical chemistry and stability of glass solutions as they form supersaturated solutions, and during their shelf life. Conclusions Thorough understanding of these aspects will elicit conscious evaluation of carrier properties and eventually facilitate rational excipient selection. Thus, full exploitation of the solid dispersion strategy may provide an appropriate answer to drug attrition due to low aqueous solubility in later stages of development.

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Spray drying is a well-established manufacturing technique which can be used to formulate amorphous solid dispersions (ASDs) which is an effective strategy to deliver poorly water soluble drugs (PWSDs). However, the inherently complex nature of the spray drying process coupled with specific characteristics of ASDs makes it an interesting area to explore. Numerous diverse factors interact in an inter-dependent manner to determine the final product properties. This review discusses the basic background of ASDs, various formulation and process variables influencing the critical quality attributes (CQAs) of the ASDs and aspects of downstream processing. Also various aspects of spray drying such as instrumentation, thermodynamics, drying kinetics, particle formation process and scale-up challenges are included. Recent advances in the spray-based drying techniques are mentioned along with some future avenues where major research thrust is needed.

Boets, E. et al. (2017) Systemic availability and metabolism of colonicderived short-chain fatty acids in healthy subjects: a stable isotope study. Journal of Physiology, 595(2), pp. 541-555. (doi:10.1113/JP272613) This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/128777/ Key Point Summary SCFAs are bacterial metabolites produced during colonic fermentation of undigested carbohydrates, such as dietary fibre and prebiotics, and could mediate the interaction between diet, the microbiota and the host. We quantified the fraction of colonic administered SCFA that could be recovered in the systemic circulation, the fraction that was excreted via breath and urine and the fraction that was used as a precursor for glucose, cholesterol and fatty acids. This information is essential to understand the molecular mechanisms by which SCFA beneficially affect physiological functions such as glucose and lipid metabolism and immune function. AbstractThe short-chain fatty acids (SCFAs), acetate, propionate and butyrate are bacterial metabolites that mediate the interaction between diet, the microbiota and the host. In this study, the systemic availability of SCFAs and their incorporation into biologically relevant molecules was quantified. Known amounts of 13 C-labelled acetate, propionate and butyrate were introduced in the colon of 12 healthy subjects using colon delivery capsules and plasma levels of 13 C-SCFAs and of 13 C-glucose, 13 C-cholesterol and 13 C-fatty acids were measured.The butyrate producing capacity of the intestinal microbiota was quantified as well. Systemic availability of colonic-administered acetate, propionate and butyrate was 36%, 9% and 2%, respectively. Conversion of acetate into butyrate (24%) was the most prevalent interconversion by the colonic microbiota and was not related to the butyrate-producing capacity in the faecal samples. Less than 1% of administered acetate was incorporated into cholesterol and <15% in fatty acids. On average, 6% of colonic propionate was incorporated into glucose. The SCFAs were mainly excreted via the lungs after oxidation to 13 CO 2 whereas less than 0.05% of the SCFAs were excreted into urine. These results will allow future evaluation and quantification of SCFAs production from 13 C-labelled fibres in the human colon by measuring 13 C-labelled SCFA concentrations in blood.

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