Taylor:Research

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Research Solubility Enhancement Many important substances including new drugs, agricultural chemicals and nutraceuticals are often very insoluble in water. This can make them very hard to formulate and deliver and may even prevent new drugs from being clinically efficacious. Several strategies have emerged to improve aqueous solubility and drug delivery including salt formation, amorphous solid dispersions, cocrystals, complexation, lipid formulations and combinations thereof. The Taylor group is actively involved in research topics pertinent to solubility enhancement and how the different enhancement methods compare with one another. The group has considerable expertise with amorphous formulations, and amorphous solid dispersions are of particular interest. Research in this area encompasses all aspects of the design, production and characterization of amorphous solid dispersions as summarized in the Figure. Dissolution of Amorphous Solid Dispersions Stabilization of an amorphous drug in the solid matrix during storage is only half the battle – the drug must also be prevented from crystallizing as the matrix hydrates during dissolution, and also prevented from precipitating from the supersaturated solution subsequently produced following dissolution. We are currently studying the dissolution behavior of amorphous solids and investigating the role of the polymer in inhibiting crystallization from either the hydrated matrix or the supersaturated solution. This research involves probing drug-polymer interactions in both the solid and solution phases, as well as the nature of any submicron structures generated during dissolution. We are also trying to understand the maximum solution concentrations achievable using solid dispersion technology. Water-Solid Interactions There are generally considered to be 5 major types of water-solid interactions affecting pharmaceutical solids. These are: adsorption to surfaces, absorption into disordered systems, deliquescence, capillary condensation and hydrate formation. In general we are interested in how these water-solid interactions influence the physical and chemical stability of single-component and multi-component pharmaceutical systems. Recently, our research has concentrated on the phenomenon of deliquescence lowering. This work has been carried out in collaboration with Professor Lisa Mauer. When two deliquescent solids are mixed together, the deliquescence point of the mixture is considerably lower than the individual deliquescence relative humidities. This means that a solution of the two components can be formed at moderate relative humidities leading to chemical and physical instabilties. We have also shown that degradation products can cause deliquescence lowering and can increase the hygroscopicity of the system. At a more fundamental level, X-Ray Photoelectron Spectroscopy is proving to be a useful tool to examine the chemistry of water on organic crystal surfaces and to probe the strength of the water-solid interactions. This research is a collaborative effort with Dr Dmitry Zemlianov, Birck Nanotechnology Center.