Research

Amorphous Systems

The amorphous form can be used as a means to enhance the aqueous solubility of very poorly water soluble drugs. However, amorphous solids frequently crystallize with time, negating any solubility advantages. We are interested in understanding why some drugs crystallize more easily than others. Also, it is well known that crystallization can be delayed or inhibited by adding polymers. The mechanism(s) of crystallization inhibition by polymers are not well understood and are being intensively investigated in the Taylor lab. We are currently comparing the inhibitory ability of various common pharmaceutical polymers in the presence and absence of moisture and as a function of temperature. In addition, we are examining the utility of novel cellulose derivatives for preparing amorphous solid dispersions with controlled release profiles, in collaboration with the lab of Professor Kevin Edgar. Recently, we have discovered that moisture can induce amorphous-amorphous phase separation in some drug polymer mixtures and we are probing the underlying intermolecular interactions and thermodynamics of these systems. We are also studying drug-polymer miscibility and investigating what factors govern if a particular drug and polymer mix. In order to address this question, it is necessary to implement high resolution analytical techniques to assess the miscibility of the systems. Techniques that are currently being evaluated include FT-Infrared Spectroscopy, X-Ray Powder Diffraction, Differential Scanning Calorimetry and various microscopic techniques. Once a solid amorphous dispersion has been successfully prepared, it is necessary to understand how enhanced solution concentrations are generated. We are therefore currently developing methods to study the extent and longevity of the supersaturation generated by dissolving amorphous solids and the influence of polymers on the solution levels attained.

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.