Formulation and Quality – Chemical
2019 PharmSci 360
Polymers have been widely used in pharmaceutical solid dispersion based products to significantly improve the drug dissolution and the subsequent absorption of some poorly soluble drugs. To successfully formulate such products, the drug needs to be highly miscible with the polymer. However the preformulation stage of screening suitable polymers is often a lengthy process requiring the use of a range semi-empirical, theoretical and experimental methods. Here we developed and report on the use of a simple hot stage microscopy based method, thermal analysis by structure characterization (TASC), to screen the miscibility of drug-polymer combinations. TASC is performed by analyzing changes in the features of crystalline drug particles that are heated in a linear fashion and melted on a thin layer of the polymer of interest. Obtaining the melting point depression of the drug by the polymer which is key for assessment of drug-polymer miscibility. The speed of TASC analysis is 20-40 times faster than with conventional differential scanning calorimetry (DSC) method. Moreover there is no loss of sensitivity. Each TASC run required only 1/1000th of the quantity of the material that is needed for a conventional DSC test. With the intension of exploring the automation potential of TASC method for rapid formulation screening, the full TASC plots of all drug-polymer pairs were analysis using PCA. The PCA results confirmed the ability of TASC to sort the drug-polymer combinations based on the degree of the melting depression which is directly related to the degree of miscibility of the drug in the polymer. This demonstrated the clear potential of TASC being developed into automatic rapid formulation screening tool for drug-polymer based formulations.