JOHN COMER*, KARL BOX, ROBERT TAYLOR
*Corresponding author
Sirius Analytical Ltd. Forest Row, RH18 5DW, United Kingdom

Abstract

This article briefly introduces a number of experimental methods that can be used to investigate supersaturation and precipitation of small-molecule drugs. Methods include solubility measurements by pH-metric methods; controlled supersaturation studies by pH-metric and UV methods; studies of the solid state using polarised light microscopy; aqueous dissolution under changing pH conditions; and biphasic dissolution. Examples illustrate how the results may be used to guide decision-making during formulation.

INTRODUCTION

Biopharmaceutics is the study of the physical and chemical properties of drugs and their proper dosage as related to the onset, duration, and intensity of drug action. It’s a practical subject that lies at the heart of drug formulation. In biopharmaceutical science there is a strong need for biorelevant in-vitro tests that are prospective and predictive of bioperformance. These in-vitro tests should be used first during development and should give guidance to product outcome. Many scientists believe that current tests are not fit-for-purpose for today’s BCS Class II and Class IV compounds in trying to assess formulation strategies, and that new tests are needed (1). Precipitation is an important example of the properties that scientists need to study (2-5).

If an orally-dosed drug precipitates in the intestine it’s not available to be absorbed, so precipitation is something that formulators would usually like to avoid. At Sirius, we have been developing new experiments to investigate precipitation, in the hope that results will guide formulators as they seek ways to make poorly soluble drugs more bioavailable. Th ...