Crystallization and dissolution of pharmaceutical compounds: An experimental approach

Abstract

In pharmaceutical industry growth and dissolution are important stages for different reasons. In industrial processes crystallization is an important operation which controls the physical properties of the material such as the crystal habit, crystal size distribution and polymorphism. For economic and technical reasons before patenting a drug it is important to search all the possible polymorphs. In the case of organic drugs which are slightly soluble in gastrointestinal fluids, the dissolution rate of the solid dosage form is an important factor determining the rate of absorption. The kinetics of solubilization will depend mainly on the crystal habit, crystal size distribution and on the polymorphs. This paper presents a laboratory study of the dissolution of crystals of an organic drug in a crystallizer equipped with an in situ conductivity probe and an UV analyzer on-line. The rate of dissolution and evolution of the crystal size distribution are measured. A solution mediated phase transition of the drug is observed. The final objective is to model the dissolution process from kinetic data and determine the influence on the dissolution of under-saturation, temperature, crystal habit and crystal size distribution.