RECRYSTALLIZATION STRATEGIES FOR BIOPHARMACEUTICS CLASSIFICATION SYSTEM CLASS II DRUGS: IMPACT ON DISSOLUTION RATE AND ORAL BIOAVAILABILITY

Abstract

For class II drugs of Biopharmaceutics Classification System (BCS), poor water solubility remained one the greatest challenge in modern pharmaceutical development. Notwithstanding, these drug can pass effortlessly through biological membranes due to their high permeability, their low dissolution in aqueous media prohibit them from absorption. Henceforth, dissolution rate emerges as rate limiting step for their absorption through oral route. Multiple formulation and particle engineering technologies, including solid dispersion, size reduction, lipid based delivery, complexation and recrystallization have been implemented for this purpose. Among them, recrystallization has emerged as a cos-effective, user friendly, and scalable method for refining dissolution by modifying crystal properties devoid of changing chemical structure. Although, it was considered purely as a refining method used during synthesis, recrystallization is now known as prevailing crystal engineering tool proficient for modifying the physical characteristics of active pharmaceutical ingredients without altering their chemical identity. The controlling factors such as temperature, solvent selection and recrystallization condition can be carefully controlled to modify crystal shape, size, surface properties, wettability, and polymorphic form. Ultimately, these changes directly impact dissolution rate and bioavailability of a drug. Here, we explored the scientific basis of recrystallization and discussed about the contribution of the process to enhance dissolution of BCS Class II drugs. Furthermore, the mechanism behind dissolution enhancement has also been elaborated.