An outlook on permeability escalation through cocrystallization for developing pharmaceuticals with improved biopharmaceutical properties

Permeability of any pharmaceutical is critically significant for its biopharmaceutical profile, therapeutic activ-ities, and deciding its dosing regimen. Approximately 35% of the marketed drugs and 30% of pipeline drugs suffer from permeability-related problems. Over the past decade, pharmaceutical cocrystals have emerged as novel tools to target poorly permeable pharmaceuticals. Incorporating a coformer inside the crystal lattice of an active pharmaceutical ingredient (API) employing weak non-covalent interactions results in the development of pharmaceutical cocrystal, which exhibits modified crystal arrangement and molecular packing compared to the parent components. Since intrinsic properties of an API rely on its crystal structure, rearranging the crystal packing is thought to manifest modulated permeability, resulting in a changed biopharmaceutical profile. Although the literature suggests cocrystallization as a well-accepted technique to address the poor permeability of pharmaceuticals, the absence of an exclaimed theory and a proper explanation behind the science of modu-lated permeability via crystal engineering technique draws strong attention to the subject. Reports investigating the structure-permeability correlation, solubility-permeability relationship, the role of lipophilic coformers, the effect of using an efflux transporter inhibitor as cocrystal formers etc., have been discussed in the present review article. This article attempts to outline the unanswered questions and gaps related to various probable mecha-nisms proposed for describing the role of cocrystallization in improving the permeability of a pharmaceutical, subsequently upgrading its bioavailability and absorption.

Automated summary

Permeability is critical for the biopharmaceutical profile and therapeutic activities of pharmaceuticals. Pharmaceutical cocrystals have emerged as a novel approach to improve the permeability of poorly permeable drugs by rearranging the crystal packing through incorporating coformers into the crystal lattice.