Advanced co-crystallization of Dolutegravir by microwave, ultrasound and supercritical fluid technology for Solubility enhancement.

Crystal engineering approach is recognized by pharmaceutical scientists as a way of improving and tailoring the physicochemical properties of active pharmaceutical ingredients (API). Co-crystallization provides advanced prospective for changing the API properties by using a much more extensive range of co-crystallizing molecules (coformers). Co-crystals are crystalline form of substance composed of two or more compounds in the same crystal lattice. Dolutegravir is a HIV integrase inhibitor, used in combination with other antiretroviral agents and is BCS-II drug. The major objective of research was to improve of solubility profile of Dolutegravir sodium by co-crystallization with suitable co-formers using microwave, ultrasound and supercritical fluid technology. Benzoic acid, Urea, Oxalic acid, Citric acid, L-asparagine were selected as co-formers on the basis Hansen solubility parameter and pKa difference method. The Co-crystals were evaluated and confirm by FTIR, DSC, SEM, XRD and Polarized light microscopy. Equilibrium aqueous solubility studies were performed for all co-crystals taking Dolutegravir as the control. Amongst various co-formers L-asparagine resulted in co-crystals with highest enhancement (22 folds) in solubility. The results reveals that Microwave assisted technique is more promising than, ultrasound and supercritical fluid technology.

Author(s): Dr. Swaroop Lahoti

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