Study on the Correlation Between Nimodipine (BCS Class II) Solubility, Dissolution Improvement, and Brain Tissue Concentration Through Cocrystallization

Background Cocrystallization by solvent evaporation was used to enhance the dissolution, physicochemical properties, and bioavailability of nimodipine (NMD). Here, we aimed to develop NMD cocrystals with improved solubility and dissolution. Thereafter, our objective was to check the changes in brain tissue concentrations before and after the cocrystal formation of NMD. Methods A 3 2 -factor design was used for product optimization by determining the desirability function. Differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy were used to confirm the formation of cocrystals. Results The saturation solubility study of NMD:SA cocrystals resulted in 9.52 mg/ml, which is 128-fold higher than that of pure NMD (0.074 mg/ml). In vitro dissolution and permeability studies showed an improvement in the percentage of drug release and permeability of NMD from cocrystals as compared to pristine NMD. An in vivo study of oral bioavailability in Wistar rats demonstrated higher plasma and brain tissue concentrations of NMD in the cocrystal form than in the conventional oral suspension. Discussions The findings of this study showed a positive correlation between nimodipine solubility, improvement in dissolution, and its effect on brain tissue concentration in Wistar rats. The improved solubility of nimodipine may lead to increased dissolution rates, which can enhance its bioavailability and therapeutic efficacy in the treatment of cerebral vasospasms.