Predictive Application of Hansen Solubility Parameters in the Design of Methocarbamol-Ascorbic Acid Cocrystals for Solubility and Dissolution Enhancement

Background

Methocarbamol, a centrally acting skeletal muscle relaxant, exhibits poor aqueous solubility, limiting its bioavailability. Cocrystallization offers a promising approach to enhance solubility and dissolution without altering pharmacological activity. This study aimed to design Methocarbamol-Ascorbic acid Cocrystals (MAC) using Hansen Solubility Parameters (HSPs) to predict miscibility and confirm improved physicochemical performance.

Materials and Methods

HSPs were calculated using the Van Krevelen-Hoftyzer group contribution method to predict drug-coformer compatibility. Cocrystals were prepared by the solvent evaporation method in a 1:1 molar ratio. Characterization was performed using Fourier-Transform Infrared Spectroscopy (FTIR), Powder X-ray Diffraction (PXRD), and Differential Scanning Calorimetry (DSC). Solubility and dissolution studies were carried out in aqueous, 0.1 N HCl, and phosphate buffer (pH 6.8) media.

Results and Discussion

Theoretical analysis indicated a Δδ value of 10.96 MPa^0.5, suggesting moderate miscibility with good hydrogen bonding potential between methocarbamol and ascorbic acid. FTIR confirmed hydrogen bonding interactions. PXRD revealed new crystalline peaks and DSC displayed altered endothermic transitions, confirming cocrystal formation. The MAC cocrystal exhibited enhanced solubility (2.07 mg/mL in 0.1 N HCl) and faster dissolution (99.3% release in 30 min) compared to pure methocarbamol (1.14 mg/mL, 87.2% release). The improvement may be attributed to hydrogen bonding and reduced lattice energy, which improved wettability and dissolution rate.

Conclusion

Cocrystallization of methocarbamol with ascorbic acid successfully enhanced solubility and dissolution behaviour. Theoretical predictions aligned with experimental outcomes, validating HSPs as an effective tool for coformer selection and demonstrating cocrystallization as a viable strategy to improve biopharmaceutical performance of poorly soluble drugs.