Improving the wetting and dissolution of ibuprofen using solventless co-milling

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Hydrophobic drugs, particularly those in BCS Class II, often exhibit poor wetting and dissolution, limiting their bioavailability.
• Traditional methods for enhancing drug solubility can involve complex formulations or organic solvents.
• Solid dispersion techniques offer a promising avenue for improving drug performance.

Purpose of the Study:

• To investigate the efficacy of a solventless co-milling technique for enhancing the wetting and dissolution of Ibuprofen, a BCS Class II drug.
• To elucidate the physical and chemical changes induced by co-milling at the drug-excipient interface.
• To evaluate the potential of this technique for other hydrophobic drugs.

Main Methods:

• Co-milling of Ibuprofen with Microcrystalline Cellulose (MCC) at a 1:1 weight ratio using a planetary ball mill.
• Characterization using Powder X-ray Diffraction (P-XRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), microscopy (Optical, FESEM), Modulated Temperature Differential Scanning Calorimetry (MTDSC), Raman microscopy, Inverse Gas Chromatography (IGC), and sessile drop method.
• Comparison with raw ibuprofen, ball-milled ibuprofen, and a physical blend.

Main Results:

• Co-milling significantly improved Ibuprofen wetting and dissolution, achieving 96% dissolution within 90 minutes.
• Co-milling induced changes in crystal level properties, including defects, strain, and reduced crystallinity, alongside increased drug-excipient interaction and hydrogen bond formation.
• Surface analysis revealed an increase in polar surface energy and transformation of the hydrophobic drug surface to a hydrophilic one due to MCC's OH groups.

Conclusions:

• Solventless co-milling is an effective technique for enhancing the wetting and dissolution of hydrophobic drugs like Ibuprofen.
• The observed improvements are attributed to alterations in crystal properties and enhanced surface hydrophilicity.
• This method holds significant potential for application with BCS Class II and IV drugs and various hydrophilic excipients.