(502e) Improving the Dissolution of Ibuprofen By Co-Milling of Ibuprofen and MCC Mixture in a Ball Mill

In this work, we investigated the improvement of dissolution of ibuprofen by co-milling the ibuprofen with microcrystalline cellulose, MCC (hydrophilic excipient) in dry mode. Ibuprofen and MCC were taken in 1:1 weight ratio and co-milled for different times in a planetary ball mill. Co-milled, v-blended and as received samples were characterized by different techniques. Particle size distribution measured using laser diffraction method exhibited a shift to lower particle size. To understand the morphology, shape and surface changes, optical microscopy and Field Emission Scanning Electron Microscopy (FE-SEM) were performed. While the crystallinity and crystal level changes (such as defects, strain energy and crystallite size etc.) were measured using Powder X-Ray Diffraction (P-XRD), the presence of different functional groups on the surface and the interactions between drug and excipient; and hydrogen bond formation was evaluated using Fourier Transform Infrared Spectroscopy (FTIR). The changes in the crystallinity due to co-milling were further confirmed using Differential Scanning Calorimetry (DSC) where the shift of melting endotherm to lower temperature was observed. Acidic and basic nature of the surface was evaluated by Inverse Gas Chromatography (IGC) measurements by acidic and basic parameters. The wettability measurements performed by the sessile drop method shows lower contact angle for co-milled samples demonstrating improvement in wettability of the ibuprofen. This is also confirmed by the dissolution test in USP Paddle II apparatus. The study shows that co-milling imparts surface hydrophilicity apart from size reduction by generating defects, dislocations and decreased crystallite size by the impact of balls on the surface. Increased interactions between carboxylic acid group and hydroxyl group result in hydrogen bond formation thereby improving the wettability and dissolution. Increase in polar surface energies and increase in the ratio of basic to acidic constant indicates hydrophilic nature of the surface which contributes to enhancing the dissolution of ibuprofen. Thus, co-milling can be an alternate solventless method to improve dissolution of BCS Class II drugs.