Twin Screw Melt Granulation: Alternative Approach for Improving Solubility and Permeability of a Non-steroidal Anti-inflammatory Drug Ibuprofen

The current research is focused on investigating the suitability of the twin screw melt granulation (TSMG) approach for improving the solubility of a non-steroidal anti-inflammatory (NSAIDs) drug (ibuprofen), by developing granules using lipid surfactants. The solubility of the drug within the solid lipid excipients (Gelucire® 48/16 and Gelucire® 50/13) was determined by differential scanning calorimetry (DSC). The formulations were developed for drug and lipid ratios of 1:1.5, 1:3, and 1:4.5 using Neusilin® US2 as a solid adsorbent carrier. The solid-state properties of the drug investigated using differential scanning calorimetry (DSC) have revealed the conversion of the drug to an amorphous form for 1:3 and 1:4.5 ratios of formulations confirmed by powder x-ray diffraction analysis (PXRD). Drug–excipient compatibility and formation of no interactions were characterized using Fourier transform infrared spectroscopy (FTIR).

The granules with a 1:3 and 1:4.5 ratios of drug and lipid have improved drug dissolution and permeation, attributing to the formation of micellar emulsions. The stability of formulation with a 1:3 ratio of drug and lipid surfactant was preserved when stored in accelerated conditions. However, the formulation with a 1:4.5 ratio of drug and lipid failed to retain the amorphous state evidenced by the recrystallization of the drug. This shows the suitability of TSMG as a single-step continuous manufacturing process for developing melt granules to improve the solubility of poorly water-soluble drug substances.

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Nyavanandi, D., Narala, S., Mandati, P. et al. Twin Screw Melt Granulation: Alternative Approach for Improving Solubility and Permeability of a Non-steroidal Anti-inflammatory Drug Ibuprofen. AAPS PharmSciTech 24, 47 (2023).
https://doi.org/10.1208/s12249-023-02512-z