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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., (© 2023. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Efinaconazole is the first azole derivative approved by FDA for the topical treatment of onychomycosis. The objective of present study was to develop and validate HPLC method for estimation of efinaconazole in ex vivo human nail permeation study samples. The chromatographic analysis was performed on a HPLC system equipped with diode array detector. The efinaconazole and internal standard (IS) were extracted from the human nail samples by using the protein precipitation method. The samples were injected on to 5 μm Polar C 18 100Å, 4.6 mm × 150 mm column. The mobile phase consisted of 0.01 M potassium dihydrogen phosphate: acetonitrile (36:64) and eluent was monitored at 205 nm. The chromatographic separation of drug and analyte was achieved using isocratic elution at flow rate of 1 mL/min with a total run time of 15 min. The efinaconazole and IS were eluted at 6.4 ± 0.5 and 8.3 ± 0.5 min, respectively. The developed method was validated as per FDA guidelines, and the results met with acceptance criteria. The method developed was specific, and the analyte concentrations were linear at range of 50 to 10000 ng/mL (R 2 ≥ 0.9981). The validated HPLC method was applied for quantifying efinaconazole in human nail permeation study samples. The permeation of efinaconazole was increased by twofolds with Labarfac CC (15135.4 ± 2233.9 ng/cm 2 ) compared to formulations containing Transcutol P (6892.0 ± 557.6 ng/cm 2 ) and Labrasol (7266.1 ± 790.6 ng/cm 2 ). The study results demonstrate that developed efinaconazole HPLC method can be employed for formulation evaluation and clinical studies., (© 2021. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)