Screening and optimization of supercritical fluid process for the preparation of albendazole solid dispersion

Solid dispersion (SD) technology has been proved to be one of the most successful techniques to enhance aqueous solubility of poorly-water soluble drugs. Supercritical fluid (SCF) using carbon dioxide (CO₂) became attractive due to its own advantages, including non-toxic, low temperature required, low cost and environmentally friendly without organic solvent. The objective of this research is to improve the solubility and dissolution rate of a poorly-water soluble and heat-labile drug albendazole (ABZ) using SCF technology. Initially, polymer screening was performed by melting point depression and correlated with the batches prepared using SCF technology. Further, process and product were optimized by solid state characterization, morphological imaging, in-vitro dissolution and MDCK permeability study. Preliminary screening indicated that Eudragit® EPO and polyvinyl alcohol (PVA) were miscible with ABZ. However, Kollidon® VA64 showed better dissolution compared to PVA, Soluplus®, HPMC-AS and PVP K30. Kollidon® VA64 was finally selected for further study due to its pH independent solubility. Solid state characterization showed substantial amorphization of ABZ in the SCF batches processed at 80 °C, 1500 psi and 2 h. SEM images revealed a porous structure of the SCF sample for water penetration which could be responsible for improved dissolution. The ABZ-SD showed tremendously higher dissolution at both pH 1.2 and 6.8 compared to plain drug and physical mixture. The presence of bile salt resulted in enhanced dissolution rate but did not affect the percentage of drug release (Q120) and pure drug dissolution. MDCK transwell study suggested that the SCF formulation showed 2-fold enhancement in permeability compared to pure ABZ. Solid dispersion of ABZ can be successfully prepared by SCF technology with enhanced solubility and dissolution.

Materials

Albendazole (ABZ) was purchased from Tokyo Chemical Industry Co., Ltd. (TCI), (Portland, OR). Gift samples of Soluplus® and Kollidon® VA64 were acquired from BASF Corporation (Florham Park, NJ, USA). Gift samples of Parteck®MXP PVA, Eudragit® EPO and AQOAT® AS-MG were acquired from EMD Millipore Sigma (Darmstadt, Germany), Evonik Industries AG (Essen, Germany) and Shin-Etsu Chemical Co., Ltd. (Niigata, Japan), respectively. Povidon K30 was purchased from Spectrum Chemical Mfg. Corp. (Gardena,

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Yi Guo, Henis Patel, Aishwarya Saraswat, Kranthi Venkat Mateti, Ketan Patel, Emilio Squillante, Screening and optimization of supercritical fluid process for the preparation of albendazole solid dispersion, Journal of Drug Delivery Science and Technology, 2023, 104852, ISSN 1773-2247,
https://doi.org/10.1016/j.jddst.2023.104852.