Corroborating various material-sparing techniques with hot melt extrusion for the preparation of triclabendazole amorphous solid dispersions
Amorphous solid dispersions (ASD) are one of the most adopted technologies for improving the solubility of novel molecules. Formulation of ASDs using solvent free methods such as hot melt extrusion (HME) has been in the spotlight off-lately. However, early-stage formulation development is tricky and a difficult bridge to pass due to limited drug availability. Material-sparing techniques (theoretical & practical) have been used for selecting suitable polymeric carriers for formulating ASDs. However, these techniques have limitations in predicting the effect of process parameters. The objective of this study is to use both theoretical and practical material-sparing techniques to optimize a polymer for the developing Triclabendazole (TBZ) ASDs.
Initial screening by theoretical approaches suggested that TBZ is highly miscible with Kollidon®VA64 (VA64) and poorly miscible with Parteck®MXP (PVA). However, results from ASDs prepared using SCFe were opposite to these predictions. ASDs prepared using either technique and both VA64 and PVA showed >200x increase in solubility. Each formulation released >85% of drug in less than 15 mins. Although the thermodynamic phase diagram suggested that VA64 was the ideal polymer for TBZ-ASDs, it has certain limitations in factoring the different elements during melt-processing and hence, practical approaches like SCFe could help in predicting the drug-polymer miscibility for HME processing.
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Materials
Triclabendazole (TBZ) (6-Chloro-5-(2,3-dichloro phenoxy)-2-(methylthio)-1H-benzo[d]imidazole) was purchased from AK Scientific (Union City, CA, USA). Gift samples of Parteck®MXP (PVA), Kollidon®VA64 (VA64), and Aquazol® were acquired from EMD Millipore Sigma (Darmstadt, Germany), BASF Corporation (Florham Park, NJ, USA), and Polymer chemistry Innovations, Inc. (Tucson, AZ, USA), respectively. HME Cleaner Plus was acquired from BioGrund GmBH (Hünstetten, Germany).
Siddhant Palekar, Hemanth K. Mamidi, Yi Guo, Richa Vartak, Ketan Patel, Corroborating various material-sparing techniques with hot melt extrusion for the preparation of triclabendazole amorphous solid dispersions, International Journal of Pharmaceutics, Volume 640, 2023, 122989, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2023.122989.
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