Exploring novel carrier for improving bioavailability of Itraconazole; Solid dispersion through Hot Melt extrusion

Kollicoat® Smartseal (Methyl methacrylate and diethylaminoethyl methacrylate copolymer dispersion) which is used for taste masking and moisture protection, has shown the ability for forming solid dispersion. The present study aimed to check its feasibility for exhibit improved pharmacokinetics when studied in-vivo in comparison to model high melting point drug-like Itraconazole. Hot-melt extrusion (HME) is a very well commercially accepted technology for solubility enhancement.

However, there are limited polymers that can be utilized due to narrow processing window, low thermoplastic behavior or impart stability to the formed amorphous solid dispersion. Thus, having a carrier, which can address all these concerns, will give the industry an additional choice of the carrier during the development of formulations. Thus, the authors have tried to address this issue and demonstrated the ability of the novel carrier to be exploited into HME technology. Solid dispersions of Itraconazole were prepared, characterized, and tested for in-vivo performance in rats. The results indicated that the carrier exhibited good thermoplastic behavior over a temperature range of 120 to 220 °C. Itraconazole had a plasticizing effect on the carrier. The in-vitro results indicated improved solubility by approx. 20 fold over plain Itraconazole.

The results of thermal analysis fosters the possibility of the formation of solid solution which converts into an amorphous form. Kollicoat Smartseal has shown high potential as a carrier to be used in HME for solubility enhancement of highly insoluble molecules like Itraconazole. It offered no processing challenges and the in-vivo results are in good agreement with in-vitro studies.

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Article information: Amit Chivate, Atul Garkal, Kartik Hariharan, Tejal Mehta. Exploring novel carrier for improving bioavailability of Itraconazole; Solid dispersion through Hot Melt extrusion, Journal of Drug Delivery Science and Technology, 2021. https://doi.org/10.1016/j.jddst.2021.102541.