Evaluation of solid carvedilol-loaded SMEDDS produced by the spray drying method and a study of related substances
In this study, various formulations of solidified carvedilol-loaded SMEDDS with high SMEDDS loading (up to 67% w/w) were produced with the spray drying process using various porous silica-based carriers. The process yield was improved with higher atomization gas flow rate during the spray drying process and with prolonged mixing time of dispersion of liquid SMEDDS and solid porous carriers prior to the spray drying process.
Highlights
Spray drying enables production of s-SMEDDS with high SMEDDS loading (up to 67% w/w).
Mixing time of dispersion before spray drying has impact on process yield.
Carrier type has impact on process yield, drug content and s-SMEDDS characteristics.
Carvedilol forms amides with fatty acids from the oily components of SMEDDS.
Depending on the choice of the carrier and the SMEDDS:carrier ratio in solid SMEDDS, different drug loading, self-microemulsifying properties, drug release rates, and released drug fractions were obtained. The products exhibited fast drug release due to preserved self-microemulsifying properties and the absence of crystalline carvedilol, which was confirmed with XRD and Raman mapping.
A decrease in drug content during the stability study was observed and investigated. This was at least partially attributed to the chemical degradation of the drug. Key degradation products determined by the LC-MS method were amides formed by in situ reaction of carvedilol with fatty acids present in the oily phase of SMEDDS.
Article information: J. Mandić, I. Kosmač, M. Kovačević, B. Hodnik, Ž. Hodnik, F. Vrečer, M. Gašperlin, B. Perissutti, A. Zvonar Pobirk. Evaluation of solid carvedilol-loaded SMEDDS produced by the spray drying method and a study of related substances, International Journal of Pharmaceutics, Volume 605, 2021. https://doi.org/10.1016/j.ijpharm.2021.120783.