Comparison of a single pharmaceutical surfactant versus intestinal biorelevant media for etravirine dissolution: Role and impact of micelle diffusivity
International Journal of Pharmaceutics, cilt.624, 2022 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 624
- Basım Tarihi: 2022
- Doi Numarası: 10.1016/j.ijpharm.2022.122015
- Dergi Adı: International Journal of Pharmaceutics
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
- Anahtar Kelimeler: Etravirine, Solubility, Dissolution, Biorelevant, Micelle, Surfactant
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Etravirine is an antiviral whose oral absorption is limited by low solubility/dissolution. The objective was to predict and compare etravirine's surfactant-mediated dissolution into polyoxyethylene-10 lauryl ether (POE) and FeSSIF-V2, including the contribution of slow micelle diffusivity. Dynamic light scattering (DLS) was used to measure the size and diffusivity values of drug-loaded micelles. In vitro intrinsic dissolution into surfactant media were predicted using a model for surfactant-mediated dissolution. Compared to maleic buffer, POE and FeSSIF-V2 increased etravirine solubility 232-fold and 8.97-fold, respectively. From DLS, micelle diffusivity of drug-loaded POE micelle and FeSSIF-V2 mixed-micelle was 5.15x10−7 cm2/s and 5.76x10−8 cm2/s, respectively. Observed and predicted dissolution enhancement into POE were 50.7 and 31.3, and 1.26 and 1.24 into FeSSIF-V2, respectively. Hence, there was high dissolution enhancement into POE, although the observed enhancement was only 21.9% of the observed solubility enhancement, reflecting the attenuating impact of the large and slowly diffusing drug-loaded POE micelles. Meanwhile, there was minimal dissolution enhancement into FeSSIF-V2, and the observed enhancement was only 14.0% of the observed solubility enhancement, reflecting the even slower diffusing drug-loaded FeSSIF-V2 mixed-micelles compared to drug-loaded POE micelles. Results are considered in light of designing a single pharmaceutical surfactant system for dissolution that mimics a FeSSIF-V2 system.