Self microemulsifying drug delivery system of lurasidone hydrochloride for enhanced oral bioavailability by lymphatic targeting: In vitro, Caco-2 cell line and in vivo evaluation

• Published in: European journal of pharmaceutical sciences Vol. 138; p. 105027
• Main Authors: Patel, Mitali H., Sawant, Krutika K.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-10-2019
• Subjects: Administration, Oral; Animals; Biological Availability; Caco-2 Cells; Cell Line, Tumor; Coumarins - chemistry; Drug Delivery Systems - methods; Emulsions - chemistry; Female; Humans; Lipids - chemistry; Lurasidone Hydrochloride - chemistry; Lurasidone Hydrochloride - metabolism; Permeability - drug effects; Rats; Rats, Sprague-Dawley; Solubility - drug effects; Surface-Active Agents - chemistry; Suspensions - chemistry; Suspensions - metabolism; Thiazoles - chemistry
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2019.105027

The global aim of this research was to develop and evaluate self-microemulsifying drug delivery system (SMEDDS) to improve oral bioavailability of Lurasidone Hydrochloride (LH). A chylomicron flow blocking approach was used to evaluate lymphatic drug transport. The developed LH-SMEDDS was composed of Capmul MCM C8 (oil), Cremophor EL (surfactant) and Transcutol HP (co-surfactant). Highest microemulsifying area was obtained at 3:1 ratio (surfactant:cosurfactant) and mean globule size was found to be 49.22 ± 1.60 nm. More than 98% drug release was obtained with LH-SMEDDS in phosphate buffer pH 6.8. Confocal microscopy and flow cytometry studies revealed higher fluorescence indicating deeper penetration across Caco-2 cells with Coumarin-6 SMEDDS as compared to Coumarin-6 solution. Mean Fluorescence Intensity (MFI) with Coumarin-6 loaded SMEDDS was increased 25.57 times with respect to Coumarin-6 solution. The permeability across Caco-2 cells was enhanced 3 times with LH-SMEDDS as compared to LH-suspension. Furthermore, Area Under Curve with LH-SMEDDS was found to be 2.92 times higher than that of LH suspension indicating improved bioavailability after formulating SMEDDS. Lymphatic transport in oral absorption of LH-SMEDDS was proved via lymphatic uptake study. All the findings suggest the effectiveness of lipid-based formulation i.e. SMEDDS of LH to augment the oral bioavailability via intestinal lymphatic pathway.
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