Intestinal Lymphatic Drug Delivery of Phenothiazines by Ex-Vivo Model: Influence of Self-Nanoemulsifying Formulation Design
Gul Shahnaz
Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Austria
Abstract:
The aim of this study was to examine the potential of self-nanoemulsifying drug delivery systems (SNEDDS) on the uptake of lipophilic, poorly water soluble phenothiazines with the isolated plasma derived chylomicron (CM) ex vivo model. The multi-component delivery systems were optimised by evaluating their ability to self-emulsify when introduced to an aqueous medium under gentle agitation. The uptake of phenothiazines by isolated plasma derived chylomicrons was investigated with short-chain triglyceride (SCT) SNEDDS, medium-chain triglyceride (MCT) SNEDDS, and a long-chain triglyceride (LCT) SNEDDS. SNEDDS was also evaluated for their stability, dispersibility, percentage transmittance and particle size analysis. For thioridazine 6-folds and for chlorpromazine 4-folds higher uptake by isolated CM could be observed with the SNEDDS formulation based on LCT compared to the drugs without formulation. However, uptake by isolated CM ex vivo was not significantly different by the SNEDDS formulation based on MCT and SCT. Compared with the isolated chylomicrons, the size of chylomicrons following SNEDDS incubation increased 3-fold for the LCT, whereas MCT and SCT incubation resulted only in a small, non-significant (P < 0.05) increase in chylomicron size. Thus, the study confirmed that the SNEDDS formulation containing phenothiazines extensively binding to isolated CM will be prone to intestinal lymphatic transport and subsequently can lead to an improvement of oral bioavailability.
Keywords: Chylomicrons, Self-nanoemulsifying drug delivery system (SNEDDS), Phenothiazines.
