Development of Lipid-Based Gastroretentive Delivery System for Gentian Extract by Double Emulsion-Melt Dispersion Technique

Jelena Mudrić; Katarina Šavikin; Ljiljana Đekić; Stefan Pavlović; Ivana Kurćubić; Svetlana Ibrić; Jelena Đuriš

doi:10.3390/pharmaceutics13122095

Development of Lipid-Based Gastroretentive Delivery System for Gentian Extract by Double Emulsion-Melt Dispersion Technique

Pharmaceutics. 2021 Dec 6;13(12):2095. doi: 10.3390/pharmaceutics13122095.

Authors

Jelena Mudrić¹, Katarina Šavikin¹, Ljiljana Đekić², Stefan Pavlović³, Ivana Kurćubić², Svetlana Ibrić², Jelena Đuriš²

Affiliations

¹ Institute for Medicinal Plants Research "Dr. Josif Pančić", Tadeuša Košćuška 1, 11000 Belgrade, Serbia.
² Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
³ Institute of Chemistry, Technology, and Metallurgy-National Institute for the Republic of Serbia, University of Belgrade, Njegoševa 12, 11001 Belgrade, Serbia.

Abstract

Gentian (Gentiana lutea L., Gentianaceae) root extract (GRE) is used for the treatment of gastrointestinal disorders. However, its bioactive potential is limited in conventional forms due to the low bioavailability and short elimination half-life of the dominant bioactive compound, gentiopicroside. The aim of study was to encapsulate GRE in the lipid-based gastroretentive delivery system that could provide high yield and encapsulation efficiency, as well as the biphasic release of gentiopicroside from the tablets obtained by direct compression. Solid lipid microparticles (SLM) loaded with GRE were prepared by freeze-drying double (W/O/W) emulsions, which were obtained by a multiple emulsion-melt dispersion technique, with GRE as the inner water phase, Gelucire^® 39/01 or 43/01, as lipid components, with or without the addition of porous silica (Sylysia^® 350) in the outer water phase. Formulated SLM powders were examined by SEM and mercury intrusion porosimetry, as well as by determination of yield, encapsulation efficiency, and flow properties. Furthermore, in vitro dissolution of gentiopicroside, the size of the dispersed systems, mechanical properties, and mucoadhesion of tablets obtained by direct compression were investigated. The results have revealed that SLM with the macroporous structure were formulated, and, consequently, the powders floated immediately in the acidic medium. Formulation with porous silica (Sylysia^® 350) and Gelucire^® 43/01 as a solid lipid was characterized with the high yield end encapsulation efficiency. Furthermore, the mucoadhesive properties of tablets obtained by direct compression of that formulation, as well as the biphasic release of gentiopicroside, presence of nanoassociates in dissolution medium, and optimal mechanical properties indicated that a promising lipid-based gastroretentive system for GRE was developed.

Keywords: Gelucire 39/01; Gelucire 43/01; SLM; Sylysia 350; biphasic release; direct compression; double (W/O/W) emulsion; gastroretentive system; gentiopicroside; mucoadhesion; solid lipid microparticles.