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

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.

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Materials: Gentian (Gentiana lutea, Gentianaceae) roots were purchased from the Institute for Medicinal Plants Research “Dr. Josif Pančić” (Belgrade, Serbia). Gelucire® 43/01 and Gelucire® 39/01 were obtained as gift samples from Gattefossé® (Saint-Priest, France). Polyglycerol polyricinoleate was obtained as a gift sample from Palsgaard® (Juelsminde, Denmark). Trehalose dihydrate was purchased from TCI Chemicals (Tokyo, Japan). Span® 80 (sorbitan oleate), Tween® 80 (polysorbate 80), Tween® 20 (polysorbate 20), and sodium chloride were obtained from Merck Co., Germany, while sodium alginate was purchased from Fisher Scientific, soybean lecithin was obtained from Serva Chemical Co. (Heidelberg, Germany), Sylysia® 350 was obtained from Fuji Silysia chemical ltd. (Kasugai Aichi, Japan). For the mucoadhesion evaluation, the mucin from a porcine stomach, Type II (Sigma-Aldrich, Shanghai, China) was used. All other chemicals were of analytical grade, including orthophosphoric acid (Sigma-Aldrich Chemie GmbH, Münich, Germany), acetonitrile (Merck, Darmstadt, Germany). Ultra-pure water was prepared using a Milli-Q purification system (Millipore, Guyancourt, France). Gentiopicroside standard was obtained from ChromaDex (Los Angeles, CA, USA).

Article information: Mudrić, J.; Šavikin, K.; Đekić, L.; Pavlović, S.; Kurćubić, I.; Ibrić, S.; Đuriš, J. Development of Lipid-Based Gastroretentive Delivery System for Gentian Extract by Double Emulsion–Melt Dispersion Technique. Pharmaceutics 2021, 13, 2095. https://doi.org/10.3390/pharmaceutics13122095