Development and Formulation of Baicalin-loaded Self-nanoemulsifying Matrix Pellets

Abstract

Baicalin is a flavone glycoside, extracted from the root of Scutellaria baicalensis Georgi, a traditional Chinese herbal medicine (Fig.1.). The root is officially listed in the Chinese Pharmacopoeia and was assumed in European Pharmacopoeia (Ph. Eur.) 9th Edition in 2018. It was shown, that the poorly water soluble and poorly permeable polyphenolic flavonoid has remarkable pharmacological effects including antioxidant, antimicrobial and anti-tumor actions1. In our previous publication the fundamental physicochemical properties influencing the pharmacokinetic behavior of baicalin like the acid-base properties, lipophilicity, permeability and solubility were thoroughly characterized. Considering the data, baicalin can be classified as class IV. according to the Biopharmaceutical Classification System (BCS)2. Self-emulsifying drug delivery systems (SEDDS) are isotropic mixtures of oil, surfactant, co-surfactant and the lipophilic compound, which are spontaneously form oil-in-water (o/w) emulsions upon mild agitation followed by dilution in gastro-intestinal fluids3. In another publication of our research group liquid SEDDS were developed and formulated to counterbalance the challenging physicochemical and pharmaceutical properties of baicalin4. Dissolution kinetics of baicalin was improved in the optimized self-nanoemulsifying system taking different types of oils, surfactants, cosurfactants, and ideal ratio of components into consideration, based on response surface methodology, using a central composite experimental design. The best composition contains Peceol® (14.29%, w/w), Kolliphor® EL (57.14%, w/w), and Transcutol® P (28.57%, w/w). Droplet size after dispergation of BSNEDDS pre-concentrate was highly desirable, with 86.75 ± 0.3553 nm. The main objective of this work was to formulate and develop baicalin-loaded solid SEDDS by transforming liquid self-emulsifying preconcentrates to solid carriers and prepare matrix pellets by extrusion-spheronization. Furthermore, the focus was put on the evaluation and analysis of fundamental relationships between drug and dosage form.