Preparation and optimization of berberine phospholipid complexes using QbD approach and in vivo evaluation for anti-inflammatory, analgesic and antipyretic activity

Abstract

Berberine (BER) is a benzylisoquinoline alkaloid found in many plants. It has high water solubilitybut its bioavailability is low in oral administration due to the first-pass effect in the liver and intestine. Phytosomesare are prepared by complexing herbal active ingredients and phospholipids (PLs). The aim of this study is to prepare BER-phospholipidcomplexes (BPCs) using the reverse phase evaporation method. In the preparation of the formulations, the effects of BER:PL ratio (w/w), reaction temperature (°C) and reaction time (h) on the specifications of the complexes such as particle size (PS), zeta potential (ZP) and encapsulation efficiency (EE%) were investigated. The distribution of PS of obtained complexes was ranging between 339-1259 nm and their ZP were within-4,27--5,15 mV. The drug EE% was relatively high. Quality by Design (QbD) methods have been used in the formulation design and selection of the optimum formulation. BPCs anti-inflammatory, analgesic and antipyretic activities are evaluated by using in vivo methods.Carrageenan-, Prostaglandin E2 (PGE2)-and serotonin-induced hind paw edema, acetic acid-induced increase in capillary permeability and subcutaneous air-pouch models for the anti-inflammatory activity, inhibition of p-benzoquinone-induced abdominal constriction and hot plate test for the analgesic activity, Freund’s complete adjuvant-induced pyrexia model for the antipyretic activity were used in mice and rats. Results showed that BPCs showed potent anti-inflammatory, analgesic and antipyretic activities at the dose of 209 mg/kg.