PALM OIL-BASED POLYESTERAMIDE AS FUNCTIONAL MATERIAL FOR SOLID DISPERSION

Abstract

Polymers play an essential role in the development of drug delivery systems by providing controlled release of active ingredients in the designed mode. Vegetable oil-based polymers are not only renewable, but also biodegradable and biocompatible when used as functional materials in pharmaceutical products. In this project, palm oil-based polyesteramide (POPEA) with distinct molecular weights (MW) of 4000-17000 Da were synthesised by reacting palm stearin with diethanolamine (molar ratio of 1: 2.7) at 110 °C, followed by the reaction with azelaic acid at the functionality molar ratio (OH:COOH) of 1: 0.84 at 150-190 °C. Stearic acid-based polyesteramide (SAPEA) with MW of 33000 Da was synthesised by reacting stearic acid with diethanolamine (molar ratio of 1:1) at 140 °C, followed by the reaction with adipic acid at functionality molar ratio (OH:COOH) of 1:1, at 170 °C.

The physicochemical properties of the synthesised polyesteramides (PEA) were determined by amine value (AOCS Tf 1b-64), acid value (AOCS Te 2a-64) and hydroxyl value (AOCS Cd 13-60). The chemical structure of PEAs was elucidated by Fourier Transform Infrared (FTIR), 13C- and 1H-Nuclear Magnetic Resonance (NMR) spectroscopies. The molecular weight distribution of PEAs was determined by Gel Permeation Chromatography (GPC).

The solid dispersion (SD) was prepared by loading 40%w/w of mefenamic acid (MA) with a combination of SAPEA and POPEA (8:2 w/w) using solvent-free melting method. All SDs prepared with different MW of POPEA demonstrated 5-7 folds enhancement in time required for 50% of drug release (T50%) and 2 folds increment in percentage of drug release compared to pure MA. Besides, they demonstrated comparable performance (P > 0.05) with the marketed formulation, fenagesic. The selected SD, SD 6 was stable in terms of drug content and solubility at room temperature and 40 ºC for up to 3 months. As for the dissolution profiles, the formulation was stable at room temperature (P > 0.05) but showed slight regression at 40 ºC (P < 0.05) under storage. SD 6 (IC50 =230 µg/mL) treatment prepared by MA equivalent concentration demonstrated comparable IC50 to pure MA (IC50 =190 µg/mL) which confirmed the safety profile of the newly synthesised PEAs.