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.
