Development of solid lipid nanoparticles of diacerein in a stable oral liquid dosage form using a central composite design

Abstract

Diacerein (DCN) is used mainly to treat degenerative diseases, such as osteoarthritis. DCN is marketed commercially in solid dosage forms. Liquid formulations of diacerein (DCN) have been hindered by its poor chemical stability in aqueous media. This work aims to develop a novel, stable, oral, liquid preparation of DCN having a concentration of 50 mg/5 ml. Solid lipid nanoparticles (SLNs) of DCN were prepared using cetyl alcohol as the lipid matrix and Tween 80® as a surfactant. A quality-by-design approach was utilized to optimize DCN-SLNs. The optimum DCN-SLNs were dispersed in a structured vehicle to formulate the liquid dosage form. This liquid preparation was subjected to accelerated stability studies at 40 °C and 75% RH for 6 months. The potential of the liquid preparation to minimize the diarrheal effect of DCN was assessed. Optimum concentrations of cetyl alcohol (2%) and Tween 80® (0.9%) were chosen to obtain the desired characteristics of SLNs. Interestingly, we determined that 0.05% of citric acid was the maximum concentration that can be added to the liquid preparation of diacerein to modify its pH without compromising its stability. The results of the stability studies show that the liquid preparation was robust and it withstood storage conditions (40 °C, 75% RH) for 6 months. The encapsulation of diacerein helps to protect it from degradation and significantly reduced the occurrence of diarrhea as a side effect (p < 0.0001). Liquid preparations of DCN-SLNs can thus be marketed as a new dosage form.