Development of dual drug loaded solid self microemulsifying drug delivery system: Exploring interfacial interactions using QbD coupled risk based approach

Abstract

Aceclofenac is widely prescribed with Febuxostat, the drug of choice in gout management, to eliminate the risk of gout flare. Though, no attempts have been made till date to combine them in single formulation. Hence, present research envisaged to develop dual drug loaded solid self microemulsifying drug delivery system addressing the associated formulation challenges. Quality by design approach was utilized to thoroughly understand various material attributes and process parameters playing vital role in formulation development. Quality Target Product Profile was laid down and failure mode and effects analysis was performed for better identification of the risks, ways to mitigate them and to put forward a control strategy. The amount of oil, surfactant and co-surfactant were identified as high risk variables, and their influence on product quality was studied using D-Optimal Mixture design considering globule size and % transmittance as dependent variables. Neusilin® US2 was selected as an adsorbent after screening of various silicates. The morphology of the oil globules in microemulsion was observed using transmission electron microscopy. Febuxostat and Aceclofenac loaded solid self microemulsifying drug delivery system also exhibited 1.87 and 4.19 fold increase in the oral bioavailability, respectively and remained stable during three months stability testing. Final risk assessment revealed that the risk associated with all the failure modes was significantly reduced after implementation of control strategy. Results collectively signified successful development of dual drug loaded solid self microemulsifying drug delivery system.