Atovaquone smart lipid system: Design, statistical optimization, and in-vitro evaluation

Abstract

The research was undertaken to design, develop and characterize the smart lipid system of an inadequate bioavailable Atovaquone (ATQ). The poor aqueous solubility and dissolution are the major constrain of inadequate bioavailability. The solubility study reveals that Labrasol-ALF (L-ALF), Tween 80, and Trancutol®P (TP) were screened as oil, surfactant, and co-surfactant, respectively. The pseudo ternary diagram was constructed to locate the appropriate amount of each ingredient, and a 1:3:1 ratio of L-ALF: Tween 80: TP was chosen. The effect of precipitation inhibitor was assessed using the parachute effect. Soluplus® (SP) was chosen as a precipitation inhibitor at 5%. Ishikawa diagram and qualitative risk assessment were performed to screen the critical material attributes (CMAs) and critical process parameters (CPPs). D-optimal mixture design was explored for the optimization of the formulation. The amount of oil, surfactant, and co-surfactant was screened as independent variables, whereas globule size, poly-dispersibility index (PDI), and solubility were designated dependent variables. The design batches were evaluated for the in-vitro dissolution rate, PDI, zeta potential, globule size, etc. The optimal region was located using an overlay plot. The optimized formulation has shown a 97.91% drug release within 1h. The value of zeta potential (-27.43mV) and PDI (0.468) indicates the stability of the formulation. The parachute effect had explored for the selection of precipitation inhibitors. SP was able to increase the solubility of ATQ and reduce the precipitation of the drug. The amount of L-ALF, Tween, 80and TP was significant for the formulation of SNEDDS. The formulation was novel, effective, patient-friendly, and industry oriented.