Statistical Development of Posaconazole Smedds via D-Optimal Mixture Design under a QBD Paradigm

Introduction: Posaconazole is a class II BCS (Biopharmaceutical Classification System) antifungal drug. Current study objective is to enhance solubility by formulating SMEDDS guided by QbD via experimental design. Methods: Solubility studies in surfactants, oils, and co-surfactants were conducted. Critical quality attributes (CQA), emulsification time (R1) and drug release (R2) were taken as dependent factors. Formulations were prepared as per d-optimal mixture design and evaluated for physico-chemical parameters and dissolution studies. Results: Maximum solubility 6.953mg/ml in Tween 40, 1.630mg/ml in Transcutol & 0.187mg/ml in Capmul MCM were selected as surfactant, co-surfactant and oil phases. Excipient compatibility was confirmed by FTIR studies. Soluplus was used as Precipitation Inhibitor. Independent factors and dependent factors were mathematically co-related by Linear model and cubic model. From Overlay plots OF1 formulation (43.30ml Capmul MCM, 20ml Tween 40, 36.69ml Transcutol) with desirability co-efficient 0.991 was optimised. This formulation Globule size is 62.7nm, PDI 0.08 and Zeta-potential -0.19 mV. Discussion: Quality target product profile was postulated and CQA assessed by experimental design. Oil, Capmul MCM influenced rate of emulsification positively but decreased drug release. Surfactant and co-surfactant increased drug release but slowed emulsification time. D-Optimal mixture design was validated by correlation co-efficient of approx. 0.9 between predicted and actual responses. Formulations followed Fickian diffusion mechanism and were stable for one month at 40°C/75% RH. Conclusion: Posaconazole solubility as SMEDDS has been enhanced.