title: Combined mixture-process variable approach: a suitable statistical tool for nanovesicular systems optimization.
abstract: OBJECTIVE
  This study aims to illustrate the applicability of combined mixture-process variable (MPV) design and modeling for optimization of nanovesicular systems.
  
  
  METHODS
  The D-optimal experimental plan studied the influence of three mixture components (MCs) and two process variables (PVs) on lercanidipine transfersomes. The MCs were phosphatidylcholine (A), sodium glycocholate (B) and lercanidipine hydrochloride (C), while the PVs were glycerol amount in the hydration mixture (D) and sonication time (E). The studied responses were Y1: particle size, Y2: zeta potential and Y3: entrapment efficiency percent (EE%). Polynomial equations were used to study the influence of MCs and PVs on each response. Response surface methodology and multiple response optimization were applied to optimize the formulation with the goals of minimizing Y1 and maximizing Y2 and Y3.
  
  
  RESULTS
  The obtained polynomial models had prediction R(2) values of 0.645, 0.947 and 0.795 for Y1, Y2 and Y3, respectively. Contour, Piepel's response trace, perturbation, and interaction plots were drawn for responses representation. The optimized formulation, A: 265 mg, B: 10 mg, C: 40 mg, D: zero g and E: 120 s, had desirability of 0.9526. The actual response values for the optimized formulation were within the two-sided 95% prediction intervals and were close to the predicted values with maximum percent deviation of 6.2%.
  
  
  CONCLUSIONS
  This indicates the validity of combined MPV design and modeling for optimization of transfersomal formulations as an example of nanovesicular systems.
authors.affiliation: a Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Cairo University , Cairo , Egypt.
authors.forename: Basant A
authors.initials: BA
authors.lastname: Habib
authors.affiliation: a Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Cairo University , Cairo , Egypt.
authors.forename: Mohamed H H
authors.initials: MH
authors.lastname: AbouGhaly
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D008962:Models, Theoretical; D010316:Particle Size
keywords: Combined mixture-process variable approach; lercanidipine nanovesicles; numerical optimization; perturbation plot; piepel’s response trace plots; response surface methodology