title: Optimizing the dermal accumulation of a tazarotene microemulsion using skin deposition modeling.
abstract: BACKGROUND
  It is well known that microemulsions are mainly utilized for their transdermal rather than their dermal drug delivery potential due to their low viscosity, and the presence of penetration enhancing surfactants and co-surfactants.
  
  
  OBJECTIVE
  Applying quality by design (QbD) principles, a tazarotene microemulsion formulation for local skin delivery was optimized by creating a control space.
  
  
  METHODS
  Critical formulation factors (CFF) were oil, surfactant/co-surfactant (SAA/CoS), and water percentages. Critical quality attributes (CQA) were globular size, microemulsion viscosity, tazarotene skin deposition, permeation, and local accumulation efficiency index.
  
  
  CONCLUSIONS
  Increasing oil percentage increased globular size, while the opposite occurred regarding SAA/CoS, (p = 0.001). Microemulsion viscosity was reduced by increasing oil and water percentages (p < 0.05), due to the inherent high viscosity of the utilized SAA/CoS. Drug deposition in the skin was reduced by increasing SAA/CoS due to the increased hydrophilicity and viscosity of the system, but increased by increasing water due to hydration effect (p = 0.009). Models with very good fit were generated, predicting the effect of CFF on globular size, microemulsion viscosity, and drug deposition. A combination of 40% oil and 45% SAA/CoS showed the maximum drug deposition of 75.1%. Clinical skin irritation study showed that the aforementioned formula was safe for topical use.
  
  
  CONCLUSIONS
  This article suggests that applying QbD tools such as experimental design is an efficient tool for drug product design.
authors.affiliation: a Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Ain Shams University , Cairo , Egypt.
authors.forename: Maha
authors.initials: M
authors.lastname: Nasr
authors.affiliation: a Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Ain Shams University , Cairo , Egypt.
authors.forename: Sameh
authors.initials: S
authors.lastname: Abdel-Hamid
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000378:metabolism*; D004655:Emulsions / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008863:Microspheres; D008954:Models, Biological; D009539:Nicotinic Acids / Q000008:administration & dosage / Q000378:metabolism*; D009924:Organ Culture Techniques; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology*; D012176:Retinoids
chemical_list: D003879:Dermatologic Agents; D004655:Emulsions; D009539:Nicotinic Acids; C086827:tazarotene; D012176:Retinoids
keywords: Control space; dermal; drug deposition; microemulsion; quality by design; topical delivery