title: QbD-based systematic development of novel optimized solid self-nanoemulsifying drug delivery systems (SNEDDS) of lovastatin with enhanced biopharmaceutical performance.
abstract: Of late, solid self-nanoemulsifying drug delivery systems (S-SNEDDS) have been extensively sought-after owing to their superior portability, drug loading, stability and patient compliance. The current studies, therefore, entail systematic development, optimization and evaluation (in vitro, in situ and in vivo) of the solid formulations of (SNEDDS) lovastatin employing rational quality by design (QbD)-based approach of formulation by design (FbD). The patient-centric quality target product profile (QTPP) and critical quality attributes (CQAs) were earmarked. Preformulation studies along with initial risk assessment facilitated the selection of lipid (i.e. Capmul MCM), surfactant (i.e. Nikkol HCO-50) and co-surfactant (i.e. Lutrol F127) as CMAs for formulation of S-SNEDDS. A face-centered cubic design (FCCD) was employed for optimization using Nikkol-HCO50 (X1) and Lutrol-F127 (X2), evaluating CQAs like globule size, liquefaction time, emulsification time, MDT, dissolution efficiency and permeation parameter. The design space was generated using apt mathematical models, and the optimum formulation was located, followed by validation of the FbD methodology. In situ SPIP and in vivo pharmacodynamic studies on the optimized formulation carried out in unisex Wistar rats, corroborated superior drug absorption and enhanced pharmacodynamic potential in regulating serum lipid levels. In a nutshell, the present studies report successful QbD-oriented development of novel oral S-SNEDDS of lovastatin with distinctly improved biopharmaceutical performance.
authors.affiliation: a UGC Centre of Advanced Studies , University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh , India and.
authors.forename: Sarwar
authors.initials: S
authors.lastname: Beg
authors.affiliation: b UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles & Nanocomposites (Biomedical Sciences) , Panjab University , Chandigarh , India.
authors.forename: Premjeet Singh
authors.initials: PS
authors.lastname: Sandhu
authors.affiliation: a UGC Centre of Advanced Studies , University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh , India and.
authors.forename: Rattandeep Singh
authors.initials: RS
authors.lastname: Batra
authors.affiliation: a UGC Centre of Advanced Studies , University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh , India and.
authors.forename: Rajneet Kaur
authors.initials: RK
authors.lastname: Khurana
authors.affiliation: a UGC Centre of Advanced Studies , University Institute of Pharmaceutical Sciences, Panjab University , Chandigarh , India and.|b UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles & Nanocomposites (Biomedical Sciences) , Panjab University , Chandigarh , India.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Singh
mesh_terms: D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D004355:Drug Stability; D004655:Emulsions / Q000737:chemistry; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D007408:Intestinal Absorption; D008148:Lovastatin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D004655:Emulsions; D000960:Hypolipidemic Agents; D013501:Surface-Active Agents; D008148:Lovastatin
keywords: Bioavailability; SEDDS; formulation by design; nanomedicine; self-emulsifying