title: Evaluation of critical formulation parameters in design and differentiation of self-microemulsifying drug delivery systems (SMEDDSs) for oral delivery of aciclovir.
abstract: The study investigated the influence of formulation parameters for design of self-microemulsifying drug delivery systems (SMEDDSs) comprising oil (medium chain triglycerides) (10%), surfactant (Labrasol(®), polysorbate 20, or Kolliphor(®) RH40), cosurfactant (Plurol(®) Oleique CC 497) (q.s. ad 100%), and cosolvent (glycerol or macrogol 400) (20% or 30%), and evaluate their potential as carriers for oral delivery of a poorly permeable antivirotic aciclovir (acyclovir). The drug loading capacity of the prepared formulations ranged from 0.18-31.66 mg/ml. Among a total of 60 formulations, three formulations meet the limits for average droplet size (Z-ave) and polydispersity index (PdI) that have been set for SMEDDSs (Z-ave≤100nm, PdI<0.250) upon spontaneous dispersion in 0.1M HCl and phosphate buffer pH 7.2. SMEDDSs with the highest aciclovir loading capacity (24.06 mg/ml and 21.12 mg/ml) provided the in vitro drug release rates of 0.325 mg cm(-2)min(-1) and 0.323 mg cm(-2)min(-1), respectively, and significantly enhanced drug permeability in the parallel artificial membrane permeability assay (PAMPA), in comparison with the pure drug substance. The results revealed that development of SMEDDSs with enhanced drug loading capacity and oral delivery potential, required optimization of hydrophilic ingredients, in terms of size of hydrophilic moiety of the surfactant, surfactant-to-cosurfactant mass ratio (Km), and log P of the cosolvent.
authors.affiliation: Apoteka Janković, Miloša Bajića 13, 21000 Novi Sad, Serbia.
authors.forename: Jovana
authors.initials: J
authors.lastname: Janković
authors.affiliation: University of Belgrade, Faculty of Pharmacy, Department of Pharmaceutical Technology and Cosmetology, Vojvode Stepe 450, 11221 Belgrade, Serbia. Electronic address: ljiljanadjek@gmail.com.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Djekic
authors.affiliation: University of Belgrade, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Dobričić
authors.affiliation: University of Belgrade, Faculty of Pharmacy, Department of Pharmaceutical Technology and Cosmetology, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Marija
authors.initials: M
authors.lastname: Primorac
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage*; D000284:Administration, Oral; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D004355:Drug Stability; D004655:Emulsions; D005989:Glycerides / Q000737:chemistry; D010316:Particle Size; D010539:Permeability; D011092:Polyethylene Glycols / Q000737:chemistry; D011136:Polysorbates / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D014280:Triglycerides / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D004655:Emulsions; D005989:Glycerides; D011136:Polysorbates; D013501:Surface-Active Agents; D014280:Triglycerides; C440220:Labrasol; D011092:Polyethylene Glycols; D000212:Acyclovir
keywords: Aciclovir; Acyclovir; In vitro drug release; Parallel artificial membrane permeability assay (PAMPA); Self-dispersing drug delivery systems; Self-microemulsifying drug delivery systems (SMEDDS)