title: Nanosuspension of efavirenz for improved oral bioavailability: formulation optimization, in vitro, in situ and in vivo evaluation.
abstract: BACKGROUND
  Nanosuspensions (NSs) of poorly water-soluble drugs are known to increase the oral bioavailability.
  
  
  OBJECTIVE
  The purpose of this study was to develop NS of efavirenz (EFV) and to investigate its potential in enhancing the oral bioavailability of EFV.
  
  
  METHODS
  EFV NS was prepared using the media milling technique. The Box-Behnken design was used for optimization of the factors affecting EFV NS. Sodium lauryl sulfate and PVP K30 were used to stabilize the NS. Freeze-dried NS was completely re-dispersed with double-distilled filtered water.
  
  
  RESULTS
  Mean particle size and zeta potential of the optimized NS were found to be 320.4 ± 3.62 nm and -32.8 ± 0.4 mV, respectively. X-ray diffraction and differential scanning calorimetric analysis indicated no phase transitions. Rate and extent of drug dissolution in the dissolution medium for NS was significantly higher compared to marketed formulation. The parallel artificial membrane permeability assay revealed that NS successfully enhanced the permeation of EFV. Results of in situ absorption studies showed a significant difference in absorption parameters such as Ka, t1/2 and uptake percentages between lyophilized NS and marketed formulation of EFV. Oral bioavailability of EFV in rabbits resulting from NS was increased by 2.19-fold compared to the marketed formulation.
  
  
  CONCLUSIONS
  Thus, it can be concluded that NS formulation of EFV can provide improved oral bioavailability due to enhanced solubility, dissolution velocity, permeability and hence absorption.
authors: Quality Assurance Laboratory, Centre of Relevance and Excellence in Novel Drug Delivery System and.
authors: Greeshma V
authors: GV
authors: Patel
authors: Vaibhav B
authors: VB
authors: Patel
authors: Abhishek
authors: A
authors: Pathak
authors: Sadhana J
authors: SJ
authors: Rajput
mesh_terms: D000284:Administration, Oral; D000480:Alkynes; D000818:Animals; D048588:Benzoxazines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003521:Cyclopropanes; D004339:Drug Compounding / Q000379:methods; D005079:Excipients / Q000737:chemistry*; D005612:Freeze Drying; D006207:Half-Life; D008297:Male; D053758:Nanoparticles; D010316:Particle Size; D010539:Permeability; D011205:Povidone / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D005079:Excipients; D018894:Reverse Transcriptase Inhibitors; D012967:Sodium Dodecyl Sulfate; D011205:Povidone; C098320:efavirenz