title: Solid self-microemulsifying drug delivery system of ritonavir.
abstract: BACKGROUND
  Ritonavir (RTV) is a human immunodeficiency virus (HIV) protease inhibitor (PI) with activity against HIV, practically insoluble in water and recommended to co-administer as a booster along with other HIV-PI to enhance their bioavailability. The present study is aimed to enhance the dissolution and oral bioavailability of water-insoluble RTV using the Solid Self-Microemulsifying Drug Delivery System (S-SMEDDS).
  
  
  OBJECTIVE
  To enhance the dissolution and oral bioavailability of water-insoluble RTV using the S-SMEDDS.
  
  
  METHODS
  Liquid SMEDDS (L-SMEDDS) of RTV was formulated by the optimizing ratio of Imwitor 988 (Oil), Cremophor EL and Cremophor RH 40 (1:1) (surfactant) and Capmul GMS K-50 (cosurfactant). Optimized L-SMEDDS showed improved dissolution rate of RTV compared to pure RTV powder. Optimized L-SMEDDS of RTV was adsorbed on Neusilin US-2 using a simple wet granulation technique with selected excipients to convert it into S-SMEDDS.
  
  
  CONCLUSIONS
  Optimized L-SMEDDS showed an improved dissolution rate of RTV compared to pure RTV powder. Droplet size of resultant microemulsion of L-SMEDDS of RTV was observed between 16 and 22 nm and independent of pH (i.e. 0.1 N HCl and water). Conversion of the crystalline form of RTV to amorphous form was observed when RTV formulated into SMEDDS form as per X-ray diffraction study. In vitro dissolution study, stability study of optimized S-SMEDDS confirmed the formulation of stable and improved dissolution of RTV. Relative bioavailability of RTV was determined in male Wistar rats and pharmacokinetic parameters were calculated by the comparison of optimized S-SMEDDS versus aqueous suspension of RTV. S-SMEDDS improved the plasma profile in terms of maximum plasma concentration (Cmax), and area under curve (AUC0-24h), which is almost twofolds higher than the aqueous suspension of RTV.
  
  
  CONCLUSIONS
  S-SMEDDS tablet of RTV was formulated successfully by adsorbing optimized L-SMEDDS of RTV on Neusilin-US2(®) as a potential carrier with enhanced solubility and relative oral bioavailability compared to pure RTV by twofolds.
authors: Department of Pharmaceutics, AISSMS College of Pharmacy , Pune , India.
authors: Ashish
authors: A
authors: Deshmukh
authors: Shirishkumar
authors: S
authors: Kulkarni
mesh_terms: D000284:Administration, Oral; D017607:Aluminum Compounds / Q000737:chemistry; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D017616:Magnesium Compounds / Q000737:chemistry; D008297:Male; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D019438:Ritonavir / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D017640:Silicates / Q000737:chemistry; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D013607:Tablets; D014961:X-Ray Diffraction
chemical_list: D017607:Aluminum Compounds; D004337:Drug Carriers; D004655:Emulsions; D005079:Excipients; D017320:HIV Protease Inhibitors; D017616:Magnesium Compounds; D017640:Silicates; D013501:Surface-Active Agents; D013607:Tablets; C033065:aluminum magnesium silicate; D019438:Ritonavir