title: Co-solvent evaporation method for enhancement of solubility and dissolution rate of poorly aqueous soluble drug simvastatin: in vitro-in vivo evaluation.
abstract: A number of synthesized chemical molecules suffer from low aqueous solubility problems. Enhancement of aqueous solubility, dissolution rate, and bioavailability of drug is a very challenging task in drug development. In the present study, solubility and dissolution of poorly aqueous soluble drug simvastatin (SIM) was enhanced using hydrophilic, low viscosity grade polymer hydroxypropyl methylcellulose (HPMC K(3)LV). The co-solvent evaporation method was developed for efficient encapsulation of hydrophobic drug in polymer micelles of HPMC K(3)LV. Spray drying and rotaevaporation method were applied for solvent evaporation. Co-solvent-evaporated mixture in solid state was determined by differential scanning calorimetry (DSC), X-ray diffraction studies (XRD), scanning electron microscopy, and Fourier-transform infrared spectroscopy. In vitro-in vivo studies were performed on co-solvent-evaporated mixture and compared with SIM. In vivo study was conducted on healthy albino rats (Wister strain), and formulations were administered by oral route. Results of the study show the conversion of crystalline form of SIM into amorphous form. The dissolution rate was remarkably increased in co-solvent-evaporated mixtures compared to SIM. co-solvent-evaporated mixtures showed better reduction in total cholesterol and triglyceride levels than the SIM. The low-viscosity grade HPMC acts as a surfactant, which enhances the wetting of drug and thus improves the solubility of drug. The co-solvent evaporation method provides good encapsulation efficiency and produces amorphous form of SIM, which gave better solubility and dissolution than the crystalline SIM.
authors.affiliation: Pharmaceutics Department, R.C. Patel College of Pharmacy, Near Karwand Naka, Shirpur 425405, Dhule, Maharashtra, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Pandya
authors.forename: Surendra
authors.initials: S
authors.lastname: Gattani
authors.forename: Pankaj
authors.initials: P
authors.lastname: Jain
authors.forename: Lokesh
authors.initials: L
authors.lastname: Khirwal
authors.forename: Sanjay
authors.initials: S
authors.lastname: Surana
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D002784:Cholesterol / Q000097:blood; D004353:Drug Evaluation, Preclinical; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017208:Rats, Wistar; D019821:Simvastatin / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012997:Solvents; D002784:Cholesterol; D019821:Simvastatin