title: Enhanced bioavailability of cinnarizine nanosuspensions by particle size engineering: Optimization and physicochemical investigations.
abstract: Cinnarizine (CIN), a poorly soluble drug with erratic bioavailability due to pH dependent solubility has limited advantage to formulate oral solid dosage forms in subject having low gastric acidity. In present study precipitation-ultrasonication was used to fabricate nanosuspensions of cinnarizine stabilized by Poly vinyl alcohol (PVA) to enhance the bioavailability. We investigated the effects of PVA concentration (X1) and solvent to antisolvent ratio (X2) on the quality attributes like mean particle size (Y1); % drug content (Y2); and time required to 90% drug release (Y3) via 3(2) factorial design. The morphology of nanosuspensions was found almost spherical by SEM observation. DSC and FT-IR studies revealed lack of significant interactions between CIN and PVA. Nanosuspensions of mean particle size 621.08 nm was achieved. The dissolution rate obtained from all formulations were markedly higher than pure CIN. Response surface methodology and optimized polynomial equations were used to select the optimal formulation i.e. 0.2% W/V of X1 and 1:42 of X2 to get the desired response Y1; 636.78 nm, Y2; 95.24% and Y3; 7.09 min that were in reasonable agreement with the observed value. The in-vivo study in rat demonstrated that Cmax and AUC0→12 values of nanosuspension were approximately 2.8-fold and 2.7-fold greater than that of reference preparation respectively.
authors.affiliation: Gayatri College of Pharmacy, Sambalpur, Odisha 768200, India. Electronic address: drbibaswanmishra@gmail.com.
authors.forename: Bibaswan
authors.initials: B
authors.lastname: Mishra
authors.affiliation: Shri Ram Murti Smarak College of Engg. and Technology (Pharmacy), Bareilly, U.P. 243202, India. Electronic address: drjagannathsahoo@gmail.com.
authors.forename: Jagannath
authors.initials: J
authors.lastname: Sahoo
authors.affiliation: Department of Zoology, Berhampur University, Ganjam, Odisha 760007, India. Electronic address: drdixit2001@gmail.com.
authors.forename: Prasanna Kumar
authors.initials: PK
authors.lastname: Dixit
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D002936:Cinnarizine / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D004339:Drug Compounding; D004355:Drug Stability; D006207:Half-Life; D008297:Male; D008855:Microscopy, Electron, Scanning; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D011142:Polyvinyl Alcohol / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D013010:Sonication; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D013535:Suspensions
chemical_list: D013535:Suspensions; D002936:Cinnarizine; D011142:Polyvinyl Alcohol
keywords: Bioavailability; Cinnarizine; Nanosuspension; Optimization; Sonoprecipitation