title: In-vitro and in-vivo study of indomethacin loaded gelatin nanoparticles.
abstract: The present research work deals with fabrication of indomethacin loaded gelatin nanoparticles prepared by double desolvation method for controlled drug delivery. Submicron polymeric particles with size < 800 nm were produced possessing narrow polydispersity index (< 0.5). Entrapment efficiency varied from 27-38% depending upon particle size. No drug polymer interaction was observed by FTIR. DSC study confirmed amorphous nature of nanoparticles. The in-vitro drug release profile showed initial burst release (> 20% in 1 hr) followed by controlled release (> 75% in 12 hr). Among the kinetic models employed, the Higuchi model showed a better fit (R2 > 0.9) with n < 0.43 (Peppas model) indicating a Fickian type of release pattern. The batch 2GA was optimum in terms of size, entrapment efficiency and drug release. Anti-inflammatory activity of the drug loaded nanoparticles (IGNP) and pure drug solution (IDM) was studied by rat paw model and IGNP significantly (P < or = 0.001) decreased the paw volume as compared to IDM. Pharmacokinetic study showed significant enhancement (P < 0.001) of various pharmacokinetic parameters. The observed t(max) value was 3 h for IGNP compared to 1 h for IDM. Cmax of IGNP had higher value (110.81 +/- 8.53 microg/mL) compared to that of IDM (51.66 +/- 7.5 microg/mL). AUC0-12 was 1009.78 +/- 80.24 and 194.33 +/- 46.76/microg x h/mL in IGNP and IDM respectively (relative bioavailability 500%). Further, a good in vitro-in vivo correlation established the formulation for future trials.
authors.affiliation: Department of Pharmaceutics, Institute of Technology, Banaras Hindu University, Varanasi 221005, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kumar
authors.forename: Ramesh C
authors.initials: RC
authors.lastname: Nagarwal
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Dhanawat
authors.forename: Jayanta Kumar
authors.initials: JK
authors.lastname: Pandit
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003692:Delayed-Action Preparations; D004355:Drug Stability; D005780:Gelatin; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007700:Kinetics; D053758:Nanoparticles; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar
chemical_list: D003692:Delayed-Action Preparations; D005780:Gelatin; D007213:Indomethacin