title: Characterization and in vitro evaluation of freeze-dried microparticles composed of granisetron-cyclodextrin complex and carboxymethylcellulose for intranasal delivery.
abstract: The aim of this study was to prepare microparticles (MPs) of granisetron (GRN) in combination with hydroxypropyl-β-cyclodextrin (HP-β-CD) and sodium carboxymethylcellulose (CMC-Na) by the simple freeze-drying method for intranasal delivery. The composition of MPs was determined from the phase-solubility study of GRN in various CDs. Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD) analysis and differential scanning calorimetry (DSC) studies were performed to evaluate possible interactions between GRN and excipients. The results indicated the formation of inclusion complex between GRN and CD, and the conversion of drug into amorphous state. The in vitro release of GRN from MPs was determined in phosphate buffered saline (pH 6.4) at 37°C. Cytotoxicity of the MPs and in vitro permeation study were conducted by using primary human nasal epithelial (HNE) cells and their monolayer system cultured by air-liquid interface (ALI) method, respectively. The MPs showed significantly higher GRN release profile compared to pure GRN. Moreover, the prepared MPs showed significantly lower cytotoxicity and higher permeation profile than that of GRN powder (p<0.05). These results suggested that the MPs composed of GRN, HP-β-CD and CMC-Na represent a simple and new GRN intranasal delivery system as an alternative to the oral and intravenous administration of GRN.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, San 56-1, Silim-Dong, Gwanak-gu, Seoul 151-742, South Korea.
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Cho
authors.forename: Prabagar
authors.initials: P
authors.lastname: Balakrishnan
authors.forename: Won-Sik
authors.initials: WS
authors.lastname: Shim
authors.forename: Suk-Jae
authors.initials: SJ
authors.lastname: Chung
authors.forename: Chang-Koo
authors.initials: CK
authors.lastname: Shim
authors.forename: Dae-Duk
authors.initials: DD
authors.lastname: Kim
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000281:Administration, Intranasal; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry*; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D004847:Epithelial Cells / Q000378:metabolism; D005079:Excipients / Q000737:chemistry; D005612:Freeze Drying; D017829:Granisetron / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D009297:Nasal Mucosa / Q000378:metabolism*; D010316:Particle Size; D010539:Permeability; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D002266:Carboxymethylcellulose Sodium; D004337:Drug Carriers; D005079:Excipients; D017829:Granisetron; D012702:Serotonin Antagonists; D047392:beta-Cyclodextrins