Investigation on processing variables for the preparation of fluconazole-loaded ethyl cellulose microspheres by modified multiple emulsion technique.
Fluconazole-loaded ethyl cellulose microspheres were prepared by alginate facilitated (water-in-oil)-in-water emulsion technology and the effects of various processing variables on the properties of microspheres were investigated. Scanning electron microscopy revealed spherical nature and smooth surface morphology of the microspheres except those prepared at higher concentration of emulsifiers and higher stirring speeds. The size of microspheres varied between 228 and 592 mum, and as high as 80% drug entrapment efficiency was obtained depending upon the processing variables. When compared up to 2 h, the drug release in pH 1.2 HCl solution was slower than in pH 7.4 phosphate buffer saline solution. However, this trend was reversed at high shear conditions. The microspheres provided extended drug release in alkaline dissolution medium and the drug release was found to be controlled by Fickian-diffusion mechanism. However, the mechanism shifted to anomalous diffusion at high shear rates and emulsifier concentrations. The aging of microspheres did not influence the drug release kinetics. However, the physical interaction between drug and excipients affected the drug dissolution behaviors. X-ray diffractometry (X-RD) and differential scanning calorimetry (DSC) analysis revealed amorphous nature of drug in the microspheres. Fourier transform infrared (FTIR) spectroscopy indicated stable character of fluconazole in the microspheres. The stability testing data also supported the stable nature of fluconazole in the microspheres. The fluconazole extracted from 80% drug-loaded formulation showed good in vitro antifungal activity against Candida albicans. Thus, proper control of the processing variables involved in this modified multiple emulsion technology could allow effective incorporation of slightly water soluble drugs into ethyl cellulose microspheres without affecting drug stability.
Maiti
Sabyasachi
S
Gupta College of Technological Sciences, Ashram More, G.T Road, Asansol, 713301 West Bengal, India. sabya245@rediffmail.com
Dey
Paramita
P
Kaity
Santanu
S
Ray
Somasree
S
Maji
Sushomasri
S
Sa
Biswanath
B
D000464:Alginates / Q000737:chemistry; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry* / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D002176:Candida albicans / Q000187:drug effects; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004339:Drug Compounding; D004655:Emulsions; D015725:Fluconazole / Q000008:administration & dosage* / Q000737:chemistry* / Q000494:pharmacology; D006601:Hexoses; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D012995:Solubility; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D013501:Surface-Active Agents; D014961:X-Ray Diffraction
D000464:Alginates; D000935:Antifungal Agents; D004337:Drug Carriers; D004655:Emulsions; D006601:Hexoses; D012997:Solvents; D013501:Surface-Active Agents; C018665:sorbitan monooleate; C013517:ethyl cellulose; D015725:Fluconazole; D002482:Cellulose