Investigation on Processing Variables for the Preparation of Fluconazole-Loaded Ethyl Cellulose Microspheres by Modified Multiple Emulsion Technique
- 534 Downloads
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 μm, 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.
Key wordsentrapment efficiency ethyl cellulose fluconazole microspheres water-in-oil-in-water (w/o/w) multiple emulsion
The authors are grateful to the authority of Gupta College of Technological Sciences, Asansol, India and Jadavpur University, Department of Pharmaceutical Technology, Kolkata, India for providing necessary facilities for this work.
- 1.Follonier N, Doelkar E. Biopharmaceutical comparison of oral multiple unit and single unit sustained release dosage forms. STP Pharm Sci. 1992;2:141–58.Google Scholar
- 3.Hincall AA, Calis S. Microsphere preparation by solvent evaporation method. In: Wise DL, editor. Handbook of pharmaceutical controlled release technology. Cambridge, MA: Taylor and Francis; 2000. p. 329–43.Google Scholar
- 10.Nagareyan N, Uchida T, Matsuyama K. Preparation and characterization of enteric microspheres containing bovine insulin by a w/o/w emulsion solvent evaporation method. Chem Pharm Bull. 1998;46:1613–7.Google Scholar
- 12.J.S. Young, K.I. Chan, and K. Yong-Hee. Preparation method for biodegradable polymeric microspheres using solvent extraction and preparation method for microspheres for treating local inflammation using the same. US Patent no. 6149944 (2000).Google Scholar
- 17.Uetrecht J, Walmsley SL. Antimicrobial and antifungal agents that act on cell membrane. In: Kalant H, Roschlau WHE, editors. Principles of medical pharmacology. New York: Oxford University Press; 1998. p. 677.Google Scholar
- 18.Parrott EL. Milling. In: Lachman L, Lieberman HA, Kanig JL, editors. The theory and practice of industrial pharmacy. Washington Square, Philadelphia: Lea & Febiger; 1991. p. 28.Google Scholar
- 36.Kim K-H, Kim K-S, Lim J-S, Shin J-S, Chung K-H. Effect of dissolution properties of p-aminosalicylic acid with chitin and chitosan mixtures. Polymer (Korea). 1988;12:56–62.Google Scholar
- 37.Carrillo-Munoz AJ, Quindos G, Tur C, Ruesga MT, Miranda Y, delValle O, et al. In-vitro antifungal activity of liposomal nystatin in comparison with nystatin, amphotericin B cholesteryl sulphate, liposomal amphotericin B, amphotericin B lipid complex, amphotericin B desoxycholate, fluconazole and itraconazole. J Antimicrob Chemother. 1999;44:397–401.PubMedCrossRefGoogle Scholar