Abstract
The purpose of this research was to prepare acyclovir niosomes in a trial to improve its poor and variable oral bioavailability. The nonionic surfactant vesicles were prepared by the conventional thin film hydration method. The lipid mixture consisted of cholesterol, span 60, and dicetyl phosphate in the molar ratio of 65:60:5, respectively. The percentage entrapment was ∼11% of acyclovir used in the hydration process. The vesicles have an average size of 0.95 µm, a most probable size of 0.8 µm, and a size range of 0.4 to 2.2 µm. Most of the niosomes have unilamellar spherical shape. In vitro drug release profile was found to follow Higuchi’s equation for free and niosomal drug. The niosomal formulation exhibited significantly retarded release compared with free drug. The in vivo study revealed that the niosomal dispersion significantly improved the oral bioavailability of acyclovir in rabbits after a single oral dose of 40 mg kg−1. The average relative bioavailability of the drug from the niosomal dispersion in relation to the free solution was 2.55 indicating more than 2-fold increase in drug bioavailability. The niosomal dispersion showed significant increase in the mean residence time (MRT) of acyclovir reflecting sustained release characteristics. In conclusion, the niosomal formulation could be a promising delivery system for acyclovir with improved oral bioavailability and prolonged drug release profiles.
Keywords: Acyclovir niosomes, oral acyclovir, bioavailability of acyclovir
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References
- 1.Erlich KS. Management of herpes simplex and varicella-zoster virus infections. West J Med. 1997;166:211–215. [PMC free article] [PubMed] [Google Scholar]
- 2.Miranda P, Krasny HC, Page DA, Elion CB. Species differences in the disposition of acyclovir. Am J Med. 1982;73:31–35. doi: 10.1016/0002-9343(82)90059-6. [DOI] [PubMed] [Google Scholar]
- 3.de Miranda P, Blum MR. Pharmacokinetics of acyclovir after intravenous and oral administration. J Antimicrob Chemother. 1983;12:29–37. doi: 10.1093/jac/12.suppl_b.29. [DOI] [PubMed] [Google Scholar]
- 4.Vergin H, Kikuta C, Mascher H, Metz R. Pharmacokinetics and bioavailability of different formulations of acyclovir. Arzneim Forsch. 1995;45:508–515. [PubMed] [Google Scholar]
- 5.Amidon GL, Lennernas H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: the correlation of n vitro drug product dissolution and in vivo bioavailability. Pharm Res. 1995;12:413–420. doi: 10.1023/A:1016212804288. [DOI] [PubMed] [Google Scholar]
- 6.US FDA. Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid dosage forms based on a biopharmaceutics classification system. 2000; Available at: www.fda.gov/cder/guidance/2062dft.pdf. Accessed November 2, 2007.
- 7.Avdeef A. pH-metric solubility. I. Solubility-pH profiles from Bjerrum plots, Gibbs buffer and pKa in solid state. Pharm Pharmacol Commun. 1998;4:165–178. [Google Scholar]
- 8.Lund W. The Pharmaceutical Codex, Principles and Practice of Pharmaceutics. London, UK: The Pharmaceutical Press; 1994. [Google Scholar]
- 9.Krenitsky TA, Hall WW, de Miranda P, Bauchamp LM, Schaeffer HJ, Whiteman P. 6- Deoxyacyclovir: a xanthine oxidase-activated prodrug of acyclovir. Proc Natl Acad Sci USA. 1984;81:3209–3213. doi: 10.1073/pnas.81.10.3209. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Lycke J, Malmestrom C, Stahle L. Acyclovir levels in serum and cerebrospinal fluid after oral administration of valacyclovir. Antimicrob Agents Chemother. 2003;47:2438–2441. doi: 10.1128/AAC.47.8.2438-2441.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Luengo J, Aranguiz T, Sepulveda J. Preliminary pharmacokinetic study to different preparations of acyclovir with β-cyclodextrin. J Pharm Sci. 2002;91:2593–2598. doi: 10.1002/jps.10245. [DOI] [PubMed] [Google Scholar]
- 12.Azmin MN, Florence AT, Handjani-Vila RM, Stuart FB, Vanlerberghe G, Whittaker JS. The effect of non-ionic surfactant vesicles (niosome) entrapment on the absorption and distribution of methotrexate in mice. J Pharm Pharmacol. 1985;37:237–242. doi: 10.1111/j.2042-7158.1985.tb05051.x. [DOI] [PubMed] [Google Scholar]
- 13.Peh KK, Yuen KH. Simple high-performance liquid chromatographic method for the determination of acyclovir in human plasma using fluorescence detection. J Chromatogr B. 1997;693:241–244. doi: 10.1016/S0378-4347(97)00041-8. [DOI] [PubMed] [Google Scholar]
- 14.McIntosh TJ. The effect of cholesterol content on the structure of phosphatidylcholine bilayers. Biochim Biophys Acta. 1978;51:43–58. doi: 10.1016/0005-2736(78)90110-4. [DOI] [PubMed] [Google Scholar]
- 15.Yoshioka T, Sternberg B, Florence AT. Preparation and properties of vesicles (niosomes) of sorbitan monoesters (span 20, 40, 60, 80) and a sorbitan triester (span 85) Inter J Pharmaceut. 1994;105:1–6. doi: 10.1016/0378-5173(94)90228-3. [DOI] [Google Scholar]
- 16.Schwender RA, Asanger M, Weder HG. N-alkyl-glucosides as detergents for the preparation of highly homogenous bilayer liposomes of visible size (60–240 nm) applying defined rates of detergent removal by dialysis. Biochem Biophys Res Commun. 1981;10:1055–1062. doi: 10.1016/0006-291X(81)91930-6. [DOI] [PubMed] [Google Scholar]
- 17.Brigden D, Fowle A, Rosling A, Collier LH, Oxford J, editors. Developments in Antiviral Therapy. London, UK: Academic Press; 1980. pp. 53–62. [Google Scholar]
- 18.Meadows KM, Dressman JB. Mechanism of acyclovir uptake in rat jejunum. Pharm Res. 1990;7:299–303. doi: 10.1023/A:1015890516119. [DOI] [PubMed] [Google Scholar]