PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
 
AAPS PharmSciTech. 2006 September; 7(3): E172–E177.
Published online 2006 September 15. doi:  10.1208/pt070377
PMCID: PMC2750519

Design and development of microemulsion drug delivery system of acyclovir for improvement of oral bioavailability

Abstract

The main purpose of this work was to develop an oral microemulsion formulation for enhancing the bioavailability of acyclovir. A Labrafac-based microemulsion formulation with Labrasol as surfactant and Plurol Oleique as cosurfactant was developed for oral delivery of acyclovir. Phase behavior and solubilization capacity of the microemulsion system were characterized, and in vivo oral absorption of acyclovir from the microemulsion was investigated in rats. A single isotropic region, which was considered to be a bicontinuous microemulsion, was found in the pseudoternary phase diagrams developed at various Labrasol:Plurol Oleique:Labrafac ratios. With the increase of Labrasol concentration, the microemulsion region area and the amount of water and Labrafac solubilized into the microemulsion system increased; however, the increase of Plurol Oleique percentage produced opposite effects. The microemulsion system was also investigated in terms of other characteristics, such as interfacial tension, viscosity, pH, refractive index, diffusion, and bioavailability. Acyclovir, a poorly soluble drug, displayed high solubility in a microemulsion formulation using Labrafac (10%). Labrasol (32%), Plurol Oleique (8%), and water (50%). The in vitro intraduodenal diffusion and in vivo study revealed an increase of bioavailability (12.78 times) after oral administration of the microemulsion formulation as compared with the commercially available tablets.

Keywords: Microemulsion, non-ionic surfactant, conductivity, interfacial tension, particle size

Full Text

The Full Text of this article is available as a PDF (234K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. O’Brien J, Campoli-Richards D. Acyclovir. An updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs. 1989;37:233–309. [PubMed]
2. McEvoy G. AHFS Drugs Information, American Society of Health System Pharmacists. Bethesda, MD: Atlantic Books; 1998. pp. 471–480.
3. Fletcher C, Bean B. Evaluation of oral acyclovir therapy. Drug Intell Clin Pharm. 1985;19:518–524. [PubMed]
4. Vergin H, Kikuta C, Mascher H, Metz R. Pharmacokinetics and bioavailability of different formulations of aciclovir. Arzneimittelforschung. 1995;45:508–515. [PubMed]
5. Charman S, Charman W, Rogge M, Wilson T, Dutko F, Pouton C. Self-emulsifying drug delivery systems: formulation and biopharmaceutic evaluation of an investigational lipophilic compounds. Pharm Res. 1992;9:87–93. doi: 10.1023/A:1018987928936. [PubMed] [Cross Ref]
6. Constantinides P, Scalart J, Lancaster C, et al. Formulation and intestinal absorption enhancement evaluation of water-in-oil microemulsions incorporating medium-chain glycerides. Pharm Res. 1994;11:1385–1390. doi: 10.1023/A:1018927402875. [PubMed] [Cross Ref]
7. Kovarik J, Muelle E, Bree J, Tetzloff W, Kutz K. Reduced inter- and intraindividual variability in cyclosporine pharmacokinetics from a microemulsion formulation. J Pharm Sci. 1994;83:444–446. doi: 10.1002/jps.2600830336. [PubMed] [Cross Ref]
8. Shah N, Carvajal M, Patel C, Infeld M, Malick A. Self-emulsifying drug delivery systems (SEDDS) with polyglycolyzed glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs. Int J Pharm. 1994;106:15–23. doi: 10.1016/0378-5173(94)90271-2. [Cross Ref]
9. Matuszewska B, Hettrick L, Bondi J, Storey D. Comparative bioavailability of L-683,443, a 5a-reductase inhibitor, from a self-emulsifying drug delivery system in beagle dogs. Int J Pharm. 1996;136:147–154. doi: 10.1016/0378-5173(96)04496-1. [Cross Ref]
10. Garti N, Aserin A, Tiunova I, Fanun MA. DSC study of water behavior in water-in-oil microemulsions stabilized by sucrose esters and butanol. Colloids Surf B: Physicochem Eng Aspects. 2000;170:1–18. doi: 10.1016/S0927-7757(00)00486-6. [Cross Ref]
11. Attwood D. Microemulsions. In: Kreuter J, editor. Colloidal Drug Delivery Systems. New York, NY: Marcel Dekker; 1994. pp. 31–71.
12. Smith P. Methods for evaluating intestinal permeability and metabolism in vitro. Pharm Biotechnol. 1996;8:13–34. [PubMed]
13. Gibaldi M, Perrier D. Pharmacokinetics. New York, NY: Marcel-Dekker; 1982.
14. Ghosh PK, Umrethia M, Majithiya RJ, Murthy RSR. Preparation and physicochemical characterisation of caprylocapryl macrogol-8-glycerides microemulsion for oral drug delivery. Ars Pharm. 2004;45:353–372.

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists