title: Release kinetics of acyclovir from a suspension of acyclovir incorporated in a cubic phase delivery system.
abstract: Acyclovir is a widely used agent in the treatment of herpes virus infections of the skin, but owing to its poor physicochemical properties in terms of bioavailability and suboptimal formulations, the treatment is far from optimal. The liquid crystalline cubic phase system has been reported to act as a bioadhesive drug delivery system. In the present study, acyclovir was suspended in a cubic phase of glycerol monooleate (GMO) and water 65%:35% w/w, and the phase behavior and release kinetics were examined. X-ray diffraction and differential scanning calorimetry (DSC) measurements demonstrated that the cubic phase containing 1%-10% (w/w) acyclovir retains its phase condition in the temperature range investigated (20 degrees C-70 degrees C). Acyclovir can be incorporated in high amounts (approximately 40% w/w) without causing phase transition, as is shown in polarized light. This is probably because of its low solubility (approximately 0.11% w/w) in the cubic phase. The release characteristics of acyclovir incorporated as a suspension (1%-5% w/w) into a cubic phase were investigated using Franz diffusion cells. Acyclovir was quantified by high-performance liquid chromatography (HPLC). The drug was readily released from the system, and the release increased with the initial drug load concentration. About 25%-50% was released after 24 h. The release is dependent on the square root of time, and the kinetics can be described by the Higuchi theory. The rate-limiting step in the release process is most likely diffusion. The suggested theory is further supported by identical release data obtained for micronized and nonmicronized acyclovir. The fluxes for 1% and 5% w/w were 380 and 900 microg/h(1/2), respectively. Comparison of the release rates of acyclovir delivered from a cubic phase and from the commercial product, Zovir cream, showed the rate to be six times faster from the cubic phase. The results indicate that the cubic phase is a promising drug delivery system for acyclovir.
authors.affiliation: Alpharma, International Pharmaceuticals Division, Copenhagen, Denmark. lise-sylvest.helledi@alpharma.dk
authors.forename: L S
authors.initials: LS
authors.lastname: Helledi
authors.forename: L
authors.initials: L
authors.lastname: Schubert
mesh_terms: D000212:Acyclovir / Q000737:chemistry*; D000998:Antiviral Agents / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D005989:Glycerides / Q000737:chemistry; D007700:Kinetics; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D000998:Antiviral Agents; D005989:Glycerides; D011108:Polymers; C422409:liquid crystal polymer; C005953:monoolein; D000212:Acyclovir