Bioadhesive Microspheres for Ophthalmic Administration of Acyclovir

Abstract

The bioavailability of acyclovir to the ophthalmic epithelium is low and when the drug is administered in ophthalmic ointment it must be applied every four hours. An emulsification technique has been used to prepare acyclovir-loaded chitosan microspheres with the aim of promoting the prolonged release of drug and increasing its ocular bioavailability. The microparticulate drug-delivery systems obtained have been characterized for their morphology and physicochemical characteristics by in-vitro dissolution tests and in-vivo ocular administration to rabbits. The results show that the microspheres obtained are always quite small--the diameters of 90% of the particles are < or = 25 microns (i.e. d 90% never exceeds 25 microns) and physicochemical characterization shows that the drug is homogeneously dispersed in an amorphous state inside the microspheres. The in-vitro dissolution profile of acyclovir from chitosan microspheres is slower than that for the raw drug. Results from in-vivo ocular administration of acyclovir-loaded microspheres to the rabbit eye show prolonged high concentrations of acyclovir and increased AUC values. The microparticulate drug-carrier seems a promising means of topical administration of acyclovir to the eye.

Floating Properties and Release Characteristics of Hollow Microspheres of Acyclovir

“…In this study, the X-ray patterns of the pure drug and the polymer are shown in Figure 4. The X-ray pattern of Eudragit S 100 showed a halo pattern (Figure 4f) indicating its existence in amorphous form, whereas that of acyclovir exhibited crystalline characteristics, as shown in Figure 4g identical to that reported by Genta et al (1997). The X-ray patterns of microspheres prepared by using different amounts of acyclovir can be seen in Figure 4a-4e), which showed a combined pattern of those of the polymer and the pure drug.…”

“…• C. The DSC thermogram obtained from this study slightly differed from the studies by Genta et al (1997) and Kristl et al (1996) indicating that the DSC curve of acyclovir exhibited a small melting endothermic peak at approximately 170…”

“…Acyclovir is almost completely unionized and has the maximum solubility (2.5 mg/ml) at pH 7.0. Various sustained release dosage forms of acyclovir had been successfully developed, including bioadhesive microspheres for ophthalmic administration (Genta et al 1997;De Jalon et al 2001), biodegradable microspheres for intravitreal administration Herrero-Vanrell et al 2000), liposomes for ocular delivery system (Law and Hung 1998;Law et al 2000), and controlled release capsules for ophthalmic administration (Tu et al 2001).…”

A study of the characteristics and in vitro permeation properties of CMC/ chitosan microparticles as a skin delivery system for vitamin E

“…Liposomes were able to delay the release of glycolic acid, and microspheres were unable to modulate active substance release even following crosslinking with glutaraldehyde, a compound causing a reduction of microsphere sizes. In previous studies, Genta et al (1997) were able to modulate the release of the acyclovir, a lypophilic drug, using chitosan microspheres with mean diameter ≤ 25 µm for ocular administration.…”

Quitosana: biopolímero funcional com potencial industrial biomédico

“…71,81 A quitosana exibe comportamento biológico favorável, tais como bioadesão, permeabilidade e características fisico-químicas interessantes, que tornam este biopolímero um material único para design de sistemas de liberação de fármaco ocular. [82][83][84][85] A quitosana é considerada um bom sistema de liberação de fármacos na cavidade bucal, visto que a sua atividade antibacteriana pode ser devida às interações eletrostáticas entre grupos amino e grupos aniônicos nas paredes celulares das bactérias provenientes de resíduos de ácidos carboxílicos e fosfolipídeos. 86 Sistemas de liberação bucal mucoadesivos desenvolvidos por hidrogéis de quitosana parecem ser apropriados para prolongar o tempo de residência da forma farmacêutica, melhorando o efeito terapêutico no tratamento de infecções localizadas, tais como doença periodontal e estomatite.…”