UNITEFA   23945
UNIDAD DE INVESTIGACION Y DESARROLLO EN TECNOLOGIA FARMACEUTICA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
In vitro ocular biocompatibility of novel HP-Β-CD acetazolamide complexes
Autor/es:
CALLES, JAVIER ADRIÁN; MORA, MARIA J.; LOPEZ-GARCÍA, ANTONIO; PALMA, SANTIAGO DANIEL; VALLÉS, ENRIQUE MARCELO; LONGHI MARCELA R.; GRANERO GLADYS E.; DIEBOLD, YOLANDA
Lugar:
Valencia
Reunión:
Congreso; Xth Spanish-Portuguese Conference on Controlled Drug Delivery ?Drug Delivery Systems from Lab to Clinic. New trends and Opportunities; 2013
Institución organizadora:
CRS Hispano - Lusa
Resumen:
INTRODUCTION Cyclodextrins (CDs) are a group of natural products formed during bacterial digestion of starch. These cyclic oligosaccharides consist of (α-1,4)-linked α-D glucopyranose units with a hydrophilic outer surface and a lipophilic central cavity CDs are able to solubilize many lipophilic water-insoluble drugs otherwise is hard to formulate in aqueous eyedrop solutions Acetazolamide (ACZ) is a carbonic anhydrase inhibitor used orally for the reduction of intraocular pressure (IOP) in patients suffering from glaucoma The two major problems that hinder the topical effectiveness of ACZ are its poor aqueous solubility (w0.7 mg/ml) and a low corneal permeability coefficient of 4.1x10-6cm/s In order to enhance the ocular bioavailability of ACZ, a multicomponent complex with hydroxypropyl-ß-cyclodextrin (HP-ß-CD) and triethanolamine (TEA) was prepared for ocular topical application. The aim of this work was to evaluate the in vitro ACZ delivery performance and the biocompatibility between ocular surface cells and ACZ complexes as a first step in the design of a topical DDS for ocular administration. RESULTS AND DISCUSSION Cell viability: Human corneal cells exposed to ACZ complexes (ACZ-HP-ß-CD and ACZ-HP-ß- CD-TEA) in concentrations of 0,1%, 0,5% and 1% (ACZ), for 24 h exhibited viabilities around 100% in all cases. Morphological details of exposed cells remained intact. Viability was not reduced when cells were exposed to higher concentrations of complexes solutions. Proliferation: Proliferation rate of human corneal cells exposed to 0,1% or 0,5% ACZ-CD complexes was equivalent to that of controls. Cells exposed to ACZ-HP-ß-CD 1% solutions showed a marked reduction in proliferation rate. Cells exposed to ACZ-HP-ß-CD-TEA 1% solutions also showed an important reduction in proliferation through the first 24 h, although they recovered their normal proliferation rate in the following 24 h. Drug delivery: CD-free formulations showed a slower ACZ release profile than those of HP-ß-CD- containing formulations, being the drug release from the physical mixture the lowest. This decrease in drug release is probably a result from the formation of an ion pair between ACZ and TEA, whose hydrophilicity and relatively larger size than the free drug might be responsible for its poor membrane permeability.