Development of an ocular delivery system based on 6-o-alkyl derivatives of ascorbic acid

SAINO, VERONICA; BURGALASSI, SUSY; MONTI DANIELA; TAMPUCCI S; PALMA, SANTIAGO DANIEL; ALBERTO ALLEMANDI, DANIEL; CHETONI PATRIZIA

Perugia. Italia

Simposio; 2nd AITUN annual meeting, Toward the Development of Drug Delivery Systems (CRS, Filial Italia); 2008

CRS Filiala Italia

Methods. The coagels (CG-ASC) were prepared with hexadecanoyl ascorbate (ASC16) obtained from Fluka, and dodecanoyl ascorbate (ASC12) that was synthesized in our laboratory. The coagels were prepared by heating 2% w/v ASC aqueous suspension containing DICH (0.1% w/v) above the phase transition temperature (65°C) and allowing the temperature to fall to room temperature thus yielding the respective coagels (CG-ASC12 2% w/v and CG-ASC16 2% w/v).In vitro study The “in vitro” release of DICH from coagels through cellulose acetate membranes (MWCO3500, Spectrum®) was carried out using a Gummer diffusion apparatus. As receptor medium 80 ml of PBS (66.7 mmol/L, pH=7.4) a 32°C was used. At the predetermined time intervals, samples of the receiving phase (10 mL) were withdrawn for analysis are replaced with an equal volume of fresh buffer. The amount of DICH released from the formulations was determined by HPLC. A suspension of 0.1% w/v DICH in PBS (pH 7.4) was chosen as reference (SDICH).In vivo study: Preliminary in vivo studies on the ocular tolerance and on ocular bioavailability of DICH in the tear fluid and in the aqueous humor of albino rabbits were also performed. For the pharmacokinetic studies 50 μl of the coagels (CG-ASC12 2% w/v and CG-ASC16 2% w/v and of the reference suspension (S-DICH) were instilled in the conjunctival sac of two groups of rabbits and at appropriate time intervals biological samples were withdrawn and analyzed by HPLC. For ocular tolerance study 30 min after administration of the ASC containing vehicles, the eyes were treated with 10 μl of fluorescein 0.1% solution and observed with a slit-lamp.Results. A profile near to a zero-order for more than four hours was obtained for the diffusion of DICH for both coagels, while, a higher amount of DICH with a profile corresponding to no-linear kinetic was realised from the suspension (S-DICH)Coagels showed a good ocular tolerability and the capacity to  ncrease the time retention of drug in the tear fluid with respect to aqueous suspension. Conclusions. Our preliminary results suggested that coagels could be a promising delivery systems for increase the activity of ophthalmic drugs.