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Abstract #17607 Published in IGR 9-2
Development of a vesicular system for effective ocular delivery of acetazolamide A comprehensive approach and successful venture
Kaur IP; Mitra AK; Aggarwal DJournal of Drug Delivery Science and Technology 2007; 17: 33-41
Acetazolamide (ACZ), a carbonic anhydrase inhibitor (CAI), is a commonly used agent administered orally for the treatment of glaucoma, but many patients cannot tolerate long-term treatment with ACZ because of its systemic side effects. Development of a topically effective formulation of ACZ has not been possible because of its unfavorable partition coefficient, solubility, permeability coefficient, and poor stability at the pH of its maximum solubility. Based on these factors and the ability of niosomes to come into complete contact with corneal and conjunctival surfaces, we used niosomal drug delivery to enhance the corneal absorption of ACZ. Furthermore, the non-ionic surfactants used in the preparation may also temporarily increase the permeability of the corneal epithelium. Earlier we reported reverse-phase evaporation (REV) as the most suitable method for preparing ACZ niosomes. Coating these niosomes with a bioadhesive polymer such as Carbopol 934P (REVbio), which prolongs the contact time of the formulation in the eyes, is another approach reported by us. Boric acid solution (2%), which is isotonic with tears, was used as a vehicle for the developed niosomal formulations because the pH of maximum stability for ACZ is 4.0. By using boric acid solution, pH was maintained between 4-5. We recommend boric acid as the vehicle for ACZ eye drops for the first time. The pharmacodynamic studies showed > 30% fall in intraocular pressure (IOP) which was sustained for up to 5 h. The effect compared well with a four-times higher concentration of dorzolamide (Dorzox), a topical CAI available in the market. Furthermore, microdialysis showed that the ACZ disposition from the REVbio formulation had a peak concentration of 14.94 μg/ml in the aqueous humor, which was almost two times higher than the concentration obtained with the equivalent amount of acetazolamide control suspension. Finally, the developed formulation was evaluated for stability, safety (in terms of its corneal cell toxicity), and the preservative's (sodium perborate) ability to retard contamination (challenge test, BP).
Dr. I.P. Kaur, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India. indupalkaur@yahoo.com
Classification:
11.16 Vehicles, delivery systems, pharmacokinetics, formulation (Part of: 11 Medical treatment)
11.13.2 Betablocker and carbon anhydrase inhibitor (Part of: 11 Medical treatment > 11.13 Combination therapy)
