Cyclodextrins in acetazolamide eye drop formulations.
The interaction of acetazolamide with beta-cyclodextrin, (beta-CD), dimethyl-beta-cyclodextrin (DM-beta-CD) and trimethyl-beta-cyclodextrin (TM-beta-CD) was monitored spectrophotometrically. The results revealed formation of equimolar complexes. The apparent solubility of acetazolamide in water was found to increase linearly with increasing CD concentration. The effect of CDs on the permeation of acetazolamide through semi-permeable membranes and the topical delivery of acetazolamide was investigated. Maximum acetazolamide penetration was obtained when just enough CD was used to keep all acetazolamide in solution. For an acetazolamide concentration of 10 mg/ml, the optimum CD concentration appeared to be 3.5 mmol/l for beta-CD, 2.8 mmol/l for TM-beta-CD and 6.0 mmol/l for DM-beta-CD. The effect of CDs on the bioavailability of acetazolamide was assessed by measuring the intraocular pressure in rabbits. The results indicated that CDs have a significant influence on the biological performance of the drug leading to augmentation in its intensity of action and bioavailability as well as prolongation in its duration of action.
Ammar
H O
HO
Department of Pharmaceutical Sciences, National Research Centre, Dokki, Cairo, Egypt.
El-Nahhas
S A
SA
Khalil
R M
RM
D000086:Acetazolamide / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D003505:Cyclodextrins / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D006207:Half-Life; D008297:Male; D009883:Ophthalmic Solutions; D011817:Rabbits; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet
D003505:Cyclodextrins; D005079:Excipients; D009883:Ophthalmic Solutions; D000086:Acetazolamide