Stability studies of topical carbonic anhydrase inhibitor 6-hydroxyethoxy-2-benzothiazole sulfonamide.
A new carbonic anhydrase inhibitor, 6-hydroxyethoxy-2-benzothiazole sulfonamide (6-hydroxyethyoxyzolamide), was studied to determine its stability in aqueous solution from pH 2.9 to 9.2 at a constant ionic strength of 0.15 M. This newly synthesized derivative of ethoxyzolamide has demonstrated clinical efficacy for use as an ophthalmic drug to lower intraocular pressure. Drug solution in sealed ampules was placed in a constant temperature over either at two temperatures (75 and 85 +/- 0.2 degrees C) or four temperatures (75, 80, 85, and 90 +/- 0.2 degrees C). Samples were analyzed by known HPLC methods. The results indicated that 6-hydroxyethoxyzolamide is most stable at pH 4 to 5.5. The aqueous drug solutions at pH 7.0 and 8.0 were, nevertheless, sufficiently stable, based on extrapolation of kinetic data at high temperatures using the experimentally determined Arrhenius equation. The degradation compound was identified by spectral analysis to have a hydroxyl group substituting for the original -SO2NH2 group.
Chiang
C H
CH
School of Pharmacy, National Defense Medical Center, Taipei, Republic of China.
Hsieh
C H
CH
Lu
D W
DW
Kao
K D
KD
D000287:Administration, Topical; D052160:Benzothiazoles; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005016:Ethoxzolamide / Q000031:analogs & derivatives* / Q000737:chemistry; D007700:Kinetics; D009883:Ophthalmic Solutions; D013696:Temperature
D052160:Benzothiazoles; D002257:Carbonic Anhydrase Inhibitors; D009883:Ophthalmic Solutions; C043694:6-hydroxyethoxzolamide; D005016:Ethoxzolamide