Enhanced stability of sulfamethoxazole and trimethoprim against oxidation using hydroxypropyl-beta-cyclodextrin.
The effect of hydroxypropyl-beta-cyclodextrin (HPbetaCD) on the chemical stability of sulfamethoxazole and trimethoprim (co-trimoxazole) under oxidation stress at 50 +/- 2 degrees C was investigated. The concentrations of sulfamethoxazole and trimethoprim in aqueous solutions (pH 5.4) containing 0, 1%, 2%, 5%, 10% and 15% w/v hydroxypropyl-beta-cyclodextrin were measured by HPLC. Both sulfamethoxazole and trimethoprim degradation appeared to follow pseudo-first order kinetics in the presence and in the absence of hydroxypropyl-beta-cyclodextrin. The observed half-lives for sulfamethoxazole and trimethoprim in 15% w/v hydroxypropyl-beta-cyclodextrin were 910 h and 609 h respectively, 11.8 and 3.4 times greater than in solutions without hydroxypropyl-beta-cyclodextrin. Using a Lineweaver-Burk equation, the half-lives for sulfamethoxazole and trimethoprim outside the complex in a solution containing 15% w/v hydroxypropyl-beta-cyclodextrin were estimated at 77 h and 193 h respectively, whereas inside the complex the half-lives were estimated at 850 h and 821 h. In terms of relative increases in stability under oxidation stress the half-lives for sulfamethoxazole and trimethoprim inside the complex were 11.0 times and 4.2 times greater than their half-lives outside the complex. In conclusion, chemical stability of sulfamethoxazole and trimethoprim in co-trimoxazole aqueous solutions under oxidation stress at 50 +/- 2 degrees C can be increased using hydroxypropyl-beta-cyclodextrin as a molecular inclusion excipient.
Pourmokhtar
M
M
School of Pharmacy, University of Tasmania, Hobart, Australia.
Jacobson
G A
GA
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000465:Algorithms; D000890:Anti-Infective Agents / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005079:Excipients; D006207:Half-Life; D006861:Hydrogen Peroxide / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D015233:Models, Statistical; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D012995:Solubility; D012996:Solutions; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000032:analysis*; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000890:Anti-Infective Agents; D005079:Excipients; D012996:Solutions; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D006861:Hydrogen Peroxide