Degradation Kinetics of Phentolamine Hydrochloride in Solution

• Published in: Journal of pharmaceutical sciences 1988-11, Vol.77 (11), p.972-976
• Main Authors: Wang, Da-Peng, Tu, Yu-Hsing, Allen, Loyd V.
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Buffers; Catalysis; Chemical Phenomena; Chemistry; Chromatography, High Pressure Liquid; General pharmacology; Hydrogen-Ion Concentration; Medical sciences; Pharmacology. Drug treatments; Phentolamine - analysis; Photolysis; Physicochemical properties. Structure-activity relationships; Solutions; Solvents; Spectrophotometry, Ultraviolet; Temperature
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1002/jps.2600771116

The degradation kinetics of phentolamine hydrochloride in aqueous solution over a pH range of 1.2 to 7.2 and its stability in propylene glycol- or polyethylene glycol 400-based solutions were investigated. The observed rate constants were shown to follow apparent first-order kinetics in all cases. The pKa determination for phentolamine hydrochloride was found to be 9.55 ± 0.10 (n = 5) at 25 ± 0.2°C. This indicated the protonated form of phentolamine occurs in the pH range of this study. The pH–rate profile indicated a pH-independent region (pH 3.1–4.9) exists with a minimum rate around pH 2.1. The catalytic effect of acetate and phosphate buffer species is ordinary. The catalytic rate constants imposed by acetic acid, acetate ion, dihydrogen phosphate ion, and monohydrogen phosphate ion were determined to be 0.018, 0.362, 0.036, and 1.470L mol−1 h−1, respectively. The salt effect in acetate and phosphate buffers followed the modified Debye-Huckel equation quite well. The ZAZB value obtained from the experiment closely predicts the charges of the reacting species. The apparent energy of activation was determined to be 19.72 kcal/mol for degradation of phentolamine hydrochloride in pH3.1, 0.1M acetate buffer solution at constant ionic strength (μ = 0.5). Irradiation with 254nm UV light at 25 ± 0.2°C showed a ninefold increase in the degradation rate compared with the light-protected control. Propylene glycol had little or no effect on the degradation of phentolamine hydrochloride at 90 ± 0.2 °C; however, polyethylene glycol 400 had a definite effect.