RESUMO
The objective of this study was to evaluate the stability of 10 commonly used active pharmaceutical ingredients compounded in oral suspensions using an internationally used suspending vehicle (SyrSpend SF PH4): alprazolam 1.0 mg/mL, atropine sulfate 0.1 mg/mL, glutamine 250.0 mg/mL, levofloxacin 50.0 mg/mL, metoprolol tartrate 10.0 mg/mL, nitrofurantoin 2.0 mg/mL, ondansetron hydrochloride 0.8 mg/mL, oxandrolone 3.0 mg/mL, pregabaline 20.0 mg/mL, riboflavin 10.0 mg/mL. All suspensions were stored at both controlled refrigeration (2°C to 8°C) and controlled room temperature (20°C to 25°C). Stability was assessed by measuring the percent recovery at varying time points throughout a 90-day period. Active pharmaceutical ingredients quantification was performed by high-performance liquid chromatography via a stability-indicating method. Given the percentage of recovery of the active pharmaceutical ingredients within the suspensions, the beyond-use date of the final products (active pharmaceutical ingredients + vehicle) was at least 90 days for all suspensions with regard to both temperatures. This suggests that the vehicle is stable for compounding active pharmaceutical ingredients from different pharmacological classes.
Assuntos
Preparações Farmacêuticas/química , Suspensões/química , Alprazolam/química , Atropina/química , Composição de Medicamentos/métodos , Estabilidade de Medicamentos , Armazenamento de Medicamentos/métodos , Glutamina/química , Levofloxacino/química , Metoprolol/química , Nitrofurantoína/química , Ondansetron/química , Oxandrolona/química , Pregabalina/química , Refrigeração/métodos , Riboflavina/química , TemperaturaRESUMO
A new spectrofluorimetric assay for the photodegradation products of the ansiolytic drug alprazolam is described. Alprazolam was found to be highly photolabile and special care should be taken to avoid light exposure during alprazolam storage and handling. The photostability of alprazolam was evaluated at pH 2.0, 3.6 and 5.0. The drug was exposed to UVA-UVB radiations, the photodegradation of alprazolam was followed by high-performance liquid chromatographic (HPLC) and the developed spectrofluorimetric assay allowed determination of the photodegradation products at very low concentrations (> or = 10(-5) M). The photoinstability was found to increase with the pH value decreasing, consequently acidic media should be avoided during the drug-development process.
Assuntos
Alprazolam/análise , Alprazolam/metabolismo , Alprazolam/química , Estabilidade de Medicamentos , Luz , Espectrometria de Fluorescência/métodosRESUMO
Accelerated thermal, hydrolytic, and photochemical degradations of alprazolam were performed under several reaction conditions. The stress studies revealed the photolability of the drug as the most adverse stability factor; the main photodegradation products were isolated and properly characterized as: triazolaminoquinoleine; 5-chloro-[5"-methyl-4H-1,2,4-triazol-4-yl]benzophenone, and 1-methyl-6-phenyl-4H-s-triazo-[4,3-alpha][1,4]benzodiazepinone. Accelerated pH-dependent studies show that the photoinstability increases as the pH decreases; at pH 9.0, photodegradation does not occur, therefore, the photochemical degradation of alprazolam was performed in buffered solutions at pH 2.0 and 3.6. The higher rate of reaction was observed at pH = 2.0; consequently, acidic conditions should be avoided and appropriate light protection is recommended during the drug-development process, storage, and handling. The main degradation route for alprazolam tablets is also photochemical.