Category: Formulation and Quality
Purpose: The objective of this study was to assess the physical and chemical stability of two strengths (5 mg and 200 mg) of testosterone in compounded topical creams. A validated stability-indicating HPLC method was used to determine the chemical stability of testosterone in compounded topical creams at ambient and accelerated conditions. The HPLC method featured both UV and mass detection.
Methods: The mobile phase was composed of methanol and water (75:25 v/v) while the stationary phase was a Waters Nova-Pak C18 column (3.9 mm x 15 cm x 4.0 µm) with the column temperature set to 40 ⁰C. The injection volume was 20 µL while the gradient flow rate was maintained at 0.75 mL/min for a run time of 15 minutes. The detection wavelength for testosterone was set to 240 nm. Testosterone stability was quantified by analytically comparing the sample cream curve to the calibration curve, using both a photo-diode array detector (PDA) and a mass detector, and calculating the percent labeled content of testosterone at fifteen points over six months for both testing conditions. Creams were stored in plastic pump containers. Room temperature and ambient relative humidity were 25±2 ⁰C and 60±5 % RH. Accelerated temperature and relative humidity were 40±2 ⁰C and 75±5 % RH.
Results: Percent labeled content of both cream strengths remained within the general USP acceptance criteria of 90% - 110% for the majority of time points tested over the 6-month time period. This was true under room temperature and accelerated conditions. Physical stability of samples stored at room temperature changed – in color, in scent, in brittleness – after 88 days while the samples stored under accelerated conditions started to change – in color, in texture, in fragility – after seven days.
Conclusion: This developed and validated method is suitable for both routine strength testing as well as stability testing of testosterone in compounded topical creams. The method was utilized to successfully quantify the real-time and accelerated stability of testosterone in two dosage strengths of topical creams. Physical stability of the creams is poor when stored under conditions of higher humidity and heat in the tested container, but is good when stored under conditions of room temperature in the tested container. Since the percent labeled content remained within the general 90% - 110% USP acceptance criteria for the majority of points tested, the results of this study may support the extension of the default beyond-use-date for topical dosage forms required by the USP (30 days).
Casey Sayre– South Jordan, Utah
Anna Burrows– South Jordan, Utah
Christopher Cox– Pleasant Grove, Utah
Meagan Wakefield– South Jordan, Utah
David Jackson– South Jordan, Utah
Omid Yazdanpanah– South Jordan, Utah
Odily Alvarado– South Jordan, Utah
Heidi Schiller– South Jordan, Utah
Krushit Patel– South Jordan, Utah