RESUMO
Adenosine is a potent endogenous mediator of vasodilation. Compounded sterile solutions of adenosine are used in cardiac catheterization lab to perform stress tests on the heart. These tests are used to determine the fractional flow reserve (FFR) and are commonly used in the management and diagnosis of cardiovascular conditions. The purpose of this study was to assess the physical and chemical stability of 2 mg/mL adenosine in 0.9% Sodium Chloride Injection, USP in polyvinyl chloride [PVC]) and polyolefin infusion bags stored at room temperature (20°C-25°C) and under refrigeration (2°C-8°C). The compounding and analytical methods used in this study were very similar to those described in the prior publications from the authors' laboratory. To ensure a uniform starting concentration of all stability samples, a batch of 2 mg/mL adenosine solution was prepared and then packaged into empty PVC and polyolefin infusion bags. These stability samples were prepared in triplicate for each bag type and storage temperature (a total of 12 samples). The infusion bag samples were assessed for stability immediately after preparation and after 1 day, 3 days, 7 days, and 14 days. At each time point, the infusion bags were first visually inspected against a light background for color change, clarity, and particulates. Aliquots were drawn from each sample at each time point for pH analysis and high-performance liquid chromatography (HPLC) analysis. Over 14 days of storage at room temperature or refrigeration, no considerable change in visual appearance or pH was observed in any bags. All samples retained 90% to 110% of the initial drug concentration. No significant degradation peaks were observed in the HPLC chromatograms.
RESUMO
Suboxone films are U.S. Food and Drug Administration approved to treat opioid dependence. While the package insert states that films should not be cut, physicians often prescribe film fractions for treatment and tapering. There is no data to support this practice, and this study was initiated to evaluate cutting methods, content uniformity, and stability of split films. Suboxone 8-mg buprenorphine/2-mg naloxone films were split using four methods: 1) ruler/razor cut, 2) scissor cut, 3) fold/rip, and 4) fold/scissor cut. United States Pharmacopeia Chapter <905> was used to evaluate the weight variation and content uniformity of split films. The stability of split films stored in polybags was evaluated over 7 days. A stability-indicating high-performance liquid chromatography method was used for content uniformity and stability evaluation. The weight variation results were acceptable for the half films from all four cutting methods, but this was not true for the quarter films. The method of ruler/razor cut was determined most favorable and used for the content uniformity test. Based on the high-performance liquid chromatography results, the half films from the ruler/razor cut method met the passing criteria of United States Pharmacopeia Chapter <905> with acceptance values of 9.8 to 10.4 for buprenorphine and 8.4 to 11.5 for naloxone (=15 is considered passing). The stability results indicated that both actives retained >97.7% of initial strength. Four cutting methods were found to be acceptable for splitting Suboxone films into half but not quarter fractions. The half films from the ruler/razor cut method also passed United States Pharmacopeia Chapter <905> content uniformity test. Both actives remained stable for 7 days when the half films were stored in polybags at room temperature.