Stability and preservative effectiveness of treprostinil sodium after dilution in common intravenous diluents

被引:20
作者
Phares, KR
Weiser, WE
Miller, SP
Myers, MA
Wade, M
机构
[1] United Therapeut Corp, Pharmaceut Dev, Res Triangle Pk, NC 27709 USA
[2] United Therapeut Corp, Analyt Chem, Res Triangle Pk, NC 27709 USA
[3] United Therapeut Corp, Microbiol, Magellan Pharmaceut Dev, Res Triangle Pk, NC 27709 USA
[4] United Therapeut Corp, Microbiol, Dev & Med Affairs, Res Triangle Pk, NC 27709 USA
关键词
concentration; contamination; dextrose; diluents; hydrogen ion concentration; hypotensive agents; injections; metacresol; preservatives; sodium chloride; stability; storage; treprostinil sodium; water for injection;
D O I
10.1093/ajhp/60.9.916
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The stability of treprostinil sodium after dilution in three common i.v. infusion vehicles was assessed. The chemical stability of treprostinil sodium was tested over a 48-hour period at 40 degreesC and 75% relative humidity after dilution in each of three diluents: sterile water for injection, 0.9% sodium chloride injection, and 5% dextrose, injection, and after passage through an i.v. delivery system. Chemical analysis was conducted by using a validated stability-indicating high-performance liquid chromatographic assay, visually inspecting the solutions, and measuring the pH of each solution. The preservative effectiveness of the solutions was tested by the recovery of inoculations of compendial microorganisms after 48 hours in dilute solutions of treprostinil sodium. All assay results for treprostinil were within 90.0% to 110.0% of the prepared solutions diluted at 0.004 and 0.13 mg/mL treprostinil sodium in sterile water for injection and 0.9% sodium chloride injection. The assay results were the same for dilute treprostinil solutions in 5%. dextrose injection at concentrations of 0.02 and 0.13 mg/mL. The pH values,for these solutions remained within acceptable values of 6.0 to 7.2 for the stability study. No change in physical appearance or any visible particulate matter was observed. Approximately 70% of metacresol, the preservative, in the dilute treprostinil sodium solutions was removed before reaching the terminal end of the tubing. None of the dilute treprostinil sodium solutions supported microbial growth in the cassette reservoirs for the organisms considered. Treprostinil sodium 0.13 mg/mL solution in sterile water for injection, 0.9% sodium, chloride for injection, and 5% dextrose for injection appeared to be stable after- storage in controlled ambulatory drug-delivery systems for 48 hours at 40 degreesC and 75% relative humidity. Treprostinil sodium 0.004 mg/mL in sterile water and 0.9% sodium-chloride for injection and 0.02 mg/mL in 5% dextrose injection was also stable under the same conditions. None of the solutions' showed signs of microbial growth.
引用
收藏
页码:916 / 922
页数:7
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