Norelgestromin/ethinyl estradiol intravenous infusion formulation optimization, stability and compatibility testing: A case study to overcome polysorbate 80 interference in chromatographic analysis.
Norelgestromin/ethinyl estradiol intravenous infusion formulation optimization, stability and compatibility testing: A case study to overcome polysorbate 80 interference in chromatographic analysis.
复制标题
诺孕曲明/乙炔雌二醇静脉输液配方优化、稳定性和相容性测试：克服聚山梨酯 80 色谱分析干扰的案例研究。
DOI：
10.1016/j.jpba.2016.03.024
复制
发表时间：
2016
影响因子：
3.4
通讯作者：
Stinchcomb,AudraL
中科院分区：
文献类型：
--
作者：
Abdallah,InasA;Hammell,DanaC;Hassan,HazemE;Stinchcomb,AudraL
诺孕曲明/炔雌醇是一种孕激素/雌激素组合激素避孕药，适用于预防女性妊娠。这些药物非常差的溶解度和润湿性，沿着它们的高效力（吸附问题），在设计静脉内（IV）制剂以评估含有这两种药物的产品的绝对生物利用度方面产生困难。本研究的目的是开发一种IV制剂，评价其在不同条件下的稳定性，并评价其与IV套件的相容性，以用于人体绝对生物利用度研究。还有，采用无菌注射用水、2.5%乙醇和2.5%聚山梨酯80作为助溶剂，制备诺孕曲明/炔雌醇IV溶液，并建立了测定聚山梨酯80基质中炔雌醇和诺孕曲明含量的选择性高效液相色谱法（HPLC）。表面活性剂体系，以从浓缩的药物储备溶液中获得25 μg炔雌醇和252 μg诺孕曲明的最终药物溶液。分别在冰箱（3.7 ± 0.6 ℃）和室温（19.5 ± 0.5 ℃）下储存后，评估浓缩贮备液和IV溶液的稳定性。进行了额外的研究，以使用具有和不具有在线过滤器的Alarias®低吸附IV给药装置检查IV溶液的稳定性。使溶液在60分钟内以1 mL/min滴下。在60 min持续时间的开始、中间和结束时获得样品。评价化学稳定性长达10天。采用HPLC法测定诺孕曲明和炔雌醇的浓度、纯度和降解产物水平。在第1天至第9天（216 h）检测时，诺孕曲明/炔雌醇IV制剂符合化学稳定性标准。9天后，储备液和IV溶液中测定的诺孕曲明浓度分别在90.0-98.5%和90.9-98.8%范围内。对于炔雌醇，贮备液和IV溶液的测定浓度分别在91.8-100.9%和92.7-100.8%范围内。发现给药装置与两种药物相容;诺孕曲明的测定浓度范围为99.2-100.3%，炔雌醇的测定浓度范围为96.3-102.7%，但在线过滤器显示炔雌醇有一定吸附;其中诺孕曲明的测定浓度范围为98.1-99.8%，炔雌醇的测定浓度范围为95.9-97.4%。炔雌醇，使用乙醇/聚山梨酯80作为助溶剂/表面活性剂系统。IV和浓缩贮备液分别在室温和冷藏条件下储存时，发现其化学稳定性长达9天。这些结果表明，该制剂是化学稳定的，并且可以在测试的时间段内使用。该IV制剂可用于评价含有诺孕曲明和炔雌醇的产品的绝对生物利用度，前提是对IV制剂进行微生物检测。
Norelgestromin/ethinyl estradiol is a progestin/estrogen combination hormonal contraceptive indicated for the prevention of pregnancy in women. The very poor solubility and wettability of these drugs, along with their high potency (adsorption issues), give rise to difficulties in designing intravenous (IV) formulations to assess absolute bioavailability of products containing both drugs. The purpose of this study was to develop an IV formulation, evaluate its stability under different conditions and evaluate its compatibility with IV sets for potential use in absolute bioavailability studies in humans. Also, a selective high-performance liquid chromatography (HPLC) method for quantification of ethinyl estradiol and norelgestromin in polysorbate 80 matrix was developed and validated.Norelgestromin/ethinyl estradiol IV solution was prepared using sterile water for injection with 2.5% ethanol and 2.5% polysorbate 80 as a cosolvent/surfactant system to obtain a final drug solution of 25 μg ethinyl estradiol and 252 μg norelgestromin from a concentrated stock drug solution. The stabilities of the concentrated stock and IV solutions were assessed after storing them in the refrigerator (3.7 ± 0.6 °C) and at room temperature (19.5 ± 0.5 °C), respectively. Additional studies were conducted to examine the stability of the IV solution using an Alarias®low sorbing IV administration set with and without an inline filter. The solution was allowed to drip at 1 mL/min over a 60 min period. Samples were obtained at the beginning, middle and end of the 60 min duration. The chemical stability was evaluated for up to 10 days. Norelgestromin and ethinyl estradiol concentration, purity, and degradant levels were determined using the HPLC method. The norelgestromin/ethinyl estradiol IV formulation met the chemical stability criteria when tested on day 1 through day 9 (216 h). Norelgestromin concentrations assayed in stock and IV solutions were in the range of 90.0–98.5% and 90.9–98.8% after 9 days, respectively. As for ethinyl estradiol, the assayed concentrations were in the range of 91.8–100.9% and 92.7–100.8% for the stock and IV solutions, respectively. The administration set was found to be compatible with both drugs; the assayed concentrations were in the range of 99.2–100.3% for norelgestromin and 96.3–102.7% for ethinyl estradiol, but the inline filter showed some adsorption of ethinyl estradiol; where the assayed concentrations were in the range of 98.1–99.8% for norelgestromin and 95.9–97.4% for ethinyl estradiol.The present study provided evidence supporting the suitability of an intravenous formulation for norelgestromin/ethinyl estradiol using ethanol/polysorbate 80 as a cosolvent/surfactant system. Both IV and concentrated stock solutions when stored at room temperature and refrigeration, respectively, were found to be chemically stable up to 9 days. These results indicated that this formulation is chemically stable and can be used over the time period tested. This IV formulation can be used to evaluate the absolute bioavailability of products containing norelgestromin and ethinyl estradiol provided that microbial testing of the IV formulation is performed.
登录
查看更多内容
第7章 粟酒裂殖酵母原生质体的制备
DOI：
--
发表时间：
1978
期刊：
影响因子：
--
作者：
J. Schwencke;M. Nagy
通讯作者：
M. Nagy
[63] 来自褶皱链霉菌的内切-β-N-乙酰氨基葡萄糖苷酶
DOI：
--
发表时间：
1978
期刊：
影响因子：
--
作者：
A. Tarentino;R. B. Trimble;F. Maley
通讯作者：
F. Maley
温氏汉逊酵母 Y-2340 5 型细胞性凝集因子的部分表征。
影响因子：
2.9
作者：
P. Yen;C. Ballou
通讯作者：
C. Ballou
酿酒酵母 mnn9 甘露糖蛋白的碳水化合物结构。
DOI：
--
发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Tsai,PK;Frevert,J;Ballou,CE
通讯作者：
Ballou,CE
影响因子：
2.9
作者：
EDGE, ASB;FALTYNEK, CR;WEBER, P
通讯作者：
WEBER, P