Stability Study Of Endostatin And Brucea Javanica Oil Emulsion Injection Related With Intravenous Admixture Dreparation

Objective:To learn the current status of cold chain management in hospitals in Zhejiang Province and investigate the stability after intravenous admixture preparation or beyond non-cold chain management of drugs that should be refrigerated for storage according to prescribing information and provide guides to rational medication management and use.Methods:Firstly, conduct a multiple-center questionnaire survey on hospital cold chain management in Zhejiang Province; Secondly, investigate the stability of endostatin in PVC infusion bags, non-PVC infusion bags and drug infusion pumps. In a simulated clinical situation, endostatin was undergone appropriate dilution with 0.9% sodium chloride injection in PVC infusion bags, non-PVC infusion bags or drug infusion pumps. Then high-performance liquid chromatography (HPLC) was employed to determine endostatin concentrations at 0,1,2,4 h or 0,4,8,16,24 h under 25 ℃ or 37 ℃. Secondly, investigate the stability of Brucea javanica oil emulsion injection and diluted infusion in non-PVC infusion bags at room temperature (25 ℃) because the package insert of this product notifies that it should be stored at a refrigerator and should be extemporaneously prepared prior to medication administration. Pharmaceutical analysis was performed on Brucea javanica oil emulsion injection and its diluted infusion prepared with 30 ml undiluted injection and 250 ml 0.9% sodium chloride injection in non-PVC infusion bags in a simulated clinical situation. The character, pH, osmotic pressure, particle fineness and content of oleic acid (gas chromatography) in the admixture were determined at different time at room temperature. Lastly, review data on room temperature stability of medications that should be refrigerated for storage according to prescribing information, by retrieving literature from Pubmed, Wanfang Database, Rxlist and Baidu Encyclopedia.Results:(1) Implementation situation is uneven when to refer to drug cold chain management in 29 hospitals of Zhejiang Province, including awareness, hardware construction, processes, medication labeling, intelligent management and patient satisfaction toward drug cold chain. Only few hospitals have achieved seamless cold chain management and standard storage for those medications requiring up to 20 ℃. 13% of hospitals fulfill drug cold chain from medication procurement section to dispensing pharmacies. Only 7% of hospitals fulfill drug cold chain from inpatient pharmacy to nursing units whereas the percentage is 10% from PIVAS to nursing units. None has established a good cold chain management on medications returning from nursing units to pharmacy. Regarding refrigeration alert in the medication labeling, outpatient pharmacy did better than inpatient pharmacy and pharmacy intravenous admixing service center (84% versus 235%, chi-square test, P=0.000008). (2) Endostatin could keep stable in PVC infusion bags or non-PVC infusion bags for at least 4 h, and remained stable 48 h in drug infusion pumps under 25 ℃ or 37 ℃. Undiluted Brucea javanica oil emulsion injection could keep stable for at least 72 h under 25 ℃, and its diluted infusion remained stable 24 h in non-PVC infusion bag under 25 ℃. (3) There are experimental studies of room temperature stability of medications that need refrigeration, involving 14 medications. There are 24 medications whose prescribing information specify room temperature stability as well as requiring refrigeration. There are 15 medications whose prescribing information do not specify room temperature stability but manufacturers have given relevant stability data. Descriptions on room temperature stability of medications that need to be refrigerated are various among package inserts of medications with same generic names but different manufactures, especially among domestic products and imported products. Some products could be stored at room temperature when technological innovations were introduced.Conclusion:There are great improvement opportunities in drug cold chain management in hospitals of Zhejiang Province. It need more resources input and higher awareness of this issue. In clinical practice, it is appropriate to administer endostatin by intravenous dripping or via automatic infusion pumps from the perspective of drug stability..In clinical practice, it is appropriate to escape the strict cold chain requirements on Brucea javanica oil emulsion injection during drug dispensing and logistics distribution. And it is unnecessary to extemporaneously prepare the infusion of Brucea javanica oil emulsion just before intravenous administration. It is of clinical significance to conduct researches on room temperature stability of medications that need refrigeration for storage according to prescribing information. Short term storage at room temperature based on evidence is beneficial to medication adherence and drug accessibility when drug cold chain measures are unavailable or not applicable. There are absence of stability data for a lot of medications that need for refrigeration. It needs further patient oriented, real world-based scientific research.