别嘌醇的个体物理化学稳定性,盐酸克林霉素,盐酸纳曲酮,作者先前已研究并发表了专利悬浮载体PCCASuspendIt®中的螺内酯和Ursodiol。因此,根据各自研究的结果,将180天的使用日期(BUD)分配给五种药物。将数据捐赠给美国药典(USP),以作为官方复合药物专著。经过广泛的审查过程,所有5项研究均获得USP批准和发表.然而,由于缺乏微生物稳定性信息,BUD限制为90天。本研究是作为后续项目进行的,目的是利用与原始研究相同的复合程序,确定这五种药物在PCCASuspendIt®中的微生物稳定性。稳定的临时产品被定义为在整个采样期间保留至少90%的初始药物浓度并且被保护免受微生物生长的产品。我们的目标是提供一个可行的,别嘌醇的复合替代品,盐酸克林霉素,盐酸纳曲酮,螺内酯和Ursodiol的触变液体剂型,延长BUD6个月以满足患者需求。鉴于所有五种药物的物理和化学稳定性先前已被USP确立并作为官方复合专著采用,额外的微生物稳定性数据将允许USP中的官方BUD延长至180天,以符合物理化学稳定性。目前的研究表明,PCCASuspendIt®中的防腐剂系统成功地保护了所有悬浮液免受USP第<51>AME测试中攻击微生物的生长。当前研究的结果与先前的物理化学研究相结合,证明了以下几点:别嘌呤醇在物理上,在PCCA中化学和微生物学稳定SuspendIt在冰箱中和室温下在10-20mg/mL的括号内浓度范围内保持180天。盐酸克林霉素在物理上,在PCCASuspendIt中化学和微生物学稳定180天,在冰箱和室温下,浓度为10-mg/mL的克林霉素。盐酸纳曲酮在物理上,在冰箱和室温下,在PCCASuspendIt中化学和微生物学稳定180天,括号内的盐酸纳曲酮浓度范围为0.5-5.0mg/mL。螺内酯是身体上的,在PCCA中化学和微生物学稳定SuspendIt在冰箱中和室温下在5mg/mL浓度的螺内酯中保持180天。乌索二醇在身体上,在冰箱和室温下,在PCCASuspendIt中化学和微生物学稳定180天,在50-100mg/mL的括号内的熊二醇浓度范围内。集体采取,当前的研究与早期的研究相结合提供了可行的,别嘌醇的复合替代品,盐酸克林霉素,盐酸纳曲酮,螺内酯和Ursodiol在悬浮载体PCCA中悬浮在液体剂型中,延长超出使用日期,以满足患者的需求。
The individual physicochemical stabilities of
Allopurinol, Clindamycin Hydrochloride, Naltrexone Hydrochloride, Spironolactone and Ursodiol in the proprietary suspending vehicle PCCA SuspendIt® have been previously studied and published by the author. Accordingly, Beyond-Use-Dates (BUDs) of 180 days were assigned to the five drugs based on the results of the respective studies. The data were donated to the United States Pharmacopeia (USP) for possible adoption as Official Compounded Drug Monographs. Following an extensive review process, all five studies were approved and published by the USP. However, due to a lack of microbiological stability information, the BUDs were limited to 90 days. The current study was undertaken as a follow-up project to determine the microbiological stability of these five drugs in PCCA SuspendIt® utilizing the same compounding procedures from the original studies. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The goal was to provide a viable, compounded alternative for
Allopurinol, Clindamycin Hydrochloride, Naltrexone Hydrochloride, Spironolactone and Ursodiol in a thixotropic liquid dosage form, with an extended BUD of 6 months to meet patient needs. Given that the physical and chemical stabilities of all five drugs have been previously established and adopted by the USP as official compounded monographs, additional microbiological stability data would allow the official BUDs in the USP to be extended to 180 days to conform to the physicochemical stabilities. The current study showed that the preservative system in PCCA SuspendIt® successfully protected all the suspensions from growth of challenge microorganisms per the USP Chapter <51> AME Test. The results of the current study combined with the previous physicochemical studies demonstrate the following:
Allopurinol is physically, chemically and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature over a bracketed
allopurinol concentration range of 10 - 20 mg/mL. Clindamycin Hydrochloride is physically, chemically and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature at a concentration of 10-mg/mL of clindamycin. Naltrexone Hydrochloride is physically, chemically and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature, over a bracketed naltrexone hydrochloride concentration range of 0.5 - 5.0 mg/mL. Spironolactone is physically, chemically and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature at a concentration of 5 mg/mL of spironolactone. Ursodiol is physically, chemically and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature, over a bracketed ursodiol concentration range of 50 - 100 mg/mL. Taken collectively, the current study in conjunction with the earlier studies provide viable, compounded alternatives for
Allopurinol, Clindamycin Hydrochloride, Naltrexone Hydrochloride, Spironolactone and Ursodiol in the suspending vehicle PCCA SuspendIt in liquid dosage forms, with an extended beyond-use-date to meet patient needs.