Supercritical carbon dioxide for drying and sterilizing parenteral dosage forms

用于肠胃外剂型干燥和灭菌的超临界二氧化碳

基本信息

批准号：
7668177
负责人：
Charles J. Decedue
金额：
$ 10万
依托单位：
SCF TECHNOLOGIES, LLC
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-06 至 2010-03-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7668177
关键词：
Affect Alcohols Amines Antineoplastic Agents Biological Biological Products Carbon Dioxide Carboxylic Acids Chemicals Clinic Dosage Forms Dose Drug usage Effectiveness Filtration Freeze Drying Goals Injectable Injection of therapeutic agent Intravenous Knowledge Lead Life Literature Measures Methods Modeling Oral Patients Pharmaceutical Preparations Phase Phase I Clinical Trials Phase II Clinical Trials Precipitation Preparation Probability Process Production Publishing Route Safety Small Business Innovation Research Grant Solutions Sterility Sterilization for infection control Sulfhydryl Compounds Techniques Technology Temperature Testing Time Vial device Water Work base chemical stability cost expectation experience food sterilization interest intraperitoneal intravenous injection killings medical food meetings microbial new technology oncology pressure public health relevance reconstitution small molecule sterility testing treatment effect

项目摘要

DESCRIPTION (provided by applicant): The long range goal of this project is to develop methods of using supercritical carbon dioxide (scCO2) to achieve terminal sterilization that meets or exceeds the USP standard of 10-6 microbial survival probability and that produces a dry drug product in a single process. The objective of this application is to identify at least one set of conditions in which the act of drying drugs by the scCO2 process known as lyophobic precipitation (LP) can also sterilize the drug product in its dispensing container as well as the chamber in which the process is conducted. The rationale behind this project is that recent observations that scCO2 can be used to effect terminal sterilization of food and medical products without damaging the product will be adaptable to the LP drying process. Many drugs, including many anticancer agents, must be administered by non-oral routes (intravenous or intraperitoneal) and therefore must be sterile for injection. For stability reasons such drugs often must be dry as well as sterile. Current technology requires a two-step process of filter-sterilization followed by lyophilization under aseptic conditions to achieve safe, stable dosage forms. To accomplish the objectives of this application two specific aims will be pursued: (1) determine the level of sterilization of drug substance and container under normal LP conditions and using tested and untested added sterilizing agents, and (2) determine the level of sterilization of the chamber under normal LP conditions and using tested and untested added sterilizing agents. The strategy to accomplish the specific aims is to measure the level of killing of standard sterility-testing biological indicators added to containers of model drug under conditions that mimic the conditions that will eventually be used commercially. Similarly, challenge doses of biological indicators will be placed in the LP chamber to determine effectiveness of sterilization of the process with and without added sterilizing agents. The expectation is that at the conclusion of this Phase I SBIR period of support, precise conditions necessary to achieve a sterilization activity level of 10-6 for drug substance contained in a dispensing container and the chamber in which the lyophobic precipitation occurs will be identified. This information will guide a Phase II application to determine the effect of treatment conditions determined in this study on the chemical stability of existing oncology drugs that possess various reactive groups (e.g., alcohols, amines, thiols, carboxylic acids, etc.) that may prove susceptible to damage. PUBLIC HEALTH RELEVANCE: This project proposes a new technique to safely dry and terminally sterilize drugs in their dispensing containers. If successful, this approach will lead to simpler processing of injectable drugs that would increase safety and lower production costs.

描述（由申请人提供）：该项目的远距离目标是开发使用超临界二氧化碳（SCCO2）实现末端灭菌的方法，该末端灭菌符合或超过USP标准的10-6微生物生存率，并在单个过程中产生干药物。该应用的目的是确定至少一组条件，在这种情况下，通过SCCO2工艺（LP）通过SCCO2工艺干燥药物的行为也可以在其分配容器以及进行该过程的腔室中对药物进行消毒。该项目背后的理由是，最近观察到SCCO2可用于在不损害该产品的情况下对食品和医疗产品的终末灭菌，这将适应LP干燥过程。许多药物，包括许多抗癌药，必须通过非口腔途径（静脉注射或腹膜内）施用，因此必须是无菌的。出于稳定原因，这种药物通常必须干燥和无菌。当前的技术需要两个步骤的滤波器化过程，然后在无菌条件下进行冻干，以实现安全，稳定的剂型。为了实现本应用程序的目标，将实现两个具体的目标：（1）在正常的LP条件下确定药物和容器的灭菌水平，并使用经过测试和未经测试的添加的灭菌剂，（2）确定在正常LP条件下腔室灭菌的水平，并使用经过测试和未测试的添加的杀菌剂。实现特定目标的策略是衡量在模拟最终将商业上使用的条件下，在模型药物容器中添加到模型药物容器中的标准不育测试生物学指标的杀死水平。同样，将在LP腔室中放置挑战剂量的生物学指标，以确定该过程的有效性，并没有添加灭菌剂。期望在此I阶段I SBIR时期的结论中，将确定将确定在分配容器中包含的药物和发生裂解质沉淀的腔室的灭菌活性水平所需的精确条件。该信息将指导II期的应用，以确定本研究确定的治疗条件对具有各种反应性基团（例如醇，胺，硫醇，羧酸等）的现有肿瘤药物的化学稳定性的影响，这些药物可能证明可能证明易于损坏。公共卫生相关性：该项目提出了一种新技术，以在分配容器中安全干燥和绝对对药物进行灭菌。如果成功的话，这种方法将导致更简单地处理可注射药物，以提高安全性并降低生产成本。