ABSTRACT
A multivariate modelling procedure is proposed in order to identify factors influencing stability, to estimate shelf-life, to select new batches for further stability testing and to evaluate changes in new batches. A model developed by the proposed procedure predicts the degradation rate constant as a function of storage temperature, pH, concentration and volume. The predicted rate constants were compared with prospectively measured rate constants, primarily from new batches stored under stress conditions, which emphasised batch differences earlier than storage under normal conditions. Strong deviations from expected rate constants led to extended testing of the batches concerned. The new data were used to upgrade the multivariate model. The procedure proposed led to the formulation of an opportunistic stability strategy (OSSY). Of the 15 batches of injectable solutions, nine batches are proposed tested by using OSSY. This led to an approximately 75% reduction in analytical measurements. Hold samples are recommended for storage under several stability conditions for back up analysis. In general, a multivariate stability model should be based on scientific data obtained from early studies, such as preformulation and formulation studies to provide both a qualitative and quantitative understanding of the mechanisms involved.
Subject(s)
Drug Stability , Contrast Media/chemistry , Dose-Response Relationship, Drug , Drug Packaging , Glass/chemistry , Hydrogen-Ion Concentration , Models, Theoretical , Multivariate Analysis , Pharmaceutical Solutions/chemistry , Temperature , Time FactorsABSTRACT
Semipermeable containers typically allow water to diffuse upon storage. The water diffusion rate of the widely distributed X-ray contrast agent Visipaque in polypropylene bottles and MR contrast agent Omniscan in polypropylene syringes has been evaluated. The goal was to develop a mathematical method for estimating the rate constant for water diffusion through the polypropylene wall as a function of several variables. The method presents an opportunity to measure the effect of the variables influencing product stability and thereby predicting the shelf-life at an early stage of the stability study. The effect of temperature, humidity, surface area, wall thickness, concentration of active ingredient and fill volume on the logarithmic rate constant for diffusion was estimated by partial least squares regression. The predictive ability of the cross-validated models was good (r = 0.99) for the two contrast agents. The models were used to predict shelf-life for relevant combinations of temperature and humidity, for the four defined climatic zones.
Subject(s)
Drug Packaging , Multivariate Analysis , Polypropylenes/chemistry , Water/chemistry , Contrast Media/chemistry , Diffusion , Dose-Response Relationship, Drug , Drug Stability , Drug Storage , Gadolinium DTPA/chemistry , Humidity , Models, Theoretical , Syringes , Temperature , Time Factors , Triiodobenzoic Acids/chemistryABSTRACT
The critically ill obstetrical patient is a challenging complex case for today's critical care nurse. Butterworth Hospital in Grand Rapids, Michigan, identified this emerging patient population and developed a collaborative multidisciplinary program to provide positive outcomes for these patients. The following case study illustrates the components of the program and its usefulness in providing individualized care for a particular critically ill obstetrical patient.
