69 International Journal of Pharmaceutical Compounding Vol. 10 No. 1 January/February 2006 P E E R R E V I E W E D The use of morphine in patient-controlled analgesia (PCA) pumps has been widely reported, 1,2 and its popularity, owing to good patient compliance, is increasing. 3,4 Patient-controlled analgesia is a relatively safe technique for pro- viding postoperative pain relief. 5,6 The intravenous (IV) route for PCA is preferred because it uses less drug and yields fewer side effects than epidural administration. 7 A benefit of IV infusion of opioids is that it maintains a constant plasma drug concentration and reduces the “peak and valley” effect; on the other hand, in the absence of an initial bolus loading injection, four to five half-lives are necessary to reach steady state. Initiating therapy with a loading dose eliminates this problem but still does not allow for rapid dos- age adjustments as analgesic requirements change. With its combi- nation of continuous infusion and intermittent low bolus doses, PCA is an answer to many patients’ needs. Until recently, standard morphine PCA solutions (100 mg/ 100 mL) were prepared extemporaneously by anesthesiologists and/ or nursing staff in the operating theater or the recovery room of our hospital. Because of the complexity of these preparations, the following problems were encountered: ■ Risk of error: Error is one of the leading causes of death in the hospital environment; 8-10 analgesics are the primary drugs con- cerned, 11 and morphine is among America’s riskiest drugs (ranked second). 12 A recent study revealed that almost half of all IV doses made up on hospital wards were associated with errors, especially in the case of “multistep” preparations. 13 The errors are mainly due to calculations, multiple manipulations, and absence of label- ing, especially in cases when a procedure is interrupted. Ready- to-use IV solutions are very helpful to avoid such errors. ■ Risk of contamination: Nosocomial infections with microorganisms of the staphylococcal species can be due to inadequate environ- mental controls 14 or the quality of aseptic manipulation tech- niques. 15 It has been noted previously that preparation of 100 mL of a solution containing morphine 1 mg/mL may require trans- fer of the contents of as many as 10 ampoules into either a bottle or a plastic infusion bag. With the advent of centralized services to provide intravenous additive solutions, hospital pharmacy departments took over the compounding of this kind of preparation. The preparation of most of theses, with the exception of those stored in glass bottles, was car- ried out via aseptic techniques, and the resulting preparations were labeled as remaining stable from several days to several months. 16-20 Solutions stored in polyvinylchloride (PVC) bags gave the poorest stability results, indicating dangerous increases in morphine con- centration and possible precipitation due to water evaporation. 17 The first attempt to develop a ready-made solution in Geneva used the Mini-bag plus (Baxter Healthcare, Deerfield, Illinois). This prep- aration included a bag of solvent with a hermetically attached vial of a morphine concentrate, which was transferred into the solvent only at the moment of use, allowing little possibility of interaction between the drug and the plasticizers present in the bag. This prep- aration was discarded for ecological reasons (restrictions on the use of PVC in Switzerland). Polypropylene (PP) IV bags have become available recently and were used in this study. One supplier of PP IV bags is Polimoon Stability of Morphine Sulfate in Polypropylene Infusion Bags for Use in Patient-Controlled Analgesia Pumps for Postoperative Pain Management Abstract The objective of this study was to develop a stable intra- venous solution of 1-mg/mL morphine sulfate in polypropy- lene bags for use in patient-controlled analgesia pumps for postoperative pain management. Three large-scale batches of 1-mg/mL morphine sulfate solution filled into polypropylene bags and terminally sterilized at 120°C for 20 minutes were used in this study. The stability of the drug was monitored at 3, 6, 12, 18, 24, and 36 months after preparation in a long- term study (25°C) and after 3 and 6 months in accelerated studies (30° and 40°C) using a stability-indicating high-per- formance liquid chromatography assay. The levels of degrada- tion products (morphine-N-oxide and pseudomorphine) were determined. Measures of physical stability included pH values, presence of subvisible particles, and weight loss. Microbiolog- ical stability was tested by performing sterility tests. There was practically no loss of morphine, and impurity contents were very low. Subvisible particles were below pharmacopeial specifications. No significant change in pH was observed and water losses were minimal. The sterility of the bags was dem- onstrated throughout the study. In conclusion, terminally sterilized 1-mg/mL morphine sulfate solution packed in poly- propylene bags is stable for at least 3 years when stored at 25°C. Tho Nguyen-Xuan, MSc, PhD Bioren SA Couvet, Switzerland William Griffiths, MRPharmS Christian Kern, MD Elisabeth Van Gessel, MD Pascal Bonnabry, PhD University Hospitals of Geneva Geneva, Switzerland