Volume 3, Issue 1 -

Background Stabilis ® is an international database on stability and compatibility of drugs. The stability data comes mainly from publications of pharmaceutical journals. As the quality of the published stability studies is not equivalent, the objective of this work was to propose a level of evidence for the physico-chemical stability studies selected for the database. Methods At first, we evaluated the main pharmacological class consulted by the users. This work was then divided into 5 steps: (1) updating of the criteria to validate a stability study, (2) creating a grid rating articles, (3) rating of the articles of stability studies for anticancer, antifungal and antiviral drugs by 2 evaluators, (4) creation of new screens in the database to enter rating, to visualize the pictograms and commentaries by the users, (5) creation of a guideline to explain the different levels of evidence. Results The main pharmacological class consulted by Stabilis ® users is the anticancer drugs and then antiinfectives. We have selected anticancer, antifungal and antiviral drugs for our study. Two hundred and forty publications were evaluated. The highest level attributed was A for anticancer and antifungal drugs and C for antiviral drugs. This difference can be explained by the fact that the majority of publications about antiviral drugs were older. The most frequent anomalies in the rating of articles were an incomplete or imperfect validation of the analytical method (high value of the coefficient of variation) and a defect in the evaluation of the stability indicating capacity. It must be noted that the level of evidence is not the quality level of the analytical method but the mixture of the quality of the method validation and of the results. This aspect was a choice of the Stabilis ® team and seems important because the security of the patient is impacted by both aspects. Conclusions This new function contributes to help the Stabilis ® users to evaluate the stability data published and to take a decision for their use in daily practice. This function will be progressively extended to other pharmacological classes of injectable drugs and then for non-injectable preparations.

Background Bendamustine is used for the treatment of non-Hodgkin lymphoma, chronic lymphocytic leukaemia and myeloma. The stability of bendamustine is highly dependent on temperature and chloride-ion concentration. Limited stability data are available. The objective of this work was to study the stability of the bendamustine reconstituted solution at 2.5 mg/mL and the diluted solution in normal saline and 1.5 % sodium chloride to evaluate a potential increase in stability. Methods A stability indicating High Performance Liquid Chromatography method with Diode Array Detection was used. A first study was carried out in glass vials and then in polyolefin containers at 0.25 and 0.60 mg/mL. Solutions were stored at room temperature and at 2–8 °C for 7 days. Results Stability was defined as a concentration above 95 % of the initial concentration [10]. The reconstituted solution at 2.5 mg/mL was stable for only 2 hours at room temperature and 8 hours at 2–8 °C. The stability of diluted solutions was in accordance with the manufacturer’s recommendations of 3.5 hours at room temperature and 48 hours at 2–8 °C. The addition of sodium chloride doesn’t increase the stability for preparation in infusion in daily practice. Conclusions The information brought by this study is an 8-hour stability of the reconstituted solution at 2–8 °C.

Background Vancomycin is increasingly administrated by continuous infusion. But the treatment of patient in intensive care need restricted volume to prevent fluid overload. The aim of the study was to evaluate the physical and chemical stability of solutions of a high concentration of vancomycin hydrochloride in 5 % glucose or 0.9 % NaCl. Methods Eight syringes of 50 mL, containing 41.66 mg/mL of vancomycin hydrochloride four syringes in 5 % glucose and four in 0.9 % NaCl were prepared and stored at ambient temperature during 48 h. Immediately after preparation and during 48 h, vancomycin hydrochloride concentrations were measured by a high-performance liquid chromatography (HPLC). Spectrophotometric absorbance at different wavelengths, pH measurement and microscopic observations were also performed. Results All solutions were physico-chemically stable during the whole period storage at ambient temperature: no color change, turbidity, precipitation or opacity, no significant pH variations or optic densities were observed in the solutions. Any crystals were seen by microscopic analysis. Solutions are considered chemically stable as the lower limit of the 95 % unilateral confidence interval on the mean remained above 90 % of the initial concentration for at least 48 h. Conclusions Solutions of vancomycin hydrochloride 41.66 mg/mL in syringe of 5 % glucose or 0.9 % NaCl are physically and chemically stable for at least 48 h when stored in syringes at ambient temperature.

Background Nitrendipine is prescribed to children for the treatment of primary hypertension (off-label use). Available specialties (Nidrel ® , Baypress ® and others generic drugs) are only marketed in tablet form, which is unsuitable for pediatric use. A hospital preparation of nitrendipine oral suspension at 5 mg/mL was developed. The aim of the study was to determine physicochemical and microbiological stability of the nitrendipine oral suspension in order to set a shelf life for the preparation. Methods A validated high-performance liquid chromatographic (HPLC) method was developed for the assay of nitrendipine. Nitrendipine oral suspensions were prepared using 20 mg Nidrel ® tablets and suspending vehicle Syrspend ® SF PH4. These preparations were packaged in amber glass bottles and stored at room temperature. The physicochemical (pH, osmolality, nitrendipine concentration, macroscopic changes) and microbiological stability of the preparation was tested over 90 days. Nitrendipine concentration at day 0 was considered as 100 % and nitrendipine concentration in subsequent samples greater than 95 % were considered stable. Results The developed HPLC method was validated in terms of linearity, accuracy, precision and specificity. After 90 days, no significant pH and osmolality variation was observed. No microbial growth was noted. Concentrations of nitrendipine were found to be always higher 95 % of the initial concentration. Conclusions Nitrendipine oral suspensions 5 mg/mL are stable for at least 90 days when stored at temperature room and in amber glass bottles. This suspension is more suitable for children than tablets and allows obtaining accurate doses based on patient’s body weight.

Sterilization is a pharmaceutical discipline constantly evolving and requiring highly qualified staff. In response to the need highlighted by French sterilization heads, the French Society for Sterilization Science (SF2S) has developed a serious game called “SteriDefi TM ”. To design the game, a literature review was carried out in order to determine the essential points to be included in its specifications. The second step was to launch the IT (Information Technology) development. In parallel, a database was drafted by a panel of 8 experts in the field of sterilization. At last, the version initially produced was tested over a two-month period. The accessibility, its settings and gameplay were evaluated and improved. Data have been collected to determine the number of user establishments and games played since it was on line. In addition, a multi-centre study is planned to measure the evolution of knowledge and the satisfaction of players with the game.