S46 european journal of pharmaceutical sciences 32S ( 2 0 0 7 ) S22–S50 by pharmacies and procedure which is compatible with the Finnish health care system. The Medication Review course is 35 credit points in total (1 cp means about 27 h working) and it takes one and a half year to pass thru. The course consists of five different mod- ules: (1) rational pharmacotherapy and medication use; (2) clinical pharmacy and pharmacotherapy; (3) tools for conduct- ing medication reviews; (4) multidisciplinary collaboration; and (5) optional studies. The studies are carried out as dis- tance learning with the support of e-learning environment, including 20 seminar/workshop days. A core element of the training is case studies and real patient cases to practice the art of conducting medication reviews. The first 26 pharmacists completed the training in May 2006. At the moment, there are 4 courses going on in different parts of the country with about 80 participants. Thus, in the end of this year there will be about 100 pharmacists in Finland who have been specialized in conducting medication reviews in different health care settings in hospitals and in ambulatory care. doi:10.1016/j.ejps.2007.05.098 P-55 Determination of stability of rapamycin following exposure to different conditions M.A. Rouf, E. Bilensoy, ˙ I. Vural, A.A. Hıncal Hacettepe University, Faculty of Pharmacy, Department of Pharma- ceutical Technology, 06100 Ankara, Turkey Objective: The objective of this study was to assess the sta- bility of rapamycin, an immunosuppressive agent, in different aqueous media for the eventual development of pharmaceu- tical dosage forms of this drug. Method: The chemical stability of rapamycin was studied in several aqueous media commonly used in the laboratory. These solutions were pH 7.4 phosphate buffered saline (PBS), pH 7.4 HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) buffer, distilled water, Ultrapure (Type I) water and reverse osmosis water. Ultrapure water was used in the prepa- ration of PBS and HEPES buffers. After preparing a rapamycin solution of 800 ng/ml in these media, they were kept at four dif- ferent conditions: in the refrigerator (4–8 ◦ C), at 25 ◦ C/daylight, at 25 ◦ C/dark and at 37 ◦ C/dark. The study was conducted according to predesigned sampling schedule ranging over a period of 4 weeks. A calibrated and validated HPLC analyt- ical method was used to analyze the stability of samples. The HPLC, Agilent 1100 Series, was equipped with an auto- sampler, a diode array detector at 277nm. A Bondapack C 18 10 m 125A, 3.9 mm× 300mm (Waters) reverse phase column was used. The mobile phase was a 80:20 methanol:water mix- ture. The injection volume was 100 L and the flow rate was 0.75 mL/min. Results: Rapamycin was found to be very unstable in PBS and HEPES buffer in all conditions, their degradation effect on the drug being slower at 4–8 ◦ C and the fastest at 37 ◦ C at which almost all drug was destroyed in 24 h. While the drug seems to be stable at refrigerator in both distilled water and ultrapure water, and to a lesser extent in reverse osmosis water, no medium could protect the drug in other conditions applied. The rate of degradation under daylight is faster than that under darkness in all media at 25 ◦ C. Conclusion: The main difference among the media used was the ionic content and total organic contents. The results clearly show that ions rather than organic contents were mainly responsible for the degradation of rapamycin. There- fore, dark condition and highly pure water free from ions should be used in the development of rapamycin formula- tions. doi:10.1016/j.ejps.2007.05.099 P-56 Inclusion complexation of rapamycin with beta-cyclodextrin to improve solubility and stability of the drug M.A. Rouf, E. Bilensoy, ˙ I. Vural, A.A. Hıncal Hacettepe University, Faculty of Pharmacy, Department of Pharma- ceutical Technology, 06100 Ankara, Turkey Objective: The objective of this study was to realize the for- mation of inclusion complex of rapamycin, a water-insoluble immunosuppressive drug, with beta-cyclodextrin in order to solve the problems associated with aqueous solubility and stability of this highly labile drug. Method: Phase solubility diagram of rapamycin in the presence beta-cyclodextrin was determined as follows; beta- cyclodextrin in a range of molar concentrations of 0, 1, 2, 4, 6, 8, 10, 12 and 16mM were dissolved in distilled water. Fixed amount of drug (400 mcg) was added to the beta-cyclodextrin solution for each molar concentration. Two different equilib- rium periods were used being 3 and 7 days. At the end of the equilibrium time, 2 mL of sample was drawn form the middle of the solution, centrifuged at 5000 rpm for 30 min. Supernatant was analyzed with a validated HPLC technique consisting of HPLC, Agilent 1100 Series equipped with an auto- sampler, a diode array detector at 277nm. A Bondapack C 18 10 m 125A, 3.9 mm × 300mm (Waters) reverse phase column was used. The mobile phase was a 80:20 methanol: water mix- ture (v/v). The injection volume was 100 L and the flow rate was 0.75 mL/min. From the phase solubility diagrams associa- tion constants for 1:1 molar ratio rapamycin:beta-cyclodextrin complex were calculated. The resulting inclusion complex was further analyzed with different techniques including Dif- ferential Scanning Calorimetry, Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy, X-ray Diffrac- tometry, proton NMR spectrometry to confirm the presence of a total or partial inclusion complex between rapamycin and beta-cyclodextrin. Results: Phase solubility diagrams indicated AL and AN type diagrams for 3-day and 7-day equilibrium times respectively. DSC, FTIR, H NMR, XRD and SEM techniques helped elucidate the structure of the inclusion complex which was believed to be partial in the light of the data. The inclusion complexes displayed a precipitation after a longer period of equilibrium time which was a result of the limited water solubility of beta- cyclodextrin itself. Conclusion: The stability problems associated with rapamycin observed in different conditions such as light, tem-