Volume 3, Issue 4 -

Background A new development in drug compounding is the production of ready-to-administer sterilized prefilled syringes. A challenge with these syringes is the method of terminal sterilization. There is no information available whether water cascade sterilization is a suitable method. We investigated the effect of this sterilization method on cyclic olefin (co)polymer (CCP/COC) syringes. Methods For two brands ten prefilled syringes were sterilized using water cascade sterilization. The closure integrity, stopper movement, weight, diameter and physical appearance were determined before and after sterilization. As sterility test, additional syringes were filled with tryptic soy broth (TSB) and sterilized. After fourteen days microbiological growth was determined. Results Closure integrity testing showed no dye penetration inside the syringe. Together with the results for weight this showed that closure integrity is guaranteed. No significant stopper movement, deviation in diameter or visual anomalies were observed. No microbiological growth in TSB was visible. Conclusions The results of this proof of principle study show that the physical and microbiological stability of the cyclic olefin (co)polymer syringes is guaranteed during sterilization using a water cascade sterilizer. These results do not rule out the necessity for further stability experiments (e. g. interaction with drug product) to further proof the concept.

Background The intolerance to Acetylsalicylic Acid (ASA) can be detected by conducting oral provocation testing (OPT), which is to gradually introduce low doses of ASA. To perform this test, hospital pharmacies compound small batches of different low-dosage ASA capsules. This work aims to validate a method for fast HPLC-UV assay that allows routine quality control and physicochemical stability studies of capsules. Methods The chromatographic separation is performed using a C18 column Kinetex (100 A, 50×4.6 mm, 2.6 µm) equipped with a precolumn C18. Separation is achieved using a mobile phase composed of water-acetonitrile-orthophosphoric acid (68:32:0.2 v/v/v) at a flow rate of 0.8 mL/min and UV detection at 237 nm. Results Validation shows that the method was suitable for routine analysis and could be used to perform stability studies. Conclusions The 5, 25, 100 and 250 mg dosed capsules show acceptable stability over 12 months, while the 1 mg dosed capsule show an unacceptable degradation of more than 15 % after 3 months. Therefore, hospital pharmacy can plan the manufacture of capsules and anticipate the requests of doctors.

Background Water-soluble vitamins are often included simultaneously in pharmaceutical formulations as food complements or in parenteral nutrition mixtures. Given their sensitivity to heat, light or pH variations, it is important to study their stability using validated stability indicating methods. We thus aimed to validate a liquid chromatography (LC) stability-indicating method for the simultaneous quantification of 5 water-soluble vitamins. Methods We analyzed four water-soluble B vitamins (nicotinamide, pyridoxine, folic acid, cyanocobalamin) and ascorbic acid using a LC method with diode array detector. They were separated on a C18 stationary phase under gradient elution of solvent A [0.2 % of metaphosphoric acid in water and acetonitrile 98:2] and solvent B (100 % acetonitrile). All vitamins were subjected to forced degradation conditions and we showed that the obtained degradation products didn’t interfere with the vitamins. Results The method allows the separation of the 5 water-soluble vitamins in a 30 minute run without any interference from the breakdown products obtained with acid/alkaline solutions, hydrogen peroxide, temperature and light. It meets all the qualitative and quantitative criteria for validation with an acceptable accuracy and good linearity. Conclusions This stability-indicating method can be used for carrying out stability studies of water-soluble vitamins in pharmaceutical preparations.

Background Microbial keratitis are severe infectionsgenerally linked to risk factors. High-doses antibiotic eye-drops could be required to avoid severe complications. In such cases, hospital pharmacists are in charge of their production given the lack of such formulations on the market. The stability of these antibiotic eye-drops is generally limited to a couple of days and publications generally do not describe addition of microbial preservatives even though it is a European Pharmacopeia requirement. The aim of this study was to describe a new ceftazidime eye-drops formulation at 50 mg/mL with a antimicrobial additive, benzalkonium chloride at 0.04 mg/mL. Methods Physico-chemical studies of this new formulation were performed by a stability indicating HPLC-UV method validated according to ICH standards, osmolality measurements, pH monitoring and visual examinations. Antimicrobial preservative efficacy was evaluated according to the method from the European Pharmacopeia. Results After 75 days at −20 °C followed by 7 days at 4 °C, or after 7 days at 4 °C, the eye-drops were stable. A degradation trend was finally observed at day 14 at 4 °C. Conclusions A new ceftazidime eye-drops formulation is proposed with a stability of 7 days. Outpatients do not need to return to the hospital pharmacy for repeat dispensing, thus possibly improving treatment compliance.

Our department of pharmacy takes over all the medical skin tests prescribed by the allergy department. The production takes place in specific premises, with qualified and calibrated equipment, by a qualified and regularly assessed staff—in compliance with the French preparation guidelines. The whole activity is under the responsibility of a pharmacist—handlings are performed by hospital pharmacy technicians. Each new intradermal skin test demand leads to a feasibility analysis—irritating nature, dilution solvent, concentration—this information is gathered in a thesaurus. The manufacturing steps are the following: prescription validation, production sheet and label printing, preparation of the needed equipment, batch numbers and expiration date checking, handling under a vertical laminar flow hood and control after production. The preparation activity increases continuously and the thesaurus currently contents 302 rows with following information: drug, dilution and reconstitution solvent, pure solution concentration and maximum concentration to test with intradermal tests. Work would prospect in costs reduction and resources optimization. Thanks to the allergists’ confidence, the partnership between the two departments can go on. This guarantees the quality of the preparations tested on patients but also the skin tests reproducibility.