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Formulation, quality control and shelf life of the experimental cytostatic drug cyclopentenyl cytosine.

This paper describes the formulation and quality control of an aqueous sterilized formulation of the experimental cytostatic drug cyclopentenyl cytosine (CPEC) to be used in Phase I/II clinical trials. The raw drug substance was extensively tested. A High Pressure Liquid Chromotography (HPLC) method was validated for the quality control of the formulated product. The aqueous formulation was found to be stable for at least 2 years at 2-8 degrees C. Sterilization (15 min at 121 degrees C) showed no influence on drug stability. The results show that CPEC can be formulated in an aqueous solution. The described HPLC method is a useful tool in the pharmaceutical quality control.

Antineoplastic Agents↗

Surgical prophylaxis in Belgian hospitals: estimate of costs and potential savings.

Between 1991 and 1995 the Belgian National Program for Surveillance of Hospital Infections (NSIH) collected data on perioperative antibiotic prophylaxis in 72 acute care hospitals. From the costs of prophylactic antibiotics for six categories of surgical procedure and from discharge summaries for hospitalization episodes nationwide, annual drug costs were estimated for 73% of Belgian surgical activity. Costs of antibiotics used in these surgical activities were estimated at 386-410 million Belgian francs (Bf) per year (US$12.1-12.9 million). After agreeing recommendations for best practice, the hypothetical costs of 'optimal' antimicrobial prophylaxis were calculated for the same selection of surgical procedures. It was calculated that savings of at least 194 million Bf (US$6.1 million) could be made if recommendations were followed closely. Only the costs borne by the National Health Insurance Institute for reimbursement of the dispensed drugs were considered in this study. Other direct costs, such as those related to drug storage, dispensing and administration, were not included.

Anti-Bacterial Agents↗

Stability and compatibility study of cefepime in comparison with ceftazidime for potential administration by continuous infusion under conditions pertinent to ambulatory treatment of cystic fibrosis patients and to administration in intensive care units.

Cefepime has been examined for stability, potential liberation of degradation products and compatibility with other drugs under conditions mimicking its potential use by continuous infusion in cystic fibrosis and intensive care patients (5-12% w/v solutions; temperatures from 20 to 37 degrees C; 1 h contact at 25 degrees C with other drugs frequently co-administered by intravenous route to these types of patients). Ceftazidime was used as a comparator based on a previous normative study with this antibiotic for the same indications. Based on a limit of max. 10% degradation, cefepime can be considered stable for a maximum of 24 h at 25 degrees C, but for only approximately 14 h at 30 degrees C, and for <10 h at 37 degrees C. Cefepime released so far unidentified degradation products if maintained at >30 degrees C for >12 h as shown from a marked increase in pH and from the development of a strong red-purple colour. Incompatibilities were observed with erythromycin, propofol, midazolam, phenytoin, piritramide, theophylline, nicardipine, N-acetylcysteine and a concentrated solution of dobutamine. We conclude that: (i) cefepime cannot be used safely by continuous infusion if containers are kept for more than a few hours at 37 degrees C (as will be the case for cystic fibrosis patients if using portable pumps carried under clothes); (ii) caution must be exercised in intensive care patients if the temperature and co-administration of other drugs is not kept under tight control. The nature and safety of the cefepime degradation products need to be studied further.

Ambulatory Care↗

Medicines and elderly people: a general practice survey.

All 151 patients of 75 years and over in one practice were visited at home to survey their health and how they managed their medicines. Altogehter 87% were on regular treatment, 34% taking three or four different drugs each day. Most were responsible for their own drugs and managed them well, but many left their drugs in exposed places and were uncertain about how to dispose of unwanted medicines. Overall they were prescribed about three times the number of drugs prescribed for the general population, and women took twice as many drugs regularly as men. Although many drugs were obtained directly from a pharmacist, his advice was rarely sought. Most were labelled, but more explicit instructions about indications for taking the drug would have been helpful, and information about hoarded drugs would have been enhanced by dispensing and expiry dates. Treatment was facilitated when patients brought their drugs to the consultation and careful records were made of repeat prescriptions. As so many patients take three or more different types of drugs each day a container in which a day's supply could be laid out would be useful.

Aged↗

Drugs for the doctor's bag revisited.

The choice of drugs to include in the GP's bag depends on the medical conditions likely to be met, the shelf-life of the products and their costs, the availability of ambulance paramedic cover and the proximity of the nearest hospital. Here, we update previous advice and suggest a list of medicines that GPs may wish to take with them on home visits for use in an emergency or other acute treatment. We include paediatric doses where appropriate and, whenever a medicine is first mentioned, our suggested formulation is given italicised and in brackets. We also enclose with this issue a card summarising parenteral doses of drugs for medical emergencies, which includes a table of mean weight for age.

Drug Storage↗

Viscoelastic characterization of compacted pharmaceutical excipient materials by analysis of frequency-dependent mechanical relaxation processes.

A newly developed method for determining the frequency-dependent complex Young's modulus was employed to analyze the mechanical response of compacted microcrystalline cellulose, sorbitol, ethyl cellulose and starch for frequencies up to 20 kHz. A Debye-like relaxation was observed in all the studied pharmaceutical excipient materials and a comparison with corresponding dielectric spectroscopy data was made. The location in frequency of the relaxation peak was shown to correlate to the measured tensile strength of the tablets, and the relaxation was interpreted as the vibrational response of the interparticle hydrogen and van der Waals bindings in the tablets. Further, the measured relaxation strength, holding information about the energy loss involved in the relaxation processes, showed that the weakest material in terms of tensile strength, starch, is the material among the four tested ones that is able to absorb the most energy within its structure when exposed to external perturbations inducing vibrations in the studied frequency range. The results indicate that mechanical relaxation analysis performed over relatively broad frequency ranges should be useful for predicting material properties of importance for the functionality of a material in applications such as, e.g., drug delivery, drug storage and handling, and also for clarifying the origin of hitherto unexplained molecular processes.

Journal Article↗