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PubMed1999

Quality of water used for haemodialysis: bacteriological and chemical parameters.

BACKGROUND: The bacterial and chemical contamination of dialysate fluids are important problems in haemodialysis therapy and may be caused by the water used for dialysate preparation. METHODS: We performed a survey of the microbiological and chemical quality of the water used in seven dialysis wards. Special attention was paid to the effects of each water treatment step, for example ion exchange, reverse osmosis and UV disinfection, on the number of bacteria (measured as colony forming units, CFU), the amount of endotoxin (endotoxin units, EU) and various chemical parameters, the main focus being on calcium, magnesium, sulphate, aluminium and heavy metals. RESULTS: CFU values exceeding the European Pharmacopeia value, determined at an incubation temperature of 22 degrees C, were found in the samples of raw water (20.0%, n=25), after ion exchange (66.7%, n=12), after reverse osmosis (33.3%, n=18) and also in samples of the dialysis water taken at the inlets (12.5%, n=40) and outlets (50.0%, n=18) of the machines. Whereas all raw water samples from the wards showed high mean values for endotoxin (0.56-9.10 EU/ml) and the endotoxin levels were often enhanced after ion exchange (0.13- >9.49 EU/ml), treatment by reverse osmosis led to a satisfactory decrease in endotoxin in all samples (<0.03 EU/ml). Sufficient reductions in calcium, magnesium and sulphate could only be achieved by the combined application of ion exchange and reverse osmosis. Mercury contamination was observed in the samples after ion exchange at three treatment plants, this was possibly caused by polluted regenerants. Increased amounts of aluminium, copper and zinc were found in water samples from different sites in the treatment systems and were caused by materials in contact with the water. CONCLUSIONS: A sufficient chemical water purification treatment system should consist of ion exchange and reverse osmosis. Attention has to be paid to the suitability of materials in contact with the water and of the chemicals used, for example regenerants or corrosion inhibitors. From the microbiological point of view, a safety UV disinfection step in the water-treatment system is favourable. To avoid bacterial recontamination periodic cleaning and disinfecting of the water-treatment and distribution systems, as well as the dialysis machine are essential. There is the need for complete guidelines regarding dialysis water that include all relevant chemical and microbiological parameters. Based on this standard, periodic examination of the water after each treatment step has to be performed.

Metals↗
PubMed1999

Amsorb: a new carbon dioxide absorbent for use in anesthetic breathing systems.

BACKGROUND: This article describes a carbon dioxide absorbent for use in anesthesia. The absorbent consists of calcium hydroxide with a compatible humectant, namely, calcium chloride. The absorbent mixture does not contain sodium or potassium hydroxide but includes two setting agents (calcium sulphate and polyvinylpyrrolidine) to improve hardness and porosity. METHODS: The resultant mixture was formulated and subjected to standardized tests for hardness, porosity, and carbon dioxide absorption. Additionally, the new absorbent was exposed in vitro to sevoflurane, desflurane, isoflurane, and enflurane to determine whether these anesthetics were degraded to either compound A or carbon monoxide. The performance data and inertness of the absorbent were compared with two currently available brands of soda lime: Intersorb (Intersurgical Ltd., Berkshire, United Kingdom) and Dragersorb (Drager, Lubeck, Germany). RESULTS: The new carbon dioxide absorbent conformed to United States Pharmacopeia specifications in terms of carbon dioxide absorption, granule hardness, and porosity. When the new material was exposed to sevoflurane (2%) in oxygen at a flow rate of 1 l/min, concentrations of compound A did not increase above those found in the parent drug (1.3-3.3 ppm). In the same experiment, mean +/-SD concentrations of compound A (32.5 +/- 4.5 ppm) were observed when both traditional brands of soda lime were used. After dehydration of the traditional soda limes, immediate exposure to desflurane (60%), enflurane (2%), and isoflurane (2%) produced concentrations of carbon monoxide of 600.0 +/- 10.0 ppm, 580.0 +/- 9.8 ppm, and 620.0 +/-10.1 ppm, respectively. In contrast, concentrations of carbon monoxide were negligible (1-3 ppm) when the anhydrous new absorbent was exposed to the same anesthetics. CONCLUSIONS: The new material is an effective carbon dioxide absorbent and is chemically unreactive with sevoflurane, enflurane, isoflurane, and desflurane.

Absorption↗
PubMed1986

Talc poudrage in the treatment of spontaneous pneumothoraces in patients with cystic fibrosis.

As patients with cystic fibrosis live longer, spontaneous pneumothoraces are seen with increasing frequency. Severe underlying pulmonary disease in these patients makes them particularly susceptible to life-threatening respiratory distress. Several modalities, including chemical sclerosis and open thoracotomy with pleurectomy, have been used to treat pneumothoraces in these patients. In the past 4 years, pneumothoraces in five patients (ages 9-22 years) with cystic fibrosis have been treated with thoracoscopy and talc poudrage. All procedures were performed under either regional or general anesthesia, depending on the age of the patient. Thoracoscopy was performed with a rod lens system and a 5.5-mm trocar, using biopsy forceps to lyse pleural adhesions, all of which ensures access to the entire pleural surface. United States Pharmacopeia-certified talc was insufflated to cover the entire pleural surface. There were no complications, and the patients had minimal pleural pain. Follow-up ranged from 6 months to 4 years. No patient has had a recurrent pneumothorax on the treated side. Thoracoscopy with talc poudrage is a preferable alternative to chemical sclerosis or thoracotomy for treating pneumothoraces in patients with cystic fibrosis. The procedure may be performed under regional anesthesia and allows rapid and complete sclerosis of the pleural cavity.

Adolescent↗
PubMed1990

Intravenous infusions of nitroprusside, dobutamine, and nitroglycerin are compatible.

It is now customary practice to couple separately metered infusions via a manifold to a common catheter that enters the patient. Nitroprusside, however, is considered incompatible with all other medications. Critically ill patients who require multiple infusions of vasoactive and inotropic medications would benefit if physicians had additional information regarding compatibility of nitroprusside with other commonly used infusions. Utilizing high-performance liquid chromatography, the authors investigated the physical and chemical compatibility of nitroprusside, dobutamine, and nitroglycerin in solutions of 5% dextrose or 0.9% NaCl at clinically relevant concentrations. All drugs were present within the guidelines of the U.S. Pharmacopeia (+/- 10%) over 24 h in NaCl, but nitroglycerin degraded over 24 h when the three drugs were mixed in dextrose. We recommend diluting these medicines in NaCl when mixtures of them would exist for greater than 4 h.

Dobutamine↗
PubMed1995

Practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit: an executive summary. Society of Critical Care Medicine.

OBJECTIVE: The development of practice parameters for intravenous analgesia and sedation for adult patients in the intensive care unit (ICU) setting for the purpose of guiding clinical practice. PARTICIPANTS: A task force of more than 40 experts in disciplines related to the use of analgesic and sedative agents in the ICU was convened from the membership of the American College of Critical Care Medicine (ACCM) and the Society of Critical Care Medicine (SCCM). EVIDENCE: The task force members provided the personal experience and determined the published literature (MEDLINE articles, textbooks, pharmacopeias, etc.) from which consensus would be sought. Published literature was reviewed and classified into one of four predetermined categories, according to study design and scientific value. CONSENSUS PROCESS: The task force met several times as a whole, and numerous times in smaller groups by teleconference, over a 1-yr period to identify the pertinent literature and arrive at consensus recommendations for the whole task force to discuss. Consideration was given to the relationship between the weight of scientific information and the experts' viewpoints. Over the next year, draft documents were composed by a task force steering committee and debated by the task force members until consensus was reached by nominal group process. The task force draft was then reviewed, assessed, and edited by the Board of Regents of the ACCM. After steering committee approval, the draft document was reviewed and approved by the SCCM Council. DATA SYNTHESIS: To facilitate rapid communication of the six recommendations contained within the complete and unabridged practice parameter document, an executive summary was prepared for publication by the ACCM Board of Regents, and this executive summary was approved by the task force steering committee and the SCCM Executive Council. CONCLUSIONS: A consensus of experts provided six recommendations with supporting data for intravenous analgesia and sedation in the ICU setting: a) morphine sulfate is the preferred analgesic agent for critically ill patients; b) fentanyl is the preferred analgesic agent for critically ill patients with hemodynamic instability, for patients manifesting symptoms of histamine release with morphine, or morphine allergy; c) hydromorphone can serve as an acceptable alternative to morphine; d) midazolam or propofol are the preferred agents only for the short-term (< 24 hrs) treatment of anxiety in the critically ill adult; e) lorazepam is the preferred agent for the prolonged treatment of anxiety in the critically ill adult; f) haloperidol is the preferred agent for the treatment of delirium in the critically ill adult. This executive summary selectively presents supporting information and is not intended as a substitute for the complete document.

Adult↗
PubMed1995

Practice parameters for sustained neuromuscular blockade in the adult critically ill patient: an executive summary. Society of Critical Care Medicine.

OBJECTIVE: The development of practice parameters for achieving sustained neuromuscular blockade in the adult critically ill patient for the purpose of guiding clinical practice. PARTICIPANTS: A task force of more than 40 experts in disciplines related to the use of neuromuscular blocking agents in the intensive care unit was convened from the membership of the American College of Critical Care Medicine (ACCM) and the Society of Critical Care Medicine (SCCM). EVIDENCE: The task force members provided the personal experience and determined the published literature (MEDLINE articles, textbooks, pharmacopeias, etc.) from which consensus would be sought. Published literature was reviewed and classified into one of four predetermined categories, according to study design and scientific value. CONSENSUS PROCESS: The task force met several times as a whole, and numerous times in smaller groups by teleconference, over a 1-yr period to identify the pertinent literature and arrive at consensus recommendations for the whole task force to discuss. Consideration was given to the relationship between the weight of scientific information and the experts' viewpoints. Over the next year, draft documents were composed by a task force steering committee and debated by the task force members until consensus was reached by nominal group process. The task force draft was then reviewed, assessed, and edited by the Board of Regents of the ACCM. After steering committee approval, the draft document was reviewed and approved by the SCCM Council. DATA SYNTHESIS: To facilitate rapid communication of the three recommendations contained within the complete and unabridged practice parameter document, an executive summary was prepared for publication by the ACCM Board of Regents, and this executive summary was approved by the task force steering committee and the SCCM Executive Council. CONCLUSIONS: A consensus of experts provided three recommendations with supporting data for achieving sustained neuromuscular blockade in critically ill patients: a) pancuronium is the preferred neuromuscular blocking agent for most critically ill patients; b) vecuronium is the preferred neuromuscular blocking agent for those patients with cardiac disease or hemodynamic instability in whom tachycardia may be deleterious; c) patients receiving neuromuscular blocking agents should be appropriately assessed for the degree of blockade that is being sustained. This executive summary selectively presents supporting information and is not intended as a substitute for the complete document.

Adult↗
PubMed2000

Formulation of trichloroacetic acid peeling solution: a bibliometric analysis.

Since the beginning of this century, trichloroacetic acid solutions of various concentrations have been used for chemical exfoliation. These solutions have been prepared by using four different formulas. To prepare a 50% solution, for instance, water may be added to 50 g of trichloroacetic acid crystals until 100 ml of solution is obtained (weight-to-volume solution). Alternatively, 50 g of water may be added to 50 g of trichloroacetic acid crystals (weight-to-weight solution), or 50 g of trichloroacetic acid crystals may be solved in 100 ml of water (weight-plus-volume solution). Finally, a saturated trichloroacetic acid solution (or "100% solution") may be diluted by an equal volume of water (dilution). Depending on the method used, these so-called 50% solutions contain 40 to 71 weight-to-volume percentages of trichloroacetic acid. From a review of 120 publications on trichloroacetic acid peeling that have appeared since 1926, it was concluded that the authors of 87 of these publications (73 percent) did not report their formula for the trichloroacetic acid solution. Any one of the four methods was reported to have been used by the 33 authors who did report their formula. Eight of 10 internationally reputed pharmacopeias were found not to include the formula of a trichloroacetic acid solution. Proper evaluation of results and prevention of complications of trichloroacetic acid chemexfoliation is only feasible if both the concentration and the formula of trichloroacetic acid solution are reported by the author. Practitioners who use a trichloroacetic acid solution need to establish that the concentration of the solution they apply corresponds with that of the solution reported in the literature.

Bibliometrics↗
PubMed2006

Personal digital assistants change management more often than paper texts and foster patient confidence.

INTRODUCTION: Rapid retrieval of information, including drug treatment options, is critical to emergency department practice. OBJECTIVES: To assess feasibility and patient acceptance of personal digital assistants and to determine the scope of management changes. METHODS: Emergency medicine residents (EMRs, n = 18) and emergency medicine attending (EMAs, n = 12) used personal digital assistants with drug database and clinical references. Text versions were also available in the emergency department. We did a prospective, random, cross-over time-motion study, recording retrieval time, source, and changes to patient care for 16 and 8 h for EMRs and EMAs, respectively. We surveyed patients for confidence in EMRs and EMAs with personal digital assistants, and perceived efficiency. RESULTS: EMRs accessed paper (n = 131) or personal digital assistant (n = 181) information on 92.3% of patients (n = 17, both). They accessed personal digital assistant on 61.4% of patients vs. 44.5% with texts (odds ratio 1.99, 95% confidence interval 1.4-2.80). Mean access times were 9.3 and 9.4 s, respectively, +1.4 for both. Personal digital assistant access was 75%/25% between pharmacopeia and clinical resource. Personal digital assistants changed drug choice in 39/181 patients (21.5%), and other management (diagnosis, treatment or disposition) in 15/181 patients (8.3%). Odds ratio for change in management for personal digital assistant vs. paper was 2.00 (95% confidence interval 1.11-3.60). We surveyed patient perception for 198 of 295 patients (67.1%). Fifty percent reported more confidence in their EMRs and EMAs with a personal digital assistant, while 5% reported less confidence. Sixty percent agreed strongly that there is too much medical information to remember. CONCLUSIONS: Personal digital assistants are feasible in an academic emergency department and change management more often than texts. EMRs accessed personal digital assistants more often than paper texts. Patient perceptions of physicians who use personal digital assistants are neutral or favorable.

Attitude of Health Personnel↗
PubMed2005

Alteplase as a catheter locking solution: in vitro evaluation of biochemical stability and antimicrobial properties.

PURPOSE: To reduce potential complications of fibrin deposition to catheter surfaces, there is increasing empiric use of alteplase as a catheter lock solution. The purpose is to evaluate the properties of alteplase when reconstituted in sterile water (SW) or bacteriostatic water (BW) for prolonged periods. MATERIALS AND METHODS: Alteplase in glass vials was reconstituted (1 mg/mL) with SW or BW (0.9% benzyl alcohol) in duplicates and stored at 37 degrees C. Biochemical assays were performed at days 0 and 7 and included optical clarity, protein concentration, percent protein monomer, and in vitro clot lysis activity. Microbiologic assays were performed on days 7 through 28 with use of a standardized antimicrobial effectiveness test (pass/fail) and pour-plate methods incubated at 22.5 degrees C (fungus, 3-7 days) or 32.5 degrees C (bacteria, 3-5 days). Organisms tested included Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Candida albicans, and Aspergillus niger. RESULTS: Biochemical assay results were as follows: on day 0, all samples were clear/colorless; protein concentrations were 1.10 mg/mL +/- 0 in SW and 1.11 mg/mL +/- 0 in BW; percent protein monomer was 8.2% +/- 0.07 in SW and 98.6% +/- 0.07 in BW; and in vitro clot lysis activity (in percent of relative activity) was 100% in all samples. On day 7, all samples were clear/colorless, protein concentrations were 1.11 mg/mL +/- 0.07 in SW and 1.11 mg/mL +/- 0.07 in BW; percent protein monomer was 97.4% +/- 0.21 in SW and 96.1% +/- 0.21 in BW; and in vitro clot lysis activity (relative activity compared with day 0) was 91% +/- 2.8 in SW and 90% +/- 2.8 in BW. Microbiologic assays (US Pharmacopeia [USP] antimicrobial effectiveness test) yielded a failing result for alteplase reconstituted in SW and a passing result for alteplase reconstituted in BW. CONCLUSIONS: Alteplase reconstituted with SW or BW remains relatively stable with retained bioactivity when stored at 37 degrees C for as long as 7 days. Despite the biochemical similarities of the two solutions, only alteplase in BW met USP criteria as an effective antimicrobial solution. Further clinical evaluation is warranted.

Biological Assay↗
PubMed2006

Role of follow-on drugs and indications on the WHO Essential Drug List.

INTRODUCTION: The World Health Organization's Essential Drug List (EDL) contains first-in-class drugs and subsequent class entrants (follow-on drugs) deemed necessary to combat diseases prevalent throughout the world, with a special emphasis on developing nations. The EDL also includes originally approved and follow-on indications. There are opposing views regarding the value of follow-on drugs and indications. Critics suggest many follow-on drugs and indications offer little or no benefit to patients. Advocates counter that follow-on drugs offer advantages in terms of improved effectiveness, compliance and patient satisfaction. OBJECTIVE: In order to inform this debate on the value of follow-on drugs and indications we examined the numbers of follow-on drugs on the EDL and the extent to which follow-on indications are recommended. METHODS: We identified all 312 drugs on the 14th edition of the EDL, omitting 72 non-pharmaceutical entities. For the 240 pharmaceutical entities we ascertained whether the Food and Drug Administration (FDA) had approved them, and, if so, when each was approved. We chose a validated therapeutic classification system - the United States Pharmacopeia's Model Guidelines for Medicare formulary management - in order to distinguish first-in-class and follow-on drugs on the EDL. Specifically, we selected the formulary key drug type as our benchmark therapeutic class. We assigned each EDL drug to a formulary key drug type. We defined first-in-class drugs as the first in each formulary key drug type, and follow-on drugs as all other drugs in each formulary key drug type. We identified follow-on indications by comparing WHO-listed indications with the original approved indication(s) by the FDA. Finally, we examined the therapeutic rating (priority vs. standard) given by the FDA to follow-on drugs on the EDL. RESULTS: Sixty-three per cent of the EDL drugs were follow-ons; 15% of the indications were follow-on indications. Fourteen drugs were listed in multiple WHO (sub) groupings; and 49% of follow-on drugs were given a priority rating by the FDA. CONCLUSIONS: In light of the fact that the EDL only includes drugs and indications deemed essential, the large number of follow-on drugs, follow-on indications, and priority-rated follow-on drugs on the EDL suggest their importance. From a public policy perspective, it may prove counterproductive to erect hurdles that impede follow-on research and development.

Developing Countries↗
PubMed2006

Microbiological study of cosmetic products during their use by consumers: health risk and efficacy of preservative systems.

AIM: To evaluate the microbial contamination of 91 cosmetics (23 o/w emulsions, 47 tensiolytes, 21 aqueous pastes) in three different states of use (intact, in-use, ending product) and the protection efficacy of the preservative systems most frequently used in the analysed cosmetic formulations. METHODS AND RESULTS: Total bacterial count, isolation and identification of pathogenic isolates were performed on the collected cosmetics. About 10.6% of tensiolytes (13.5% bath foam, 6.7% shampoo, 10% liquid soaps) were contaminated by Staphylococcus warneri, Staphylococcus epidermidis and Pseudomonas putida. The efficacy of the preservative systems of two cosmetic products, tested against standard micro-organisms (Staphylococcus aureus ATCC 4338 and Pseudomonas aeruginosa ATCC 9027) and two isolates from cosmetics in this study (S. epidermidis and P. putida), satisfied the Cosmetics, Toiletries, and Fragrance Association and Official Italian Pharmacopeia criteria, while only one tested cosmetic respected the Rapid Challenge Test criterion. CONCLUSIONS: Contaminated cosmetic products are relatively uncommon, but some products, unable to suppress the growth of several micro-organisms, represent a potential health hazard. SIGNIFICANCE AND IMPACT OF THE STUDY: The challenge test may be performed not only during the preparation of the preservative system in the intact cosmetics, but also be used to evaluate the protection efficacy during their use.

Bacteria↗
PubMed1999

Storage temperatures of out-of-hospital medications.

OBJECTIVES: To determine whether temperatures inside drug boxes used in the out-of-hospital setting are within the U.S. Pharmacopeia recommendations for "controlled room temperature," which is defined as a temperature maintained between 15 degrees C and 30 degrees C with a mean kinetic temperature less than 25 degrees C, and to determine whether time-temperature indicator labels can reliably monitor mean kinetic temperatures. METHODS: Two methods were used to monitor temperatures: miniature electronic temperature recorders and color-changing time-temperature indicator labels. These were placed in drug storage boxes of advanced life support units over three summer months and two winter months. RESULTS: In summer, the electronic recorders logged temperatures exceeding 30 degrees C in all drug storage boxes, ranging from 3% to 29% of the total time. The mean kinetic temperatures by location for the whole period ranged from 21 degrees C to 30 degrees C. In the winter, the electronic recorders logged temperatures exceeding 30 degrees C at one location 2% of the total time. There were significant temperature excursions below 15 degrees C at all locations, ranging from 16% to 90% of the total time. At one location, there were temperature readings below 0 degrees C for 9% of the total time. The mean kinetic temperatures obtained from the electronic recorders and the indicator labels differed by less than 1 degrees C. CONCLUSIONS: This study demonstrates that out-of-hospital medications are subject to temperatures both above and below recommended storage temperatures. Time-temperature indicator labels can reliably monitor exposure to elevated temperatures.

Cold Temperature↗
PubMed2007

The effect of calcium hydroxide root filling on dentin fracture strength.

This in vitro study measured the effect of calcium hydroxide root filling on the microtensile fracture strength (MTFS) of teeth. A total of 40 extracted human disease-free permanent maxillary incisors were hand and rotary instrumented and vertically compacted with United States Pharmacopeia (USP) calcium hydroxide. The teeth were stored in a moist environment for 7, 28, and 84 days. As a control group, 10 teeth were vertically compacted with gutta percha and sealer. The MTFS of the teeth was measured (Mpa) using an Instron machine. Data were assessed statistically using an unpaired t-test (P value). The intracanal placement of calcium hydroxide weakened the MTFS of teeth by 13.9 Mpa per 77 days: an average of 0.157 MPa day-1. Between 7 and 84 days, the MTFS of the dentin was reduced by 43.9%. This difference was statistically significant (P < 0.05). A statistical difference (P < 0.05) was observed between the mean MTFS of the calcium hydroxide-filled dentin between 7 days (45.7 MPa) and 28 days (35.6 MPa) and also between 7 and 84 days (31.8 MPa). There was also a significant difference (P < 0.05) between the MTFS of the calcium hydroxide-filled dentin after 84 days (31.8 MPa) and the gutta percha-filled dentin (41.3 MPa) when used as a control root filling material. The weakening of the dentin by 23-43.9% following root canal filling with calcium hydroxide provides compelling evidence to re-evaluate the daily usage of this material in endodontic therapy.

Calcium Hydroxide↗
PubMed1983

Tensile strength requirements for sutures.

The official requirements for sutures in Australia are those of British Pharmacopoeia (B.P.). The results of a survey conducted by this Laboratory indicate that the B.P. test and specifications for knot pull strength are no longer appropriate for sutures currently available in this country. It is suggested that tensile strength measurements on sutures should be carried out, without prior soaking, using the load cell type of constant rate of extension apparatus rather than the pendulum type tester specified in the B.P. Use of a simple knot is suitable for testing synthetic sutures, but the surgeon's knot is preferred for catgut. All products tested easily met both the B.P. and the United States Pharmacopeia (U.S.P.) requirements for tensile strength.

Australia↗
PubMed1984

The determination of leachable chromium from chromicized catgut sutures.

Application of the British Pharmacopoeia (BP) Analytical procedure for the determination of leachable chromium to samples of catgut sutures yielded fading coloured solutions and was considered to constitute a poor basis for an analytical method. The United States Pharmacopeia (USP) method and an adaptation of the American Public Health Association (APHA) method were explored and found to give linear responses over the concentration range of interest. Both these methods were applied to a series of samples and the results obtained were different as the APHA method measures total chromium while the USP procedure determines only chromium (VI).

Animals↗
PubMed1986

Content uniformity of microdose tablets (dosage 1 microgram--10 mg) produced by fluid bed granulation of interactive mixtures.

Tablets (100 mg), containing microdose quantities of micronized model drug (1 microgram--10 mg), were produced from interactive powder mixtures which had been fluid bed granulated. Granulation prevents adhesion unit and constituent segregation occurring during compression. Single tablet assays were performed on 100 tablets from each batch. The content of tablets fell within +/- 15% of the mean, and the coefficient of variation was less than 5% (99% confidence) for all batches. Skewness in the content distribution showed little evidence of superpotent tablets and indicated the absence of significant agglomerates of particles of the micronized component. However, there was some indication that the mixtures produced were not totally agglomerate free. These results demonstrate that the true potential of interactive mixing may be realized, provided segregation in the mixture can be eliminated. The distribution of micronized model drug, as a function of carrier particle size, was determined for the different concentration mixtures before and after granulation. When 0.1-2% interactive mixtures were sieved gently, the proportions of micronized material adhering to the different size fractions of carrier were similar. However, the very low concentration mixtures (0.001-0.03%) proved to be relatively unstable, a significant proportion of the micronized component being transferred from the mixtures to the metal surfaces of the sieves. Granulation of the mixtures in a fluidized bed produced a uniform distribution of micronized material throughout the different sized granules. These granules were stable during vibration on the sieves and when compressed. All samples of tablets met the United States Pharmacopeia XXI content uniformity requirements.

Drug Compounding↗
PubMed2002

Comparison of bioavailability and metabolism with two commercial formulations of cyclosporine a in rats.

The bioavailability and metabolism of cyclosporine A (CsA) capsules were compared with two bioequivalent (Food and Drug Administration approved) preparations in rats. Two groups of Wistar-Kyoto rats were given 10 mg/kg q.d. of Sandimmun Neoral (NEO), Novartis Pharma, and CsA (United States Pharmacopeia modified), Eon Labs (EON), as capsules dissolved in water by oral gavage. After reaching steady-state (SS), rats were euthanized 2, 4, 8, 12, and 24 h after dosing. Parallel to this investigation, a single dose (SD) study was also performed. CsA and CsA metabolite concentrations of AM1, AM4N, and AM9 were determined by high-performance liquid chromatography in kidney, whole blood, and urine. The bioavailability of EON was 15% lower [area under the curve (AUC)(SS blood CsA), 27.9 +/- 3.69 mg. h/l] in the blood and was 40% lower (AUC(SS kidney CsA), 136.2 +/- 21.2 mg. h/l) in the kidney in contrast to NEO (AUC(SS blood CsA), 32.1 +/- 4.32 mg. h/l and AUC(SS kidney CsA), 220.8 +/- 29.5 mg. h/l). In contrast, the plasma AM4N level was significantly elevated in group receiving EON (AUC(SS blood AM4N), 4.1 +/- 0.42 mg. h/l) compared with the other group treated with NEO (AUC(SS blood AM4N), 2.9 +/- 0.39 mg. h/l). In the kidneys, no significant differences were observed concerning the AM4N concentrations of NEO (AUC(SS kidney AM4N), 11.8 +/- 1.87 mg. h/l) versus EON (AUC(SS kidney AM4N), 12.1 +/- 2.14 mg. h/l), but AM1 was increased (AUC(SS kidney AM1), 54.3 +/- 11.2 mg. h/l) in comparison to NEO (AUC(SS kidney AM1), 20.5 +/- 3.56 mg. h/l). Furthermore, EON produced a larger amount of AM4N in the urine (5.8 +/- 0.85 mcirog/24 h versus 2.2 +/- 0.95 microg/24 h). Similar results were obtained with the SD study. Although the clinical consequences of our results remain at present unknown, the data suggest differences in CsA disposition that may affect drug efficacy and safety and merit further investigation in humans.

Animals↗
PubMed1977

Inflammatory effects of endotoxin-like contaminants in commonly used protein preparations.

Protein preparations from commercial suppliers are contaminated with bacterial endotoxins. The continued use of these preparations indicates that many researchers are unaware of this, and they may attribute all observed effects to the proteins themselves. Intravitreous injection of bovine serum albumin has an initial inflammatory effect on the rabbit eye which occurs before an immune reaction to the antigen itself can develop. This direct inflammatory effect can be fully accounted for by endotoxin-like contaminants which are present in protein preparations obtained from commercial suppliers. A pharmaceutical (U.S. Pharmacopeia) serum albumin preparation contains no detectable endotoxin, and has no initial inflammatory effect on the eye. Since endotoxins, even in minute amounts, have a variety of effects, the use of such contaminated protein preparations in biological research can lead to erroneous conclusions and should, therefore, be avoided.

Animals↗