Quantitative design of drug compatibility by weighted modification method.
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AIM: To set up a new method for designing and quantitatively analyzing drug compatibility. METHODS: Drugs for compatibility were divided into 6 dose levels which were evenly distributed to 6 compound groups according to a fixed design. A new mathematical model was set up to fit the dose-effect data of 6 groups. The coefficients, obtained from the model, reflected the dose-effect relationship and the important degree of every drug in combination. According to the coefficients, the drugs in compatibility could be distinguished into principal drug, synergist, inferior, antagonist, and assistant. Because compatibility in the maximal effect group was nearly (or was) an optimal one in 6 groups, the doses in the group were taken as a base for further modification which considered interaction among drugs. The results of the modification were demonstrated by further experiment. This method was applied to design and to quantitatively analyze the compatibility of allantoin, metronidazole, and dexamethasone sodium phosphate by 2 effect indices in mice. RESULTS: This new method was able to effectively determine important degree of drugs in combination, and to optimize their doses for designing compatibility. CONCLUSION: This weighted modification method is a highly efficient, accurate, and practical means for designing and quantitatively analyzing drug compatibility. (+info)
Stability and compatibility of ceftazidime administered by continuous infusion to intensive care patients.
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The stability and compatibility of ceftazidime have been examined in the context of its potential use in concentrated solutions for continuous infusion in patients suffering from severe nosocomial pneumonia and receiving other intravenous medications by the same route. Ceftazidime stability in 4 to 12% solutions was found satisfactory (<10% degradation) for 24 h if kept at a temperature of 25 degrees C (77 degrees F) maximum. Studies mimicking the simultaneous administration of ceftazidime and other drugs as done in clinics showed physical incompatibilities with vancomycin, nicardipine, midazolam, and propofol and a chemical incompatibility with N-acetylcystein. Concentrated solutions (50 mg/ml) of erythromycin or clarithromycin caused the appearance of a precipitate, whereas gentamicin, tobramycin, amikacin, isepamicin, fluconazole, ketamine, sufentanil, valproic acid, furosemide, uradipil, and a standard amino acid solution were physically and chemically compatible. (+info)
Use of beta-cyclodextrins to prevent modifications of the properties of carbopol hydrogels due to carbopol-drug interactions.
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Carbomers are carboxyvinylic derivatives that are widely used in the manufacture of hydrogel dosage forms. Because of their anionic nature and large number of acid groups, they tend to interact with cationic substances, and with other hydrophilic polymers containing alcohol groups. Here, we report a study of interactions between the carbomer Carbopol and the cationic drug propranolol hydrochloride in the solid state and in solution, and of the effects of such interactions on the properties of the hydrogel. We found that the drug forms an insoluble ionic complex with the polymer, modifying all of the hydrogel properties studied (swelling, release, bioadhesion). The inclusion of beta-cyclodextrin in the formulation reduces polymer/drug interactions, so that hydrogel properties remain unchanged. This is probably attributable to formation of inclusion complexes of beta-cyclodextrin and the drug, so that the drug is prevented from interacting with the polymer. (+info)
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.
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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. (+info)
Formulation study for lansoprazole fast-disintegrating tablet. II. Effect of triethyl citrate on the quality of the products.
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The purpose of this study was to develop enteric-coated microgranules for the lansoprazole fast-disintegrating tablet (LFDT), which is a rapidly disintegrating tablet containing enteric-coated microgranules. In our previous study, it was clarified that sufficient flexibility of the enteric layer was achieved by the optimized combined ratio of methacrylic acid copolymer dispersion to ethyl acrylate-methyl methacrylate copolymer dispersion and adding the optimized concentration of triethyl citrate to reduce the damage during the compression process. However, since triethyl citrate has an unpleasant bitter taste and is especially incompatible with lansoprazole, it adversely affects the taste and stability of lansoprazole in the enteric-coated microgranules. The enteric layer containing macrogol 6000 was proven useful to improve the unpleasant bitter taste and stability of lansoprazole, because macrogol 6000 does not have an unpleasant bitter taste and is more compatible than triethyl citerate. By covering the inner (first enteric layer) and outer side (third enteric layer) of the enteric layer containing triethyl citrate (second enteric layer) with the enteric layer containing macrogol 6000, we resolved the stability problem of lansoprazole and the unpleasant bitter taste. Finally, we developed enteric-coated microgranules comprising seven layers: 1) core, 2) active compound layer, 3) intermediate layer, 4) first enteric layer, 5) second enteric layer, 6) third enteric layer, and 7) over coating layer. The enteric-coated microgranules have the multiple functions of reducing the damage to the enteric layer during the compression process, improving the stability of lansoprazole, and masking the unpleasant bitter taste. (+info)
Heart disease and depression: don't ignore the relationship.
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Evidence is mounting that depression is a risk factor for the development of cardiovascular disease and portends a worse outcome in cardiac patients. Depression can be easily diagnosed and safely treated in cardiac patients, but it is undertreated. (+info)
Have dentin adhesives become too hydrophilic?
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This review discusses current trends in the development of dentin adhesives and the possibility that some classes of currently available adhesives are too hydrophilic. Manufacturers have reformulated dentin adhesives to make them more compatible for bonding to intrinsically moist, acid-etched dentin by adding 2-hydroxyethyl methacrylate and other hydrophilic resin monomers. These 3-step adhesives work well but are more time consuming to use and more sensitive to technique than the newer, simplified adhesives. When primers are mixed with adhesives in 2-step single-bottle adhesives and self-etching primers, the adhesives are more permeable to water and hence absorb more water over time than previous generations of adhesives. The most recent single-step self-etching adhesives are even more hydrophilic and hence more permeable to water derived from the underlying bonded dentin. This permeability can lead to a wide variety of seemingly unrelated problems, including incompatibility of chemically or dual-cured composites with simplified adhesives and expedited degradation of resin-dentin bonds. (+info)
Stability of heparin and physical compatibility of heparin/antibiotic solutions in concentrations appropriate for antibiotic lock therapy.
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OBJECTIVES: The purpose of this study was to determine the biological stability of heparin and to test for physical compatibility in heparin/antibiotic solutions in concentrations suitable for antibiotic lock therapy. METHODS: Solutions were prepared with heparin 5000 U/mL or heparin 10 U/mL and cefazolin 10 mg/mL, ampicillin 10 mg/mL, or piperacillin 40 mg/mL. Solutions of vancomycin 2.5 mg/mL with heparin 5000 U/mL and vancomycin 2 mg/mL with heparin 10 U/mL were also prepared. The ability of each solution to elevate the activated partial thromboplastin time (APTT) of pooled normal plasma and the physical compatibility of the solutions were assessed for 14 days. RESULTS: The APTT levels never varied by more than 16.4% from baseline. Physical incompatibility never occurred before day 14 in any of the solutions. CONCLUSIONS: Mixing of antibiotics in the concentrations chosen for the study had no clinically significant effect on biological heparin activity, and all solutions were physically compatible for at least 14 days. (+info)