EFFECT OF DOSAGE FORM ON DRUG ABSORPTION A FREQUENT VARIABLE IN CLINICAL PHARMACOLOGY.
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Aluminium (Al ) is abundant in our environment and is a contaminant of electrolyte solutions used in the manufacture of Total Parenteral Nutrition (TPN) solutions administered to neonates, who are unable to tolerate oral feeding. Previous studies by McHalsky et al. (1) have shown concern over the levels of aluminium in parenteral products, and there are special considerations needed with regard to neonatal TPN solutions, (2). It is felt that neurotoxicology and abnormalities of bone histology may be seen with aluminium deposition in the tissues. In the present study it was shown that the average aluminium contamination in TPN solutions was in the order of 205 micrograms/L. It is well documented that aluminium is chelated successfully in dialysis solutions by desferrioxamine (DFO), Allain et al. (3). Using an AA spectrophotometer equipped with a graphite furnace, the average amount of aluminium in compounded neonatal TPN solutions was determined. Equimolar amounts of DFO to aluminium were added to various neonatal TPN formulations, and the physical stability of each solution was determined using microscopic and electronic particle counting analysis. This study suggests that aluminium can be irreversibly chelated with DFO and stable TPN solutions can be prepared.
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A simple sensitive and specific spectrofluorometric method was developed for the determination of nimodipine (NDP) in pharmaceutical preparations and human urine. The method is based on reduction of nimodipine with Zn/HCl and measuring the obtained fluorescence at 425 nm after excitation at 360 nm. The factors affecting the development of the fluorophore and its stability were studied and optimized. The effect of some surfactants such as beta-cyclodextrin (betaCD), carboxymethylcelullose (CMC), sodium dodecyl sulphate (SDS) and Triton X-100, on the fluorescence intensity was studied. The fluorescence intensity-concentration plot is rectilinear over the range 0.1-5.0 microg/ml in presence of Triton X-100 with a minimum detectability limit of 0.06 microg/ml (1.62 x 10(-7) M). The proposed method was successfully applied to commercial tablets containing NDP, the percentage recovery agreed well with those obtained using the official methods. The method was further extended to the in vitro determination of NDP in spiked human urine samples. The % recovery was 102.1 +/- 2.54 (n = 4). A proposal of the reduction reaction pathway was postulated.
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The pharmacokinetics of gidazepam administered in tablets prepared using different technologies was studied in rabbits. The optimum properties (high relative bioaccessibility and low degree of dealkylation of the parent substance) were observed for the tablets fabricated using a solid disperse system.
After briefly reporting the basic concepts of indirect UV detection in HPLC, methods for the quantitative determination of ethanol, glycerol and isopropanol in pharmaceutical forms for human use, and propylene glycol and N,N-dimethylacetamide in pharmaceutical form for veterinary use are proposed. Nicotinamide, sulfanilamide and isoniazid are used as UV-absorbing components (probes) of mobile phase. The last two are new probes suitably selected and proposed to optimize the determination. Also, the dependence of method sensitivity from the probe concentration is shown. Good accuracies and precisions are obtained. The methods are simple and quick and the assays of the analytes do not go through interferences from the other substances present in the pharmaceutical forms.
The application of direct-current differential electrolytic potentiometry to the nonaqueous titration of amino acids was investigated. The basic character of amino acids in acetic acid was enhanced to permit their direct titration with perchloric acid. A pair of antimony electrodes was used as an indicating system. The shapes of the titration curves obtained were almost symmetrical with sharp peaks. The optimum current density for those titrations was found to be 1-2 microA/cm2. The procedure was applied successfully to the determination of certain amino acids in drug formulations, and the results were favorably compared statistically with those obtained by official methods.
OBJECTIVE: To prepare anticancer nanoparticles for targeting therapy for oral cancer lymph node metastasis. METHODS: The activated carbon nanoparticles (CH-NP) were prepared for drug carrier. Pingyangmycin (PYM), a high sensitive anticancer drug for oral squamous cell carcinoma, were selected as model drug. The activated carbon nanoparticles and PYM were mixed with saline and shaken 20 minutes so that PYM was absorbed on activated carbon enough, resulting in a new formulation of PYM (PYM-CH-NP). The absorbency of PYM on activated carbon nanoparticles was evaluated. RESULTS: The diameter distribution for CH-NP ranged form 136 nm, to 540 nm, the average diameter was 176 nm. The proportion of CH-NP to PYM was increased and more absorbency of PYM on activated carbon nanoparticles was achieved. CONCLUSION: The activated carbon nanoparticles has high absorbency of PYM. The new formulation PYM-CH-NP can be used as targeting therapy of cervical lymph node metastasis by peri-cancer submucosal injection.
Seven days after a subcutaneous inoculation of 5 x 10(5) P388 leukemia cells into the foot pad of the left hind paw of donor mouse, aclarubicin (0.2mg/kg body weight) was injected subcutaneously into the hind paw of the opposite foot pad in the form of ACR-CH or aclarubicin aqueous solution. On day 10, the left popliteal and the lower para-aortic lymph nodes taken from each donor were transferred intraperitoneally to a normal recipient mouse. The combined survival time of recipients and the viable P388 leukemia cell number in popliteal and para-aortic lymph nodes were estimated with a calibration formula. Our results showed that the survival curve of recipients given ACR-CH was statistically improved compared with that of other treatment groups.
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The aim of the study was to lower the immunosuppressory, prooxidant and hepatotoxic effects of rifampicin and cephalexin by their immobilization in erythrocyte vehicles. The experiments were performed on Wistar rats with the use of rifampicin, cephalexin and lysozyme (ZAO Ferane) and hemodes (6% aqueous saline solution of low molecular polyvinylpyrrolidone, mol. wt. 12600+/-2700). Rifampicin- and cephalexin-entrapped erythrocytes were prepared. Spectrophotometric procedures for quantitative assay of the immobilized antibiotics were developed. The impact of the solution concentration and incubation time on the level of the antibiotic entrapping was studied. The erythrocyte vehicles were shown to be able to entrap the antibiotics for 9 days and to preserve their stability for 24 hours. It was observed that the increase of the immunosuppressory, prooxidant and hepatotoxic effects of the antibiotics administered without the vehicles to the laboratory animals infected by staphylococci was dose-dependent. The use of the antibiotics entrapped in the erythrocyte vehicles stimulated the immune reactivity of the animals and normalized the indices of lipid peroxidation, the antioxidant system, cytolysis and cholestasis.
The effect of humidity and temperature on the stability of enalapril maleate (ENA) in tablets have been studied. Tablets with ENA were stored in final packs (blisters) and without final packs in the atmosphere of increased humidity (76.4 % RH) and in the temperature range from 313 K to 333 K (forced degradation test). Degradation of ENA in tablets stored in final packs and without final packs followed the first order reaction model. During this study, the product of hydrolysis of the ester group and intramolecular cyclization have been observed. Thermodynamic parameters (activation energies, enthalpy and entropy) for the decomposition of ENA in tablets were calculated.