[Optimization of the technology and a study of rectal drug forms. II. The technology and biopharmaceutical study of molded suppositories of sodium mephenaminate].
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According to its aromatic nitro group acetylaminonitropropoxybenzene (Falimint) can be determined polarographically. The typical behavior of the nitro group becomes evident by the elektrochemical reduction. The investigation has shown two phases of reduction with pH-depended half-wave-potential shifts, so that a two-step mechanism is conceivable. Using direct current polarography the substance is determined in a concentration range from 1 to 100 micrograms/ml. Low elektroaktive background signals within the potential range the four-electron reduction step are the basis for the determination of the active agent in saliva, urine and blood plasma without any extracting procedures. It is possible to identify the substance by means of oscilloand square-wave-polarography. The resulting polarogrammes are typically for the p-nitrophenyl structure. Further a new quantitativ polarographic method, named sample-DC-polarography on the stationary mercury electrode is discussed for the determination of Falimint in blood plasma without any steps of separation and cleaning in the concentration range of 0,1-3,0 micrograms/ml.
The absorption of Depogen was studied on an in vitro model and in various laboratory animals using stoichiometrically equivalent doses of drotaverin (No-Spa) calculated for drotaverin base for comparison. Blood levels of the drug were assessed by radiochemical and microchemical methods. Based on the results obtained and pharmacokinetic properties, the expectable optimal dosage and formulations for the possible field of indication were elaborated.
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2-Acetamino-4-nitropropoxybenzene is metabolized almost completely. Till now in urine of man seven components have been detected. The main way of metabolism is the oxidation of the propoxy group to a carboxyl group. Also the deacetylated compound of this acid has been found to a certain extent. A further metabolite is supposed to be oxidized in the side chain in another way. In a higher extent dealkylation to 2-acetamino-4-nitrophenol takes place which is eliminated probably in conjugation with glucuronic acid. Free 2-acetamino-4-nitrophenol and 2-amino-4-nitrophenol respectively are only detectable in traces. Deacetylation of 2-amino-4-nitropropoxybenzene takes place only in a very small extent. Till now metabolites with reduced nitro group haven't been found.
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The possibility of insulin administration in suppository dosage form was studied, using different carriers. Highly significantly insulin absorption from the rabbit rectum was obtained by inserting insulin suppositories containing Brij 58 as absorption-promoting surfactant.
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