Selection of the vehicle for topical administration of drugs.
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Biomedical subjects
Publications and source records attributed to B C Lippold.
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The drug release from an ointment that contains dissolved drug depends on the kind of preparation and on the time of storage. This indicates a relationship between shear treatment (disruption of the gel matrix) and liberation rate. With increasing storage time of the ointment the liberation rate decreases due to the increasing diffusional resistance of the reforming gel matrix.
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The pharmaceutical-technological measure of varied salt formation acts on the in vivo diffusion processes of quaternary tridihexethyl (gastro-intestinal absorption, transperitoneal diffusion) in principle in the same manner as it acts on the in vitro diffusion processes (membrane diffusion): Due to the formation of corresponding ion pairs, lipophilic counterions of opposite sign facilitate the passage through membranes. In contrast, the direct pharmacodynamic activity (spasmolysis at the isolated jejunum of the rat) is not changed by varying the counterions of opposite sign.
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Distribution studies in vitro predict increasing absorption rates in vivo with increasing distribution coefficients up to a limiting value. Buccal absorption tests with homologous, quaternary cholinesterbromides of benzilic acid do not confirm this hypothesis. The reasons could be the rather hydrophilic properties of the mucosal membranes and thus adsorption of drug to the mucosa. The evaluation of results with undissociated homologous carboxylic acids, however, shows a good correlation between the prediction from in vitro studies and the buccal absorption test.
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The partition of homologous quaternary esters of benzilic acid is studied in a modified three-phase model according to Schulmann (water-n-octanol-water). The logarithms of the partition coefficients of the compounds increase linearly with increasing alkyl chain. The rate determining step for the interphase transport of hydrophilic compound is the diffusion through the organic diffusion layer. The rate constants for the transfer from the aqueous to the organic phase increase linearly with the corresponding partition coefficient, whereas the rate constants for the reverse reaction are not influenced. With increasing chain length the diffusion through the aqueous diffusion layer becomes rate determining for the interphase transport. Thus the rate constants for the transfer from the aqueous to the organic phase are independent of partition coefficients. The rate constants for the reverse transfer are inversely proportional to the corresponding partition coefficients. The half-lives of the transfer of the homologous compounds under sink conditions show a minimum between the heptyl and octyl derivative. The equilibration time decreases with increasing agitation, concentration and temperature. The significance of the results for biological problems is discussed.
The addition of NaBr, Na-butansulfonate or Na-trichloracetat increases the partition coefficients of homologous quaternary cholinesters of benzilic acid between n-octanol and water. In a three-phase model (water/n-octanol/water) thus the rates of equilibration increase considerably for hydrophilic compounds.
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