K H Kostka

Caritas-Krankenhaus Lebach, Lebach, Saarland, Germany

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Publications (5)27.82 Total impact

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    ABSTRACT: This work investigates in vitro finite dose skin absorption of the model compounds flufenamic acid and caffeine experimentally and mathematically. The mass balance in different skin compartments (donor, stratum corneum (SC), deeper skin layers (DSL), lateral skin parts and acceptor) is analyzed as a function of time. For both substances high amounts were found in the lateral skin compartment after 6 hours of incubation, which emphasizes not to elide these parts in the modeling. Here, three different mathematical models were investigated and tested with the experimental data: a pharmacokinetic model (PK), a detailed microscopic two-dimensional diffusion model (MICRO) and a macroscopic homogenized diffusion model (MACRO). While the PK model was fitted to the experimental data, the MICRO and the MACRO models employed input parameters derived from infinite dose studies to predict the underlying diffusion process. All models could satisfyingly predict or describe the experimental data. The PK model and MACRO model also feature the lateral parts.
    Journal of Controlled Release 10/2012; · 7.63 Impact Factor
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    ABSTRACT: The objective of this work was to develop a simple and inexpensive transdermal formulation containing Nortriptyline Hydrochloride (NTH) for smoking cessation support therapy. Hydroxypropyl-methyl-cellulose was chosen as polymer and a mixture of transdermal enhancers (selected from previous research) was incorporated. The formulations were characterised in terms of appearance, thickness, uniformity of NTH content, release and skin permeation. Release studies demonstrated controlled release for four formulations. Diffusion studies were performed through human heat separated epidermis (HHSE) using Franz Diffusion Cells (FDC). Patches provided different fluxes varying from 20.39 ± 7.09 μg/(cm2 h) to 256.19 ± 94.62 μg/(cm2 h). The penetration profiles of NTH within the stratum corneum (SC) and deeper skin layers (DSL) were established after three administration periods (3 h, 6 h, and 24 h). Skin changes induced by the application of the patches were observed by confocal laser scanning microscopy (CLSM). The highest flux obtained would provide the recommended doses for smoke cessation support therapy (25–75 mg per day) with a 2 cm × 2 cm patch or a 3.5 cm × 3.5 cm patch, respectively, without skin damage evidence.
    International Journal of Pharmaceutics 07/2009; · 3.99 Impact Factor
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    ABSTRACT: Investigations to determine pH profiles across human stratum corneum (SC), in vivo as well as in vitro, were carried out using the tape stripping technique and a flat surface pH electrode. This method was extended to the deeper skin layers (=viable epidermis+dermis; DSL) in vitro. Statistically significant changes in the pH values were detected in the SC between in vivo and in vitro investigations and also between male and female skin in vivo. For the DSL, no gender-dependent differences in pH were observed. While the results achieved for the SC are in accordance with data already published in the literature, the values for the DSL were surprising: An alkaline pH, with a steep increase of about two pH units in the first 100 microm of the DSL and a plateau of this level was thereafter detected. Research was also done to examine the influence of different in vitro test systems on the results of pH measurements across the skin. A permeation model (Franz diffusion cell; FD-C) and a penetration model (Saarbruecken penetration model; SB-M) were compared. Experiments were carried out concerning the incubation time as well as the pH of the acceptor solution in the FD-C. Independent of the test system used, no change in the pH profiles could be observed for the SC, but a strong effect of the acceptor medium and its pH on the pH profiles across the DSL could be demonstrated using the FD-C, which showed itself partly after 30 min in statistically significant differences between incubated and formerly frozen skin. The results after the use of buffer solutions with different pH values, the pH across the DSL seemed to come into line with the one of the buffer solution, which was investigated for acidic as well as alkaline pH values. The results obtained with the flat surface pH electrode were confirmed using two different dyes: the pH-dependent fluorescent dye carboxy-SNARF-1 and the pH indicator bromthymolblue.
    European Journal of Pharmaceutics and Biopharmaceutics 02/2003; 55(1):57-65. · 3.83 Impact Factor
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    ABSTRACT: In a comparative study, two different in vitro cutaneous test systems were examined: (1) The Franz diffusion cell (FD-C), a test system to study drug permeation through the skin and to obtain data like steady state flux and lag time as well as permeability and diffusion coefficients. (2) The Saarbruecken penetration model (SB-M), a test system to investigate drug penetration into different skin layers and after varying incubation times to acquire values about the quasi steady state drug amounts in the stratum corneum (SC). Three drug concentrations (0.9, 0.45 and 0.225%) of a lipophilic model drug preparation, flufenamic acid in wool alcohols ointment, were applied on the skin's surface using 'infinite dose' conditions. Trypsin-isolated SC, heat-separated epidermis, full-thickness skin and reconstructed human skin (RHS) served as skin membranes in the FD-C, while the SB-M experiments were only carried out using full-thickness skin. Increasing steady state flux data and m(ss) values (steady state drug amount in the SC) were detectable after the application of rising drug amounts. Concerning the permeability of the used skin membranes in establishing barrier properties, the following rank order was observed: RHS>SC> or =epidermis>full skin. The flux data of the FD-C experiments for isolated SC, separated epidermis and RHS were linearly related with the m(ss) values of the SB-M investigations, allowing a direct comparison of permeation with penetration parameters. Concerning the drug amount in the SC, previous investigations succeeded in the establishment of an in vivo/in vitro correlation. Based on the results presented here, the prediction of drug amounts present in the SC after different incubation times in vivo is now possible after penetration as well as permeation experiments using the lipophilic model drug preparation, flufenamic acid in wool alcohols ointment.
    Journal of Controlled Release 08/2001; 75(3):283-95. · 7.63 Impact Factor
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    ABSTRACT: Two in vitro test systems used to study drug penetration into human skin--the Franz diffusion cell (FD-C) and the Saarbruecken penetration model (SB-M)--were evaluated, and the results were compared with data gained under analogous in vivo conditions. Excised human skin was used in all in vitro experiments. Flufenamic acid dissolved in wool alcohols ointment, was chosen as a model drug, and the preparation was applied using 'infinite dose' conditions. To acquire quantitative information about the drug penetration, the skin was segmented into surface parallel sections at the end of each experiment, first by tape stripping the stratum corneum (SC), and second by cutting the deeper skin layers with a cryomicrotome. The flufenamic acid was extracted from each sample and assayed by high performance liquid chromatography (HPLC). For in vivo experiments, only the tape stripping technique was used. a) Drug penetration into the SC: In both in vitro test systems the total drug amounts detected in the SC were found to increase over the different incubation times. Similar conditions were obtained in vivo, but on a lower level. Using Michaelis-Menten kinetics, the m(max) value was calculated for the skin of two donors. The relations of the m(max) values for the FD-C and the SB-M closely correspond (1.26 [donor 1] and 1.29 [donor 2]). A direct linear correlation of the drug amount in the SC and the time data were found for in vivo with both in vitro test systems. b) Drug penetration into the deeper skin layers: The detected drug amounts in the deeper skin layers continuously increased with the incubation time in the SB-M, while in the FD-C, only very small drug amounts were observed after incubation times of 30 and 60 minutes. It was also noticed, that the drug amounts rose steeply at time points 3 and 6 hours. Additional studies showed a remarkable penetration of water into the skin from the basolateral acceptor compartment in the FD-C. This could explain the different drug transport into the deeper skin layers between the two in vitro test systems. Both in vitro models showed comparable results for the drug penetration into the SC and a robust correlation with in vitro data. Different results were obtained for the deeper skin layers. Whether a correlation between in vitro and in vivo data is also possible here has to be investigated by further experiments.
    Pharmaceutical Research 01/2001; 17(12):1475-81. · 4.74 Impact Factor