Publications by authors named "Stefan Horkovics-Kovats"

The purpose of this study was to develop a deterministic permeation model (DPM) that predicts the in vitro release profile of an active ingredient (API) embedded in hydroxypropyl-methylcellulose (HPMC) matrix tablets based on Raman spectra. So far in the literature, such mechanistic models were utilized only for formulation optimization (off-line dissolution prediction), while the real-time prediction of dissolution profiles based on Process Analytical Technology (PAT) data was performed by empirical methods such as Partial Least Squares (PLS) regression. Our work represents a novel conceptual approach that utilizes a mechanistic model to predict dissolution profiles based on data yielded by PAT tools.

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The similarity of the dissolution time profiles is routinely determined by various statistical methods, e.g. by calculating the f similarity factor, by calculating the multivariate statistical distance or determining the confidence interval of f metrics using the bootstrapping method.

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In spite of the fact that dissolution time profiles of 250mg ursodeoxycholic acid (UCDA) capsules developed by Sponsor and 250mg hard capsules produced by Ursofalk®, Dr. Falk Pharma GmbH, indicated similarity (f=60.6), a bioavailability study indicated unexpected differences in the formulations.

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In order to improve the bioavailability of substances with limited water-solubility, they are often formulated as nanoparticles. Nanoparticles show enhanced dissolution properties when compared to large particles. In this paper a dissolution theory is presented that comprehensively describes the dissolution properties of both large- and nanoparticles.

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Disintegration of finished dosage forms (FDF) and drug dissolution are fundamentally important processes that affect bioavailability. Established theories do not account for disintegration and usually assume sink conditions for drug dissolution that often do not apply. We present the theory to describe the disintegration of FDF with subsequent dissolution of liberated particles containing the active pharmaceutical ingredient (API) and its application using population data analysis.

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Enterohepatic recirculation (EHC) can greatly enhance plasma drug exposures and therapeutic effects. This study aimed to develop a population pharmacokinetic model that can simultaneously characterize the extent and time-course of EHC in three species using fimasartan, a novel angiotensin II receptor blocker, as a model drug. All fimasartan plasma concentration profiles in 32 rats (intravenous doses, 0.

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Dissolution profile of a finished dosage form (FDF) contains hidden information regarding the disintegration of the form and the particle properties of the active pharmaceutical ingredient. Here, an extraction of this information from the dissolution profile without limitation to sink conditions is provided. In the article, mathematical relationships between the continuously measured dissolution profile of an FDF containing uniform or heterogeneous particles and its disintegration rate are developed.

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Clarithromycin decreases CYP3A4 activity and thus gradually inhibits its own metabolism as well as that of coadministered drugs. The aim of this study was to obtain an understanding of the time course of these changes. The plasma concentration-time profiles of clarithromycin and its active metabolite, 14(R)-hydroxy-clarithromycin, in 12 young healthy volunteers after oral administration of a clarithromycin suspension (500 mg twice a day [b.

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A 17-compartment linear pharmacokinetic model is designed, describing the complex process of enterohepatic circulation as a superposition of the net (remetabolizationfree) enterohepatic circulation, and remetabolization with subsequent intestinal absorption of the parent drug. Basically, the model is built by doubling the model describing the circulation of the parent drug in the body, so that the remetabolizable metabolite circulates in a model of the same structure as does the parent compound. The two submodels are cross-connected with arrows denoting the transition of the particular substance into the complementary part of the complex model.

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To characterize the dissolution of particles, a dissolution rate coefficient alpha, consisting of a geometric factor gamma and material constant mu, was introduced. The impact of the particle geometry on the initial rate of dissolution was assessed for spherical, cubic and tetrahedral particles. Additionally, a description of dissolution of samples containing multiple populations of particles was derived.

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The objective of this study was to identify differences in disposition and esterase hydrolysis of ramipril between male and female volunteers. Plasma concentration and area under the concentration-time curve until the last measured concentration (AUCt) data of ramipril and its active metabolite ramiprilat (-diacid) were obtained from a randomised, cross-over bioequivalence study in 36 subjects (18 females and 18 males). Participants received a single 5-mg oral dose of two different formulations of ramipril (Formulation I and II).

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The aim of this pharmacokinetic evaluation was to show the effect of the extra methyl group in simvastatin on esterase hydrolysis between lovastatin and simvastatin in male and female volunteers. This study was based on the plasma concentration-time curves and the pharmacokinetics of lovastatin and simvastatin with its respective active metabolite statin-beta-hydroxy acid obtained from two different bioequivalence studies, each with 18 females and 18 males. Results were: The group of female volunteers showed a higher yield of the active metabolite beta-hydroxy acid than the group of males (p < 0.

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The objective of this study was to identify differences in disposition and esterase hydrolysis of ramipril between male and female volunteers. Plasma concentration and area under the concentration-time curve until the last measured concentration (AUCt) data of ramipril and its active metabolite ramiprilat (-diacid) were obtained from a randomised, cross-over bioequivalence study in 36 subjects (18 females and 18 males). Participants received a single 5-mg oral dose of two different formulations of ramipril (Formulation I and II).

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Analysing discrete as well as continuous linear autonomous pharmacokinetic models, it is shown that their asymptotic behaviour is independent of the rates of kinetic processes and timing of drug application. Consequently, for the description of pharmacokinetic endpoints, i.e.

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