Application of a Novel Dissolution Medium with Lipids for In Vitro Simulation of the Postprandial Gastric Content.

Food can change various physiological parameters along the gastrointestinal tract, potentially impacting postprandial drug absorption. It is thus important to consider different in vivo conditions during in vitro studies. Therefore, a novel dissolution medium simulating variable postprandial pH values and lipid concentrations was developed and used in this study.

Development Dynamics of Health and Social Infrastructure for the Long-term Care - the Case of the Posavje Region.

Background And Purpose: The populations of rural areas across Europe, especially Slovenia, are ageing rapidly and the areas themselves are becoming depopulated. Therefore, this study aims to contribute to our understanding of the population dynamics and provide a method for forecasting housing and other long-term care needs.

Method: The surveys questioned those responsible for long-term care, the caretakers in institutional care, and current and potential homecare users in rural areas of Slovenia.

The Influence of Simulated Fasted Gastrointestinal pH Profiles on Diclofenac Sodium Dissolution in a Glass-Bead Flow-Through System.

High inter- and intra-individual variability in the pH of fluids in the human gastrointestinal (GI) tract has been described in the literature. The aim of this study was to assess the influence of physiological variability in fasted pH profiles of media along the GI tract on diclofenac sodium (DF-Na) dissolution from matrix tablets. Four individual in vivo fasted pH profiles were selected from the literature that differed in pH values and transit times from the stomach to the proximal colon.

Analysis of factors influencing gastric emptying of pellets in a fed state.

Objectives: The aim of the present study is to evaluate the influence of factors such as biopharmaceutical properties and study protocol on the emptying of pellets from the human stomach in a fed state.

Methods: A systematic literature search for data on human gastric emptying of pellets from a fed stomach state investigated by γ-scintigraphy was carried out. After selection of comparable data, a joint statistical analysis on the basis of multiple linear regression with 132 individual t50 values (time for 50% of the pellets to be emptied from the stomach) was performed.

In vitro-in vivo-in silico approach in biopharmaceutical characterization of ibuprofen IR and SR tablets.

Within the last decades, physiologically based pharmacokinetic models have emerged into a biopharmaceutical toolkit that has been proven useful in understanding how physicochemical, formulation and physiological factors affect oral drug absorption. The purpose of this study was to develop a drug specific physiologically based pharmacokinetic model that will allow mechanistic interpretation of oral absorption from dosage forms exhibiting different in vitro and different in vivo performance (i.e.

Analysis of small intestinal transit and colon arrival times of non-disintegrating tablets administered in the fasted state.

In this study individual data on tablet gastrointestinal transit times (i.e. gastric emptying, small intestinal transit, ileocecal junction residence, and colon arrival times) were obtained from literature in order to present and analyze their distributions and relationships.

Influence of the physiological variability of fasted gastric pH and tablet retention time on the variability of in vitro dissolution and simulated plasma profiles.

The aim of the present study was to show that the physiological variability of fasted gastric pH and tablet gastric retention time contributes to the overall variability of simulated plasma profiles of diclofenac. Those two parameters were implemented into dissolution study and plasma profiles were simulated under assumptions that in vitro dissolution well represents that occurring in vivo, and that absorption profiles are identical to dissolution profiles, as diclofenac is a highly permeable drug. Dissolution experiments were performed using USP 2 apparatus and two consecutive dissolution media, namely, an acidic medium of various pH (ranging from 1-3), where tablets were kept for a certain time (10-200 min), and phosphate buffer (pH 6.

The role of individual gastric emptying of pellets in the prediction of diclofenac in vivo dissolution.

The objective of the present study was to check for the possibility to successfully predict individual in vivo dissolution/absorption profiles resulting from fasted administration of a diclofenac extended release pellet formulation. For this purpose dissolution profiles were generated with different dissolution setups using a set of media reflecting pH-conditions in the different segments of the gastrointestinal tract. Since gastric emptying of pellets seemed to be a critical factor for in vivo drug release, a set of different gastric residence times was screened in in vitro studies.

Enhanced therapeutic effect of LK-423 in treating experimentally induced colitis in rats when administered in colon delivery microcapsules.

LK-423 is a phthalimido-desmuramyl-dipeptide derivative with immunomodulating activity. In the present study the therapeutic efficacy of a colon-specific drug delivery system–LK-423 microcapsules–was examined in the 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced ulcerative colitis model in rats. The colon-specific delivery of the drug using microcapsules relies on the combination of pH (outer gastroresistant coating), time (inner retard coating of Eudragit® RS and RL) and enzyme (pectin core) controlled drug release mechanisms.

Gastric emptying of non-disintegrating solid drug delivery systems in fasted state: relevance to drug dissolution.

Importance Of The Field: Knowledge of gastric emptying (GE) of solid drug delivery systems (DDS) is meaningful for the development of new DDS as it enables the design of in vitro dissolution experiments with conditions close to those in vivo in order to predict drug plasma concentration profiles with high reliability.

Areas Covered In This Review: Gastric emptying of non-disintegrating pellets, tablets and mini-tablets in the fasted state is described on the basis of various studies performed in the last 30 years, which have evaluated the emptying process mostly by gamma scintigraphy. Different influences on GE and mathematical models describing GE kinetics of single and multiunit dosage forms are represented.

Physicochemical and preclinical pharmacokinetic and toxicological evaluation of LK-423--a new phthalimido-desmuramyl-dipeptide derivative with immunomodulating activity.

Introduction: LK-423 is a new phthalimido-desmuramyl-dipeptide derivative with immunomodulating activity. As optimized delivery to the site of action appears crucial for further preclinical development of LK-423, the aim of this study was to perform a physicochemical and preclinical pharmacokinetic and toxicological evaluation.

Methods: The solubility, partition coefficient, permeability, and stability profile were determined.

Antioxidant levels in the pig urinary bladder: distribution within the bladder wall and in the urothelium derived from different bladder regions.

This study was designed to determine the antioxidant levels in the urinary bladder wall layers as well as urothelium derived from different bladder regions. Samples of the urothelium, lamina propria, muscularis, and serosa were prepared from the pig's urinary bladder body, while samples used for regional mapping of the urothelium were prepared from trigone, ventral and dorsal middle bladder body, and apex region. Activities of superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase were determined.

Effects of UGT1A1*28 polymorphism on raloxifene pharmacokinetics and pharmacodynamics.

Aims: Raloxifene concentrations were reported to correlate approximately with serum bilirubin levels. Bilirubin is a typical UGT1A1 substrate. Based on these facts, we postulated a hypothesis that UGT1A1 is the key enzyme for metabolic clearance of raloxifene and that the common UGT1A1*28 polymorphism significantly contributes to the large pharmacokinetic variability of raloxifene.

Gastric emptying of pellets under fasting conditions: a mathematical model.

Purpose: To develop a mathematical model that would adequately describe human gastric emptying of pellets under fasting conditions of healthy subjects.

Methods: Scintigraphic profiles representing the gastric emptying of pellets were obtained from the literature. Altogether 19 individual and three mean scintigraphic profiles were collected.

Rapid differentiation of superficial urothelial cells after chitosan-induced desquamation.

Superficial cell desquamation followed by differentiation of newly exposed superficial cells induces regeneration of the urinary bladder epithelium, urothelium. In the present work, chitosan was evaluated as a new inducer of urothelial cell desquamation, in order to study the regeneration of mouse urothelial cells in vivo. Intravesical application of chitosan dispersion caused complete removal of only the superficial layer of cells within 20 min of treatment.

Heparin decreases permeability of pig urinary bladder wall preliminarily enhanced by chitosan.

Chitosan significantly increases the permeability of the isolated pig urinary bladder wall by causing urothelial desquamation, the extent of which depends also on the concentration of the polymer. By desquamation permeability barriers of the urothelium are removed. To gain additional insight into the mechanism by which chitosan acts an absorption enhancer into urinary bladder mucosa, we evaluated the influence of a polysaccharide heparin on the permeability of isolated pig urinary bladder wall preliminarily treated with chitosan.

Shape optimization and characterization of polysaccharide beads prepared by ionotropic gelation.

The shape of drug loaded polysaccharide beads produced by ionotropic gelation has been optimized, with the aim of producing spherical beads suitable for further technological operations, such as coating. The optimization was performed on a model system sodium alginate/theophylline by inclusion of various fillers. Incorporation of excipients markedly influenced the morphological characteristics of the beads.

Development and validation of a liquid chromatography-tandem mass spectrometry assay for determination of raloxifene and its metabolites in human plasma.

This paper describes the development and validation of a method for the detection of raloxifene (Ral) and its two glucuronide metabolites, raloxifene-6-glucuronide (M1) and raloxifene-4'-glucuronide (M2), in human plasma samples. Both glucuronides were synthesized enzymatically, purified and used as authentic standards. The assay involves a simple solid phase extraction (SPE) procedure of 0.

Permeability of pig urinary bladder wall: time and concentration dependent effect of chitosan.

Chitosan in 0.5% w/v concentration enhanced the permeability of the isolated pig urinary bladder wall by desquamation of the urothelium as ascertained in our previous study. The aim of the present work was to determine the time and concentration dependence of chitosan's effect on the permeation of a model drug into the bladder wall and to establish if the mechanism of permeation enhancement depends on the concentration of chitosan used.

HPLC analysis of raloxifene hydrochloride and its application to drug quality control studies.

Raloxifene hydrochloride is a selective estrogen receptor modulator and is currently being used for prevention of osteoporosis in postmenopausal women. In this article, a high performance liquid chromatography (HPLC) method for detection of raloxifene hydrochloride was developed and validated using an ultraviolet (UV) and coulometric detectors. Limit of quantification (LOQ) was 0.

Permeability of pig urinary bladder wall: the effect of chitosan and the role of calcium.

Chitosan is a cationic polysaccharide widely employed as an absorption enhancer. The aim of this work was to examine the effect of chitosan on the permeability of isolated pig urinary bladder wall as well as to determine the role of calcium ions in this process. Besides permeability studies, scanning electron microscopy and fluorescent microscopy were applied to get an insight into the mechanism by which chitosan increases the permeability of urinary bladder wall.

Effect of preparation temperature in solvent evaporation process on Eudragit RS microsphere properties.

Eudragit RS 100 microspheres containing ketoprofen as a model drug were prepared by the solvent evaporation method using an acetone/liquid paraffin solvent system. The influence of various preparation temperatures: 10, 25, 35, and 40 degrees C, on particle size and morphology, drug content and release kinetics, and drug crystal state was evaluated. With increasing temperature, microsphere average size was found to increase and particle size distribution to widen significantly.

The correlation between zeta potential and mucoadhesion strength on pig vesical mucosa.

The detachment forces of various polymers are frequently measured to determine their mucoadhesion strength. As the process of mucoadhesion is a consequence of interactions between the mucus layer on mucosa and mucoadhesive polymers, it is greatly dependent on mucus and polymer structure including their charge. It is also known that the glycosaminoglycan layer, which covers the urinary bladder mucosa surface, is highly negatively charged.

The influence of chitosan on in vitro properties of Eudragit RS microspheres.

Eudragit RS microspheres containing chitosan hydrochloride were prepared by the solvent evaporation method using acetone/liquid paraffin solvent system and their properties were compared with Eudragit RS microspheres without chitosan, prepared in our previous study. Different stirring rates were applied (400-1200 rpm) and drug content, Higuchi dissolution rate constant, surface and structure characteristics of the microspheres were determined for each size fraction. An increase in average particle size with a reduction of stirring rate appeared in limited interval in both series.