W. Weitschies - Academia.edu (original) (raw)
Papers by W. Weitschies
marker monitoring allows to characterize effects of exogenous factors
European Journal of Pharmaceutics and Biopharmaceutics, 2015
Lately, drug-coated balloons have been introduced in interventional cardiology as an approach to ... more Lately, drug-coated balloons have been introduced in interventional cardiology as an approach to treat occluded blood vessel. They were developed for the rapid transfer of antiproliferative drugs during the angioplasty procedure in stenosed vessels with the intent to reduce the risk of restenosis. In this study five different paclitaxel (PTX) balloon coatings were tested in vitro in order to examine how solvents and additives influence coating stability and drug transfer rates. PTX-coated balloons were advanced through a guiding catheter and a simulated coronary artery pathway under perfusion and were then inflated in a hydrogel acceptor compartment. The fractions transferred to the gel, remaining on the balloon and the PTX lost in the simulated coronary pathway were then analysed. The results obtained suggest that the solvent used for the coating process strongly influences the surface structure and the stability of the coating. Ethanol/water and acetone based PTX coatings showed the lowest drug transfer rates to the simulated vessel wall (both <1%) due to their high drug losses during the prior passage through the coronary artery model (more than 95%). Balloons coated with PTX from ethyl acetate-solutions showed smaller drug loss (83% ± 9%), but most of the remaining PTX was not transferred (mean balloon residue approximately 15%). Beside the solvent, especially the use of additives seemed to have a great impact on transfer properties. The balloon pre-treatment with a crosslinked polyvinylpyrrolidone (PVP) film was able to increase the PTX transfer rate from less than 1% (without PVP) to approximately 6%. The best results in this study were obtained for balloon coatings with commercially available SeQuentÓ Please balloons containing the contrast agent iopromide. For this formulation drug transfer rates of approximately 17% were determined. Fluorescence microscopic imaging could visualize the particulate transfer of labelled PTX from the balloon surface during dilatation. The findings of this study underline the importance of drug adhesion and coating stability for the efficiency of PTX transfer.
The Journal of Clinical Pharmacology, 2014
During antibiotic treatments, active residuals reaching the colon profoundly affect the bacterial... more During antibiotic treatments, active residuals reaching the colon profoundly affect the bacterial flora resulting in the emergence of resistance. To prevent these effects, we developed an enteric‐coated formulated activated‐charcoal based product, DAV132, meant to deliver its adsorbent to the ileum and neutralize antibiotic residues in the proximal colon. In a randomized, control, crossover study, the plasma pharmacokinetics of the probe drugs amoxicillin (500 mg) absorbed in the proximal intestine, and sulfapyridine (25 mg) metabolized from sulfasalazine in the cecum and rapidly absorbed, were compared after a single administration in 18 healthy subjects who had received DAV132, uncoated formulated activated charcoal (FAC) or water 16 and 8 hours before, concomitantly with the probe drugs, and 8 hours thereafter. The AUC0–96 h of amoxicillin was reduced by more than 70% when it was taken with FAC, but bioequivalent when it was taken with water or DAV132. By contrast, the AUC0–96 h ...
Journal of pharmaceutical sciences, Jan 19, 2014
Gastrointestinal (GI) pH and temperature profiles under fasted-state conditions were investigated... more Gastrointestinal (GI) pH and temperature profiles under fasted-state conditions were investigated in two studies with each 10 healthy human subjects using the IntelliCap(®) system. This telemetric drug delivery device enabled the determination of gastric emptying time, small bowel transit time, and colon arrival time by significant pH and temperature changes. The study results revealed high variability of GI pH and transit times. The gastric transit of IntelliCap(®) was characterized by high fluctuations of the pH with mean values ranging from pH 1.7 to pH 4.7. Gastric emptying was observed after 7-202 min (median: 30 min). During small bowel transit, which had a duration of 67-532 min (median: 247 min), pH values increased slightly from pH 5.9-6.3 in proximal parts to pH 7.4-7.8 in distal parts. Colonic pH conditions were characterized by values fluctuating mainly between pH 5 and pH 8. The pH profiles and transit times described in this work are highly relevant for the comprehensi...
Nanotechnology, 2004
Expression von Cadherinen im sich entwickelnden Cortex cerebri von Maus und Frettchen Forschungst... more Expression von Cadherinen im sich entwickelnden Cortex cerebri von Maus und Frettchen Forschungsthema:
Food Funct., 2014
The paper presents an international consensus for a standardised staticin vitrodigestion method f... more The paper presents an international consensus for a standardised staticin vitrodigestion method for food.
European Journal of Pharmaceutics and Biopharmaceutics, 2008
The prediction of the in vivo drug release characteristics of modified release oral dosage forms ... more The prediction of the in vivo drug release characteristics of modified release oral dosage forms by in vitro dissolution tests is a prerequisite for successful product development. A novel dissolution test apparatus that mimics the physical conditions experienced by an oral formulation during gastrointestinal transit was developed. This included the simulation of pressure forces exerted by gut wall motility, shear forces generated during propagation, and loss of water contact when the dosage form is located in an intestinal air pocket. The new apparatus was evaluated using a diclofenac extended release (ER) tablet. The in vitro dissolution profiles were compared between the novel test apparatus and a conventional dissolution apparatus (USP II). These data were compared with the profiles of plasma concentration versus time that were obtained after the administration of an ER tablet to 24 healthy volunteers under fasting conditions. Multiple peaks were observed in individual plasma concentration-time profiles after the intake of the reference ER tablet. Standard dissolution testing showed typical characteristics of an almost continuous release for this formulation; however, dissolution testing with the novel apparatus suggested that the diclofenac release from the ER tablets would be extremely variable and dependent on the applied stress. The data suggest that the observed multiple peaks of plasma concentration after dosing of the ER diclofenac tablets are most probably caused by sensitivity to physical stress events during gastrointestinal transit.
European Journal of Pharmaceutics and Biopharmaceutics, 2010
To validate Magnetic Moment Imaging (MMI) for the investigation of gastrointestinal transit and d... more To validate Magnetic Moment Imaging (MMI) for the investigation of gastrointestinal transit and disintegration of solid dosage forms and to correlate the MMI findings with the corresponding gamma scintigraphic data. Materials and methods: Three magnetic tablets (MTs) were investigated using in vitro and in vivo tests. The clinical study was a four-way, crossover study with the following arms: (a) immediate-release tablets administered in fasted state; (b) immediate-release tablets administered after 400 mL of Clinutren Ò ISO; (c) enteric-coated tablets administered in the fasted state; and (d) non-disintegrating tablets studied in the lightly fed state (100 mL of Clinutren Ò ISO). Results: In both the in vitro and in vivo studies, tablets were detected successfully by MMI and scintigraphy. There was a good correlation between gastric residence times and positional data (in the x, y and y, z-axes). In addition, MMI revealed early swelling behaviour of the tablet matrix. There was excellent agreement for the disintegration times of MT(A) in the fasted arm (scintigraphy 12.0 ± 4.4 min, MMI 11.8 ± 4.4 min). In the MT(A)-fed arm, onset times determined by scintigraphy were delayed in three subjects when compared to the corresponding MMI results. Delayed disintegration was observed with MT(A) administered after food (p < 0.01) in both the techniques. Conclusion: The MMI device is a reliable imaging tool for tracking the transit and disintegration of a magnetic tablet through the gastrointestinal tract.
European Journal of Pharmaceutical Sciences, 2014
are expected to significantly reduce demand for animal experiments in the future as well as reduc... more are expected to significantly reduce demand for animal experiments in the future as well as reducing the number of human bioequivalence studies required to bridge formulations after manufacturing or composition changes.
Journal of Controlled Release, 2005
Gastrointestinal motility and transport as well as concomitant food intake are factors that are k... more Gastrointestinal motility and transport as well as concomitant food intake are factors that are known to influence pharmacokinetics derived after intake of extended release dosage forms. However, the mechanisms behind these influencing factors are mostly unknown. In this study the gastrointestinal transit and the in vivo drug release of magnetically labelled extended release tablets containing felodipine were monitored together with the drug absorption phase of pharmacokinetics under fasting and fed conditions in six healthy volunteers using Magnetic Marker Monitoring. It was found that the in vivo drug release profiles of the tablets compared well under fasting and fed conditions. However, the plasma concentration profiles were strongly influenced by concomitant food intake. This could be attributed to elongated residence of the tablets in proximal parts of the stomach, resulting in delayed drug absorption and the occurrence of late high plasma peak concentrations. The lag time until the first appearance of felodipine in plasma and the residence time of the tablets in the proximal stomach, were found to be directly correlated. The study shows that increased plasma peak drug concentrations after intake of extended release formulations together with food can be explained by poor mixing in the proximal part of the stomach and are not necessarily due to failure of the formulation to control drug release (dose dumping).
Einleitung: Alpha-Rezeptorenblocker werden bei verschiedenen Indikationen systemisch verordnet un... more Einleitung: Alpha-Rezeptorenblocker werden bei verschiedenen Indikationen systemisch verordnet und können Veränderungen der Iris wie beispielsweise eine reduzierte Mydriasis und erhöhte Mobilität während der Kataraktoperation verursachen. Methodik: Es ist hinlänglich[zum vollständigen Text gelangen Sie über die oben angegebene URL]
Nanoparticulate contrast agents have long been used in diagnostic imaging. In Germany, particulat... more Nanoparticulate contrast agents have long been used in diagnostic imaging. In Germany, particulate contrast agents are currently approved for ultrasound imaging and magnetic resonance imaging. All ultrasound contrast agents are based on gas-filled microbubbles. The best documented application of ultrasound contrast agents in oncology is for diagnosing focal liver lesions. In magnetic resonance imaging, crystalline iron oxides are used as nanoparticulate contrast agents. Their primary application is also the diagnosis of focal liver lesions. Magnetic nanoparticles also have applications in many scientific endeavors as stable labels that can be detected with extremely high sensitivity. Current research approaches deal with extending the use of particulate contrast agents to molecular diagnostics and therapeutic applications.
Die Pharmazie, 2017
Gastroresistant capsules are obtained mostly by using modified-release fill in hard capsules, or ... more Gastroresistant capsules are obtained mostly by using modified-release fill in hard capsules, or by coating the gelatin shell with acid-resistant polymers. Modification of the material used at the stage when the capsule shell is produced would reduce the complexity and cost of introducing new products to the market. Gastroresistant gelatin films were obtained by using commercial cellulose acetate phthalate (aqueous dispersion Aquacoat® CPD). Only films casted from non-alkalized mixtures showed no visible disintegration at pH from 1.2 (simulated gastric fluid) to 4.5 (phosphate buffer). Elasticity of the dry films was comparable with the one determined for non-modified gelatin films, however tear resistance was 2-fold smaller, but still acceptable for practical application.
Науково-теоретичний альманах "Грані", 2017
Розглянуто феномен діяльної любові. Концептуалізовано поняття діяльної любові у філософії В. Соло... more Розглянуто феномен діяльної любові. Концептуалізовано поняття діяльної любові у філософії В. Соловйова, виділені її альтруїстичні прояви і зазначені ключові складники цього поняття. Оцінено вплив поглядів Платона, Р. Декарта, Б. Спінози, І. Канта, Г. Гегеля, Г. Сковороди та П. Юркевича на формування ідей В. Соловйова. Виявлені компаративні зв’язки з ідеями Е. Фромма, К. Льюїса, Х. Ортега-і-Гассета, П. Тілліха, Г. Марселя, П. Брюкнера. Встановлено, що діяльна любов – це моральна любов, яка надихає людину на здійснення добра для іншої людини; вона заснована на повазі до іншої особистості і на визнанні її неповторності та індивідуальності. Діяльна любов тотожна доброму відношенню, проте включає в себе акт дії, який веде до перетворення як окремої людини, так і всього суспільства в цілому. Встановлено дев’ять проявів діяльної любові: великодушність, безкорисливість, щедрість, терпіння, щирість, індивідуальна спрямованість, позачасовість, свобода від зовнішніх перешкод і прагнення до єдн...
Zeitschrift für Gastroenterologie, 2004
Journal of Controlled Release, 2015
The intraluminal conditions of the fed stomach are critical for drug release from solid oral dosa... more The intraluminal conditions of the fed stomach are critical for drug release from solid oral dosage forms and thus, often associated with the occurrence of food effects on oral bioavailability. In this study, intragastric pH and pressure profiles present after the ingestion of the high-caloric, high-fat (964 kcal) FDA standard breakfast were investigated in 19 healthy human subjects by using the telemetric SmartPill® capsule system (26 × 13 mm). Since the gastric emptying of such large non-digestible objects is typically accomplished by the migrating motor complex phase III activity, the time required for recurrence of fasted state motility determined the gastric emptying time (GET). Following the diet recommendations of the FDA guidance on food effect studies, the mean GET of the telemetric motility capsule was 15.3 ± 4.7 h. Thus, the high caloric value of the standard breakfast impeded gastric emptying before lunch in 18 out of 19 subjects. During its gastric transit, the capsule was exposed to highly dynamic conditions in terms of pH and pressure, which were mainly dependent on further meal and liquid intake, as well as the intragastric capsule deposition behavior. Maximum pH values in the stomach were measured immediately after capsule intake. The median pH value of the 5 min period after capsule ingestion ranged between pH 3.3 and 5.3. Subsequently, the pH decreased relatively constantly and reached minimum values of pH 0-1 after approximately 4 h. The maximum pressure within the stomach amounted to 293 ± 109 mbar and was clearly higher than the maximum pressure measured at the ileocaecal junction (60 ± 35 mbar). The physiological data on the intraluminal conditions within the fed stomach generated in this study will hopefully contribute to a better understanding of food effects on oral drug product performance.
Clinical pharmacology and therapeutics, 2013
Szmulewitz and Ratain expressed concerns in their article "Playing Russian Roulette With Tyr... more Szmulewitz and Ratain expressed concerns in their article "Playing Russian Roulette With Tyrosine Kinase Inhibitors," published in the March 2013 issue. This Commentary is intended to add emphasis to the concerns they raised as well as to draw the attention of the clinical pharmacology community to additional critical issues related to oral administration of modern anticancer medication.
Die Pharmazie, 2013
For estradiol (E2) the separation of the degradation products delta6- and delta9,11-E2 is especia... more For estradiol (E2) the separation of the degradation products delta6- and delta9,11-E2 is especially challenging due to their structural similarity. There is no method described in the literature yet which adequately addresses this problem. The present study describes a HPLC method for the separation and quantitation of E2 and its degradation products 6alpha-hydroxy-E2, 6beta-hydroxy-E2, 6-keto-E2, delta9,11-E2, beta-equilenol and delta6-E2. The method employs a Kinetex PFP analytical column, using methanol and deionized water as mobile phases. Different UV- and fluorescence detection modes were used for maximal sensitivity and specificity. The applicability and capability of the method was demonstrated for Vagifem tablets. Finally, the method was validated with respect to selectivity, sensitivity, linearity, precision and accuracy.
Biomedizinische Technik. Biomedical engineering, 1990
marker monitoring allows to characterize effects of exogenous factors
European Journal of Pharmaceutics and Biopharmaceutics, 2015
Lately, drug-coated balloons have been introduced in interventional cardiology as an approach to ... more Lately, drug-coated balloons have been introduced in interventional cardiology as an approach to treat occluded blood vessel. They were developed for the rapid transfer of antiproliferative drugs during the angioplasty procedure in stenosed vessels with the intent to reduce the risk of restenosis. In this study five different paclitaxel (PTX) balloon coatings were tested in vitro in order to examine how solvents and additives influence coating stability and drug transfer rates. PTX-coated balloons were advanced through a guiding catheter and a simulated coronary artery pathway under perfusion and were then inflated in a hydrogel acceptor compartment. The fractions transferred to the gel, remaining on the balloon and the PTX lost in the simulated coronary pathway were then analysed. The results obtained suggest that the solvent used for the coating process strongly influences the surface structure and the stability of the coating. Ethanol/water and acetone based PTX coatings showed the lowest drug transfer rates to the simulated vessel wall (both <1%) due to their high drug losses during the prior passage through the coronary artery model (more than 95%). Balloons coated with PTX from ethyl acetate-solutions showed smaller drug loss (83% ± 9%), but most of the remaining PTX was not transferred (mean balloon residue approximately 15%). Beside the solvent, especially the use of additives seemed to have a great impact on transfer properties. The balloon pre-treatment with a crosslinked polyvinylpyrrolidone (PVP) film was able to increase the PTX transfer rate from less than 1% (without PVP) to approximately 6%. The best results in this study were obtained for balloon coatings with commercially available SeQuentÓ Please balloons containing the contrast agent iopromide. For this formulation drug transfer rates of approximately 17% were determined. Fluorescence microscopic imaging could visualize the particulate transfer of labelled PTX from the balloon surface during dilatation. The findings of this study underline the importance of drug adhesion and coating stability for the efficiency of PTX transfer.
The Journal of Clinical Pharmacology, 2014
During antibiotic treatments, active residuals reaching the colon profoundly affect the bacterial... more During antibiotic treatments, active residuals reaching the colon profoundly affect the bacterial flora resulting in the emergence of resistance. To prevent these effects, we developed an enteric‐coated formulated activated‐charcoal based product, DAV132, meant to deliver its adsorbent to the ileum and neutralize antibiotic residues in the proximal colon. In a randomized, control, crossover study, the plasma pharmacokinetics of the probe drugs amoxicillin (500 mg) absorbed in the proximal intestine, and sulfapyridine (25 mg) metabolized from sulfasalazine in the cecum and rapidly absorbed, were compared after a single administration in 18 healthy subjects who had received DAV132, uncoated formulated activated charcoal (FAC) or water 16 and 8 hours before, concomitantly with the probe drugs, and 8 hours thereafter. The AUC0–96 h of amoxicillin was reduced by more than 70% when it was taken with FAC, but bioequivalent when it was taken with water or DAV132. By contrast, the AUC0–96 h ...
Journal of pharmaceutical sciences, Jan 19, 2014
Gastrointestinal (GI) pH and temperature profiles under fasted-state conditions were investigated... more Gastrointestinal (GI) pH and temperature profiles under fasted-state conditions were investigated in two studies with each 10 healthy human subjects using the IntelliCap(®) system. This telemetric drug delivery device enabled the determination of gastric emptying time, small bowel transit time, and colon arrival time by significant pH and temperature changes. The study results revealed high variability of GI pH and transit times. The gastric transit of IntelliCap(®) was characterized by high fluctuations of the pH with mean values ranging from pH 1.7 to pH 4.7. Gastric emptying was observed after 7-202 min (median: 30 min). During small bowel transit, which had a duration of 67-532 min (median: 247 min), pH values increased slightly from pH 5.9-6.3 in proximal parts to pH 7.4-7.8 in distal parts. Colonic pH conditions were characterized by values fluctuating mainly between pH 5 and pH 8. The pH profiles and transit times described in this work are highly relevant for the comprehensi...
Nanotechnology, 2004
Expression von Cadherinen im sich entwickelnden Cortex cerebri von Maus und Frettchen Forschungst... more Expression von Cadherinen im sich entwickelnden Cortex cerebri von Maus und Frettchen Forschungsthema:
Food Funct., 2014
The paper presents an international consensus for a standardised staticin vitrodigestion method f... more The paper presents an international consensus for a standardised staticin vitrodigestion method for food.
European Journal of Pharmaceutics and Biopharmaceutics, 2008
The prediction of the in vivo drug release characteristics of modified release oral dosage forms ... more The prediction of the in vivo drug release characteristics of modified release oral dosage forms by in vitro dissolution tests is a prerequisite for successful product development. A novel dissolution test apparatus that mimics the physical conditions experienced by an oral formulation during gastrointestinal transit was developed. This included the simulation of pressure forces exerted by gut wall motility, shear forces generated during propagation, and loss of water contact when the dosage form is located in an intestinal air pocket. The new apparatus was evaluated using a diclofenac extended release (ER) tablet. The in vitro dissolution profiles were compared between the novel test apparatus and a conventional dissolution apparatus (USP II). These data were compared with the profiles of plasma concentration versus time that were obtained after the administration of an ER tablet to 24 healthy volunteers under fasting conditions. Multiple peaks were observed in individual plasma concentration-time profiles after the intake of the reference ER tablet. Standard dissolution testing showed typical characteristics of an almost continuous release for this formulation; however, dissolution testing with the novel apparatus suggested that the diclofenac release from the ER tablets would be extremely variable and dependent on the applied stress. The data suggest that the observed multiple peaks of plasma concentration after dosing of the ER diclofenac tablets are most probably caused by sensitivity to physical stress events during gastrointestinal transit.
European Journal of Pharmaceutics and Biopharmaceutics, 2010
To validate Magnetic Moment Imaging (MMI) for the investigation of gastrointestinal transit and d... more To validate Magnetic Moment Imaging (MMI) for the investigation of gastrointestinal transit and disintegration of solid dosage forms and to correlate the MMI findings with the corresponding gamma scintigraphic data. Materials and methods: Three magnetic tablets (MTs) were investigated using in vitro and in vivo tests. The clinical study was a four-way, crossover study with the following arms: (a) immediate-release tablets administered in fasted state; (b) immediate-release tablets administered after 400 mL of Clinutren Ò ISO; (c) enteric-coated tablets administered in the fasted state; and (d) non-disintegrating tablets studied in the lightly fed state (100 mL of Clinutren Ò ISO). Results: In both the in vitro and in vivo studies, tablets were detected successfully by MMI and scintigraphy. There was a good correlation between gastric residence times and positional data (in the x, y and y, z-axes). In addition, MMI revealed early swelling behaviour of the tablet matrix. There was excellent agreement for the disintegration times of MT(A) in the fasted arm (scintigraphy 12.0 ± 4.4 min, MMI 11.8 ± 4.4 min). In the MT(A)-fed arm, onset times determined by scintigraphy were delayed in three subjects when compared to the corresponding MMI results. Delayed disintegration was observed with MT(A) administered after food (p < 0.01) in both the techniques. Conclusion: The MMI device is a reliable imaging tool for tracking the transit and disintegration of a magnetic tablet through the gastrointestinal tract.
European Journal of Pharmaceutical Sciences, 2014
are expected to significantly reduce demand for animal experiments in the future as well as reduc... more are expected to significantly reduce demand for animal experiments in the future as well as reducing the number of human bioequivalence studies required to bridge formulations after manufacturing or composition changes.
Journal of Controlled Release, 2005
Gastrointestinal motility and transport as well as concomitant food intake are factors that are k... more Gastrointestinal motility and transport as well as concomitant food intake are factors that are known to influence pharmacokinetics derived after intake of extended release dosage forms. However, the mechanisms behind these influencing factors are mostly unknown. In this study the gastrointestinal transit and the in vivo drug release of magnetically labelled extended release tablets containing felodipine were monitored together with the drug absorption phase of pharmacokinetics under fasting and fed conditions in six healthy volunteers using Magnetic Marker Monitoring. It was found that the in vivo drug release profiles of the tablets compared well under fasting and fed conditions. However, the plasma concentration profiles were strongly influenced by concomitant food intake. This could be attributed to elongated residence of the tablets in proximal parts of the stomach, resulting in delayed drug absorption and the occurrence of late high plasma peak concentrations. The lag time until the first appearance of felodipine in plasma and the residence time of the tablets in the proximal stomach, were found to be directly correlated. The study shows that increased plasma peak drug concentrations after intake of extended release formulations together with food can be explained by poor mixing in the proximal part of the stomach and are not necessarily due to failure of the formulation to control drug release (dose dumping).
Einleitung: Alpha-Rezeptorenblocker werden bei verschiedenen Indikationen systemisch verordnet un... more Einleitung: Alpha-Rezeptorenblocker werden bei verschiedenen Indikationen systemisch verordnet und können Veränderungen der Iris wie beispielsweise eine reduzierte Mydriasis und erhöhte Mobilität während der Kataraktoperation verursachen. Methodik: Es ist hinlänglich[zum vollständigen Text gelangen Sie über die oben angegebene URL]
Nanoparticulate contrast agents have long been used in diagnostic imaging. In Germany, particulat... more Nanoparticulate contrast agents have long been used in diagnostic imaging. In Germany, particulate contrast agents are currently approved for ultrasound imaging and magnetic resonance imaging. All ultrasound contrast agents are based on gas-filled microbubbles. The best documented application of ultrasound contrast agents in oncology is for diagnosing focal liver lesions. In magnetic resonance imaging, crystalline iron oxides are used as nanoparticulate contrast agents. Their primary application is also the diagnosis of focal liver lesions. Magnetic nanoparticles also have applications in many scientific endeavors as stable labels that can be detected with extremely high sensitivity. Current research approaches deal with extending the use of particulate contrast agents to molecular diagnostics and therapeutic applications.
Die Pharmazie, 2017
Gastroresistant capsules are obtained mostly by using modified-release fill in hard capsules, or ... more Gastroresistant capsules are obtained mostly by using modified-release fill in hard capsules, or by coating the gelatin shell with acid-resistant polymers. Modification of the material used at the stage when the capsule shell is produced would reduce the complexity and cost of introducing new products to the market. Gastroresistant gelatin films were obtained by using commercial cellulose acetate phthalate (aqueous dispersion Aquacoat® CPD). Only films casted from non-alkalized mixtures showed no visible disintegration at pH from 1.2 (simulated gastric fluid) to 4.5 (phosphate buffer). Elasticity of the dry films was comparable with the one determined for non-modified gelatin films, however tear resistance was 2-fold smaller, but still acceptable for practical application.
Науково-теоретичний альманах "Грані", 2017
Розглянуто феномен діяльної любові. Концептуалізовано поняття діяльної любові у філософії В. Соло... more Розглянуто феномен діяльної любові. Концептуалізовано поняття діяльної любові у філософії В. Соловйова, виділені її альтруїстичні прояви і зазначені ключові складники цього поняття. Оцінено вплив поглядів Платона, Р. Декарта, Б. Спінози, І. Канта, Г. Гегеля, Г. Сковороди та П. Юркевича на формування ідей В. Соловйова. Виявлені компаративні зв’язки з ідеями Е. Фромма, К. Льюїса, Х. Ортега-і-Гассета, П. Тілліха, Г. Марселя, П. Брюкнера. Встановлено, що діяльна любов – це моральна любов, яка надихає людину на здійснення добра для іншої людини; вона заснована на повазі до іншої особистості і на визнанні її неповторності та індивідуальності. Діяльна любов тотожна доброму відношенню, проте включає в себе акт дії, який веде до перетворення як окремої людини, так і всього суспільства в цілому. Встановлено дев’ять проявів діяльної любові: великодушність, безкорисливість, щедрість, терпіння, щирість, індивідуальна спрямованість, позачасовість, свобода від зовнішніх перешкод і прагнення до єдн...
Zeitschrift für Gastroenterologie, 2004
Journal of Controlled Release, 2015
The intraluminal conditions of the fed stomach are critical for drug release from solid oral dosa... more The intraluminal conditions of the fed stomach are critical for drug release from solid oral dosage forms and thus, often associated with the occurrence of food effects on oral bioavailability. In this study, intragastric pH and pressure profiles present after the ingestion of the high-caloric, high-fat (964 kcal) FDA standard breakfast were investigated in 19 healthy human subjects by using the telemetric SmartPill® capsule system (26 × 13 mm). Since the gastric emptying of such large non-digestible objects is typically accomplished by the migrating motor complex phase III activity, the time required for recurrence of fasted state motility determined the gastric emptying time (GET). Following the diet recommendations of the FDA guidance on food effect studies, the mean GET of the telemetric motility capsule was 15.3 ± 4.7 h. Thus, the high caloric value of the standard breakfast impeded gastric emptying before lunch in 18 out of 19 subjects. During its gastric transit, the capsule was exposed to highly dynamic conditions in terms of pH and pressure, which were mainly dependent on further meal and liquid intake, as well as the intragastric capsule deposition behavior. Maximum pH values in the stomach were measured immediately after capsule intake. The median pH value of the 5 min period after capsule ingestion ranged between pH 3.3 and 5.3. Subsequently, the pH decreased relatively constantly and reached minimum values of pH 0-1 after approximately 4 h. The maximum pressure within the stomach amounted to 293 ± 109 mbar and was clearly higher than the maximum pressure measured at the ileocaecal junction (60 ± 35 mbar). The physiological data on the intraluminal conditions within the fed stomach generated in this study will hopefully contribute to a better understanding of food effects on oral drug product performance.
Clinical pharmacology and therapeutics, 2013
Szmulewitz and Ratain expressed concerns in their article "Playing Russian Roulette With Tyr... more Szmulewitz and Ratain expressed concerns in their article "Playing Russian Roulette With Tyrosine Kinase Inhibitors," published in the March 2013 issue. This Commentary is intended to add emphasis to the concerns they raised as well as to draw the attention of the clinical pharmacology community to additional critical issues related to oral administration of modern anticancer medication.
Die Pharmazie, 2013
For estradiol (E2) the separation of the degradation products delta6- and delta9,11-E2 is especia... more For estradiol (E2) the separation of the degradation products delta6- and delta9,11-E2 is especially challenging due to their structural similarity. There is no method described in the literature yet which adequately addresses this problem. The present study describes a HPLC method for the separation and quantitation of E2 and its degradation products 6alpha-hydroxy-E2, 6beta-hydroxy-E2, 6-keto-E2, delta9,11-E2, beta-equilenol and delta6-E2. The method employs a Kinetex PFP analytical column, using methanol and deionized water as mobile phases. Different UV- and fluorescence detection modes were used for maximal sensitivity and specificity. The applicability and capability of the method was demonstrated for Vagifem tablets. Finally, the method was validated with respect to selectivity, sensitivity, linearity, precision and accuracy.
Biomedizinische Technik. Biomedical engineering, 1990