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August 2005 - October 2011
Publications
Publications (73)
Background/Objectives: The aim of the present study was to develop lactose-free formulations of rivaroxaban, a novel oral anticoagulant used for the treatment and prevention of blood clotting. As a BCS Class II drug, rivaroxaban is characterized by poor solubility in aqueous media, posing a significant formulation challenge. Methods: To address thi...
In vivo studies of formulation performance with in vitro and/or in silico simulations are often limited by significant gaps in our knowledge of the interaction between administered dosage forms and the human gastrointestinal tract. This work presents a novel approach for the investigation of gastric motility influence on dosage form performance, by...
Tableting of biomolecules is a challenging formulation phase due to their sensitivity to various process parameters, such as compression pressure, process dynamics, or the temperature generated. In the present study, pancreatin was employed as a model enzyme mixture, which was formulated in tablet form utilizing the synergistic effects of brittle a...
Gastric mechanical stress often impacts drug dissolution from solid oral dosage forms, but in vitro experiments cannot recreate the substantial variability of gastric motility in a reasonable time. This study, for the first time, combines a novel dissolution apparatus with the design of experiments (DoE) and machine learning (ML) to overcome this o...
Biorelevant dissolution tests of oral solid dosage forms open the gate to valid in vitro-in vivo predictions (IVIVP). A recently developed apparatus, PhysioCell, allows mimicking the fluid flow and pressure waves occurring in the human fasted stomach. In this work, we used the PhysioCell to perform IVIVP for vortioxetine immediate-release (IR) tabl...
Virtual bioequivalence trial (VBE) simulations based on (semi)mechanistic in vitro-in vivo (IVIV) modeling have gained a huge interest in the pharmaceutical industry. Sophisticated commercially available software allows modeling variable drug fates in the gastrointestinal tract (GIT). Surprisingly, the between-subject and inter-occasion variability...
The physiologically relevant dissolution apparatuses simulate various aspects of gastrointestinal physiology and help to understand and predict the in vivo behavior of an oral dosage form. In this paper, we present and characterize for the first time a novel bio-relevant dissolution apparatus — PhysioCell®;. We evaluated the impact of several facto...
Sprinkle formulations represent an interesting concept of medicinal products aimed at the steadily growing population of patients suffering from swallowing difficulties (dysphagia). In the present work, immediate-release sprinkle MUPS (multiple-unit pellet system) containing rosuvastatin calcium as a model drug substance was successfully developed....
Poor water dissolution of active pharmaceutical ingredients (API) limits the rate of absorption from the gastrointestinal tract. Increasing the pH of a solid form microenvironment can enhance the dissolution of weakly acidic drugs, but data on this phenomenon in a physiologically relevant bicarbonate media are lacking. In this paper, we examined th...
Reliable and stable tablet formulations for rosuvastatin calcium in four strengths: 5 mg, 10 mg, 20 mg and 40 mg have been developed. Rosuvastatin is a cholesterol-lowering statin drug and is known to be unstable during storage. The possibility of its stabilization with inorganic salts of multivalent metals has already been reported in the literatu...
The bioavailability of orally administered bisphosphonates is very low (< 1%) due to their short absorption window in the proximal duodenum and high affinity for food. Food ingredients are able to bind the drug, but the presence of food extends the residence time of bisphosphonates in the absorption window. Therefore, the main goal of this study is...
This collection of contributions from the European Network on Understanding Gastrointestinal Absorption-related Processes (UNGAP) community assembly aims to provide information on some of the current and newer methods employed to study the behaviour of medicines. It is the product of interactions in the immediate pre-Covid period when UNGAP members...
Novel calcium phosphate-based starter pellets were used to develop a biphasic-release multiple-unit pellet system (MUPS) with diclofenac sodium as a model drug in the form of hard gelatin capsules. For comparative purposes, corresponding formulations based on the inert cores made of microcrystalline cellulose, sucrose and isomalt were prepared. The...
Sustained-release (SR) formulations may appear advantageous in first-in-human (FIH) study of innovative medicines. The newly developed SR matrix tablets require prolonged maintenance of API concentration in plasma and should be reliably assessed for the risk of uncontrolled release of the drug. In the present study, we describe the development of a...
ELISA has become a standard analytical tool in the numerous branches of science and industry. Processing of the ELISA results may be a multistep process, often requiring a prior adaptation, using proprietary software, or exporting the results into external internet platforms. It may be problematic in the light of good documentation practices and ma...
Diclofenac sodium was used as a model drug for preparation of delayed-release (DR) multiparticulates, which were further processed into solid oral dosage forms such as capsules and tablets. Multiple unit pellets systems (MUPS) were prepared from different types of starter pellets (inert cores) including microcrystalline cellulose pellets, sugar sph...
Development of generic extended-release (ER) formulations is challenging. Especially under fed conditions, the risk of failure in bioequivalence trials is high because of long gastric residence times and susceptibility to food effects. We describe the development of a generic trazodone ER formulation that was aided with a biorelevant dissolution ev...
The first and an essential step of medication’s path inside the human body is a dissolution of an active pharmaceutical ingridient. A dissolution of oral dosage forms occurs as a result of physicochemical and mechanical stresses which are found in gastrointestinal tract. This results in dissolution of the API, which becomes ready for the next step...
In this work, we developed a fast, highly efficient, and environmentally friendly catalytic system for classical free-radical polymerization (FRP) utilizing a high-pressure (HP) approach. The application of HP for thermally-induced, bulk FRP of 1-vinyl-2-pyrrolidone (VP) allowed to eliminate the current limitation of ambient-pressure polymerization...
Niacin (nicotinic acid, NA) is administered orally as an antihyperlipidemic agent in extended-release (ER) tablets in high doses. Due to rapid absorption and extensive metabolism (non-linear pharmacokinetics), the drug plasma levels are highly variable, which may correlate with side effects. Interestingly, this erratic drug delivery behavior of nia...
Open Research Biopharmaceutical Internships Support (ORBIS) is an international, Horizon 2020 project funded by Maria Skłodowska-Curie Actions, Research and Innovation Staff Exchange (RISE) programme. Six academic institutions and four pharmaceutical companies from seven countries cooperate with the aim to improve the preclinical pathway of medicin...
In this paper, we studied the impact of saccharides having a similar backbone but differing in the degree of freedom, local molecular mobility, flexibility of the ring and intermolecular interactions on the glass-forming ability (GFA) of naproxen (NAP) in binary mixtures. For this purpose, a series of methyl and acetyl derivatives of glucose (GLS)...
The subject of the invention is a method of pressure polymerization of 1-vinyl-2-pyrrolidone (VP), enabling the production of chemically pure poly(1-vinyl-2-pyrrolidone) PVP, consisting in the monomer in the form of 1-vinyl-2-pyrrolidone (VP ) with a purity preferably above 99%, is mixed with a thermoinitiator in the form of azobis(isobutyronitrile...
In this paper, comprehensive calorimetric, structural, inter- and intramolecular dynamics measurements with the use of Differential Scanning Calorimetry (DSC), X-ray diffraction (XRD), Broadband Dielectric and Fourier Transform Infrared (FTIR) spectroscopies have been applied to investigate properties of itraconazole (ITZ) glasses obtained via slow...
The advantages of local therapy for the treatment of inflammatory bowel disease (IBD) are generally accepted. However, the effectiveness of such treatment is often limited due to insufficient targeting of the inflammatory lesions using classical modified release (MR) formulations. The exisiting MR products cannot always provide the therapeutically...
Immediate release, compositionally proportional formulations of acyclovir comprising porous tribasic calcium phosphate were developed and compared with commercial tablets. Comparison of the dissolution behavior was carried out using a compendial method, as well as with the help of a biorelevant dissolution stress test device, which simulates physio...
Liquid crystalline (LC) materials and their non-medical applications have been known for decades, especially in the production of displays, however the pharmaceutical implications of the LC state are inadequately appreciated and experimental data misunderstood leading to possible errors, especially in relation to physical stability of medicines. Th...
The ORBIS project (Open Research Biopharmaceutical Internships Support) is dedicated to pharmaceutical development studies and is based on staff exchange. The lead institution on this project is Poznań University of Medical Sciences (PUMS) with Prof. Janina Lulek the grant coordinator. The ORBIS consortium comprises academic institutions and pharma...
Grapefruit juice (GFJ) is known to affect the bioavailability of drugs in different ways. Despite the influence on gastrointestinal enzymes and transporters, the influence on gastrointestinal fluid kinetics is regarded to be relevant for the absorption of several drugs. Thus, it was the aim of this pilot study to investigate the gastric and intesti...
The presented work describes the formulation and characterization of modified release glassy solid dosage forms (GSDFs) containing an amorphous nifedipine, as a model BCS (Biopharmaceutical Classification System) class II drug. The GSDFs were prepared by melting nifedipine together with octaacetyl sucrose. Dissolution profiles, measured under stand...
The development of gastroretentive dosage forms can be significantly enhanced by the reliable estimation of gastroretentive properties in vitro. In this context, it is mandatory to consider the propulsive contraction waves that occur in the antral region of the stomach, since they are regarded as the major physiological hurdle to overcome. Therefor...
The objective of this study was to investigate the suitability of "Eudragit® RL/Eudragit® L55" (RL/L55) blend coatings for a pH-independent release of acidic drugs. A coating for ketoprofen and naproxen mini tablets was developed showing constant drug release rate under pharmacopeial two-stage test conditions for at least 300min. To simulate drug r...
Objectives
For the treatment of inflammatory bowel disease, the development of pH responsive modified release dosage forms is one of the most common approaches to achieve targeted drug delivery. In this study, the dissolution behaviour of eight different modified release (MR) products containing 800 mg mesalazine was investigated.Methods
The perfor...
This work aims at increasing solubility and dissolution rate of ziprasidone free base-Biopharmaceutics Classifaction System (BCS) class II compound. The authors describe a practical approach to amorphization and highlight problems that may occur during the development of formulations containing amorphous ziprasidone, which was obtained by grinding...
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...
Different experimental and theoretical techniques were applied to investigate basic physical properties of very stable and homogeneous solid dispersions formed by itraconazole and octaacetylmaltose. Differential scanning calorimetry as well as semi-empirical calculations have indicated that liquid crystalline ordering in itraconazole was completely...
The aim of the present study was to develop film-coated tablets which release a minor amount of the active pharmaceutical ingredient (API) into the stomach and small intestine, yet show a sharp increase of drug release in the colon. Tablets containing the model drug Diclofenac-Na, microcrystalline cellulose as a filler (MT), as well as tablets cons...
Gastroretentive drug delivery systems are retained in the stomach for a sufficient time interval, releasing the drug in a controlled manner. According to literature, the floating principle is the most frequently used formulation approach for gastric retention. However, many publications lack information of the floating forces, the impact of differe...
The aim of this magnetic resonance imaging (MRI) study was to investigate gastric emptying after intake of a high-caloric and high-fat standard meal as recommended by FDA and EMA for food-effect bioavailability and fed bioequivalence studies. 12 healthy human subjects (7 male, 5 female) received the standard meal after an overnight fast. MRI was pe...
Pressure-sensitive dosage forms have been developed that are intended for pulsatile delivery of drugs to the proximal small intestine. The novel dosage forms are composed of insoluble shell and either a hard fat W32 or polyethylene glycol (PEG) 1000 core that are both liquidizing at body temperature. The release is triggered by predominant pressure...
The purpose of this work was to develop a new pressure-sensitive dosage form that breaks and releases its content in a fasted stomach at the predominant pressure at the pylorus. The content of the dosage form should be liquid so that the active pharmaceutical ingredient quickly reaches maximum absorption in the upper small intestine. For this purpo...
The aim of the present work was the investigation of robustness and reliability of drug release from 50 to 400 mg quetiapine extended release HPMC matrix tablets towards mechanical stresses of biorelevant intensity. The tests were performed under standard conditions (USP apparatus II) as well as under simulated gastrointestinal stress conditions. M...
Comprehensive molecular dynamics studies of vitrified and cryogrounded itraconazole (Itr) were performed at ambient and elevated pressure. DSC measurements yielded besides melting and glass transition observed during heating and cooling of both samples two further endothermic events at around T = 363 K and T = 346 K. The nature of these transitions...
The hydrogen carbonate buffer is considered as the most biorelevant buffer system for the simulation of intestinal conditions and covers the physiological pH range of the luminal fluids from pH 5.5 to about pH 8.4. The pH value of a hydrogen carbonate buffer is the result of a complex and dynamic interplay of the concentration of hydrogen carbonate...
A novel bio-relevant in vitro dissolution device was designed to mimic intragastric conditions after food intake paying particular consideration to mechanical aspects. the Fed Stomach Model (FSM). The FSM represents a fully computer-controlled dynamic flow-through system, in which dosage forms are hosted in so-called gastric vessels. Dosage form mo...
This paper presents comprehensive studies on the molecular dynamics of pharmaceutically important substance, posaconazole. In order to characterize relaxation dynamics in the supercooled liquid and glassy states of posaconazole dielectric and mechanical spectroscopies were applied. Dielectric data have indicated multiple relaxation process that app...
Current compendial dissolution and disintegrating testing is unable to mimic physiological conditions affecting gastric drug release from immediate release dosage forms. In order to obtain more realistic data, a novel test setup was developed that we term a 'dynamic open flow through test apparatus'. It is based on the previously described dissolut...
Intragastric drug release from solid oral dosage forms can be affected by altered physicochemical and mechanical conditions in the upper gastrointestinal (GI) tract. Food effects may lead to changes of one or more pharmacokinetic parameters and, hence, influence drug plasma levels. This can result in severe consequences such as adverse drug reactio...
Food effects on drug release and absorption from solid oral dosage forms are a common biopharmaceutical problem. The fed state is characterized by different motility and secretory activity of the complete gastrointestinal (GI) tract compared to fasting conditions. Due to long gastric transit times, the postprandial stomach plays an essential role f...
The bicarbonate buffer is considered as the most biorelevant buffer system for the simulation of intestinal conditions. However, its use in dissolution testing of solid oral dosage forms is very limited. The reason for this is the thermodynamic instability of the solution containing hydrogen carbonate ions and carbonic acid. The spontaneous loss of...
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 reflect...
The in-vivo performance of oral modified-release dosage forms is determined by the interplay of various physiological- and dosage-form-derived parameters. Thus it is often a challenge to predict the in-vivo drug-release behaviour from modified-release dosage forms based solely on in-vitro release rates.
For a long time the most common procedure to...
A novel liquefied gas based drug delivery system for the oral delivery of liquid and semi-solid drug formulations is presented. The capsule-shaped system is equipped with a capillary as an element controlling the release rate. The delivery mechanism is based on a constant vapor pressure produced by isopentane as a low-boiling liquefied gas. The liq...
A novel oral drug delivery system for the controlled release of liquid drugs, drug solutions, and semisolid drug preparations is presented that is utilizing the constant vapor pressure of liquefied gas. The system is equipped with a capillary as an element determining the drug delivery rate and contains a liquefied propellant with a suitable boilin...
The prediction of the in vivo drug release characteristics of modified release (MR) oral dosage forms by in vitro dissolution tests is a prerequisite for successful product development.
To improve the predictive power of dissolution testing, the authors recently developed a new dissolution test apparatus that simulates physical conditions of the ga...
The goal of the safe and efficient pharmacotherapy can be increasingly achieved by means of dosage forms with desired technological and biopharmaceutical properties · The appliance of dosage forms of selected, modified drug release characteristics enables improvement of the bioavailability of the drug substance by simultaneous reduction of the side...
Dissolution characteristics of four extended release (ER) generic formulations of diclofenac sodium were examined.
The aim of this study was to compare the drug dissolution behavior of diclofenac ER generics to clarify whether the products are characterized by comparable dissolution characteristics under the applied test conditions.
The investigati...
Functional formulations providing protection of nutritional products against gastric juice or a capable of delivering them to distinct areas of the gastrointestinal tract are increasingly utilized by the food industry. However, the application of functional excipients that are established in pharmaceutical applications is limited in case of food pr...
In order to improve the predictability of dissolution testing new apparatuses have been proposed that mimic hydrodynamic and mechanical conditions in the gastrointestinal tract. In this study tested were four different nifedipine extended release (ER) formulations using the paddle apparatus and the reciprocating cylinder as pharmacopoeial test devi...
The aim of our studies was to investigate the dissolution characteristics of six extended-release nifedipine tablets with a dosage strength of 20 mg that are marketed in the European Union. All investigated products were homogenous matrix tablets having identical dosing regimens. The products can be substituted for originator products and other ER...
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 th...
