Iron-Based Metal-Organic Frameworks as a Theranostic Carrier for Local Tuberculosis Therapy.

PURPOSE: The purpose of the study was initial evaluation of applicability of metal organic framework (MOF) Fe-MIL-101-NH2 as a theranostic carrier of antituberculous drug in terms of its functionality, i.e. drug loading, drug dissolution, magnetic resonance imaging (MRI) contrast and cytotoxic safety. METHODS: Fe-MIL-101-NH2 was characterized using X-ray powder diffraction, FTIR spectrometry and scanning electron microscopy. The particle size analysis was determined using laser diffraction. Magnetic resonance relaxometry and MRI were carried out on phantoms of the MOF system suspended in polymer solution. Drug dissolution studies were conducted using Franz cells. For MOF cytotoxicity, commercially available fibroblasts L929 were cultured in Eagle's Minimum Essential Medium supplemented with 10% fetal bovine serum. RESULTS: MOF particles were loaded with 12% of isoniazid. The particle size (3.37-6.45 µm) depended on the micronization method used. The proposed drug delivery system can also serve as the MRI contrast agent. The drug dissolution showed extended release of isoniazid. MOF particles accumulated in the L929 fibroblast cytoplasmic area, suggesting MOF release the drug inside the cells. The cytotoxicity confirmed safety of MOF system. CONCLUSIONS: The application of MOF for extended release inhalable system proposes the novel strategy for delivery of standard antimycobacterial agents combined with monitoring of their distribution within the lung tissue.

Melts of Octaacetyl Sucrose as Oral-Modified Release Dosage Forms for Delivery of Poorly Soluble Compound in Stable Amorphous Form.

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 standard and biorelevant conditions, were compared to those obtained from commercially available formulations containing nifedipine such as modified release (MR) tablets and osmotic release oral system (OROS). The results indicate that the dissolution profiles of the GSDFs with nifedipine are neither affected by the pH of the dissolution media, type and concentration of surfactants, nor by simulated mechanical stress of biorelevant intensity. Furthermore, it was found that the dissolution profiles of the novel dosage forms were similar to the profiles obtained from the nifedipine OROS. The formulation of GSDFs is relatively simple, and the dosage forms were found to have favorable dissolution characteristics.

The Relationship Between the Evolution of an Internal Structure and Drug Dissolution from Controlled-Release Matrix Tablets.

In the last decade, imaging has been introduced as a supplementary method to the dissolution tests, but a direct relationship of dissolution and imaging data has been almost completely overlooked. The purpose of this study was to assess the feasibility of relating magnetic resonance imaging (MRI) and dissolution data to elucidate dissolution profile features (i.e., kinetics, kinetics changes, and variability). Commercial, hydroxypropylmethyl cellulose-based quetiapine fumarate controlled-release matrix tablets were studied using the following two methods: (i) MRI inside the USP4 apparatus with subsequent machine learning-based image segmentation and (ii) dissolution testing with piecewise dissolution modeling. Obtained data were analyzed together using statistical data processing methods, including multiple linear regression. As a result, in this case, zeroth order release was found to be a consequence of internal structure evolution (interplay between region's areas-e.g., linear relationship between interface and core), which eventually resulted in core disappearance. Dry core disappearance had an impact on (i) changes in dissolution kinetics (from zeroth order to nonlinear) and (ii) an increase in variability of drug dissolution results. It can be concluded that it is feasible to parameterize changes in micro/meso morphology of hydrated, controlled release, swellable matrices using MRI to establish a causal relationship between the changes in morphology and drug dissolution. Presented results open new perspectives in practical application of combined MRI/dissolution to controlled-release drug products.

[Metal-Organic Frameworks: A New Class of Mesoporous Materials and Potential Possibilities of Their Use in Pharmaceutical Technology]. / Sieci metaloorganiczne (MOF) - nowa grupa mezoporowatych polimerów koordynacyjnych i ich potencjalne zastosowanie w technologii postaci leku.

Metal-organic frameworks (MOFs) belong to the new class of mesoporous, hybrid materials composed of metal ions and organic binding ligands. Their unique features: wide range of chemical building components, which enables obtaining biocompatible materials, and high surface area and loading capacity, make them promising drug delivery vehicles for therapeutic agents. The ability to tune their structures and porosities provides better adjustment for adsorbed drug molecule. Moreover, MOFs functionalized with ligands or antibodies can be used in cancer targeted therapy. Through the incorporation of paramagnetic metal ions into the structure, MOFs are suited to serve as magnetic resonance imaging (MRI) contrast agents. Combining drug delivery ability with imaging properties of MOFs indicates their potential use as theranostic agents and makes possible monitoring drug delivery within the body after administration in the real time. The aim of the present study is to characterize a new class of compounds and to present potential possibilities of their use as excipients in pharmaceutical technology .

Magnetic resonance microscopy for assessment of morphological changes in hydrating hydroxypropylmethylcellulose matrix tablets in situ-is it possible to detect phenomena related to drug dissolution within the hydrated matrices?

PURPOSE: So far, the hydrated part of the HPMC matrix has commonly been denoted as a "gel" or "pseudogel" layer. No MRI-based results have been published regarding observation of internal phenomena related to drug dissolution inside swelling polymeric matrices during hydration. The purpose of the study was to detect such phenomena. METHODS: Multiparametric, spatially and temporally resolved T2 MR relaxometry, in situ, was applied to study formation of the hydration progress in HPMC matrix tablets loaded with L-dopa and ketoprofen using a 11.7 T MRI system. Two spin-echo based pulse sequences were used, one of them specifically designed to study short T2 signals. RESULTS: Two components in the T2 decay envelope were estimated and spatial distributions of their parameters, i.e. amplitudes and T2 values, were obtained. Based on the data, different region formation patterns (i.e. multilayer structure) were registered depending on drug presence and solubility. Inside the matrix with incorporated sparingly soluble drug a specific layer formation due to drug dissolution was detected, whereas a matrix with very slightly soluble drug does not form distinct external "gel-like" layer. CONCLUSIONS: We have introduced a new paradigm in the characterization of hydrating matrices using (1)H MRI methods. It reflects molecular mobility and concentration of water inside the hydrated matrix. For the first time, drug dissolution related phenomena, i.e. particular front and region formation, were observed by MRI methods.

3D Printed Drug Delivery Systems in Action-Magnetic Resonance Imaging and Relaxometry for Monitoring Mass Transport Phenomena.

The hypothesis of the study was that (1) 3D printed drug delivery systems (DDS) could be characterized in situ during drug release using NMR/MRI techniques in terms of mass transport phenomena description (interfacial phenomena), particularly for systems dealing with two mobile phases (e.g., water and low molecular weight liquid polymer); (2) consequently, it could be possible to deduce how these interfacial mass transport phenomena influence functional properties of 3D printed DDS. Matrix drug delivery systems, prepared using masked stereolithography (MSLA), containing poly(ethylene glycol) diacrylate (PEGDA) and low molecular weight polyethylene glycol (PEG) with ropinirole hydrochloride (RH) were studied as example formulations. The PEGDA to PEG (mobile phase) concentration ratio influenced drug release. It was reflected in spatiotemporal changes in parametric T2 relaxation time (T2) and amplitude (A) images obtained using magnetic resonance imaging (MRI) and T1-T2 relaxation time correlations obtained using low-field time-domain nuclear magnetic resonance (LF TD NMR) relaxometry during incubation in water. For most of the tested formulations, two signal components related to PEG and water were assessed in the hydrated matrices by MRI relaxometry (parametric T2/A images). The PEG component faded out due to outward PEG diffusion and was gradually replaced by the water component. Both components spatially and temporally changed their parameters, reflecting evolving water-polymer interactions. The study shows that dynamic phenomena related to bidirectional mass transport can be quantified in situ using NMR and MRI techniques to gain insight into drug release mechanisms from 3D printed DDS systems.

Can 3D Printed Tablets Be Bioequivalent and How to Test It: A PBPK Model Based Virtual Bioequivalence Study for Ropinirole Modified Release Tablets.

As the field of personalized dosing develops, the pharmaceutical manufacturing industry needs to offer flexibility in terms of tailoring the drug release and strength to the individual patient's needs. One of the promising tools which have such capacity is 3D printing technology. However, manufacturing small batches of drugs for each patient might lead to huge test burden, including the need to conduct bioequivalence trials of formulations to support the change of equipment or strength. In this paper we demonstrate how to use 3D printing in conjunction with virtual bioequivalence trials based on physiologically based pharmacokinetic (PBPK) modeling. For this purpose, we developed 3D printed ropinirole formulations and tested their bioequivalence with the reference product Polpix. The Simcyp simulator and previously developed ropinirole PBPK model were used for the clinical trial simulations. The Weibull-fitted dissolution profiles of test and reference formulations were used as inputs for the model. The virtual bioequivalence trials were run using parallel design. The study power of 80% was reached using 125 individuals. The study demonstrated how to use PBPK modeling in conjunction with 3D printing to test the virtual bioequivalence of newly developed formulations. This virtual experiment demonstrated the bioequivalence of one of the newly developed formulations with a reference product available on a market.

Development of a Formulation and In Vitro Evaluation of a Pulmonary Drug Delivery System for a Novel Janus Kinase (JAK) Inhibitor, CPL409116.

The pursuit of targeted therapies for cytokine-dependent diseases has led to the discovery of Janus kinase (JAK) inhibitors, a promising class of drugs. Among them, CPL409116, a selective dual JAK and rho-associated protein kinase inhibitor (ROCK), has demonstrated potential for treating conditions such as pulmonary fibrosis exacerbated by the COVID-19 pandemic. This study investigated the feasibility of delivering CPL409116 via inhalation, with the aim of minimizing the systemic adverse effects associated with oral administration. Two micronization methods, jet milling and spray drying, were assessed for CPL409116, with spray drying chosen for its ability to produce an amorphous form of the compound. Moreover, parameters such as the mixing energy, drug load, and force control agent significantly influenced the fine particle fraction (FPF), a critical parameter for pulmonary drug delivery. This study provides insights into optimizing the formulation parameters to enhance the delivery efficiency of CPL409116 to the lungs, offering potential for improved therapeutic outcomes in cytokine-dependent pulmonary diseases.

Spatially resolved polymer mobilization revisited - Three-dimensional, UltraShort Echo Time (3D UTE) magnetic resonance imaging of sodium alginate matrix tablets.

HYPOTHESIS: Three-dimensional 1H UltraShort Echo Time magnetic resonance imaging (1H 3D UTE MRI) of the matrix tablet made of hydrophilic polymer hydrated in heavy water (D2O) will allow investigation of the hydration-induced spatiotemporal evolution of the material originally included in the matrix tablet during manufacturing (i.e., polymer chains and bound water). EXPERIMENTS: The oblong-shaped sodium alginate matrix tablets were used to verify the hypothesis. The matrix was measured before and during hydration in D2O for up to 2 h using the 1H 3D UTE MRI. Five echo times (first at 20 µs) were used, resulting in five three-dimensional images (one image for each echo time). In chosen cross-sections, two parametric images, i.e., amplitude and T2* relaxation time maps, were calculated using "pixel-by-pixel" mono-exponential fitting. FINDINGS: The regions of the alginate matrix with T2* shorter than 600 µs were analyzed before (air-dry matrix) and during hydration (parametric, spatiotemporal analysis). During the study, only hydrogen nuclei (protons) pre-existing in the air-dry sample (polymer and bound water) were monitored because the hydration medium (D2O) was not visible. As a result, it was found that morphological changes in regions having T2* shorter than 300 µs were the effect of fast initial water ingress into the core of the matrix and subsequent polymer mobilization (early hydration providing additional 5% w/w hydration medium content relating to air-dry matrix). In particular, evolving layers in T2* maps were detected, and a fracture network was formed shortly after the matrix immersion in D2O. The current study presented a coherent picture of polymer mobilization accompanied by local polymer density decrease. We concluded, that the T2* mapping using 3D UTE MRI can effectively be applied as a polymer mobilization marker.

Low-field time-domain NMR relaxometry for studying polymer hydration and mobilization in sodium alginate matrix tablets.

Sodium alginate is used in various industries, including food, pharmaceutical, and agriculture. Matrix systems, e.g., tablets, and granules, are macro samples with incorporated active substances. During hydration, they are neither equilibrated nor homogenous. Phenomena occurring during hydration of such systems are complex, determine their functional properties and hence require multimodal analysis. Still, there's a lack of comprehensive view. The study aimed to obtain unique characteristics of the sodium alginate matrix during hydration, particularly considering polymer mobilization phenomena using low-field time-domain NMR relaxometry in H2O and D2O. An increase in total signal during 4 h of hydration in D2O of ca. 30 µV resulted from polymer/water mobilization. Modes in T1-T2 maps and changes in their amplitudes reflected physicochemical state of the polymer/water system: e.g. air-dry polymer mode (T1/T2 ~ 600) and two mobilized polymer/water modes (at T1/T2 ~ 40 and T1/T2 ~ 20). The study describes the approach to evaluating the hydration of the sodium alginate matrix in terms of the temporal evolution of proton pools: those existing in the matrix before hydration and those entering the matrix from the bulk water. It provides data complementary to spatially resolved methods like MRI and microCT.

Optimization of Se- and Zn-Enriched Mycelium of Lentinula edodes (Berk.) Pegler as a Dietary Supplement with Immunostimulatory Activity.

Mycelial cultures of Lentinula edodes, an edible and medicinal mushroom, have been used in our previous research to obtain selenium-containing immunomodulatory preparations. Our current attempts to obtain a new preparation containing both selenium and zinc, two micronutrients necessary for the functioning of the immune system, extended our interest in the simultaneous accumulation of these elements by mycelia growing in media enriched with selenite and zinc(II) ions. Subsequently, we have studied the effects of new L. edodes mycelium water extracts with different concentrations of selenium and zinc on the activation of T cell fraction in human peripheral blood mononuclear cells (PBMCs). Flow cytometry analysis was used to measure the expression of activation markers on human CD4+ and CD8+ T cells stimulated by anti-CD3 and anti-CD3/CD28 antibodies (Abs). It was demonstrated that statistically significant changes were observed for PD-1 and CD25 antigens on CD8+ T cells. The selenium and zinc content in the examined preparations modified the immunomodulatory activity of mycelial polysaccharides; however, the mechanisms of action of various active ingredients in the mycelial extracts seem to be different.

Magnetic resonance microscopy for assessment of morphological changes in hydrating hydroxypropylmethyl cellulose matrix tablets in situ.

PURPOSE: To resolve contradictions found in morphology of hydrating hydroxypropylmethyl cellulose (HPMC) matrix as studied using Magnetic Resonance Imaging (MRI) techniques. Until now, two approaches were used in the literature: either two or three regions that differ in physicochemical properties were identified. METHODS: Multiparametric, spatially and temporally resolved T(2) MR relaxometry in situ was applied to study the hydration progress in HPMC matrix tablets using a 11.7 T MRI system. Two spin-echo based pulse sequences-one of them designed to specifically study short T(2) signals-were used. RESULTS: Two components in the T(2) decay envelope were estimated and spatial distributions of their parameters, i.e. amplitudes and T(2) values, were obtained. Based on the data, five different regions and their temporal evolution were identified: dry glassy, hydrated solid like, two interface layers and gel layer. The regions were found to be separated by four evolving fronts identified as penetration, full hydration, total gelification and apparent erosion. CONCLUSIONS: The MRI results showed morphological details of the hydrating HPMC matrices matching compound theoretical models. The proposed method will allow for adequate evaluation of controlled release polymeric matrix systems loaded with drug substances of different solubility.

The role-playing game to increase students' activity and engagement in the teaching process - A pilot study of research & development campaign.

BACKGROUND AND PURPOSE: The purpose of the study was to develop and test a simple role-playing game (RPG) dedicated to the generic drug product research and development (R&D) process and evaluate the level of acceptance of this teaching method among pharmacy students. EDUCATIONAL ACTIVITY AND SETTING: Students were divided into small groups and participated in the RPG adventures, which led to descriptive characteristics of the development process of the fictional drug product. The depiction of the process in the adventure considered the milestones and obligatory actions to achieve the R&D goal. FINDINGS: The voluntary survey was completed by 59% (n = 72) of participants. Over 90% of the respondents stated that the game helped them better understand generic drug development. The RPG application allowed a narrative description of the process with the possibility of students' involvement in drug development that mixed regulatory, analytical, and technological issues. SUMMARY: The application of the RPG allowed the creation of a narrative description of the process with the possibility of involving students in complicated problematics concerning drug development that mixed regulatory, analytical, and technological aspects of this process.

Quality Control Dissolution Data Is Biopredictive for a Modified Release Ropinirole Formulation: Virtual Experiment with the Use of Re-Developed and Verified PBPK Model.

Physiologically based pharmacokinetic and absorption modeling are being used by industry and regulatory bodies to address various scientifically challenging questions. While there is high confidence in the prediction of exposure for the BCS class I drugs administered as immediate-release formulations, in the case of prolonged-release formulations, special attention should be given to the input dissolution data. Our goal was to develop and verify a PBPK model for a BCS class I compound, ropinirole, and check the biopredictiveness of the dissolution data for the prolonged-release formulation administered by Parkinson's patients. The model was built based on quality control dissolution data reported in the certificates of analysis and verified with the use of data derived from five clinical trial reports. The simulated pharmacokinetic parameters being within a two-fold range of the observed values confirmed acceptable model performance, in vivo relevance of the in vitro dissolution profiles, and indirectly indicated ropinirole stable release from the formulation in the patients' gastro-intestinal tract. Ropinirole PBPK model will be used for exploring potential clinical scenarios while developing a new formulation.

Development of Composite, Reinforced, Highly Drug-Loaded Pharmaceutical Printlets Manufactured by Selective Laser Sintering-In Search of Relevant Excipients for Pharmaceutical 3D Printing.

3D printing by selective laser sintering (SLS) of high-dose drug delivery systems using pure brittle crystalline active pharmaceutical ingredients (API) is possible but impractical. Currently used pharmaceutical grade excipients, including polymers, are primarily designed for powder compression, ensuring good mechanical properties. Using these excipients for SLS usually leads to poor mechanical properties of printed tablets (printlets). Composite printlets consisting of sintered carbon-stained polyamide (PA12) and metronidazole (Met) were manufactured by SLS to overcome the issue. The printlets were characterized using DSC and IR spectroscopy together with an assessment of mechanical properties. Functional properties of the printlets, i.e., drug release in USP3 and USP4 apparatus together with flotation assessment, were evaluated. The printlets contained 80 to 90% of Met (therapeutic dose ca. 600 mg), had hardness above 40 N (comparable with compressed tablets) and were of good quality with internal porous structure, which assured flotation. The thermal stability of the composite material and the identity of its constituents were confirmed. Elastic PA12 mesh maintained the shape and structure of the printlets during drug dissolution and flotation. Laser speed and the addition of an osmotic agent in low content influenced drug release virtually not changing composition of the printlet; time to release 80% of Met varied from 0.5 to 5 h. Composite printlets consisting of elastic insoluble PA12 mesh filled with high content of crystalline Met were manufactured by 3D SLS printing. Dissolution modification by the addition of an osmotic agent was demonstrated. The study shows the need to define the requirements for excipients dedicated to 3D printing and to search for appropriate materials for this purpose.

Magnetic resonance imaging and image analysis for assessment of HPMC matrix tablets structural evolution in USP Apparatus 4.

PURPOSE: The purpose of the study was to present a methodology for the processing of Magnetic Resonance Imaging (MRI) data for the quantification of the dosage form matrix evolution during drug dissolution. The results of the study were verified by comparison with other approaches presented in literature. METHODS: A commercially available, HPMC-based quetiapine fumarate tablet was studied with a 4.7T MR system. Imaging was performed inside an MRI probe-head coupled with a flow-through cell for 12 h in circulating water. The images were segmented into three regions using threshold-based segmentation algorithms due to trimodal structure of the image intensity histograms. RESULTS: Temporal evolution of dry glassy, swollen glassy and gel regions was monitored. The characteristic features were observed: initial high expansion rate of the swollen glassy and gel layers due to initial water uptake, dry glassy core disappearance and maximum area of swollen glassy region at 4 h, and subsequent gel layer thickness increase at the expense of swollen glassy layer. CONCLUSIONS: The temporal evolution of an HPMC-based tablet by means of noninvasive MRI integrated with USP Apparatus 4 was found to be consistent with both the theoretical model based on polymer disentanglement concentration and experimental VIS/FTIR studies.

Efficacy and Safety of Different Formulations of Calcipotriol/Betamethasone Dipropionate in Psoriasis: Gel, Foam, and Ointment.

Preparations containing calcipotriol combined with betamethasone dipropionate (in the forms of ointment, gel, and foam) are available for the topical treatment of psoriasis. This review summarizes the differences in the efficacy and safety of these formulations, as well as the preferences of patients with various forms of psoriasis (plaque, scalp, and nail psoriasis). It has been documented that foams provide higher bioavailability, resulting in increased efficacy in plaque psoriasis compared to ointments and gels. Gels or foams are preferred by patients for their different practical qualities (e.g., gels for "easy application", and foams for "immediate relief"). The available data indicate that ointments may be the most effective formulation in nail psoriasis, and gels are preferred by patients with scalp psoriasis because of their cosmetic features. Treatment with a foam formulation is associated with a lower number of medical appointments compared to treatment with an ointment and with a lower probability of developing indications for systemic treatment. The safety profiles of foams, ointments, and gels are comparable, with the most common adverse effect being pruritus at the application site (in 5.8% of the patients). A long-term proactive maintenance therapy markedly reduces the number of relapses and is likely to close the gap between topical and systemic treatment in psoriasis.

Hydration Patterns in Sodium Alginate Polymeric Matrix Tablets-The Result of Drug Substance Incorporation.

The purpose was to show, using destructive/nondestructive methods, that the interplay between water, tablet structure, and composition determine the unique spatiotemporal hydration pattern of polymer-based matrices. The tablets containing a 1:1 w/w mixture of sodium alginate with salicylic acid (ALG/SA) or sodium salicylate (ALG/SNA) were studied using Karl Fischer titration, differential scanning calorimetry, X-ray microtomography, and magnetic resonance imaging. As the principal results, matrix specific features were detected, e.g., "locking" of the internal part of the matrix (ALG/SA); existence of lamellar region associated with detection of free/freezing water (ALG/SA); existence of water penetrating the matrix forming specific region preceding infiltration layer (ALG/SNA); switch in the onset temperature of endothermic water peak associated with an increase in the fraction of non-freezing water weight per dry matrix weight in the infiltration layer (ALG/SNA). The existence of complicated spatiotemporal hydration patterns influenced by matrix composition and molecular properties of constituents has been demonstrated.

Spatiotemporal Analysis of Hydration Mechanism in Sodium Alginate Matrix Tablets.

Methods of spatiotemporal characterization of nonequilibrated polymer based matrices are still immature and imperfect. The purpose of the study was to develop the methodology for the spatiotemporal characterization of water transport and properties in alginate tablets under hydration. The regions of low water content were spatially and temporally sampled using Karl Fisher and Differential Scanning Callorimetry (spatial distribution of freezing/nonfreezing water) with spatial resolution of 1 mm. In the regions of high water content, where sampling was infeasible due to gel/sol consistency, magnetic resonance imaging (MRI) enabled characterization with an order of magnitude higher spatial resolution. The minimally hydrated layer (MHL), infiltration layer (IL) and fully hydrated layer (FHL) were identified in the unilaterally hydrated matrices. The MHL gained water from the first hour of incubation (5-10% w/w) and at 4 h total water content was 29-39% with nonfreezing pool of 28-29%. The water content in the IL was 45-47% and at 4 h it reached ~50% with the nonfreezing pool of 28% and T2 relaxation time < 10 ms. The FHL consisted of gel and sol layer with water content of 85-86% with a nonfreezing pool of 11% at 4 h and T2 in the range 20-200 ms. Hybrid destructive/nondestructive analysis of alginate matrices under hydration was proposed. It allowed assessing the temporal changes of water distribution, its mobility and interaction with matrices in identified layers.

Novel application of MRI technique combined with flow-through cell dissolution apparatus as supportive discriminatory test for evaluation of controlled release formulations.

Dissolution studies cannot distinguish phenomena occurring inside the dosage forms when studying formulation with similar dissolution profiles-such formulations can behave differently when considering their physical changes. The application of flow-through dissolution apparatus integrated with magnetic resonance imaging (MRI) system for discriminative evaluation of controlled release dosage forms with similar dissolution profiles was presented. Hydrodynamically balanced systems (HBS) containing L: -dopa and various grades hydroxypropyl methylcelluloses were prepared. The dissolution studies of L: -dopa were performed at high field (4.7 T) MR system with MR-compatible flow-through cell. MRI was done with 0.14 x 0.14 x 1-mm spatial resolution and temporal resolution of 10 min to record changes of HBS parameters during dissolution in 0.1 M HCl. Structural and geometrical changes were evaluated using the following parameters: total area of HBS cross-section, its Feret's diameter, perimeter and circularity, area of hydrogel layer, and "dry core" area. While the dissolution profiles of L: -dopa were similar, the image analysis revealed differences in the structural and geometrical changes of the HBS. The mechanism of drug release from polymeric matrices is a result of synergy of several different phenomena occurring during dissolution and may differ between formulations, yet giving similar dissolution profiles. A multivariate analysis was performed to create a model taking into account dissolution data, data from MRI, information about chemical structure, and polymer viscosity. It provided a single model for all the formulations which was confirmed to be competent. The presented method has merit as a potential Process Analytical Technology tool.