Spray drying and hot-melt extrusion are among the most prevalent preparation techniques used in the pharmaceutical industry to produce amorphous solid dispersions (ASDs). This study advances previous research by integrating sample production, comprehensive analytical characterization, intrinsic dissolution rate measurements, and assessments of the behavior of ASDs under elevated temperature and humidity conditions. The study focuses on indomethacin, a widely used model for poorly soluble drugs, processed with PVP K30 or HPMC E5, both commonly used polymers. The findings demonstrate that hot-melt extruded samples exhibit superior stability against recrystallization, whereas spray dried samples achieve higher intrinsic dissolution rates. Furthermore, PVP K30 significantly outperforms HPMC E5 in the co-processing of indomethacin, enhancing both the intrinsic dissolution rate and the stability.

• Klíčová slova
• Amorphous solid dispersions, Dissolution, Hot-melt extrusion, Recrystallization, Spray drying, Stability,
• MeSH
• chemie farmaceutická metody   MeSH
• deriváty hypromelózy chemie   MeSH
• indomethacin * chemie   MeSH
• krystalizace * MeSH
• povidon chemie   MeSH
• příprava léků metody   MeSH
• rozpustnost * MeSH
• sprejové sušení * MeSH
• stabilita léku * MeSH
• technologie extruze tavenin * metody   MeSH
• uvolňování léčiv MeSH
• vlhkost MeSH
• vysoká teplota MeSH
• vysoušení metody   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• deriváty hypromelózy MeSH
• indomethacin * MeSH
• povidon MeSH

In recent years, deep eutectic solvents (DESs) with their outstanding solubilization properties have emerged as strong candidates for oral enabling formulations of poorly soluble drugs. This study explores the use of drug-based therapeutic DESs (THEDESs) to solubilize a poorly soluble compound with the aim of providing a fixed-dose combination of two complementary therapeutic agents. Specifically, potential anticancer effects of ibuprofen (IBU) are harnessed in a novel type of THEDES to dissolve higher amounts of abiraterone acetate (AbAc), an antitumor agent. Four IBU-based combinations were studied: 1:4 M ratio with octanoic acid (OctA), 1:5 with nonanoic acid (NonA), 1:3 with decanoic acid (DeA) or 1:2 with dodecanoic acid (DoA). Fatty acids of different chain lengths were analyzed and discussed considering surface charge densities obtained via quantum chemistry. The THEDESs listed could apparently dissolve AbAc amounts up to 1311.0 ± 125.4 mg/g in IBU:OctA THEDES, 1151.7 ± 22.2 mg/g in IBU:NonA, 1160.4 ± 33.5 mg/g in IBU:DeA, and 231.3 ± 10.7 mg/g in IBU:DoA. In vitro dissolution of the simultaneously released drugs reached 37.8 ± 9.0 % to 64.2 ± 1.0 % for IBU and 5.0 ± 3.3 % to 19.4 ± 0.1 % for AbAc. This increased to between 60.4 ± 2.8 % and 79.4 ± 5.0 % of released IBU, and 23.6 ± 1.0 % to 57.3 ± 5.8 % of released AbAc, with 20 % (w/w) Tween 80 added to the formulations. This showed the significant potential of drug-containing THEDESs as solubilizing agents for poorly soluble drugs, in the form of fixed-dose combinations of synergistic APIs.

• Klíčová slova
• Cancer treatment(s), Deep eutectic solvent(s), Enabling formulation(s), Eutectic mixture(s), Novel pharmaceutic(s), Therapeutic deep eutectic solvent(s),
• MeSH
• abirateron * chemie   aplikace a dávkování   MeSH
• antitumorózní látky chemie   aplikace a dávkování   MeSH
• chemie farmaceutická metody   MeSH
• fixní kombinace léků MeSH
• ibuprofen * chemie   aplikace a dávkování   MeSH
• mastné kyseliny chemie   MeSH
• příprava léků metody   MeSH
• rozpouštědla * chemie   MeSH
• rozpustnost * MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• abirateron * MeSH
• antitumorózní látky MeSH
• fixní kombinace léků MeSH
• ibuprofen * MeSH
• mastné kyseliny MeSH
• rozpouštědla * MeSH

Transforming poorly soluble active pharmaceutical ingredients (APIs) into a nanoparticulate form is a proven way of improving their dissolution characteristics. The preparation of API nanosuspensions is commonly achieved by wet-stirred media milling. The challenge lies in converting the nanosuspension into a solid dosage form without compromising its re-dispersibility. In the present work, an API nanosuspension was combined with additional excipients and used as abinder in fluid-bed granulation to obtain granules with systematically varying dissolution properties. Specifically, polymeric excipients (hydroxypropyl methylcellulose grade E5 and polyvinylpyrrolidone grade K30) were used in the nanosuspension binder to granulate microcrystalline cellulose or Pearlitol CR-H substrate. The resulting granules were used as feed material to prepare minitablets whose combination enabled the formation of multi-unit dosage form (MUDF) capsules with tuneable drug release profiles, paving the way to rational design and manufacturing of precision medicines.

• Klíčová slova
• Dissolution, Fluid-bed granulation, Minitablets, Nanosuspension, Precision medicine,
• MeSH
• celulosa chemie   MeSH
• chemie farmaceutická metody   MeSH
• deriváty hypromelózy * chemie   MeSH
• nanočástice * chemie   MeSH
• pomocné látky * chemie   MeSH
• povidon * chemie   MeSH
• příprava léků * metody   MeSH
• rozpustnost * MeSH
• suspenze * MeSH
• tablety MeSH
• uvolňování léčiv * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• celulosa MeSH
• deriváty hypromelózy * MeSH
• microcrystalline cellulose MeSH Prohlížeč
• pomocné látky * MeSH
• povidon * MeSH
• suspenze * MeSH
• tablety MeSH

The development of stimuli-responsive drug delivery systems enables targeted delivery and environment-controlled drug release, thereby minimizing off-target effects and systemic toxicity. We prepared and studied tailor-made dual-responsive systems (thermo- and pH-) based on synthetic diblock copolymers consisting of a fully hydrophilic block of poly[N-(1,3-dihydroxypropyl)methacrylamide] (poly(DHPMA)) and a thermoresponsive block of poly[N-(2,2-dimethyl-1,3-dioxan-5-yl)methacrylamide] (poly(DHPMA-acetal)) as drug delivery and smart stimuli-responsive materials. The copolymers were designed for eventual medical application to be fully soluble in aqueous solutions at 25 °C. However, they form well-defined nanoparticles with hydrodynamic diameters of 50-800 nm when heated above the transition temperature of 27-31 °C. This temperature range is carefully tailored to align with the human body's physiological conditions. The formation of the nanoparticles and their subsequent decomposition was studied using dynamic light scattering (DLS), transmission electron microscopy (TEM), isothermal titration calorimetry (ITC), and nuclear magnetic resonance (NMR). 1H NMR studies confirmed that after approximately 20 h of incubation at pH 5, which closely mimics tumor microenvironment, approximately 40% of the acetal groups were hydrolyzed, and the thermoresponsive behavior of the copolymers was lost. This smart polymer response led to disintegration of the supramolecular structures, possibly releasing the therapeutic cargo. By tuning the transition temperature to the values relevant for medical applications, we ensure precise and effective drug release. In addition, our systems did not exhibit any cytotoxicity against any of the three cell lines. Our findings underscore the immense potential of these nanoparticles as eventual advanced drug delivery systems, especially for cancer therapy.

• Klíčová slova
• RAFT polymerization, drug delivery systems, pH-sensitive polymers, self-assembling block copolymers, thermoresponsive polymers,
• MeSH
• antitumorózní látky chemie   farmakologie   chemická syntéza   aplikace a dávkování   MeSH
• biokompatibilní materiály chemie   farmakologie   chemická syntéza   MeSH
• doxorubicin chemie   farmakologie   MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• molekulární struktura MeSH
• nanočástice * chemie   MeSH
• nosiče léků chemie   MeSH
• polymery * chemie   chemická syntéza   farmakologie   MeSH
• systémy cílené aplikace léků MeSH
• teplota * MeSH
• testování materiálů * MeSH
• uvolňování léčiv MeSH
• velikost částic * MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antitumorózní látky MeSH
• biokompatibilní materiály MeSH
• doxorubicin MeSH
• nosiče léků MeSH
• polymery * MeSH

OBJECTIVE: This research aims to design and evaluate an enteric-coated hard capsule dosage form for targeted delivery of biological materials, such as FMT (fecal microbiota transplant) or live microbes, to the distal parts of the GIT. The capsules are designed to be internally protected against destruction by hydrophilic filling during passage through the digestive tract. METHODS: Hard gelatin capsules and DRcapsTMcapsules based on HPMC and gellan were used to encapsulate a hydrophilic body temperature-liquefying gelatin hydrogel with caffeine or insoluble iron oxide mixture. Different combinations of polymers were tested for the internal (ethylcellulose, Eudragit® E, and polyvinyl acetate) and external (Eudragit® S, Acryl-EZE®, and cellacefate) coating. The external protects against the acidic gastric environment, while the internal protects against the liquid hydrophilic filling during passage. Coated capsules were evaluated using standard disintegration and modified dissolution methods for delayed-release dosage forms. RESULTS: Combining suitable internal (ethylcellulose 1.0 %) and external (Eudragit® S 20.0 %) coating of DRcapsTM capsules with the wiping and immersion method achieved colonic release times. While most coated capsules met the pharmaceutical requirements for delayed release, one combination stood out. Colonic times were indicated by the dissolution of soluble caffeine (during 120-720 min) measured by the dissolution method, and capsule rupture was indicated by the release of insoluble iron oxide (after 480 min) measured by the disintegration method. This promising result demonstrates the composition's suitability and potential to protect the content until it's released, inspiring hope for the future of colon-targeted delivery systems and its potential for the pharmaceutical and biomedical fields. CONCLUSION: Innovative and easy capsule coatings offer significant potential for targeted drugs, especially FMT water suspension, to the GIT, preferably the colon. The administration method is robust and not considerably affected by the quantity of internal or external coatings. It can be performed in regular laboratories without specialized individual and personalized treatment equipment, making it a practical and feasible method for drug delivery.

• Klíčová slova
• Capsules, Coating, Immersion method, Novel approach in delayed-release dosage form with potential benefits for individual treatment, Principal component analysis,
• MeSH
• bakteriální polysacharidy chemie   MeSH
• biokompatibilní materiály chemie   MeSH
• celulosa * chemie   analogy a deriváty   MeSH
• deriváty hypromelózy chemie   MeSH
• hydrofobní a hydrofilní interakce * MeSH
• hydrogely chemie   MeSH
• kofein chemie   aplikace a dávkování   MeSH
• kolon * metabolismus   MeSH
• kyseliny polymethakrylové chemie   MeSH
• léky s prodlouženým účinkem chemie   MeSH
• polymery chemie   MeSH
• polyvinyly chemie   MeSH
• systémy cílené aplikace léků * metody   MeSH
• tobolky * MeSH
• uvolňování léčiv * MeSH
• želatina * chemie   MeSH
• železité sloučeniny chemie   aplikace a dávkování   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bakteriální polysacharidy MeSH
• biokompatibilní materiály MeSH
• celulosa * MeSH
• deriváty hypromelózy MeSH
• ethyl cellulose MeSH Prohlížeč
• ferric oxide MeSH Prohlížeč
• gellan gum MeSH Prohlížeč
• hydrogely MeSH
• kofein MeSH
• kyseliny polymethakrylové MeSH
• léky s prodlouženým účinkem MeSH
• methylmethacrylate-methacrylic acid copolymer MeSH Prohlížeč
• polymery MeSH
• polyvinyl acetate MeSH Prohlížeč
• polyvinyly MeSH
• tobolky * MeSH
• želatina * MeSH
• železité sloučeniny MeSH

The utilization of 3D printing- digital light processing (DLP) technique, for the direct fabrication of microneedles encounters the problem of drug solubility in printing resin, especially if it is predominantly composed of water. The possible solution how to ensure ideal belonging of drug and water-based printing resin is its pre-formulation in nanosuspension such as nanocrystals. This study investigates the feasibility of this approach on a resin containing nanocrystals of imiquimod (IMQ), an active used in (pre)cancerous skin conditions, well known for its problematic solubility and bioavailability. The resin blend of polyethylene glycol diacrylate and N-vinylpyrrolidone, and lithium phenyl-2,4,6-trimethylbenzoylphosphinate as a photoinitiator, was used, mixed with IMQ nanocrystals in water. The final microneedle-patches had 36 cylindrical microneedles arranged in a square grid, measuring approximately 600 μm in height and 500 μm in diameter. They contained 5wt% IMQ, which is equivalent to a commercially available cream. The homogeneity of IMQ distribution in the matrix was higher for nanocrystals compared to usual crystalline form. The release of IMQ from the patches was determined ex vivo in natural skin and revealed a 48% increase in efficacy for nanocrystal formulations compared to the crystalline form of IMQ.

• Klíčová slova
• 3D printing, Dermal delivery, Imiquimod, Microneedles, Nanocrystals,
• MeSH
• 3D tisk * MeSH
• aplikace kožní MeSH
• imichimod * chemie   aplikace a dávkování   MeSH
• jehly * MeSH
• kožní absorpce MeSH
• kůže metabolismus   MeSH
• mikroinjekce přístrojové vybavení   MeSH
• nanočástice * chemie   aplikace a dávkování   MeSH
• polyethylenglykoly chemie   aplikace a dávkování   MeSH
• povidon chemie   MeSH
• rozpustnost * MeSH
• systémy cílené aplikace léků přístrojové vybavení   MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imichimod * MeSH
• poly(ethylene glycol)diacrylate MeSH Prohlížeč
• polyethylenglykoly MeSH
• povidon MeSH

Free radical polymerization technique was used to formulate Poloxamer-188 based hydrogels for controlled delivery. A total of seven formulations were formulated with varying concentrations of polymer, monomer ad cross linker. In order to assess the structural properties of the formulated hydrogels, Fourier Transform Infrared Spectroscopy (FTIR), Thermogravimetric analysis (TGA), Differential Scanning Calorimetry (DSC), Scanning electron microscopy (SEM), and X-ray diffraction (XRD) were carried out. To assess the effect of pH on the release of the drug from the polymeric system, drug release studies were carried in pH 1.2 and 7.4 and it was found that release of the drug was significant in pH 7.4 as compared to that of pH 1.2 which confirmed the pH responsiveness of the system. Different kinetic models were also applied to the drug release to evaluate the mechanism of the drug release from the system. To determine the safety and biocompatibility of the system, toxicity study was also carried out for which healthy rabbits were selected and formulated hydrogels were orally administered to the rabbits. The results obtained suggested that the formulated poloxamer-188 hydrogels are biocompatible with biological system and have the potential to serve as controlled drug delivery vehicles.

• MeSH
• akrylové pryskyřice * chemie   MeSH
• diferenciální skenovací kalorimetrie MeSH
• difrakce rentgenového záření MeSH
• hydrogely * chemie   MeSH
• koncentrace vodíkových iontů MeSH
• králíci MeSH
• léky s prodlouženým účinkem chemie   farmakokinetika   MeSH
• mikroskopie elektronová rastrovací MeSH
• nosiče léků chemie   MeSH
• poloxamer * chemie   MeSH
• spektroskopie infračervená s Fourierovou transformací MeSH
• systémy cílené aplikace léků MeSH
• termogravimetrie MeSH
• timolol * aplikace a dávkování   farmakokinetika   chemie   MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• akrylové pryskyřice * MeSH
• carbopol 940 MeSH Prohlížeč
• hydrogely * MeSH
• léky s prodlouženým účinkem MeSH
• nosiče léků MeSH
• poloxamer * MeSH
• timolol * MeSH

The effective treatment of inflammatory diseases, particularly their chronic forms, is a key task of modern medicine. Herein, we report the synthesis and evaluation of biocompatible polymer conjugates based on N-2-(hydroxypropyl)methacrylamide copolymers enabling the controlled release of acetylsalicylic acid (ASA)-based anti-inflammatory drugs under specific stimuli. All polymer nanotherapeutics were proposed as water-soluble drug delivery systems with a hydrodynamic size below 10 nm ensuring suitability for the parenteral application and preventing opsonization by the reticuloendothelial system. The nanotherapeutics bearing an ester-bound ASA exhibited long-term release of the ASA/salicylic acid mixture, while the nanotherapeutics carrying salicylic acid hydrazide (SAH) ensured the selective release of SAH in the acidic inflammatory environment thanks to the pH-sensitive hydrazone bond between the polymer carrier and SAH. The ASA- and SAH-containing nanotherapeutics inhibited both cyclooxygenase isoforms and/or the production of pro-inflammatory mediators. Thanks to their favorable design, they can preferentially accumulate in the inflamed tissue, resulting in reduced side effects and lower dosage, and thus more effective and safer treatment.

• Klíčová slova
• Acetylsalicylic acid, Drug delivery, HPMA, Inflammation, Nanotherapeutics, Salicylic acid hydrazide,
• MeSH
• akrylamidy chemie   farmakologie   aplikace a dávkování   MeSH
• antiflogistika farmakologie   aplikace a dávkování   chemie   MeSH
• Aspirin * aplikace a dávkování   farmakologie   chemie   MeSH
• cyklooxygenasy metabolismus   MeSH
• inhibitory cyklooxygenasy farmakologie   aplikace a dávkování   chemie   MeSH
• léky s prodlouženým účinkem * MeSH
• mediátory zánětu metabolismus   MeSH
• myši MeSH
• nanočástice * chemie   MeSH
• nosiče léků chemie   MeSH
• polymery * chemie   aplikace a dávkování   MeSH
• uvolňování léčiv MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• akrylamidy MeSH
• antiflogistika MeSH
• Aspirin * MeSH
• cyklooxygenasy MeSH
• inhibitory cyklooxygenasy MeSH
• léky s prodlouženým účinkem * MeSH
• mediátory zánětu MeSH
• N-(2-hydroxypropyl)methacrylamide MeSH Prohlížeč
• nosiče léků MeSH
• polymery * MeSH

Polysaccharides like hyaluronan (HA) and chondroitin sulfate (CS) are native of the brain's extracellular matrix crucial for myelination and brain maturation. Despite extensive research on HA and CS as drug delivery systems (DDS), their high water solubility limits their application as drug carriers. This study introduces an injectable DDS using aldehyde-modified hyaluronic acid (HAOX) hydrogel containing polyelectrolyte complexes (PEC) formed with calcium, gelatin, and either CS or aldehyde-modified CS (CSOX) to deliver minocycline for Multiple Sclerosis therapy. PECs with CSOX enable covalent crosslinking to HAOX, creating immobilized PECs (HAOX_PECOX), while those with CS remain unbound (HAOX_PECS). The in situ forming DDS can be administered via a 20 G needle, with rapid gelation preventing premature leakage. The system integrates into an implanted device for minocycline release through either Fickian or anomalous diffusion, depending on PEC immobilization. HAOX_PECOX reduced burst release by 88 %, with a duration of 127 h for 50 % release. The DDS exhibited an elastic modulus of 3800 Pa and a low swelling ratio (0-1 %), enabling precise control of minocycline release kinetics. Released minocycline reduced IL-6 secretion in the Whole Blood Monocytes Activation Test, suggesting that DDS formation may not alter the biological activity of the loaded drug.

• Klíčová slova
• Chondroitin sulphate, Hyaluronic acid, Hydrogel, Minocycline, Polyelectrolyte complexes,
• MeSH
• aldehydy chemie   MeSH
• chondroitin sulfáty * chemie   MeSH
• hydrogely * chemie   farmakologie   MeSH
• interleukin-6 metabolismus   MeSH
• kyselina hyaluronová * chemie   MeSH
• lidé MeSH
• minocyklin * chemie   farmakologie   aplikace a dávkování   MeSH
• nosiče léků * chemie   MeSH
• polyelektrolyty * chemie   MeSH
• systémy cílené aplikace léků metody   MeSH
• uvolňování léčiv MeSH
• želatina * chemie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aldehydy MeSH
• chondroitin sulfáty * MeSH
• hydrogely * MeSH
• interleukin-6 MeSH
• kyselina hyaluronová * MeSH
• minocyklin * MeSH
• nosiče léků * MeSH
• polyelektrolyty * MeSH
• želatina * MeSH

In this work, the solid-liquid equilibrium (SLE) curve for ten active pharmaceutical ingredients (APIs) with the polymer polyvinylpyrrolidone (PVP) K12 was purely predicted using the Conductor-like Screening Model for Real Solvents (COSMO-RS). In particular, two COSMO-RS-based strategies were followed (i.e., a traditional approach and an expedited approach), and their performances were compared. The veracity of the predicted SLE curves was assessed via a comparison with their respective SLE dataset that was obtained using the step-wise dissolution (S-WD) method. Overall, the COSMO-RS-based API-PVP K12 SLE curves were in satisfactory agreement with the S-WD-based data points. Of the twenty predicted SLE curves, only two were found to be in strong disagreement with the corresponding experimental values (both modeled using the expedited approach). Hence, it was recommended to use the traditional approach when predicting the API-polymer SLE curve. At the present moment, COSMO-RS may be an effective computational tool for the expeditious screening of API-polymer compatibility, particularly in the case of promising novel APIs, for which experimental datasets are likely limited or non-existent.

• Klíčová slova
• Amorphous solid dispersion, COSMO-RS, Drug–polymer, Phase diagram, Solid–liquid equilibrium, Solubility,
• MeSH
• chemie farmaceutická metody   MeSH
• léčivé přípravky chemie   MeSH
• polymery chemie   MeSH
• povidon * chemie   MeSH
• rozpouštědla chemie   MeSH
• rozpustnost MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• léčivé přípravky MeSH
• polymery MeSH
• povidon * MeSH
• rozpouštědla MeSH