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.
- MeSH
- 3D tisk * MeSH
- aplikace kožní MeSH
- imichimod * chemie aplikace a dávkování MeSH
- jehly * MeSH
- kožní absorpce MeSH
- kůže metabolismus MeSH
- lékové transportní systémy přístrojové vybavení MeSH
- mikroinjekce přístrojové vybavení MeSH
- nanočástice * chemie aplikace a dávkování MeSH
- polyethylenglykoly chemie aplikace a dávkování MeSH
- povidon chemie MeSH
- rozpustnost * MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články 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
- lékové transportní systémy 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
- 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
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.
- 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
- lékové transportní systémy * metody MeSH
- léky s prodlouženým účinkem chemie MeSH
- polymery chemie MeSH
- polyvinyly chemie MeSH
- tobolky * MeSH
- uvolňování léčiv * MeSH
- želatina * chemie MeSH
- železité sloučeniny chemie aplikace a dávkování MeSH
- Publikační typ
- časopisecké články MeSH
Lékové formy s elektronickým prvkem je možné zařadit mezi jedny z nejmodernějších a nejinovativnějších lékových systémů posledních několika dekád. Inkorporace elektronického/digitálního prvku nabízí řadu výhod, jako např. možnost přesného načasování uvolnění léčivé látky v požadované lokaci gastrointestinálního traktu, sběr biometrických dat, či nezpochybnitelný průkaz adherence pacienta k terapii. V současné době je možné pozorovat vývoj oboru do dvou hlavních směrů. Tím prvním je využití těchto systémů ve spojení s řízeným uvolňováním při absorpčních a obecně farmakokinetických studiích nových látek. Druhým směrem je pak digitální monitoring adherence k léčbě. Tento stručný přehled pojednává krátce o historii problematiky, přináší informace o obou zmíněných odvětvích a zmiňuje zásadní zástupce obou skupin a jejich využití.
Delivery systems with an electronic element can be classified as one of the last few decades' most modern and innovative pharmaceutical systems. Incorporating an electronic/digital element offers several advantages, such as the possibility of the precise timing of the drug released in the desired location of the gastrointestinal tract, collection of biometric data, or indisputable proof of the patient's adherence to therapy. Currently, it is possible to observe the development of the field in two main directions. The first one is using these systems in conjunction with the controlled release principle in absorption and general pharmacokinetic studies of new substances. The second direction is digital monitoring of therapy adherence. This brief overview briefly mentions the field's history, brings information about the two main branches, and states the essential systems of both branches and their use.
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.
- 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
Sildenafil citrate has low oral bioavailability, systemic adverse effects, and a relatively delayed action. These issues may be addressed through direct transdermal delivery to the penis. This study aims to investigate the microemulsion formulation of the drug for effective transdermal delivery. Sildenafil citrate was formulated as a microemulsion using clove oil, dimethyl sulphoxide, phosphate buffer (pH 7), propylene glycol, Tween®80, and distilled water. Different proportions of these components were used to create six formulations of the microemulsion (F1-F6), which were then characterised by their physical appearance and clarity, pH, viscosity, conductivity, percent transmission, and droplet size. Furthermore, the stability, content analysis, in-vitro drug release, and transdermal permeation of sildenafil citrate from the generated drug-loaded microemulsions were studied. All prepared formulas contained nano-sized oil droplets (less than 20 nm), and the pH values were within the range of skin pH; however, two formulas were not transparent. Additionally, all formulations were thermodynamically stable, passing freeze-thaw, heating-cooling, and centrifugation tests. Next, the formulas demonstrated zero-order release kinetics, indicating that they can provide a sustained release profile for sildenafil citrate. Finally, the microemulsion formulation exhibited a 2.8-fold enhancement in skin permeation compared with that of the sildenafil citrate suspension. The prepared microemulsions demonstrated beneficial physical properties and skin permeation profiles that are promising for the local administration of sildenafil citrate.
- Klíčová slova
- mikroemulze,
- MeSH
- aplikace kožní * MeSH
- emulze MeSH
- hřebíčkový olej MeSH
- krysa rodu rattus MeSH
- lékové formy MeSH
- modely u zvířat MeSH
- permeabilita MeSH
- příprava léků metody MeSH
- sildenafil citrát * aplikace a dávkování farmakokinetika farmakologie MeSH
- stabilita léku MeSH
- suspenze MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- klinická studie 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.
There is increasing pharmaceutical interest in deep eutectic solvents not only as a green alternative to organic solvents in drug manufacturing, but also as liquid formulation for drug delivery. The present work introduces a hydrophobic deep eutectic solvent (HDES) to the field of lipid-based formulations (LBF). Phase behavior of a mixture with 2:1 M ratio of decanoic- to dodecanoic acid was studied experimentally and described by thermodynamic modelling. Venetoclax was selected as a hydrophobic model drug and studied by atomistic molecular dynamics simulations of the mixtures. As a result, valuable molecular insights were gained into the interaction networks between the different components. Moreover, experimentally the HDES showed greatly enhanced drug solubilization compared to conventional glyceride-based vehicles, but aqueous dispersion behavior was limited. Hence surfactants were studied for their ability to improve aqueous dispersion and addition of Tween 80 resulted in lowest droplet sizes and high in vitro drug release. In conclusion, the combination of HDES with surfactant(s) provides a novel LBF with high pharmaceutical potential. However, the components must be finely balanced to keep the integrity of the solubilizing HDES, while enabling sufficient dispersion and drug release.
- MeSH
- farmaceutická chemie metody MeSH
- hydrofobní a hydrofilní interakce * MeSH
- kyseliny laurové chemie MeSH
- lipidy * chemie MeSH
- oleje chemie MeSH
- polysorbáty chemie MeSH
- povrchově aktivní látky * chemie MeSH
- příprava léků * metody MeSH
- rozpouštědla * chemie MeSH
- rozpustnost * MeSH
- simulace molekulární dynamiky * MeSH
- sulfonamidy chemie aplikace a dávkování MeSH
- uvolňování léčiv * MeSH
- Publikační typ
- časopisecké články 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.
- MeSH
- aldehydy chemie MeSH
- chondroitinsulfáty * chemie MeSH
- hydrogely * chemie farmakologie MeSH
- interleukin-6 metabolismus MeSH
- kyselina hyaluronová * chemie MeSH
- lékové transportní systémy metody MeSH
- lidé MeSH
- minocyklin * chemie farmakologie aplikace a dávkování MeSH
- nosiče léků * chemie MeSH
- polyelektrolyty * chemie MeSH
- uvolňování léčiv MeSH
- želatina * chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Co-milling is an effective technique for improving dissolution rate limited absorption characteristics of poorly water-soluble drugs. However, there is a scarcity of models available to forecast the magnitude of dissolution rate improvement caused by co-milling. Therefore, this study endeavoured to quantitatively predict the increase in dissolution by co-milling based on drug properties. Using a biorelevant dissolution setup, a series of 29 structurally diverse and crystalline drugs were screened in co-milled and physically blended mixtures with Polyvinylpyrrolidone K25. Co-Milling Dissolution Ratios after 15 min (COMDR15 min) and 60 min (COMDR60 min) drug release were predicted by variable selection in the framework of a partial least squares (PLS) regression. The model forecasts the COMDR15 min (R2 = 0.82 and Q2 = 0.77) and COMDR60 min (R2 = 0.87 and Q2 = 0.84) with small differences in root mean square errors of training and test sets by selecting four drug properties. Based on three of these selected variables, applicable multiple linear regression equations were developed with a high predictive power of R2 = 0.83 (COMDR15 min) and R2 = 0.84 (COMDR60 min). The most influential predictor variable was the median drug particle size before milling, followed by the calculated drug logD6.5 value, the calculated molecular descriptor Kappa 3 and the apparent solubility of drugs after 24 h dissolution. The study demonstrates the feasibility of forecasting the dissolution rate improvements of poorly water-solube drugs through co-milling. These models can be applied as computational tools to guide formulation in early stage development.
