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
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.
- MeSH
- deriváty hypromelózy chemie MeSH
- farmaceutická chemie metody 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
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.
Novým osobním ochranným prostředkem je obličejová maska vybavená nanovlákenným filtrem s enkapsulovaným jodovaným povidonem, která byla vyvinuta a otestována při klinické zkoušce. Filtr s funkcionalizovanými nanovlákny se vyznačuje nízkým průtokovým (vdechovým) odporem, umožňuje tudíž pohodlné dýchání a minimalizuje vdechování vzduchu procházejícího mimo filtr. Filtr je díky přítomnosti aktivní látky vhodný i pro aplikaci po nechráněné virové expozici. Uskutečněná zkouška prokázala, že testovaný nanovlákenný filtr s jodovaným povidonem se vyznačuje pomalým uvolňováním jódu, které minimalizuje vedlejší účinky, ale zachovává dezinfekční účinnost. Z výsledků naší klinické zkoušky provedené na 207 pozitivně testovaných pacientech se SARS-CoV-2, kteří nosili osobní ochranné prostředky po dobu 4–8 hodin denně po dobu 1 až 4 dnů, vyplynulo, že i množství jódu pouhých 0,00028 ppm postačovalo k významnému snížení reprodukčního čísla a také k ochraně před závažným průběhem onemocnění.
The novel personal protection equipment based on a face mask equipped with a nanofiber filter functionalized with povidone iodine has been developed and tested in a clinical trial. This nanofiber filter was characterized with a low flow resistance and, thus, allowed comfortable breathing. The performed study proved that the novel nanofiber filter with incorporated povidone-iodine was characterized with a slow release of iodine which minimized side effects but kept disinfection efficiency. Our clinical study performed on 207 positively tested SARS-CoV-2 patients wearing the PPE for 4–8 hours daily for 1 to 4 days has shown that even the iodine amount as low as 0.00028 ppm was sufficient to significantly decrease the reproduction number and, very importantly, to protect against severe course of disease.
Flavonoids are considered as health-protecting food constituents. The testing of their biological effects is however hampered by their low oral absorption and complex metabolism. In order to investigate the direct effect(s) of unmetabolized flavonoid, a preparation in a biologically friendly solvent for intravenous administration is needed. Isorhamnetin, a natural flavonoid and a human metabolite of the most frequently tested flavonoid quercetin, has very low water solubility (<3.5 μg/mL). The aim of this study was to improve its solubility to enable intravenous administration and to test its pharmacokinetics in an animal model. By using polyvinylpyrrolidone (PVP10) and benzalkonium chloride, we were able to improve the solubility approximately 600 times to 2.1 mg/mL. This solution was then administered intravenously at a dose of 0.5 mg/kg of isorhamnetin to rats and its pharmacokinetics was analyzed. The pharmacokinetics of isorhamnetin corresponded to two compartmental model with a rapid initial distribution phase (t1/2α: 5.7 ± 4.3 min) and a slower elimination phase (t1/2β: 61 ± 47.5 min). Two sulfate metabolites were also identified. PVP10 and benzalkonium did not modify the properties of isorhamnetin (iron chelation and reduction, and cell penetration) substantially. In conclusion, the novel preparation reported in this study is suitable for future testing of isorhamnetin effects under in vivo conditions.
- MeSH
- benzalkoniové sloučeniny farmakokinetika chemie MeSH
- intravenózní podání * MeSH
- krysa rodu rattus MeSH
- potkani Wistar MeSH
- povidon * chemie MeSH
- quercetin * farmakokinetika analogy a deriváty aplikace a dávkování chemie MeSH
- rozpustnost * MeSH
- voda * chemie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví 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.
BACKGROUND: To prevent infectious complications after transrectal ultrasound-guided prostate biopsy (TRUS-PB), some studies have investigated the efficacy of rectal disinfection using povidone-iodine (PI) and antibiotic prophylaxis (AP). OBJECTIVE: To summarize available data and compare the efficacy of rectal disinfection using PI with non-PI methods prior to TRUS-PB. EVIDENCE ACQUISITION: Three databases were queried through November 2023 for randomized controlled trials (RCTs) analyzing patients who underwent TRUS-PB. We compared the effectiveness of rectal disinfection between PI groups and non-PI groups with or without AP. The primary outcomes of interest were the rates of overall infectious complications, fever, and sepsis. Subgroups analyses were conducted to assess the differential outcomes in patients using fluoroquinolone groups compared to those using other antibiotics groups. EVIDENCE SYNTHESIS: We included ten RCTs in the meta-analyses. The overall rates of infectious complications were significantly lower when rectal disinfection with PI was performed (RR 0.56, 95% CI 0.42-0.74, p < 0.001). Compared to AP monotherapy, the combination of AP and PI was associated with significantly lower risk of infectious complications (RR 0.54, 95% CI 0.40-0.73, p < 0.001) and fever (RR 0.47, 95% CI 0.30-0.75, p = 0.001), but not with sepsis (RR 0.49, 95% CI 0.23-1.04, p = 0.06). The use of fluoroquinolone antibiotics was associated with a lower risk of infectious complications and fever compared to non-FQ antibiotics. CONCLUSION: Rectal disinfection with PI significantly reduces the rates of infectious complications and fever in patients undergoing TRUS-PB. However, this approach does not show a significant impact on reducing the rate of sepsis following the procedure.
- MeSH
- antibiotická profylaxe metody MeSH
- antiinfekční látky lokální * terapeutické užití aplikace a dávkování MeSH
- dezinfekce metody MeSH
- jodovaný povidon * terapeutické užití aplikace a dávkování MeSH
- lidé MeSH
- nádory prostaty patologie MeSH
- prostata * patologie MeSH
- rektum * MeSH
- ultrazvukem navigovaná biopsie * škodlivé účinky metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- systematický přehled MeSH
Vrozený chylothorax je závažné a obtížně léčitelné onemocnění s vysokou mortalitou. Použitím chemické pleurodézy lze omezit nutnost chirurgické léčby, avšak dosud není kvůli nedostatku důkazů jednoznačná shoda nad optimální chemickou látkou. Ve dvou kazuistikách popisujeme vlastní zkušenost s chemickou pleurodézou jodovaným povidonem u novorozenců s vrozeným chylothoraxem. Pacientům jsme podali 2 ml/kg roztoku 4% jodovaného povidonu intrapleurálně cestou hrudního drénu, který byl po podání na 4 hodiny zasvorkován. V obou případech bylo nutné opakované podání k úplnému potlačení tvorby chylu. Podle našich zkušeností použití chemické pleurodézy jodovaným povidonem rychle, účinně a bez nežádoucích účinků zabrání další tvorbě pleurálního výpotku. Od prvního použití této metody v roce 2003 bylo publikováno 20 případů aplikace novorozencům v léčbě kongenitálního chylothoraxu. Jejich přehled a zhodnocení jsou součástí sdělení. Celková úspěšnost i procento přežití dosahují 80 %.
Congenital chylothorax is a serious neonatal condition with high mortality and difficult management. Chemical pleurodesis can limit the need for surgical treatment, but there is no consensus on the optimal chemical agent for the lack of solid evidence. We report our experience with povidone-iodine (PVI) chemical pleurodesis in two neonates with congenital chylothorax. Pleurodesis consisted in the injection of 2 ml/kg of a 4% povidone iodine solution inside the pleural space, leaving the pleural tube clamped for the subsequent 4 hours. In both cases, repeated doses of povidone-iodine were required to completely stop chyle formation. Based on our experience, chemical pleurodesis with povidone-iodine promptly and definitely stopped pleural effusion, with no side effect observed. Since its first use in 2003, we provide analysis of all published neonatal case reports concerning PVI chemical pleurodesis in congenital chylothorax (n = 20), with both success and survival rate at 80 %.
- MeSH
- chylotorax * terapie MeSH
- jodovaný povidon terapeutické užití MeSH
- lidé MeSH
- novorozenec MeSH
- pleurodéza metody MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
There is a growing interest in using deep eutectic solvents (DES) as a pharmaceutical delivery system for poorly water-soluble compounds. To reduce the risk of drug precipitation following oral administration, this study addresses the hypothesis that directly including a polymeric precipitation inhibitor (PI) in a DES mixture could obtain a polymer-embedded deep eutectic system (PEDES) as a novel bio-enabling formulation principle. Following broad formulation screening, a PEDES embedding 15% w/w of polyvinyl pyrrolidone K30 (PVP) in L-carnitine:ethylene glycol (1:4, molar ratio) DES was successfully formulated as a supersaturating formulation using indomethacin as model compound. The drug solubility of 175.6 mg/mL obtained in DES was remarkably high, and upon release (phosphate buffer, pH 6.5) a maximum supersaturation factor of 9.8 was recorded, whereby the release kinetics displayed a suitable "parachute effect". The formulation was further characterized to include a molecular dynamics simulation. It can be concluded that PEDES appears to be a viable novel formulation approach, setting solid grounds for further research to assess the full potential of this novel type of supersaturating drug delivery system.
