The rising demands on discriminatory and prediction abilities of dissolution methods and the increasing complexity of new drug products are the main driving forces of the progress in this field. The research moves forward as imperfections and shortcomings of classical methods are being described, and where the capabilities of the contemporary methods are insufficient, new methods are being developed. The review discusses these advances with respect to the issues that currently draw the most attention, i.e. correct simulation of hydrodynamics and stress forces, maintenance of sink conditions, study of precipitation, use of biorelevant media and the employment of more physiologically relevant methods in general.
Different batches of atorvastatin, represented by two immediate release formulation designs, were studied using a novel dynamic dissolution apparatus, simulating stomach and small intestine. A universal dissolution method was employed which simulated the physiology of human gastrointestinal tract, including the precise chyme transit behavior and biorelevant conditions. The multicompartmental dissolution data allowed direct observation and qualitative discrimination of the differences resulting from highly pH dependent dissolution behavior of the tested batches. Further evaluation of results was performed using IVIVC/IVIVR development. While satisfactory correlation could not be achieved using a conventional deconvolution based-model, promising results were obtained through the use of a nonconventional approach exploiting the complex compartmental dissolution data.
- MeSH
- Atorvastatin chemistry therapeutic use MeSH
- Chemistry, Pharmaceutical MeSH
- Gastrointestinal Tract drug effects physiology MeSH
- Humans MeSH
- Intestine, Small drug effects MeSH
- Drug Liberation * MeSH
- Equipment and Supplies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Modern pharmaceutical technology still seeks new excipients and investigates the further use in already known ones. An example is magnesium aluminometasilicate Neusilin® US2 (NEU), a commonly used inert filler with unique properties that are usable in various pharmaceutical fields of interest. We aimed to explore its application in hypromellose matrix systems (HPMC content 10-30%) compared to the traditionally used microcrystalline cellulose (MCC) PH 102. The properties of powder mixtures and directly compressed tablets containing individual fillers NEU or MCC, or their blend with ratios of 1.5:1, 1:1, and 0.5:1 were investigated. Besides the routine pharmaceutical testing, we have enriched the matrices' evaluation with a biorelevant dynamic dissolution study and advanced statistical analysis. Under the USP apparatus 2 dissolution test, NEU, individually, did not provide advantages compared to MCC. The primary limitations were the burst effect increase followed by faster drug release at the 10-20% HPMC concentrations. However, the biorelevant dynamic dissolution study did not confirm these findings and showed similarities in dissolution profiles. It indicates the limitations of pharmacopoeial methods in matrix tablet development. Surprisingly, the NEU/MCC blend matrices at the same HPMC concentration showed technologically advantageous properties. Besides improved flowability, tablet hardness, and a positive impact on the in vitro drug dissolution profile toward zero-order kinetics, the USP 2 dissolution data of the samples N75M50 and N50M50 showed a similarity to those obtained from the dynamic biorelevant apparatus with multi-compartment structure. This finding demonstrates the more predictable in vivo behaviour of the developed matrix systems in human organisms.
- Publication type
- Journal Article MeSH
Burst drug release is often considered a negative phenomenon resulting in unexpected toxicity or tissue irritation. Optimal release of a highly soluble active pharmaceutical ingredient (API) from hypromellose (HPMC) matrices is technologically impossible; therefore, a combination of polymers is required for burst effect reduction. Promising variant could be seen in combination of HPMC and insoluble Eudragits® as water dispersions. These can be applied only on API/insoluble filler mixture as over-wetting prevention. The main hurdle is a limited water absorption capacity (WAC) of filler. Therefore, the object of this study was to investigate the dissolution behavior of levetiracetam from HPMC/Eudragit®NE matrices using magnesium aluminometasilicate (Neusilin® US2) as filler with excellent WAC. Part of this study was also to assess influence of thermal treatment on quality parameters of matrices. The use of Neusilin® allowed the application of Eudragit® dispersion to API/Neusilin® mixture in one step during high-shear wet granulation. HPMC was added extragranularly. Obtained matrices were investigated for qualitative characteristics, NMR solid-state spectroscopy (ssNMR), gel layer dynamic parameters, SEM, and principal component analysis (PCA). Decrease in burst effect (max. of 33.6%) and dissolution rate, increase in fitting to zero-order kinetics, and paradoxical reduction in gel layer thickness were observed with rising Eudragit® NE concentration. The explanation was done by ssNMR, which clearly showed a significant reduction of the API particle size (150-500 nm) in granules as effect of surfactant present in dispersion in dependence on Eudragit®NE amount. This change in API particle size resulted in a significantly larger interface between these two entities. Based on ANOVA and PCA, thermal treatment was not revealed as a useful procedure for this system.
- MeSH
- Administration, Oral MeSH
- Gels MeSH
- Polymethacrylic Acids administration & dosage chemistry metabolism MeSH
- Delayed-Action Preparations administration & dosage chemistry metabolism MeSH
- Magnetic Resonance Spectroscopy methods MeSH
- Excipients chemistry MeSH
- Solubility MeSH
- Silicates administration & dosage chemistry metabolism MeSH
- Aluminum Compounds administration & dosage chemistry metabolism MeSH
- Magnesium Compounds administration & dosage chemistry metabolism MeSH
- Drug Liberation MeSH
- Particle Size MeSH
- Publication type
- Journal Article MeSH
The solubility of weakly basic drugs in passage through gastrointestinal tract leads to their pH-dependent release from extended release formulations and to lower drug absorption and bioavailability. The aim of this study was to modulate the micro-environmental pH of hypromellose/montanglycol wax matrices and to observe its influence on the release of weakly basic drug verapamil hydrochloride (VH) with a pH-dependent solubility with respect to gel layer formation and its dynamics. For this study, malic and succinic acids differing in their solubility and pKa were selected as pH modifiers. The dissolution studies were performed by the method of changing pH. Within the same conditions, pH, thickness, and penetration force of the gel layer were measured as well. From the PCA sub-model, it is evident that a higher acid concentration ensured lower gel pH and conditions for higher drug solubility, thus creating larger gel layer with smaller rigidity, resulting in higher VH release during the dissolution test. Incorporation of stronger and more soluble malic acid (100 mg/tablet) created the most acidic and the thickest gel layer through which a total of 74% of VH was released. Despite having lower strength and solubility, matrices containing succinic acid (100 mg/tablet) released a comparable 71% of VH in a manner close to zero-order kinetics. The thinner and less rigid gel layers of the succinic acid matrices allowed an even slightly faster VH release at pH 6.8 than from matrices containing malic acid. Thus acid solubility is more parametrically significant than acid pKa for drug release at pH 6.8.
- MeSH
- Hypromellose Derivatives * MeSH
- Gels MeSH
- Kinetics MeSH
- Hydrogen-Ion Concentration MeSH
- Delayed-Action Preparations chemistry MeSH
- Malates chemistry MeSH
- Multivariate Analysis MeSH
- Solubility MeSH
- Succinates chemistry MeSH
- Tablets MeSH
- Drug Liberation MeSH
- Verapamil administration & dosage chemistry metabolism MeSH
- Waxes * MeSH
- Publication type
- Journal Article MeSH
The evolution of CO2 levels was studied in the ventilated and unventilated Nagel Dome chamber (the Císarská Cave) with- and without human presence. Based on a simplified dynamic model and CO2/Rn data (222Rn considered as a conservative tracer), two types of CO2-fluxes into the chamber were distinguished: (1) the natural input of (2-4) x 10(-6) m3 s(-1), corresponding to a flux of (8.5-17) x 10(-10) m3 m(-2) s(-1) and (2) an anthropogenic input of (0.6-2.5) x 10(-4) m3 s(-1), corresponding to an average partial flux of (4.8-7.7) x 10(-6) m3 s(-1) person(-1). The chamber ventilation rates were calculated in the range from 0.033 to 0.155 h(-1). Comparison of the chamber CO2-levels with chamber dripwater chemistry indicates that the peak CO2-concentrations during stay of persons (log p(CO2) approximately -2.97, -2.89, and -2.83) do not reach the theoretical values at which dripwater carbonate species and air CO2 are at equilibrium (log p(CO2[DW]) approximately -2.76 to -2.79). This means that CO2-degassing of the dripwaters will continue, increasing supersaturation with respect to calcite (dripwater saturation index defined as SI(calcite) = a(Ca2+)a(CO3(2-))/10(-8.4) varied in the range from 0.76 to 0.86). The p(CO2[DW]) values, however, would easily be exceeded if the period of person stay in the chamber had been slightly extended (from 2.85 to 4 h under given conditions). In such case, the dripwater CO2-degassing would be inverted into CO2-dissolution and dripwater supersaturation would decrease. Achieving the threshold values at which water become aggressive to calcite (log p(CO2[EK]) approximately -1.99, -2.02, and -1.84) would require extreme conditions, e.g., simultaneous presence of 100 persons in the cave chamber for 14 h. The study should contribute to a better preservation of cave environment.
- MeSH
- Financing, Organized MeSH
- Geological Phenomena MeSH
- Geology MeSH
- Humans MeSH
- Environmental Monitoring MeSH
- Carbon Dioxide analysis MeSH
- Air Pollutants, Radioactive analysis MeSH
- Radon analysis MeSH
- Seasons MeSH
- Models, Theoretical MeSH
- Ventilation MeSH
- Environment MeSH
- Check Tag
- Humans MeSH
- Geographicals
- Czech Republic MeSH
Kvalitativní studie má za cíl podrobně zmapovat fenomén spousifikace: Co se stane, když dítě převezme zodpovědnost, kompetence jednoho z rodičů? Za jakých okolností se tyto situace stávají? Jaké má spousifikace konkrétní projevy? Do jaké míry je aktivní rodič a do jaké míry dítě při přebírání kompetencí? Výzkum probíhal realizováním 4 ohniskových skupin po 8 – 10 respondentech a 11 individuálních rozhovoru u dětí ve věku 11–17 let, se zaměřením na narušení hranic v jednotlivých rodinách, vliv na konkrétní osobnost jedince a jeho rodinu. Respondenti byli ze středisek výchovné péče v Brně a ze všeobecného gymnázia. Tyto ohniskové skupiny a individuální rozhovory byly nahrávány, analyzovány pomocí programu Atlas.ti a kódovány. Z analýzy vzešly tři charakteristiky tohoto jevu: kategorie jednotlivých typů spousifikace (typologie činností, ve kterých dítě může přebírat kompetence za svého rodiče a díky kterým je za určitých okolností partnerem svému rodiči), kategorie okolností vzniku spousifikace (zmapování situací a okolností, za kterých mohou být narušeny hranice rodinného systému a dítě se stává svému rodiči partnerem) a do jaké míry je dítě aktivním činitelem (do jaké míry bylo dítě do partnerského vztahu vtahováno rodičem, a do jaké míry dítě začne absentujícího partnera v jeho roli samo nahrazovat).
The qualitative research study is focused on conceptualization of the spousification phenomenon. What happens when a child takes responsibilities or competencies of his parent? Under what circumstances did this situations happened? What are the symptoms? And who is active in this relationship – parent/child? The study was designed as a detail analysis of 4 focus groups (8–10 respondents) and 11 interviews by children aged 11–17 years focusing on the disruption boundaries of individual families and influence on the personality of the child and his family. They were organized with children with conduct disorders and with children from general population. This focus groups and interviews were recorded, analyzed and coded in program Atlas.ti. We came to the three characteristics of this phenomenon: categories of spousification (typology of activities in which the child can take over the competences for his parent and thanks to which, under certain circumstances, a partner of his parent), categories of circumstances (mapping of the situations and the circumstances under which they may cause boundary dissolution and the child becomes spouse to his parent), and the extent to which the child is an active agent (the extent to which the child is drawn into a relationship of his parent, and the extent to which a child begins substitute a role of his absent spouse/partner).
- Keywords
- spousifikace, parentifikace,
- MeSH
- Child Behavior psychology MeSH
- Adolescent Behavior psychology MeSH
- Child MeSH
- Family Conflict * psychology MeSH
- Qualitative Research MeSH
- Humans MeSH
- Adolescent MeSH
- Single-Parent Family psychology MeSH
- Single Parent psychology MeSH
- Parents psychology MeSH
- Parenting * psychology MeSH
- Family psychology MeSH
- Family Relations psychology MeSH
- Interviews as Topic MeSH
- Parent-Child Relations * MeSH
- Focus Groups MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Female MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
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
- Chemistry, Pharmaceutical methods MeSH
- Hydrophobic and Hydrophilic Interactions * MeSH
- Lauric Acids chemistry MeSH
- Lipids * chemistry MeSH
- Oils chemistry MeSH
- Polysorbates chemistry MeSH
- Surface-Active Agents * chemistry MeSH
- Drug Compounding * methods MeSH
- Solvents * chemistry MeSH
- Solubility * MeSH
- Molecular Dynamics Simulation * MeSH
- Sulfonamides chemistry administration & dosage MeSH
- Drug Liberation * MeSH
- Publication type
- Journal Article MeSH
Particle size is a key parameter when dealing with drug particle formation, delivery or dissolution. The correct measurement of particle size depends on various factors, such as sample preparation or dilution, but also on the choice of method for its characterization. In this work, we study the process of precipitation of poorly water-soluble drug Valsartan from supersaturated solution in the presence of nonionic surfactant Tween 20. Several techniques including dynamic light scattering (DLS) operated in several measuring modes, optical microscope (OM) and static light scattering (SLS) were used to analyze the kinetics of particle formation. As concluded by the results, the increase in turbidity of the solution seriously limits the application of classical DLS to properly measure the particle size and polydispersity. One way to get around this restriction is by dilution, which however results in a decrease in the size of Valsartan particles in the studied population. In contrast, here we present for a first time technique based on modulated 3D cross correlation DLS equipped with the sample goniometer to determine size of submicron particles of the drug in highly turbid solutions. Additionally, a modified OM was used to measure micron-sized particles for samples without any dilution in a continuous mode. Measured particle sizes combined with measured Valsartan concentration allowed us to identify mechanism responsible for the particle formation from supersaturated solutions. The main mechanism, as it is shown in this work, is covering surface of precipitate particles by the amount of used Tween 20.
OBJECTIVE: Dental hypersensitivity remains widespread, underscoring the need for materials that can effectively seal dental tubules. This study evaluated the potential of bioactive-glass-infused hydroxyethyl cellulose gels in this context. METHODS: Five gels were synthesized, each containing 20% bioactive glass (specifically, 45S5, S53P4, Biomin F, and Biomin C), with an additional blank gel serving as a control. Subjected to two months of accelerated aging at 37 ± 2 °C, these gels were assessed for key properties: viscosity, water disintegration time, pH level, consistency, adhesion to glass, and element release capability. RESULTS: Across the board, the gels facilitated the release of calcium, phosphate, and silicon ions, raising the pH from 9.00 ± 0.10 to 9.7 ± 0.0-a range conducive to remineralization. Dissolution in water occurred within 30-50 min post-application. Viscosity readings showed variability, with 45S5 reaching 6337 ± 24 mPa/s and Biomin F at 3269 ± 18 mPa/s after two months. Initial adhesion for the blank gel was measured at 0.27 ± 0.04 Pa, increasing to 0.73 ± 0.06 Pa for the others over time. Gels can release elements upon contact with water (Ca- Biomin C 104.8 ± 15.7 mg/L; Na- Biomin F 76.30 ± 11.44 mg/L; P- Biomin C 2.623 ± 0.393 mg/L; Si- 45S5-45.15 ± 6.77mg/L, F- Biomin F- 3.256 ± 0.651mg/L; Cl- Biomin C 135.5 ± 20.3 mg/L after 45 min). CONCLUSIONS: These findings highlight the gels' capacity to kickstart the remineralization process by delivering critical ions needed for enamel layer reconstruction. Further exploration in more dynamic, real-world conditions is recommended to fully ascertain their practical utility.
- Publication type
- Journal Article MeSH
