Two-phase dissolution test
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Roller compaction is often utilized as the first step to improve flow properties and homogeneity of pharmaceutical mixtures. Since the dry granulation process is less complicated than its counterparts in the industry, it is possible to perform screening experiments readily to investigate granulate quality for further operations. In this study, the aim of the investigation focused on the effect of roller compaction on the dissolution of granules and tablets of two pharmaceutical formulations that contain APIs of different biopharmaceutical classification. This study underscores the benefits of granule dissolution testing as a crucial early-stage technique for optimizing granulate quality and facilitating progression through formulation manufacturing operations. For active pharmaceutical ingredients characterized by poor dissolution properties, this approach provides valuable insights during the initial development phases. By integrating granule dissolution testing into the development process, product manufacturability can be enhanced and optimal product performance can be ensured.
Biorelevant dissolution instruments represent an important tool for pharmaceutical research and development. These instruments are designed to simulate the dissolution of drug formulations in conditions most closely mimicking the gastrointestinal tract. In this work, we focused on the optimization of dissolution compartments/vessels for an updated version of the biorelevant dissolution apparatus-Golem v2. We designed eight compartments of uniform size but different inner geometry. The dissolution performance of the compartments was tested using immediate release caffeine tablets and evaluated by standard statistical methods and principal component analysis. Based on two phases of dissolution testing (using 250 and 100 mL of dissolution medium), we selected two compartment types yielding the highest measurement reproducibility. We also confirmed a statistically ssignificant effect of agitation rate and dissolution volume on the extent of drug dissolved and measurement reproducibility.
Titanium biomaterials are widely used in the medical field due to their biocompatibility and excellent corrosion and mechanical resistance. However, these materials have no antibacterial properties. To obtain an antibacterial active surface, a nanostructure of Ti6Al4V alloy was created. This specific nanostructure contained nanotubes and micro-cavities and was used as a substrate for silver anchoring. The electrochemical approach to silver reduction was studied. It is a common approach for silver deposition and in this work, inhomogeneities in the nanostructure were used as a preferential area for silver localisation. The galvanostatic regimen of deposition allowed for a technically quantitative process and the required silver placement. The experimental conditions used enabled testing and silver dissolution rate evaluation within a reasonable time span. Based on the corrosion and analytical results (EDS, XPS and ICP-MS), a two-phase silver release mechanism was confirmed. The openings of the individual nanotubes were filled with silver nanoparticles, whose release was relatively fast. By contrast, the silver anchored inside the cavities allowed the silver to release gradually. Antibacterial efficiency against Staphylococcus aureus and Escherichia coli was successfully demonstrated. Cytotoxicity testing with murine fibroblasts showed cell metabolic activity far above the normative limit of 70%.
- MeSH
- antibakteriální látky aplikace a dávkování chemie farmakologie MeSH
- biokompatibilní materiály chemie MeSH
- buněčné linie MeSH
- Escherichia coli účinky léků MeSH
- infekce vyvolané Escherichia coli farmakoterapie MeSH
- lékové transportní systémy metody MeSH
- lidé MeSH
- myši MeSH
- nanostruktury chemie MeSH
- protézy a implantáty MeSH
- stafylokokové infekce farmakoterapie MeSH
- Staphylococcus aureus účinky léků MeSH
- stříbro aplikace a dávkování chemie farmakologie MeSH
- titan chemie MeSH
- uvolňování léčiv MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Aqueous two-phase systems (ATPSs) were screened for the production of 6-aminopenicillanic acid (6-APA) catalyzed by penicillin acylase, followed by the extractive separation of 6-APA from the reaction mixture. The key point of this study was to find an ATPS exhibiting a large difference in the partition coefficients of the biocatalyst and reaction products. Several ATPSs based on polyethylene glycol (PEG)/phosphate, PEG/citrate, and PEG/dextran were tested. We found that an ATPS consisting of 15 wt% of PEG 4000, 10 wt% of phosphates, 75 wt% of water (pH value 8.0 after dissolution) provided optimal separation of 6-APA from the enzyme. While the 6-APA was mainly found in the top PEG phase, the free enzyme favored the bottom salt-rich phase. This ATPS also fulfils other important requirements: (i) high buffering capacity, reducing an undesirable pH decrease due to the dissociation of phenylacetic acid (the side product of the reaction), (ii) a relatively low cost of the ATPS components, (iii) the possibility of electrophoretic transport of fine droplets as well as the reaction products for both the acceleration of phase separation and the enhancement of 6-APA concentration in the product stream. Extraction experiments in microcapillary and batch systems showed that the transport of 6-APA formed in the salt-rich phase to the corresponding PEG phase could occur within 30 s. The experimental results described form a base of knowledge for the development of continuously operating integrated microfluidic reactors-separators driven by an electric field for the efficient production of 6-APA.
Liquisolid systems are an innovative dosage form used for enhancing dissolution rate and improving in vivo bioavailability of poorly soluble drugs. These formulations require specific evaluation methods for their quality assurance (e.g., evaluation of angle of slide, contact angle, or water absorption ratio). The presented study is focused on the preparation, modern in vitro testing, and evaluation of differences of liquisolid systems containing varying amounts of a drug in liquid state (polyethylene glycol 400 solution of rosuvastatin) in relation to an aluminometasilicate carrier (Neusilin US2). Liquisolid powders used for the formulation of final tablets were prepared using two different methods: simple blending and spraying of drug solution onto a carrier in fluid bed equipment. The obtained results imply that the amount of liquid phase in relation to carrier material had an effect on the hardness, friability, and disintegration of tablets, as well as their height. The use of spraying technique enhanced flow properties of the prepared mixtures, increased hardness values, decreased friability, and improved homogeneity of the final dosage form.
- MeSH
- kyseliny stearové chemie MeSH
- laktosa chemie MeSH
- lidé MeSH
- polyethylenglykoly chemie MeSH
- rosuvastatin kalcium chemie MeSH
- silikáty chemie MeSH
- sloučeniny hliníku chemie MeSH
- sloučeniny hořčíku chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The international standard ISO 23317:2014 for the in vitro testing of inorganic biomaterials in simulated body fluid (SBF) uses TRIS buffer to maintain neutral pH. In our previous papers, we investigated the interaction of a glass-ceramic scaffold with TRIS and HEPES buffers. Both of them speeded up glass-ceramic dissolution and hydroxyapatite (HAp) precipitation, thereby demonstrating their unsuitability for the in vitro testing of highly reactive biomaterials. In this article, we tested MOPS buffer (3-[N-morpholino] propanesulfonic acid), another amino acid from the group of "Goods buffers". A highly reactive glass-ceramic scaffold (derived from Bioglass®) was exposed to SBF under static-dynamic conditions for 13/15 days. The kinetics and morphology of the newly precipitated HAp were studied using two different concentrations of (PO4 )3- ions in SBF. The pH value and the SiIV , Ca2+ , and (PO4 )3- concentrations in the SBF leachate samples were measured every day (AAS, spectrophotometry). The glass-ceramic scaffold was monitored by SEM/EDS, XRD, WD-XRF, and BET before and after 1, 3, 7, 11, and 13/15 days of exposure. As in the case of TRIS and HEPES, the preferential dissolution of the glass-ceramic crystalline phase (Combeite) was observed, but less intensively. The lower concentration of (PO4 )3- ions slowed down the kinetics of HAp precipitation, thereby causing the disintegration of the scaffold structure. This phenomenon shows that the HAp phase was predominately generated by the presence of (PO4 )3- ions in the SBF, not in the glass-ceramic material. Irrespective of this, MOPS buffer is not suitable for the maintenance of pH in SBF.
An international standard (ISO: 23317:2014) exists for the in vitro testing of inorganic biomaterials in simulated body fluid (SBF). This standard uses TRIS buffer to maintain neutral pH in SBF, but in our previous paper, we showed that the interaction of a tested glass-ceramic material with TRIS can produce false-positive results. In this study, we evaluated whether the HEPES buffer, which also belongs to the group of Good´s buffers, would be more suitable for SBF. We compared its suitability in two media: SBF with HEPES and demineralized water with HEPES. The tested scaffold (45S5 bioactive glass-based) was exposed to the media under a static-dynamic arrangement (solutions were replaced on a daily basis) for 15 days. Leachate samples were collected daily for the analysis of Ca2+ ions and Si (AAS), (PO4 )3- ions (UV-VIS), and to measure pH. The glass-ceramic scaffold was analyzed by SEM/EDS, XRD, and WD-XRF before and after 0.3, 1, 3, 7, 11, and 15 days of exposure. Our results confirmed the rapid selective dissolution of the glass-ceramic crystalline phase (Combeite) containing Ca2+ ions due to the presence of HEPES, hydroxyapatite supersaturation being reached within 24 h in both solutions. These new results suggest that, like TRIS, HEPES buffer is not suitable for the in vitro testing of highly reactive inorganic biomaterials (glass, glass-ceramics). The ISO standard for such tests requires revision, but HEPES is not a viable alternative to TRIS buffer. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 143-152, 2018.
