Ramanovu spektroskopii lze v chemii použít nejen k určování chemického složení, ale také pro získávání dalších informací o struktuře materiálu. Ve spektrech semikrystalických polymerů lze nalézt vzájemně odlišné pásy charakteristické pro krystalickou nebo amorfní fázi, stanovit z nich krystalinitu a z ní odhadnout míru degradace polymeru. V předložené studii byly vyhodnoceny změny raménka pásu na vlnočtu 1733 cm−1 v Ramanových spektrech vlákna z poly(p-dioxanonu) podrobeného hydrolytické degradaci. Pro různě dlouhé doby degradace byly vypočteny obsahy ploch pod raménkem tohoto pásu a též byl proveden jeho modelový rozklad na předpokládané píky krystalické a amorfní fáze. Obsahy ploch pod raménkem i parametry modelových píků byly porovnány s hodnotami krystalinity získanými pomocí diferenční skenovací kalorimetrie, přičemž bylo dosaženo dobré shody. Tato práce ukazuje příklad využití Ramanovy spektroskopie při studiu hydrolytické degradace polymerů.
Raman spectroscopy can be used in chemistry not just to determine chemical composition, but also to obtain further information on the material structure. In the spectra of semi-crystalline polymers, distinct bands characteristic of the crystalline or the amorphous phase can be found, the degree of crystallinity determined from them, and the degree of polymer degradation estimated from the crystallinity. In the present study, changes in the 1733 cm−1 band shoulder in Raman spectra of poly(p-dioxanone) fibres subjected to hydrolytic degradation were evaluated. For different degradation periods, the areas under the shoulder of this band were calculated and a model deconvolution of this band into assumed crystalline and amorphous peaks was also performed. The areas under the shoulder, as well as the model peaks' parameters, were compared with the crystallinity values obtained by differential scanning calorimetry, achieving a good agreement. This work shows an example of using Raman spectroscopy when studying the hydrolytic degradation of polymers.
A film-forming system (FFS) represents a convenient topical dosage form for drug delivery. In this study, a non-commercial poly(lactic-co-glycolic acid) (PLGA) was chosen to formulate an FFS containing salicylic acid (SA) and methyl salicylate (MS). This unique combination is advantageous from a therapeutic point of view, as it enabled modified salicylate release. It is beneficial from a technological perspective too, because it improved thermal, rheological, and adhesive properties of the in situ film. DSC revealed complete dissolution of SA and good miscibility of MS with the polymer. MS also ensures optimal viscoelastic and adhesive properties of the film, leading to prolonged and sustained drug release. The hydrolysis of MS to active SA was very slow at skin pH 5.5, but it apparently occurred at physiological pH 7.4. The film structure is homogeneous without cracks, unlike some commercial preparations. The dissolution study of salicylates revealed different courses in their release and the influence of MS concentration in the film. The formulated PLGA-based FFS containing 5 % SA and 10 % MS is promising for sustained and prolonged local delivery of salicylates, used mainly for keratolytic and anti-inflammatory actions and pain relief.
- MeSH
- aplikace kožní MeSH
- aplikace lokální MeSH
- farmaceutická chemie metody MeSH
- koncentrace vodíkových iontů MeSH
- kopolymer kyseliny glykolové a mléčné * chemie MeSH
- kůže metabolismus MeSH
- kyselina mléčná * chemie MeSH
- kyselina polyglykolová * chemie MeSH
- kyselina salicylová * aplikace a dávkování chemie farmakokinetika MeSH
- lékové transportní systémy * metody MeSH
- léky s prodlouženým účinkem MeSH
- rozpustnost MeSH
- salicylany * aplikace a dávkování chemie farmakokinetika MeSH
- uvolňování léčiv MeSH
- Publikační typ
- časopisecké články MeSH
Testing the hemocompatibility of medical devices after their interaction with blood entails the need to evaluate the activation of blood elements and the degree of their coagulation and adhesion to the device surface. One possible way to achieve this is to use scanning electron microscopy (SEM). The aim was to develop a novel SEM-based method to assess the thrombogenic potential of medical devices and their adhesiveness to blood cells. As a part of this task, also find a convenient procedure of efficient and non-destructive sample fixation for SEM while reducing the use of highly toxic substances and shortening the fixation time. A polymeric surgical mesh was exposed to blood so that blood elements adhered to its surface. Such prepared samples were then chemically fixed for a subsequent SEM measurement; a number of fixation procedures were tested to find the optimal one. The fixation results were evaluated from SEM images, and the degree of blood elements' adhesion was determined from the images using ImageJ software. The best fixation was achieved with the May-Grünwald solution, which is less toxic than chemicals traditionally used. Moreover, manipulation with highly toxic osmium tetroxide can be avoided in the proposed procedure. A convenient methodology for SEM image analysis has been developed too, enabling to quantitatively evaluate the interaction of blood with the surfaces of various medical devices. Our method replaces the subjective assessment of surface coverage with a better-defined procedure, thus offering more precise and reliable results.
- MeSH
- histologické techniky * MeSH
- mikroskopie elektronová rastrovací MeSH
- oxid osmičelý * MeSH
- Publikační typ
- časopisecké články MeSH
Due to the possibility of designing various spatial structures, three-dimensional printing can be implemented in the production of customized medicines. Nevertheless, the use of these methods for the production of dosage forms requires further optimization, understanding, and development of printouts' quality verification mechanisms. Therefore, the goal of our work was the preparation and advanced characterization of 3D printed orodispersible tablets (ODTs) containing fluconazole, printed by the fused deposition modeling (FDM) method. We prepared and analyzed 7 printable filaments containing from 10% to 70% fluconazole, used as model API. Obtaining a FDM-printable filament with such a high API content makes our work unique. In addition, we confirmed the 12-month stability of the formulation, which, to our knowledge, is the first study of this type. Next, we printed 10 series of porous tablets containing 50 mg of API from both fresh and stored filaments containing 20 %, 40 %, or 70 % fluconazole. We confirmed the high quality and precision of the printouts using scanning electron microscopy. The detailed analysis of the tablets' disintegration process included the Pharmacopeial test, but also the surface dissolution imaging analysis (SDI) and the test simulating oral conditions performed in own-constructed apparatus. For each composition, we obtained tablets disintegrating in less than 3 min, i.e., meeting the criteria for ODTs required by the European Pharmacopeia. The filaments' storage at ambient conditions did not affect the quality of the tablets. All printed tablets released over 95% of the fluconazole within 30 min. Moreover, the printouts were stable for two weeks.
- MeSH
- 3D tisk * MeSH
- farmaceutická technologie metody MeSH
- flukonazol * MeSH
- poréznost MeSH
- tablety chemie MeSH
- uvolňování léčiv MeSH
- Publikační typ
- časopisecké články MeSH
An important feature of orodispersible tablets (ODTs) is the convenient administration of the drugs, in some cases, faster onset of action, stability maintenance, and dose precision. This work focused on the preparation of ODTs containing mannitol-based co-processed excipients Prosolv® ODT G2, Ludiflash® and Parteck® ODT in combination with tramadol, captopril, and domperidone by direct compression. Prosolv® ODT G2 showed high energy of plastic deformation due to the content of microcrystalline cellulose. Parteck® ODT provided compact tablets due to the content of granulated mannitol. All drugs decreased tensile strength, increased friability, prolonged disintegration time, and decreased the porosity of tablets. Tablets containing Prosolv® ODT G2 with captopril, domperidone, and tramadol; and Parteck® ODT with domperidone met the requirements for ODTs production, i.e., friability ≤ 1% and disintegration time ≤ 180 s, fast wetting time, high water absorption ratio, and adequate tensile strength. The disintegration time was tested using both the pharmacopeial method and the BJKSN-13 apparatus. The results indicate the significant difference between these methods, with the disintegration time being longer when tested with the BJKSN-13 instrument.
Co-processed dry binders for ODTs are important multifunctional excipients for tablet manufacturing by direct compression. Testing their binary mixtures with lubricants is an important aspect of their use in combination with drugs. The aim of this study was to evaluate the rheological and compression properties of lubricated mixtures of co-processed dry binders Parteck® ODT, Prosolv® ODT G2 and Ludiflash®, and subsequently also the compactability and disintegration time of the tablets made thereof. The lubricants employed were magnesium stearate and sodium stearyl fumarate in the concentrations of 0.5% and 1%. The best flowability was shown by Prosolv® ODT G2 combined with magnesium stearate in the concentration of 0.5%. Lubricated mixtures with Prosolv® ODT G2 showed a lower angle of internal friction as well as lower pre-compression energy values. The values of plastic deformation energy were the highest in the case of Prosolv® ODT G2, which was also reflected in the highest tablet strength. On the contrary, the ejection force values were the lowest for this co-processed dry binder. Magnesium stearate reduced the ejection force more effectively than sodium stearyl fumarate. Prosolv® ODT G2 tablets exhibited the highest tensile strength and shortest disintegration time.
- MeSH
- lubrikanty * MeSH
- pevnost v tahu MeSH
- pomocné látky * MeSH
- tablety MeSH
- Publikační typ
- časopisecké články MeSH
Although progress is evident in the effective treatment of joint replacement-related infections, it still remains a serious issue in orthopedics. As an example, the local application of antibiotics-impregnated bone grafts supplies the high drug levels without systemic side effects. However, antibiotics in the powder or solution form could be a risk for local toxicity and do not allow sustained drug release. The present study evaluated the use of an antibiotic gel, a water-in-oil emulsion, and a PLGA microparticulate solid dispersion as depot delivery systems impregnating bone grafts for the treatment of joint replacement-related infections. The results of rheological and bioadhesive tests revealed the suitability of these formulations for the impregnation of bone grafts. Moreover, no negative effect on proliferation and viability of bone marrow mesenchymal stem cells was detected. An ex vivo dissolution test of vancomycin hydrochloride and gentamicin sulphate from the impregnated bone grafts showed a reduced burst and prolonged drug release. The PLGA-based formulation proved to be particularly promising, as one-day burst release drugs was only 15% followed with sustained antibiotics release with zero-order kinetics. The results of this study will be the basis for the development of a new product in the Tissue Section of the University Hospital for the treatment of bone defects and infections of joint replacements.
- MeSH
- antibakteriální látky farmakologie terapeutické užití MeSH
- artroplastiky kloubů * MeSH
- emulze MeSH
- gentamiciny MeSH
- lékové transportní systémy MeSH
- lidé MeSH
- prášky, zásypy, pudry MeSH
- transplantace hematopoetických kmenových buněk * MeSH
- vankomycin MeSH
- voda MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Additive manufacturing technologies are considered as a potential way to support individualized pharmacotherapy due to the possibility of the production of small batches of customized tablets characterized by complex structures. We designed five different shapes and analyzed the effect of the surface/mass ratio, the influence of excipients, and storage conditions on the disintegration time of tablets printed using the fused deposition modeling method. As model pharmaceutical active ingredients (APIs), we used paracetamol and domperidone, characterized by different thermal properties, classified into the various Biopharmaceutical Classification System groups. We found that the high surface/mass ratio of the designed tablet shapes together with the addition of mannitol and controlled humidity storage conditions turned out to be crucial for fast tablet's disintegration. As a result, mean disintegration time was reduced from 5 min 46 s to 2 min 22 s, and from 11 min 43 s to 2 min 25 s for paracetamol- and domperidone-loaded tablets, respectively, fulfilling the European Pharmacopeia requirement for orodispersible tablets (ODTs). The tablet's immediate release characteristics were confirmed during the dissolution study: over 80% of APIs were released from printlets within 15 min. Thus, this study proved the possibility of using fused deposition modeling for the preparation of ODTs.
- Publikační typ
- časopisecké články MeSH
As proven in clinical trials, superficial fungal infections can be effectively treated by single topical application of terbinafine hydrochloride (Ter-HCl) in a film forming system (FFS). Poly(lactic-co-glycolic acid) (PLGA) derivatives, originally synthesized with intention to get carriers with optimized properties for drug delivery, and multifunctional plasticizers - ethyl pyruvate, methyl salicylate, or triacetin - were used for formulation of Ter-HCl loaded FFSs. After spraying, a biodegradable, transparent, adhesive, and occlusive thin layer is formed on the skin, representing drug depot. In situ formed films were characterized by thermal, structural, viscoelastic, and antifungal properties as well as drug release and skin penetration. DSC and SEM showed fully amorphous films with Ter-HCl dissolved in PLGA in high concentration (up to 15%). FFSs are viscoelastic fluids with viscosity which can be easily adjusted by the type of plasticizer used and its concentration. The formulations showed excellent bioadhesion properties, thus ensuring persistence on the skin. In situ film based on branched PLGA/A plasticized with 10% of ethyl pyruvate allowed prolonged release of Ter-HCl by linear kinetics for the first 6 days with a total time of almost 14 days. During ex vivo human skin penetration experiment, Ter-HCl was found to be located only in its target layer, the epidermis. According to our results, plasticized branched PLGA derivatives loaded by Ter-HCl are suitable for the development of FFSs for superficial fungal infections treatment.
- MeSH
- antifungální látky MeSH
- lidé MeSH
- mykózy * MeSH
- nosiče léků * MeSH
- terbinafin MeSH
- uvolňování léčiv MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Although the systemic administration of terbinafine is quite well tolerated, topical treatment of the local infections is often preferred. New formulation strategies in topical antifungal therapy represent the polymeric nanoparticles (NPs). We successfully employed the originally synthesized PLGA derivatives of branched architectures of various molar masses, branching ratio, and high number of terminal hydroxyl or carboxyl groups for compounding of terbinafine loaded nanoparticles by nanoprecipitation method. Employing the polymers with tailored properties allowed us to formulate the NPs with desired particle size, loading capacity for drug, mucoadhesive properties, and drug release profile. The hydrophobicity and the polyester concentration revealed the main impact on the NPs size ranging from 100 to 600 nm. The stability of the nanosuspension is demonstrated by zeta potential >25 mV, and polydispersity index values <0.2. We used terbinafine in its less dissolved form of the base to increase the drug loading and delay the release. Cationic surfactant as stabilizer give the NPs high positive surface charge enhancing the adhesion to the mucosal surfaces. All formulations provided prolonged sustained release of terbinafine for several days. Antimicrobial potential has been proven by agar-well diffusion method.
- MeSH
- antifungální látky aplikace a dávkování chemie MeSH
- aplikace lokální MeSH
- hydrofobní a hydrofilní interakce MeSH
- kationty MeSH
- kopolymer kyseliny glykolové a mléčné chemie MeSH
- nanočástice chemie MeSH
- nosiče léků chemie MeSH
- povrchově aktivní látky chemie MeSH
- povrchové vlastnosti MeSH
- příprava léků metody MeSH
- rozpustnost MeSH
- terbinafin aplikace a dávkování chemie MeSH
- uvolňování léčiv MeSH
- velikost částic MeSH
- viskozita MeSH
- Publikační typ
- časopisecké články MeSH
