Medfazna reologija: Pregled merilnih tehnik in njen pomen v disperzijah in elekrostatskemu sukanju

Interfacial rheological properties have yet to be thoroughly explored. Only recently, methods have been introduced that provide sufficient sensitivity to reliably determine viscoelastic interfacial properties. In general, interfacial rheology describes the relationship between the deformation of an interface and the stresses exerted on it. Due to the variety in deformations of the interfacial layer (shear and expansions or compressions), the field of interfacial rheology is divided into the subcategories of shear and dilatational rheology. While shear rheology is primarily linked to the long-term stability of dispersions, dilatational rheology provides information regarding short-term stability. Interfacial rheological characteristics become relevant in systems with large interfacial areas, such as emulsions and foams, and in processes that lead to a large increase in the interfacial area such as electrospinning of nanofibers.Medfazne reološke lastnosti so še dokaj neraziskane. Šele pred kratkim so razvili metode, s katerimi je mogoče z zadostno občutljivostjo in natančnostjo določiti viskoelastične lastnosti medfaze. Medfazna reologija opisuje odnos med deformacijo medfaze in silo, ki to deformacijo povzroči. Zaradi različnih deformacij medfazne plasti (strig in raztezanje, oziroma krčenje) se tudi medfazna reologija deli na strižno in dilatacijsko. Strižne reološke lastnosti medfaze se odražajo v dolgotrajni stabilnosti disperzij, medtem ko sedilatacijske predvsem v kratkotrajni stabilnosti. Poznavanje medfaznih reoloških lastnosti je pomembno v sistemih z velikimi medfaznimi površinami, kot so emulzije in pene ter pri procesih, kjer pride do velikega povečanja medfazne površine, kot je elektrostatsko sukanje nanovlaken

Nanofibers and their biomedical use

The idea of creating replacement for damaged or diseased tissue, which will mimic the physiological conditions and simultaneously promote regeneration by patients\u27 own cells, has been a major challenge in the biomedicine for more than a decade. Therefore, nanofibers are a promising solution to address these challenges. These are solid polymer fibers with nanosized diameter, which show improved properties compared to the materials of larger dimensions or forms and therefore cause different biological responses. On the nanometric level, nanofibers provide a biomimetic environment, on the micrometric scale three-dimensional architecture with the desired surface properties regarding the intended application within the body, while on the macrometric scale mechanical strength and physiological acceptability. In the review, the development of nanofibers as tissue scaffolds, modern wound dressings for chronic wound therapy and drug delivery systems is highlighted. Research substantiates the effectiveness of nanofibers for enhanced tissue regeneration, but ascertains that evidences from clinical studies are currently lacking. Nevertheless, due to the development of nano- and bio-sciences, products on the market can be expected in the near future

Image-Based Investigation : Biorelevant Solubility of α and γ Indomethacin

Solubility is a physicochemical property highly dependent on the solid-state form of a compound. Thus, alteration of a compound’s solid-state form can be undertaken to enhance the solubility of poorly soluble drug compounds. In the Biopharmaceutics Classification System (BCS), drugs are classified on the basis of their aqueous solubility and permeability. However, aqueous solubility does not always correlate best with in vivo solubility and consequently bioavailability. Therefore, the use of biorelevant media is a more suitable approach for mimicking in vivo conditions. Here, assessed with a novel image-based single-particle-analysis (SPA) method, we report a constant ratio of solubility increase of 3.3 ± 0.5 between the α and γ solid-state forms of indomethacin in biorelevant media. The ratio was independent of pH, ionic strength, and surfactant concentration, which all change as the drug passes through the gastrointestinal tract. On the basis of the solubility ratio, a free-energy difference between the two polymorphic forms of 2.9 kJ/mol was estimated. Lastly, the use of the SPA approach to assess solubility has proven to be simple, fast, and both solvent- and sample-sparing, making it an attractive tool for drug development.Peer reviewe

MRI study of hydrophilic xanthan tablets with incorporated model drug

Magnetic resonance imaging was used to study swelling dynamics and hydrogel formation of xanthan tablets with or without Pentoxifylline drug in water and HCl pH 1.2 media at two different ionic strengths. Significant changes were observed only in the erosion front positions leading to different hydrogel thicknesses. The impact of the drug on the hydrogel thickness was found to be dependent on the medium conditions at high enough drug amount. The drug does not change the hydrogel thickness in water medium, whereas in acid medium the presence of the drug results in thinner hydrogel. The increased ionic strength in water medium also leads to formation of the thinner hydrogel layer in tablets with high enough drug content, while the effect of NaCl in HCl pH 1.2 medium is very small

Application of miscibility analysis and determination of Soluplus solubility map for development of carvedilol-loaded nanofibers

Electrospinning was used to produce carvedilol-loaded Soluplus polymer nanofibers using a systematic approach. Miscibility between drug and polymer was determined through calculation of the interaction parameter, chi, and the difference between the total solubility parameters, Delta d(t). A solubility map for Soluplus was obtained by examining different solvent systems, carrying out electrospinning, and characterizing the nanofibers formed. Miscibility studies showed that carvedilol and Soluplus can form a miscible system (chi = -2.3054; Delta delta(t) lt 7.0 MPa1/2). Based on the Soluplus solubility map, acetone: chloroform (90: 10; w/w) represents a suitable solvent system for electrospinning of carvedilol-loaded Soluplus nanofibers. Scanning electron microscopy of these nanofiber samples showed smooth surface morphology. The nanofibers had a regular cylindrical morphology. Beads appeared along the nanofibers more frequently in formulations with lower percentages of carvedilol. Differential scanning calorimetry showed no melting endothermic peak for carvedilol, which suggests its complete conversion from the crystalline to the amorphous form (at polymer: carvedilol 1: 1). The infrared spectrum of the carvedilol-loaded Soluplus nanofibers showed no characteristic carvedilol peak at 3344.5 cm(-1), which suggests interactions between carvedilol and Soluplus. Dissolution studies of these nanofibers showed improved pure carvedilol dissolution properties, with >85% of the carvedilol released in the first 15 min, versus 20% for pure carvedilol. The use of miscibility analysis and polymer solubility studies demonstrate great technological potential to tackle the challenge for inadequate dissolution of poorly water-soluble drugs.This is peer-reviewed version of the following article: Kaljević, O.; Đuriš, J.; Čalija, B.; Lavrić, Z.; Kristl, J.; Ibrić, S. Application of Miscibility Analysis and Determination of Soluplus Solubility Map for Development of Carvedilol-Loaded Nanofibers. International Journal of Pharmaceutics 2017, 533 (2), 445–454. [https://doi.org/10.1016/j.ijpharm.2017.05.017

Magnetic resonance methods as a prognostic tool for the biorelevant behavior of xanthan tablets

Hydrophilic matrix tablets with controlled drug release have been used extensively as one of the most successful oral drug delivery systems for optimizing therapeutic efficacy. In this work, magnetic resonance imaging (MRI) is used to study the influence of various pHs and mechanical stresses caused by medium flow (at rest, 80, or 150 mL/min) on swelling and on pentoxifylline release from xanthan (Xan) tablets. Moreover, a bimodal MRI system with simultaneous release testing enables measurements of hydrogel thickness and drug release, both under the same experimental conditions and at the same time. The results show that in water, the hydrogel structure is weaker and less resistant to erosion than the Xan structure in the acid medium. Different hydrogel structures affect drug release with erosion controlled release in water and diffusion controlled release in the acid medium. Mechanical stress simulating gastrointestinal contraction has no effect on the hard hydrogel in the acid medium where the release is independent of the tested stress, while it affects the release from the weak hydrogel in water with faster release under high stress. Our findings suggest that simultaneous MR imaging and drug release from matrix tablets together provide a valuable prognostic tool for prolonged drug delivery design

Magnetic Resonance Methods as a Prognostic Tool for the Biorelevant Behavior of Xanthan Tablets

Hydrophilic matrix tablets with controlled drug release have been used extensively as one of the most successful oral drug delivery systems for optimizing therapeutic efficacy. In this work, magnetic resonance imaging (MRI) is used to study the influence of various pHs and mechanical stresses caused by medium flow (at rest, 80, or 150 mL/min) on swelling and on pentoxifylline release from xanthan (Xan) tablets. Moreover, a bimodal MRI system with simultaneous release testing enables measurements of hydrogel thickness and drug release, both under the same experimental conditions and at the same time. The results show that in water, the hydrogel structure is weaker and less resistant to erosion than the Xan structure in the acid medium. Different hydrogel structures affect drug release with erosion controlled release in water and diffusion controlled release in the acid medium. Mechanical stress simulating gastrointestinal contraction has no effect on the hard hydrogel in the acid medium where the release is independent of the tested stress, while it affects the release from the weak hydrogel in water with faster release under high stress. Our findings suggest that simultaneous MR imaging and drug release from matrix tablets together provide a valuable prognostic tool for prolonged drug delivery design