Electrospinning is an efficient and flexible method for nanofiber production, but it is influenced by many systemic, process, and environmental parameters that govern the electrospun product ...morphology. This study systematically investigates the influence of relative humidity (RH) on the electrospinning process. The results showed that the morphology of the electrospun product (shape and diameter) can be manipulated with precise regulation of RH during electrospinning. Because the diameter of nanofibers correlates with their rigidity, it was shown that RH control can lead to manipulation of material mechanical properties. Finally, based on the solution's rheological parameter—namely, phase shift angle—we were able to predict the loss of homogenous nanofiber structure in correlation with RH conditions during electrospinning. This research addresses the mechanism of RH impact on the electrospinning process and offers the background to exploit it in order to better control nanomaterial properties and alter its applicability.
The formation of a gel coat around xanthan (Xan) tablets, empty or loaded with pentoxifylline (PF), and its release in media differing in pH and ionic strength by NMR, MR imaging, and two release ...methods were studied. The T 1 and T 2 NMR relaxation times in gels depend predominantly on Xan concentration; the presence of PF has negligible influence on them. It is interesting that the matrix swelling is primarily regulated by Xan despite high drug loading (25%, 50%). The gastric pH and high ionic strength of the media do not influence the position of the penetration and swelling fronts but do affect the erosion front and gel thickness. The different release profiles obtained in mixing and nonmixing in vitro methods are the consequence of matrix hydration level and erosion at the surface. In water and in diluted acid medium with low ionic strength, the main release mechanism is erosion, whereas in other media (pH 1.2, μ ≥ 0.20 M), anomalous transport dominates as was found out by fitting of measured data with theoretical model. Besides the in vitro investigation that mimics gastric conditions, mathematical modeling makes the product development more successful.
Compressibility of wet processed granules of same model placbo mixture was superior to dry processed mixtures measured via Heckel and Walker models and net energy using force–displacement data.
The ...purpose of this study was to investigate the influence of various powder agglomeration processes on tableting mixture flow and compaction properties. Four different granulation methods of the same model placebo formulation were tested at a semi-industrial scale and their properties were compared to those of the directly compressed mixture. The wet granulated mixtures had superior flow properties compared to other mixtures and showed better compressibility, measured by the Heckel and Walker models. This was attributed to work hardening due to the double particle processing and also to shorter contact times due to higher initial densities of dry granulated mixtures, allowing a shorter time for deformation. A strong linear correlation was established between the Heckel and Walker coefficients, which was further confirmed by the net energy results of force–displacement measurements. It was shown that the Walker model had slightly better discriminative power to differentiate tableting mixtures according to compressibility. The compactibility was considerably lower for the slugged mixture; however, the roller-compacted mixture produced tablets with unexpectedly high tensile strength. In conclusion, it is important to emphasize that general assumptions like higher porosity ⇒ better compressibility or better compressibility ⇒ better compactibility cannot be established for complex tableting mixtures.
The key element in drug release from hydrophilic matrix tablets is the gel layer that regulates the penetration of water and controls drug dissolution and diffusion. We have selected magnetic ...resonance imaging (MRI) as the method of choice for visualizing the dynamic processes occurring during the swelling of xanthan tablets in a variety of media. The aims were (i) to develop a new method using MRI for accurate determination of penetration, swelling and erosion fronts, (ii) to investigate the effects of pH and ionic strength on swelling, and (iii) to study the influence of structural changes in xanthan gel on drug release. Two dimensional (2D) MRI and one dimensional single point imaging (SPI) of swollen xanthan tablets were recorded, together with
T
2 mapping. The border between dry and hydrated glassy xanthan—the penetration front—was determined from 1D SPI signal intensity profiles. The erosion front was obtained from signal intensity profiles of 2D MR images. The swelling front, where xanthan is transformed from a glassy to a rubbery state (gel formation), was determined from
T
2 profiles. Further, the new combination of MRI methods for swelling front determination enables to explain the appearance of the unusual “bright front” observed on 2D MR images in tablets swollen in HCl pH 1.2 media, which represents the position of swelling front. All six media studied, differing in pH and ionic strength, penetrate through the whole tablet in 4
h
±
0.3
h, but formation of the gel layer is significantly delayed. Unexpectedly, the position of the swelling front was the same, independently of the different xanthan gel structures formed under different conditions of pH and ionic strength. The position of the erosion front, on the other hand, is strongly dependent on pH and ionic strength, as reflected in different thicknesses of the gel layers. The latter are seen to be the consequence of the different hydrodynamic radii of the xanthan molecules, which affect the drug release kinetics. The slowest release of pentoxifylline was observed in water where the thickest gel was formed, whereas the fastest release was observed in HCl pH 1.2, in which the gel layer was thinnest. Moreover, experiments simulating physiological conditions showed that changes of pH and ionic strength influence the xanthan gel structure relatively quickly, and consequently the drug release kinetics. It is therefore concluded that drug release is greatly influenced by changes in the xanthan molecular conformation, as reflected in changed thickness of the gel layer. A new method utilizing combination of SPI, multi-echo MRI and
T
2 mapping eliminates the limitations of standard methods used in previous studies for determining moving fronts and improves current understanding of the dynamic processes involved in polymer swelling.
MRI signal intensity and
T
2 were used to determine the position of penetration, swelling and erosion fronts during swelling of xanthan matrix tablets.
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When a cationic drug like doxazosin mesylate (DM) is incorporated into matrix tablets made of anionic polyelectrolytes carrageenans (CARRs) of different types (κ-, ι-, λ-CARR), DM–CARR interactions ...have a strong impact on drug release. To investigate these interactions, special DM ion-selective membrane electrode was made and applied for construction of binding isotherms. Isotherms were treated by the Zimm–Bragg theory and cooperative binding model. It was demonstrated that binding of doxazosin cations, DH+, to CARRs is cooperative. It starts at very low drug concentrations with strong electrostatic interactions followed by aggregation of DH+ ions. Hydrophobic interactions between bound DH+ substantially contribute to the extent of binding. The strength of interactions increases with increasing negative charge of CARRs. At saturation, the number of DM molecules bound per repeat unit depends on the charge and steric distribution of binding sites on CARRs. Drug release rates of DM from CARR matrices were in accordance with the cooperativity binding constants: the weakest binding resulted in the fastest release. However it was proven that prolonged drug release is possible only by several processes running simultaneously, i.e., by swelling and erosion of CARR matrices on one side and electrostatic interactions and cooperativity effects on the other.
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► Physical properties of PVA solutions in broad concentration range are investigated. ► Behavior of low concentrated PVA solutions is not predictive for high concentrated ones. ► The ...correlations between solution parameters and electrospinning outcome are explored. ► For effective electrospinning PVA solutions should exert a hydrophilic sol structure. ► The study represents guidance for successful electrospinning of other polymers.
Nanofibers prepared from poly (vinyl alcohol) (PVA) using the electrospinning process have received a great deal of attention over the past decade due to their outstanding characteristics and their applicability in the field of biomedicine, coupled with their innovative preparation. However, the success of the electrospinning process depends strongly on the parameters of the source polymer solution. Of these parameters the majority of published papers routinely examine the viscosity, conductivity and surface tension, while other, indeed crucial, physical characteristics are only rarely investigated. In the present work, the emphasis was also on a comprehensive investigation of the bulk and interfacial rheology as well as on the small-angle X-ray scattering (SAXS) of PVA solutions. A detailed analysis revealed rearrangements of the molecules in the solutions depending on the polymer concentration proved by measured surface tension, determined apparent specific volume and radius of gyration. Further, we found out that smooth nanofibers are formed only from those PVA solutions, where properly firm internal polymer structures that can be oriented in the direction of an applied electric field, enable complete polymer elongation during the electrospinning. It is important to note that this is the first time that such an extensive study has been made and, our findings provide a better insight into the physical properties of the solutions for electrospinning as well as their decisive influence on the formation of the nanofibers.
It is challenging to achieve mechanically robust drug-release profiles from hydrophilic matrices containing a high dose of a drug with good solubility. However, a mechanically robust drug release ...over prolonged period of time can be achieved, especially if the viscosity and amount of the polymer is sufficiently high, above the “threshold values.” The goal of this research was to determine the hydroxypropyl cellulose (HPC) and hydroxypropyl methylcellulose (HPMC) polymer threshold amount that would enable robust drug release from matrix tablets containing a high dose of levetiracetam as a class I model drug according to the Biopharmaceutical Classification System (BCS). For this purpose, formulations containing HPC or HPMC of similar viscosity range, but in different amounts, were prepared. Based on the dissolution results, two final formulations were selected for additional
in vitro
and
in vivo
evaluation to confirm the robustness and to show bioequivalence. Tablets were exposed to various stress conditions
in vitro
with the use of different mechanically stress-inducing dissolution methods. The
in vitro
results were compared with
in vivo
results obtained from fasted and fed bioequivalence studies. Under both conditions, the formulations were bioequivalent and food had a negligible influence on the pharmacokinetic parameters
C
max
and area under the curve (AUC). It was concluded that the drug release from both selected formulations is mechanically robust and that HPC and HPMC polymers with intrinsic viscosities above 9 dL/g and in quantities above 30% enable good mechanical resistance, which ensures bioequivalence. In addition, HPC matrices were found to be more mechanically robust compared to HPMC.
Periodontal disease is chronic inflammation of periodontal tissues resulting in formation of periodontal pockets, periodontal attachment loss and progressive destruction of the ligament and alveolar ...bone. This review gives an update on periodontal disease pathogenesis, which is important for the development of novel methods and delivery systems for its treatment. The available treatment approaches, including removal of dental plaque, modulation of the host inflammatory response, and regeneration of periodontal tissue, are reviewed and their drawbacks discussed. Furthermore the latest achievements involving development of nanomedicines, which represent a new approach to better treatment of periodontal disease, are highlighted. They enable local drug delivery to particular tissues, cells, or subcellular compartments in periodontal pockets, either to biofilm pathogens or host cells, as well as control the release of incorporated drugs, usually antibiotic or anti-inflammatory. Specific examples of the nanocarriers or nanomaterials such as liposomes, lipid and polymeric nanoparticles, nanocrystals, dendrimers, and nanofibers under development for the treatment of periodontal disease are also clearly reviewed. Nanofibers are of special interest as nanodelivery systems and scaffolds for the regeneration of periodontal tissue. Finally, the future outlook of novel therapeutic approaches involving nanodelivery systems in the treatment of periodontal disease is provided.
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The number of poorly water-soluble drug candidates is rapidly increasing; this represents a major challenge for the pharmaceutical industry. As a consequence, novel formulation ...approaches are required. Furthermore, if such a drug candidate is intended for the therapy of a specific group of the population, such as geriatric or pediatric, the formulation challenge is even greater, with the need to produce a dosage form that is acceptable for specific patients. Therefore, the goal of our study was to explore electrospun polycaprolactone (PCL) nanofibers as a novel nanodelivery system adopted for the oromucosal administration of poorly water-soluble drugs. The nanofibers were evaluated in comparison with polymer films loaded with ibuprofen or carvedilol as the model drugs. Scanning electron microscopy revealed that the amount of incorporated drug affects the diameter and the morphology of the nanofibers. The average fiber diameter increased with a higher drug loading, whereas the morphology of the nanofibers was noticeably changed in the case of nanofibers with 50% and 60% ibuprofen. The incorporation of drugs into the electrospun PCL nanofibers was observed to reduce their crystallinity. Based on the morphology of the nanofibers and the films, and the differential scanning calorimetry results obtained in this study, it can be assumed that the drugs incorporated into the nanofibers were partially molecularly dispersed in the PCL matrix and partially in the form of dispersed nanocrystals. The incorporation of both model drugs into the PCL nanofibers significantly improved their dissolution rates. The PCL nanofibers released almost 100% of the incorporated ibuprofen in 4h, whereas only up to 77% of the incorporated carvedilol was released during the same time period, indicating the influence of the drug’s properties, such as molecular weight and solubility, on its release from the PCL matrix. The obtained results clearly demonstrated the advantages of the new nanodelivery system compared to the drug-loaded polymer films that were used as the reference formulation. As a result, electrospinning was shown to be a very promising nanotechnology-based approach to the formulation of poorly water-soluble drugs in order to enhance their dissolution. In addition, the great potential of the produced drug-loaded PCL nanofiber mats for subsequent formulation as oromucosal drug delivery systems for children and the elderly was confirmed.
Detailed knowledge based on new developments, especially in analytical techniques, is needed for characterizing polymer excipients. Inverse gas chromatography (IGC) is a useful method for ...investigating polymer surfaces in terms of thermodynamic parameters. The aim of our work was to study the correlation between polymer surface properties determined with IGC and the mechanisms of release of water-soluble pentoxifylline and vancomycin hydrochloride from cellulose ether matrices. Tablets were made of hydroxypropyl (HPC), hydroxyethyl (HEC) or hydroxypropylmethyl (HPMC) cellulose and contained 25% of drug. Differences in dispersive component of the surface free energy for these polymers were relatively small and ranged from 26 to 33
mN/m. However, polar properties, expressed as specific component of the enthalpy of adsorption and as acid–base properties show larger differences between the polymers and demonstrate their relative polarity in the order HEC
>
HPMC
>
HPC, which correlates well with water sorption on bulky polymers and with the swelling degree of polymer matrices. The release of pentoxifylline and vancomycin from HPC is governed mainly by Fickian diffusion, whereas from HEC the relaxation of polymer chains is important too. The analysis of the release profiles in the light of Peppas–Sahlin model lead to the conclusion that the surface properties of the cellulose ethers influence the interactions with water and the release mechanisms of the drug. It was found out, that data obtained by IGC enable rapid inference about the behaviour of polymers in water and the release of water-soluble drugs.
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