Solubility–spinnability map and model for the preparation of fibres of polyethylene (terephthalate) using gyration and pressure

AbstractThe selection of a solvent or a solvent system is a fundamental and a crucial step in spinning fibres using a selected process. Solvent selection determines the critical minimum polymer concentration and the critical minimum chain entanglement which allows the spinning of nanofibres rather than other hybrid morphologies such as beaded structures. Pressurised gyration, which simultaneously combines the use of gas pressure and rotation, is used as the processing and forming route for spinning fibres in this work. This study investigates 23 different solvents and solvent systems spread on a wide area of a Teas graph and able to dissolve the functional polymer polyethylene (terephthalate) (PET) and spin products by the application of pressurised gyration. The results are mapped on a Teas graph to identify the solubility–spinnability region. Based on this solubility–spinnability region, various solvents and binary solvent systems that allow the making of PET fibres are suggested. Scaling laws for the relationship between polymer concentration and specific viscosity are identified. The structural evolution in the fibres prepared is elucidated. For the first time, a mathematical model to scale fibre diameter with respect to flow properties and processing parameters encountered in pressurised gyration has been successfully developed

pH Alteration in Plant-Mediated Green Synthesis and Its Resultant Impact on Antimicrobial Properties of Silver Nanoparticles (AgNPs)

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)Plant-mediated green synthesis is a cost-effective and eco-friendly process used to synthesize metallic nanoparticles. Experimental pH is of interest due to its ability to influence nanoparticle size and shape; however, little has been explored in comparison to the influence of this parameter on the therapeutic potential of resultant metallic nanoparticles. Our work investigated the influence of pH alternation on antimicrobial properties of plant-mediated green synthesized (using Spinacia oleracea leaf extract) silver nanoparticles. We further investigated if the antimicrobial activity was sustained at 8 weeks (after initial green synthesis). Antimicrobial properties were evaluated against Escherichia coli, Staphylococcus aureus, and Candida albicans. Our work confirmed that experimental pH in plant-mediated green synthesis of silver nanoparticles influenced their resultant antimicrobial properties. Silver nanoparticles generated at experimental pH 4.5, and nine showed activity against E. coli which was sustained at various levels over 8 weeks. No antimicrobial activity was observed against S. aureus, and weak antimicrobial activity against C. albicans. These interesting findings highlight the importance of experimental pH. Further understanding of the role experimental pH plays on resultant metallic nanoparticle properties as it relates to biological and therapeutic impact is required, which will have an impact on wider applications beyond antimicrobial activity.Peer reviewe

The development of progesterone-loaded nanofibers using pressurized gyration: A novel approach to vaginal delivery for the prevention of pre-term birth

Recent evidence has continued to support the applicability of progesterone in preventing preterm birth, hence the development of an appropriate vaginal delivery system for this drug would be of considerable interest. Here, we describe the development of progesterone-loaded bioadhesive nanofibers using pressurized gyration for potential incorporation into a vaginal insert, with a particular view to addressing the challenges of incorporating a poorly water-soluble drug into a hydrophilic nanofiber carrier. Polyethylene oxide and carboxymethyl cellulose were chosen as polymers to develop the carrier systems, based on previous evidence of their yielding mucoadhesive nanofibers using the pressurized gyration technique. The fabrication parameters such as solvent system, initial drug loading and polymer composition were varied to facilitate optimisation of fiber structure and efficiency of drug incorporation. Such studies resulted in the formation of nanofibers with satisfactory surface appearance, diameters in the region of 400 nm and loading of up to 25% progesterone. Thermal and spectroscopic analyses indicated that the drug was incorporated in a nanocrystalline state. Release from the drug-loaded fibers indicated comparable rates of progesterone dissolution to that of Cyclogest, a commercially available progesterone pessary, allowing release over a period of hours. Overall, the study has shown that pressurized gyration may produce bioadhesive progesterone-loaded nanofibers which have satisfactory loading of a poorly water-soluble drug as well as having suitable structural and release properties. The technique is also capable of producing fibers at a yield commensurate with practical applicability, hence we believe that the approach shows considerable promise for the development of progesterone dosage forms for vaginal application

Thermal Behavior of Benzoic Acid/Isonicotinamide Binary Cocrystals

YesA comprehensive study of the thermal behavior of the 1:1 and 2:1 benzoic acid/isonicotinamide cocrystals is reported. The 1:1 material shows a simple unit cell expansion followed by melting upon heating. The 2:1 crystal exhibits more complex behavior. Its unit cell first expands upon heating, as a result of C–H···π interactions being lengthened. It then is converted into the 1:1 crystal, as demonstrated by significant changes in its X-ray diffraction pattern. The loss of 1 equiv of benzoic acid is confirmed by thermogravimetric analysis–mass spectrometry. Hot stage microscopy confirms that, as intuitively expected, the transformation begins at the crystal surface. The temperature at which conversion occurs is highly dependent on the sample mass and geometry, being reduced when the sample is under a gas flow or has a greater exposed surface area but increased when the heating rate is elevated

Development of micro-fibrous solid dispersions of poorly water-soluble drugs in sucrose using temperature-controlled centrifugal spinning

Solid dispersion technology represents a successful approach to addressing the bioavailability issues caused by the low aqueous solubility of many Biopharmaceutics Classification System (BCS) Class II drugs. In this study, the use of high-yield manufacture of fiber-based dispersion is explored as an alternative approach to monolith production methods. A temperature-controlled solvent-free centrifugal spinning process was used to produce sucrose-based microfibers containing the poorly water-soluble drugs olanzapine and piroxicam (both BCS Class II); these were successfully incorporated into the microfibers and the basic characteristics of fiber diameter, glassy behavior, drug loading capacity and drug-sucrose interaction assessment were measured. Scanning electron microscopy revealed that bead-free drug-loaded microfibers with homogenous morphology and diameter in the range of a few micrometers were prepared using our process. Differential scanning calorimetric and X-ray diffraction analyses showed that both drug and carrier were present in the amorphous state in the microfibers, although in the case of piroxicam-loaded microfibers, the presence of small amounts of crystalline drug was observed under polarized light microscopy and in Fourier transform infrared spectra. Drug dissolution performance was evaluated under both sink and non-sink conditions and was found to be significantly enhanced compared to the corresponding crystalline physical mixtures and pure drugs, with evidence of supersaturation behavior noted under non-sink conditions. This study has demonstrated that microfiber-based dispersions may be manufactured by the centrifugal spinning process and may possess characteristics that are favorable for the enhanced dissolution and oral absorption of drugs. © 2016 The Authors

Exploiting Endocytosis for Non-Spherical Nanoparticle Cellular Uptake

Several challenges exist for successful nanoparticle cellular uptake—they must be able to cross many physical barriers to reach their target and overcome the cell membrane. A strategy to overcome this challenge is to exploit natural uptake mechanisms namely passive and endocytic (i.e., clathrin- and caveolin-dependent/-independent endocytosis, macropinocytosis and phagocytosis). The influence of nanoparticle material and size is well documented and understood compared to the influence of nanomaterial shape. Generally, nanoparticle shape is referred to as being either spherical or non-spherical and is known to be an important factor in many processes. Nanoparticle shape-dependent effects in areas such as immune response, cancer drug delivery, theranostics and overall implications for nanomedicines are of great interest. Studies have looked at the cellular uptake of spherical NPs, however, fewer in comparison have investigated the cellular uptake of non-spherical NPs. This review explores the exploitation of endocytic pathways for mainly inorganic non-spherical (shapes of focus include rod, triangular, star-shaped and nanospiked) nanoparticles cellular uptake. The role of mathematical modelling as predictive tools for non-spherical nanoparticle cellular uptake is also reviewed. Both quantitative structure-activity relationship (QSAR) and continuum membrane modelling have been used to gain greater insight into the cellular uptake of complex non-spherical NPs at a greater depth difficult to achieve using experimental methods

A Design Approach to Optimise Secure Remote Three-Dimensional (3D) Printing:A Proof-of-Concept Study towards Advancement in Telemedicine

Telemedicine is defined as the delivery of healthcare services at a distance using electronic means. The incorporation of 3D printing in the telemedicine cycle could result in pharmacists designing and manufacturing personalised medicines based on the electronic prescription received. Even with the advantages of telemedicine, numerous barriers to the uptake hinder the wider uptake. Of particular concern is the cyber risk associated with the remote digital transfer of the computer-aided design (CAD) file (acting as the electronic prescription) to the 3D printer and the reproducibility of the resultant printed medicinal products. This proof-of-concept study aimed to explore the application of secure remote 3D printing of model solid dosage forms using the patented technology, DEFEND3D, which is designed to enhance cybersecurity and intellectual property (IP) protection. The size, shape, and colour of the remote 3D-printed model medicinal products were also evaluated to ensure the end-product quality was user-focused. Thermoplastic polyurethane (TPU) and poly(lactic) acid (PLA) were chosen as model polymers due to their flexibility in preventing breakage printing and ease of printing with fused deposition modelling (FDM). Our work confirmed the potential of secure remote 3D (FDM) printing of prototype solid dosage forms resulting in products with good reproducibility, resolution, and quality towards advancements in telemedicine and digital pharmacies. The limitation of the work presented here was the use of model polymers and not pharmaceutically relevant polymers. Further work could be conducted using the same designs chosen in this study with pharmaceutically relevant polymers used in hot-melt extrusion (HME) with shown suitability for FDM 3D printing. However, it should be noted that any challenges that may occur with pharmaceutically relevant polymers are likely to be related to the polymer’s printability and printer choice as opposed to the ability of the CAD file to be transferred to the printer remotely

Solid microcrystalline dispersion films as a new strategy to improve the dissolution rate of poorly water soluble drugs: A case study using olanzapine

In this study, we evaluate the dissolution rate enhancement of solid microcrystalline dispersion (SMD) films of olanzapine (OLZ) formulated with four water-soluble polymers namely poly(N-vinylpyrrolidone) (PVP), poloxamer 188 (P188), poloxamer 407 (P407) and Soluplus®(SLP). Prepared formulations were characterised to determine particle size, morphology, hydrogen bonding interactions, thermal characteristics as well as in vitro dissolution studies conducted under sink conditions (pH 6.8). Particle size of OLZ in all formulations ranged between 42 and 58 μm. Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR), Differential Scanning Calorimetry (DSC) and Hot-Stage Microscopy (HSM) studies confirmed OLZ was well maintained in its crystalline state during the formulation process. In vitro dissolution studies showed immediate drug release from all formulation when compared to the drug alone. The greatest increase in in vitro dissolution rate was observed in formulations containing P188 most likely due to its enhanced hydrophilic and surfactant properties compared to the other agents used. Overall, this study successfully generated OLZ loaded SMD films with improved in vitro dissolution rates which is highly likely to result in improved oral bioavailability in vivo