A spectroscopic and thermal investigation into the relationship between composition, secondary structure and physical characteristics of electrospun zein nanofibers

Electrospun zein nanofibers have attracted interest as drug delivery systems due to their propensity for controlled drug release, flexible structure and low toxicity. However, comparatively little is known regarding the relationship between production method and fiber characteristics, both in terms of fiber architecture and protein structure. Here we use a range of imaging and spectroscopic techniques to elucidate the effects of solvent composition on zein secondary structure, fiber diameter and fiber integrity, plus we utilize the new technique of transition temperature microscopy to examine the thermal properties of the fibers. Zein nanofibers were prepared using ethanol, acetic acid and water mixes as solvents, alone and with plasticizers (polyethylene glycol, glycerol) and casein. Electrospinning was performed under controlled conditions and the products characterized using scanning electron microscopy (SEM), attenuated total reflection Fourier Transform infrared spectrometry (ATR - FTIR) and transition temperature microscopy (TTM). The choice of solvent, concentration and voltage, alongside the presence of additives (plasticizers and casein) were noted to influence both the diameter of the fibers and the tendency for bead formation. A relationship was noted between protein secondary structure and fiber architecture, with an enhanced β-sheet content, enhanced by the inclusion of casein, being associated with higher beading. In addition, thermal imaging of electrospun zein fiber mats was successfully achieved using TTM via two dimensional mapping of the softening temperatures across the spun samples, in particular demonstrating the plasticizing effects of the polyethylene glycol and glycerol

Microfibrous Solid Dispersions of Poorly Water-Soluble Drugs Produced via Centrifugal Spinning: Unexpected Dissolution Behavior on Recrystallization

Temperature-controlled, solvent-free centrifugal spinning may be used as a means of rapid production of amorphous solid dispersions in the form of drug-loaded sucrose microfibers. However, due to the high content of amorphous sucrose in the formulations, such microfibers may be highly hygroscopic and unstable on storage. In this study, we explore both the effects of water uptake of the microfibers and the consequences of deliberate recrystallization for the associated dissolution profiles. The stability of sucrose microfibers loaded with three selected BCS class II model drugs (itraconazole (ITZ), olanzapine (OLZ), and piroxicam (PRX)) was investigated under four different relative humidity conditions (11, 33, 53, and 75% RH) at 25 °C for 8 months, particularly focusing on the effect of the highest level of moisture (75% RH) on the morphology, size, drug distribution, physical state, and dissolution performance of microfibers. While all samples were stable at 11% RH, at 33% RH the ITZ-sucrose system showed greater resistance against devitrification compared to the OLZ- and PRX-sucrose systems. For all three samples, the freshly prepared microfibers showed enhanced dissolution and supersaturation compared to the drug alone and physical mixes; surprisingly, the dissolution advantage was largely maintained or even enhanced (in the case of ITZ) following the moisture-induced recrystallization under 75% RH. Therefore, this study suggests that the moisture-induced recrystallization process may result in considerable dissolution enhancement compared to the drug alone, while overcoming the physical stability risks associated with the amorphous state

Preparation and evaluation of azithromycin binary solid dispersions using various polyethylene glycols for the improvement of the drug solubility and dissolution rate

ABSTRACT Azithromycin is a water-insoluble drug, with a very low bioavailability. In order to increase the solubility and dissolution rate, and consequently increase the bioavailability of poorly-soluble drugs (such as azithromycin), various techniques can be applied. One of such techniques is "solid dispersion". This technique is frequently used to improve the dissolution rate of poorly water-soluble compounds. Owing to its low solubility and dissolution rate, azithromycin does not have a suitable bioavailability. Therefore, the main purpose of this investigation was to increase the solubility and dissolution rate of azithromycin by preparing its solid dispersion, using different Polyethylene glycols (PEG). Preparations of solid dispersions and physical mixtures of azithromycin were made using PEG 4000, 6000, 8000, 12000 and 20000 in various ratios, based on the solvent evaporation method. From the studied drug release profile, it was discovered that the dissolution rate of the physical mixture, as the well as the solid dispersions, were higher than those of the drug alone. There was no chemical incompatibility between the drug and polymer from the observed Infrared (IR) spectra. Drug-polymer interactions were also investigated using Differential Scanning Calorimetry (DSC), Powder X-Ray Diffraction (PXRD) and Scanning Election Microscopy (SEM). In conclusion, the dissolution rate and solubility of azithromycin were found to improve significantly, using hydrophilic carriers, especially PEG 6000

Characterisation of the solid and solution state properties of drug dispersions in polyethylene glycols

SIGLEAvailable from British Library Document Supply Centre-DSC:DX193852 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Journal of Pharmacy and Pharmacology

ill;1652hal.;30c

An investigation into the effects of residual water on the glass transition temperature of polylactide microspheres using modulated temperature DSC

The objective of the study was to ascertain residual water levels in polylactide and polylactide-co-glycolide microspheres prepared using the solvent evaporation technique and to investigate the effects of that water on the glass transitional behaviour of the microspheres. Microspheres were prepared from polylactic acid (PLA) and polylactide-co-glycolide (PLGA) 50:50 and 75:25 using a standard solvent evaporation technique. The glass transition was measured as a function of drying conditions using modulated temperature DSC. The microspheres were found to contain very low levels of dichloromethane, while residual water levels of up to circa 3% w/w were noted after freeze or oven drying, these levels being higher for microspheres containing higher glycolic acid levels. The residual water was found to lower the Tg following the Gordon–Taylor relationship. The data indicate that the microparticles may retain significant water levels following standard preparation and drying protocols and that this drying may markedly lower the Tg of the spheres

A thermorheological investigation into the gelation and phase separation of hydroxypropyl methylcellulose aqueous systems

The thermorheological properties of a range of hydroxypropyl methylcellulose (HPMC) solutions have been studied with a view to determining the concentration and substitution dependence of the gelation process. Solutions containing up to 20% w/v HPMC were prepared using three grades of material (METHOCEL1 E4M, F4M, K4M). Rheological studies were performed using a TA AR1000-N Rheometer. Temperature sweeps were performed at a rate of 2°C/min between 20 and 90°C at 1.0Hz and at 4.7Pa, while frequency sweeps were performed at 4.7Pa. A series of thermal transitions were observed for the E4M systems with a minimum seen at approximately 60°C followed by an increase in moduli at approximately 70°C, while on cooling an increase in moduli is seen over a wide range of temperatures, commencing at approximately 70°C and plateauing at 50°C. Comparison with frequency sweep data for the 2% E4M solutions indicated liquid-like behaviour at 25 and 55°C with a lower frequency dependence and considerably higher moduli seen at 85°C. Macroscopic examination of the 2% gels indicated that clouding was seen at ca. 42°C, while phase separation was apparent at 55°C. Comparison with F4M and K4M systems indicated a similar behaviour pattern, although the decrease in moduli and phase separation occurred at a higher temperature for the K4M systems. It is suggested that on heating HPMC solutions, the transitions indicated by the thermorheological studies relate to phase separation causing a decrease in moduli, followed by an increase in moduli which may correspond to gelation of the polymer rich phase. This process of phase separation has not been previously considered in the context of the rheology of HPMC thermogelation and may have implications for the behaviour of solutions of this material in a practical environment