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

The influence of drug physical state on the dissolution enhancement of solid dispersions prepared via hot-melt extrusion: A case study using olanzapine

In this study, we examine the relationship between the physical structure and dissolution behavior of olanzapine (OLZ) prepared via hot-melt extrusion in three polymers [polyvinylpyrrolidone (PVP) K30, polyvinylpyrrolidone-co-vinyl acetate (PVPVA) 6:4, and Soluplus® (SLP)]. In particular, we examine whether full amorphicity is necessary to achieve a favorable dissolution profile. Drug–polymer miscibility was estimated using melting point depression and Hansen solubility parameters. Solid dispersions were characterized using differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy. All the polymers were found to be miscible with OLZ in a decreasing order of PVP>PVPVA>SLP. At a lower extrusion temperature (160°C), PVP generated fully amorphous dispersions with OLZ, whereas the formulations with PVPVA and SLP contained 14%–16% crystalline OLZ. Increasing the extrusion temperature to 180°C allowed the preparation of fully amorphous systems with PVPVA and SLP. Despite these differences, the dissolution rates of these preparations were comparable, with PVP showing a lower release rate despite being fully amorphous. These findings suggested that, at least in the particular case of OLZ, the absence of crystalline material may not be critical to the dissolution performance. We suggest alternative key factors determining dissolution, particularly the dissolution behavior of the polymers themselves

In vitro drug release from acetylated high amylose starch-zein films for oral colon-specific drug delivery

This study describes the preparation of free films of zein with and without acetylated high amylose maize starch (HAS) and their corresponding coated tablets as a novel approach to colonic drug delivery. We hypothesise that the embedding of a digestible starch component within the inert zein would allow the film to remain intact until the large intestine is reached. Free films of zein alone and starch/zein were prepared and characterized. SEM and AFM images of film surface showed that films were morphologically inhomogeneous, particularly at lower HAS/Zein ratios; however, nanothermal analysis data suggested that these differences in appearance within the same film are not compositional differences. Moreover, FT-IR could detect no molecular interaction between the two polymers. Paracetamol tablets were coated with HAS/Zein aqueous based coatings of different compositions to a TWG of 20%. Drug release from zein alone and 1:5 HAS/Zein coated tablets under upper gastrointestinal conditions (pH 1.2, pH 6.8 with pepsin and pancreatin included) was very similar (for example approximately 12% and 14% of the drug was released, respectively, after 6 h in a sequential in vitro test), suggesting that release in this region is limited and is not influenced by the presence of HAS in the ratio to zein under study. Studies using an in vitro colon model showed that under simulated colonic conditions, the drug release was significantly (p < 0.05) more rapid from 1:5 HAS/Zein, compared to the zein alone coating formulation. These data therefore support the potential use of zein-starch mixed films for colonic targeting purposes

Application of nanotechnology for the development of microbicides

The vaginal route is increasingly being considered for both local and systemic delivery of drugs, especially those unsuitable for oral administration. One of the opportunities offered by this route but yet to be fully utilised is the administration of microbicides. Microbicides have an unprecedented potential for mitigating the global burden from HIV infection as heterosexual contact accounts for most of the new infections occurring in sub-Saharan Africa, the region with the highest prevalent rates. Decades of efforts and massive investment of resources into developing an ideal microbicide have resulted in disappointing outcomes, as attested by several clinical trials assessing the suitability of those formulated so far. The highly complex and multi-level biochemical interactions that must occur among the virus, host cells and the drug for transmission to be halted means that a less sophisticated approach to formulating a microbicide e.g. conventional gels, etc may have to give way for a different formulation approach. Nanotechnology has been identified to offer prospects for fabricating structures with high capability of disrupting HIV transmission. In this review, predominant challenges seen in microbicide development have been highlighted and possible ways of surmounting them suggested. Furthermore, formulations utilising some of these highly promising nanostructures such as liposomes, nanofibres and nanoparticles have been discussed. A perspective on how a tripartite collaboration among governments and their agencies, the pharmaceutical industry and academic scientists to facilitate the development of an ideal microbicide in a timely manner has also been briefly deliberated

Mucoadhesion of Progesterone-Loaded Drug Delivery Nanofiber Constructs

Mucoadhesive delivery systems have attracted remarkable interest recently, especially for their potential to prolong dosage form resident times at sites of application such as the vagina or nasal cavity, thereby improving convenience and compliance as a result of less frequent dosage. Mucoadhesive capabilities need to be routinely quantified during the development of these systems. This is however logistically challenging due to difficulties in obtaining and preparing viable mucosa tissues for experiments. Utilizing artificial membranes as a suitable alternative for quicker and easier analyses of mucoadhesion of these systems is currently being explored. In this study, the mucoadhesive interactions between progesterone-loaded fibers (with varying carboxymethyl cellulose (CMC) content) and either artificial (cellulose acetate) or mucosa membranes are investigated by texture analysis and results across models are compared. Mucoadhesion to artificial membrane was about 10 times that of mucosa, though statistically significant (p = 0.027) association between the 2 data sets was observed. Furthermore, a hypothesis relating fiber–mucosa interfacial roughness (and unfilled void spaces on mucosa) to mucoadhesion, deduced from some classical mucoadhesion theories, was tested to determine its validity. Points of interaction between the fiber and mucosa membrane were examined using atomic force microscopy (AFM) to determine the depths of interpenetration and unfilled voids/roughness, features crucial to mucoadhesion according to the diffusion and mechanical theories of mucoadhesion. A Kendall’s tau and Goodman–Kruskal’s gamma tests established a monotonic relationship between detaching forces and roughness, significant with p-values of 0.014 and 0.027, respectively. A similar relationship between CMC concentration and interfacial roughness was also confirmed. We conclude that AFM analysis of surface geometry following mucoadhesion can be explored for quantifying mucoadhesion as data from interfacial images correlates significantly with corresponding detaching forces, a well-established function of mucoadhesion

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

Making nanofibres of mucoadhesive polymer blends for vaginal therapies

Nanofibres from mucoadhesive polymers could combine their material properties with unique structural characteristics for superior drug delivery performance. However, due to their chain structure a significant proportion of mucoadhesive polymers such as polysaccharides cannot be easily spun into fibres. In this study, we demonstrate the possibility of using polymer blends for the preparation of nanofibres that offer substantial mucoadhesive capabilities. Fibres from four different polymers were obtained by pressurised gyration at different working pressures and a rotation speed of 24,000 rpm. Electron microscopy indicates that structurally well-defined fibres with diameters from less than 100 nm upwards were successfully produced. Quantitative relationships between the physical properties and fibre characteristics were established while the fibre compositions were confirmed to contain features likely to confer mucoadhesive properties. Finally, a combination of texture analysis and atomic force microscopy was used to verify the benefit of transforming polymer powders into nanofibre structures, as far as mucoadhesive potential is concerned

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

Dielectric Analysis of Pharmacetical Systems

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