Evolution of Surface Nanopores in Pressurised Gyrospun Polymeric Microfibers

The selection of a solvent or solvent system and the ensuing polymer–solvent interactions are crucial factors affecting the preparation of fibers with multiple morphologies. A range of poly(methylmethacrylate) fibers were prepared by pressurised gyration using acetone, chloroform, N,N-dimethylformamide (DMF), ethyl acetate and dichloromethane as solvents. It was found that microscale fibers with surface nanopores were formed when using chloroform, ethyl acetate and dichloromethane and poreless fibers were formed when using acetone and DMF as the solvent. These observations are explained on the basis of the physical properties of the solvents and mechanisms of pore formation. The formation of porous fibers is caused by many solvent properties such as volatility, solubility parameters, vapour pressure and surface tension. Cross-sectional images show that the nanopores are only on the surface of the fibers and they were not inter-connected. Further, the results show that fibers with desired nanopores (40–400 nm) can be prepared by carefully selecting the solvent and applied pressure in the gyration process

Core/shell microencapsulation of indomethacin/paracetamol by co-axial electrohydrodynamic atomization

Core/shell microparticles for development of drug delivery systems were prepared using co-axial electrohydrodynamic atomization technique in order to develop fixed dose combined formulations incorporating paracetamol and indomethacin as model drugs. The developed drug delivery systems offered successful co-encapsulation of paracetamol and indomethacin with high drug encapsulation efficiencies of 54% and 69% for paracetamol and indomethacin, respectively. The developed formulations were further characterised with respect to their morphology, drug release profile and possible interactions. In comparison to the release rate of the free indomethacin, the developed formulation resulted in enhanced dissolution rate of indomethacin. This study demonstrates a versatile polymeric platform where multiple drug encapsulation and co-delivery is made possible by utilizing co-axial electrohydrodynamic atomization. The proposed system offered high processing yield of 60–70%, as a single-step platform for preparation of fixed dose formulations for oral drug delivery, particularly in geriatric therapy

A Comparison of Electric-Field-Driven and Pressure-Driven Fiber Generation Methods for Drug Delivery

Polymeric fibers are prepared by using electric field driven fiber production technology-electrospinning and pressure driven fiber production technology-pressurized gyration. Fibers of four different polymers: polyvinylidene fluoride (PVDF), poly(methyl methacrylate (PMMA), poly(N-isopropylacrylamide), and polyvinylpyridine (PVP), are spun by both techniques and differences are analyzed for their suitability as drug carriers. The diameters of electrospun fibers are larger in some cases (PVDF and PMMA), producing fibers with lower surface area. Pressurized gyration allows for a higher rate of fiber production. Additionally, drug-loaded PVP fibers are prepared by using two poorly water-soluble drugs (Amphotericin B and Itraconazole). In vitro dissolution studies show differences in release rate between the two types of fibers. Drug-loaded gyrospun fibers release the drugs faster within 15 min compared to the drug-loaded electrospun fibers. The findings suggest pressurized gyration is a promising and scalable approach to rapid fiber production for drug delivery when compared to electrospinning

Copolymer Composition and Nanoparticle Configuration Enhance in vitro Drug Release Behavior of Poorly Water-soluble Progesterone for Oral Formulations

HYPOTHESIS: Developing oral formulations to enable effective release of poorly water-soluble drugs like progesterone is a major challenge in pharmaceutics. Coaxial electrospray can generate drug-loaded nanoparticles of strategic compositions and configurations to enhance physiological dissolution and bioavailability of poorly water-soluble drug progesterone. EXPERIMENTS: ix formulations comprising nanoparticles encapsulating progesterone in different poly(lactide-co-glycolide) (PLGA) matrix configurations and compositions were fabricated and characterized in terms of morphology, molecular crystallinity, drug encapsulation efficiency and release behavior. FINDINGS: A protocol of fabrication conditions to achieve 100% drug encapsulation efficiency in nanoparticles was developed. Scanning electron microscopy shows smooth and spherical morphology of 472.1± 54.8 to 588.0± 92.1 nm in diameter. Multiphoton Airyscan super-resolution confocal microscopy revealed core-shell nanoparticle configuration. Fourier transform infrared spectroscopy confirmed presence of PLGA and progesterone in all formulations. Diffractometry indicated amorphous state of the encapsulated drug. UV-vis spectroscopy showed drug release increased with hydrophilic copolymer glycolide ratio while core-shell formulations with progesterone co-dissolved in PLGA core exhibited enhanced release over five hours at 79.9± 1.4% and 70.7± 3.5% for LA:GA 50:50 and 75:25 in comparison with pure progesterone without polymer matrix in the core at 67.0± 1.7% and 57.5± 2.8%, respectively. Computational modeling showed good agreement with the experimental drug release behavior in vitro

Electrosprayed microparticles for intestinal delivery of prednisolone

Single and coaxial electrospraying was used to prepare Eudragit L100-55 polymer microparticles containing prednisolone as the active pharmaceutical ingredient. Different compositions of prednisolone and Eudragit L100-55 were used to develop five different formulations with different polymer : drug ratios. The resultant microparticles had a toroidal shape with a narrow size distribution. Prednisolone was present in an amorphous physical state, as confirmed by X-ray diffraction analysis. Dissolution studies were carried out in order to investigate the feasibility of the proposed system for site-specific release of prednisolone. The release rates were interpreted in terms of diffusion-controlled release. It was shown that utilization of pH-responsive Eudragit L100-55 could minimize the release of prednisolone in the acidic conditions of the stomach, which was followed by rapid release as the pH of the release medium was adjusted to 6.8 after the first 2 h. This is especially desirable for the treatment of conditions including inflammatory bowel disease and colon cancer

Advanced drug delivery systems prepared by electrospinning

This thesis describes fast dissolving and sustained release drug delivery systems prepared using electrospinning. Chapter 1 provides a detailed literature review, and Chapter 2 gives details of the materials and methods used. Chapter 3 details the preparation of fibers of poly(vinyl pyrrolidone) (PVP) and Eudragit L100-55 loaded with mebeverine hydrochloride, a drug used to treat irritable bowel syndrome. The drug was amorphously distributed in the fibers. The PVP based fibers dissolved very quickly (within 10s) when added to an aqueous medium, while Eudragit L100-55 fibers were able to retard drug release in acidic environments representative of the stomach and provide sustained release in media representative of the lower parts of the gastro-intestinal tract. Chapter 4 explores the generation of fast dissolving paracetamol/caffeine/PVP fibres for use as paediatric formulations. A flavouring agent was also incorporated. The fiber mats disintegrated in around 300 ms, and freed all the embedded drug into solution by 2 min. In Chapter 5, fibers were prepared in which the anti-cancer drug fluorouracil (5-FU) was combined with PVP, a phospholipid and cholesterol or trehalose. When added to water, the components of the fibers self-assembled to form drug-loaded liposomes. Although the inclusion of cholesterol and trehalose was observed to have an effect on the liposome size and surface charge, the drug release properties were essentially the same for all the formulations. In Chapter 6, fast-dissolving 5-FU nanofibers were first prepared with PVP. The mats showed cytotoxicity towards a leukaemia cell line, but not to a prostate cancer cell line. Fibers were of 5-FU and Eudragit L100-55 and S100 were also generated. Monolithic fibers gave considerable release at pH1.0. Core/shell fibers with a Eudragit S100 shell and 5-FU in the core ameliorated this issue to some extent, but considerable release at pH 1.0 was still observed