David L. Tomasko

Microencapsulation of Naproxen Using Rapid Expansion of Supercritical Solutions

The rapid expansion of supercritical solutions (RESS) process was used to produce polymeric microparticles or microspheres loaded with pharmaceuticals for drug delivery applications. Poly(l‐lactic acid) (l‐PLA), naproxen, and a mixture of naproxen/l‐PLA were dissolved in supercritical CO2 and precipitated by the RESS process. Composite particles appear as a naproxen core encapsulated in a polymer coating. The solubility of l‐PLA and naproxen/l‐PLA has been measured at 333.15 K and pressures ranging from 90 to 200 bar by using a dynamic flow apparatus. The lattice fluid theory of Sanchez and Lacombe was tested for its correlative and predictive capability of modeling these supercritical fluid mixtures. The solubility data are combined with morphology studies to investigate the effects of fluid phase interactions on particle formation using RESS.

Tailoring of specific interactions to modify the morphology of naproxen

Abstract Microscopy and spectroscopy were used to deduce the effect of intermolecular hydrogen bonding on the morphology of a recrystallized pharmaceutical compound. Samples of recrystallized naproxen, (+)-6-methoxy-α-methylnaphthaleneacetic acid, were prepared from solutions of benzene, acetone, and methanol resulting in particles with aspect ratios of 2, 3.5, and 5.5, respectively, as determined by SEM imaging. XRDS indicated that the recrystallization did not affect lattice structure. Solubility measurements, UV/Vis, fluorescence, and FTIR spectroscopy were used to investigate specific interactions in solution including solvent–solute hydrogen bonding and solute self-association. The results failed to reveal π orbital conjugation of naproxen even in saturated solutions, but indicated hydrogen bonding of naproxen with the solvent as well as the formation of cyclic naproxen dimers in solution. FTIR microscopy indicated a correlation between solvent and monomeric hydroxyl content in the crystals confirming the effect of solvent on naproxen morphology. The results of this study demonstrate the utility of spectroscopic techniques to tailor specific interactions to modify particle morphology.

CO2 Foaming of Polymer Nanocomposite Blends

Nanoparticles are suitable to nucleate small foam cells and simultaneously reinforce the thin foam cell walls. In this paper, it is found that the foam morphology and the physical properties are greatly influenced by the dispersion of nanoclay, the clay surface modification, and the nanocomposite blend morphology. The addition of nanoclay to polystyrene (PS) strongly affects the nucleation of foam bubbles, especially after exfoliation and proper surface modification. CO2 appears to nucleate on the solid clay surface with a CO2-affinitive surface modifier. PS/(PMMA/MHABS) nanocomposite blends composed of polystyrene and poly(methyl methacrylate)/nanoclay exfoliated nanocomposite show an unexpected trend that bubble nucleation inversely correlates with domain size, where the bigger PMMA/MHABS domains are significant in nucleating more bubbles. The total influence volume, formed by the CO2 diffusion from the PMMA/MHABS phase to the PS phase where CO2 concentration decreases from a high value in the former to a low value in the latter, is related to the domain size and determines the nucleation efficiency in the PS phase. The physical properties of PS nanocomposites exhibit unique behaviour in the presence of CO2.

Development of a Polymeric Patch Impregnated with Naproxen as a Model of Transdermal Sustained Release System

This paper describes the preparation and characterization of transdermal patches impregnated with naproxen. A mixture of ethylene vinyl acetate and Eudragit E100 (80:20, w/w) is used as a polymeric matrix to obtain a thin membrane to be impregnated. Drug impregnation is carried out under pressurized CO(2) as a processing medium according to a two-step procedure. The patch is first soaked at 1000 psi and 22 °C for 2 h, and then foamed as a result of the rapid release of CO(2) pressure in order to increase the porosity of the surface. Subsequently, the naproxen solution is placed in contact with the membrane and then soaked in CO(2) at 450 psi and 37 °C for 2.5 h to enhance the mass transfer of drug into the polymer matrix. The characterization of the resulting samples by liquid chromatography, microscopy, and calorimetry provides information on naproxen content and distribution. Patches synthesized in this way are loaded with about 1% naproxen. The drug release and diffusion process through a membrane have been studied chromatographically using a Franz diffusion cell. Results have shown that a sustained delivery for more than 24 h is obtained.

Novel Dense CO2 Technique for β-Galactosidase Immobilization in Polystyrene Microchannels

In this study we design new fabrication techniques and demonstrate the potential of using dense CO2 for facilitating crucial steps in the fabrication of polymeric lab-on-a-chip microdevices by embedding biomolecules at temperatures well below the polymers glass transition temperature (T(g)). These new techniques are environmentally friendly and done without the use of a clean room. Carbon dioxide at 40 degrees C and between 4.48 and 6.89 MPa was used to immobilize the biologically active molecule, beta-galactosidase (beta-gal), on the surface of polystyrene microchannels. To our knowledge, this is the first time dense CO2 has been used to directly immobilize an enzyme in a microchannel. beta-gal activity was maintained and shown via a fluorescent reaction product, after enzyme immobilization and microchannel capping by the designed fabrication steps at 40 degrees C and pressures up to 6.89 MPa.

Processing of epoxy resins using carbon dioxide as an antisolvent

Abstract The use of carbon dioxide as an antisolvent for the production of polymeric particles is well documented. However, development of operating parameters to control particle size and morphology in this process has been generally lacking. In an attempt to gain a better understanding of processing conditions on particle formation, we present results on precipitation of epoxy resin powders with and without surfactants in the liquid phase including a comparison of cocurrent and countercurrent flow configurations and higher solute concentrations for increased throughput. It can be inferred from the results that for this system, mixing, nucleation, and growth phenomena in the precipitation chamber are more significant than the jet break-up effects created by the kinetic energy of the liquid solution as it is forced through the nozzle.

Biocompatible electrospun polymer blends for biomedical applications.

Blends of natural and synthetic polymers have received considerable attention as biomaterials due to the potential to optimize both mechanical and bioactive properties. Electrospinning of biocompatible polymers is an efficient method producing biomimetic topographies suited to various applications. In the ultimate application, electrospun scaffolds must also incorporate drug/protein delivery for effective cell growth and tissue repair. This study explored the suitability of a ternary Polymethylmethacrylate-Polycaprolactone-gelatin blend in the preparation of electrospun scaffolds for biomedical applications. Tuning the blend composition allows control over scaffold mechanical properties and degradation rate. Significant improvements were observed in the mechanical properties of the blend compared with the individual components. In order to study drug delivery potential, triblends were impregnated with the model compound Rhodamine-B using sub/supercritical CO₂ infusion under benign conditions. Results show significantly distinct release profiles of the impregnated dye from the triblends. Specific factors such as porosity, degradation rate, stress relaxation, dye-polymer interactions, play key roles in impregnation and release. Each polymer component of the triblends shows distinct behavior during impregnation and release process. This affects the aforementioned factors and the release profiles of the dye. Careful control over blend composition and infusion conditions creates the flexibility needed to produce biocompatible electrospun scaffolds for a variety of biomedical applications.

Removal of Pollutants from Solid Matrices Using Supercritical Fluids

Abstract Several supercritical fluid extraction (SCFE) processes have been proposed for removing toxic and intractable organic compounds from a range of contaminated solids. These include soil remediation and the regeneration of adsorbents used to treat wastewater streams such as granular activated carbon (GAC). As a separation technique for environmental control, SCFE has several distinct advantages over conventional liquid extraction methods and incineration. Most notably, the contaminant is removed from the solvent in a concentrated form via a change in pressure or temperature and can be completely separated upon expansion to atmospheric pressure. The viability of SCFE hinges on process conditions such as solvent-feed ratio and solvent recycle ratio. The necessity of recycling solvent complicates the contaminant separation step since a complete reduction to atmospheric pressure would create large recompression costs. Because of this, the pressure and temperature dependence of contaminant solubility mus...

Effects of orthopedic implants with a polycaprolactone polymer coating containing bone morphogenetic protein-2 on osseointegration in bones of sheep

OBJECTIVE To determine elution characteristics of bone morphogenetic protein (BMP)-2 from a polycaprolactone coating applied to orthopedic implants and determine effects of this coating on osseointegration. ANIMALS 6 sheep. PROCEDURES An in vitro study was conducted to determine BMP-2 elution from polycaprolactone-coated implants. An in vivo study was conducted to determine the effects on osseointegration when the polycaprolactone with BMP-2 coating was applied to bone screws. Osseointegration was assessed via radiography, measurement of peak removal torque and bone mineral density, and histomorphometric analysis. Physiologic response was assessed by measuring serum bone-specific alkaline phosphatase activity and uptake of bone markers. RESULTS Mean +/- SD elution on day 1 of the in vitro study was 263 +/- 152 pg/d, which then maintained a plateau at 59.8 +/- 29.1 pg/d. Mean peak removal torque for screws coated with polycalprolactone and BMP-2 (0.91 +/- 0.65 dN x m) and screws coated with polycaprolactone alone (0.97 +/- 1.30 dN.m) did not differ significantly from that for the control screws (2.34 +/- 1.62 dN x m). Mean bone mineral densities were 0.535 +/- 0.060 g/cm(2), 0.596 +/- 0.093 g/cm(2), and 0.524 +/- 0.142 g/cm(2) for the polycaprolactone-BMP-2-coated, polycaprolactone-coated, and control screws, respectively, and did not differ significantly among groups. Histologically, bone was in closer apposition to the implant with the control screws than with either of the coated screws. CONCLUSIONS AND CLINICAL RELEVANCE BMP-2 within the polycaprolactone coating did not stimulate osteogenesis. The polycaprolactone coating appeared to cause a barrier effect that prevented formation of new bone. A longer period or use of another carrier polymer may result in increased osseointegration.

Understanding drug release from PCL/gelatin electrospun blends

Electrospinning is one of the efficient processes to fabricate polymeric fibrous scaffolds for several biomedical applications. Several studies have published to demonstrate drug release from electrospun scaffolds. Blends of natural and synthetic electrospun fibers provide excellent platform to combine mechanical and bioactive properties. Drug release from polymer blends is a complex process. Drug release from polymer can be dominated by one or more of following mechanisms: polymer erosion, relaxation, and degradation. In this study, electrospun polycaprolactone (PCL)–gelatin blends are investigated to understand release mechanism of Rhodamine B dye. Also, this article summarizes the effect of high-pressure carbon dioxide on drug loading and release from PCL–gelatin fibers. Results indicate that release media diffusion is a dominant mechanism for PCL–gelatin electrospun fibers. Thickness of electrospun mat becomes critical for blends with gelatin. As gelatin is highly soluble in water and has tendency of gelation, it affects diffusion of release media in and out of scaffold. This article is a key step forward in understanding release from electrospun blends.