Biomedical subjects

Neil R Foster

Publications and source records attributed to Neil R Foster.

5 recordsLinked to original sources

PubMed2006

Dense gas processing of polymeric controlled release formulations.

Dense gas techniques, which utilize the properties of fluids in the vicinity of their critical points, are of increasing interest in the processing of pharmaceuticals. It is generally known that dense gases can be used for extractions, chromatographic separations and chemical synthesis due to their liquid-like solvation power and gas-like mass-transfer properties. The processes can be conducted at moderate operating conditions and are thus suitable for many heat-labile compounds such as proteins, biocompatible polymers and pharmaceuticals. Recent applications of dense gas techniques include micronization, crystallization of high-purity particles, sterilization and preparation of microencapsulated drug formulations. The following paper provides a brief overview of dense gases and various processing techniques to fabricate polymeric drug-loaded formulations for controlled release purposes.

Chemistry, Pharmaceutical↗

PubMed2006

Dense gas processing of micron-sized drug formulations incorporating hydroxypropylated and methylated beta-cyclodextrin.

PURPOSE: Because of their importance in pharmaceutical applications, hydroxypropyl-beta-cyclodextrin and methyl-beta-cyclodextrin have been selected to study the formation of micronized complexes incorporating active pharmaceutical ingredients (APIs) and cyclodextrins (CDs) by dense gas (DG) processing. METHODS: A single-step DG technique was used as an alternative to conventional methods for the manufacturing of API/CD complexes. The DG technology is highly attractive in the pharmaceutical industry because of its potential to generate micronized particles with controlled particle size distributions at moderate operating conditions. The effect of the aerosol solvent extraction system (ASES) processing on the dissolution performance of naproxen (NPX) was examined. RESULTS: The CDs were produced as microspheres smaller than 3 microm. The coprecipitation of each CD with NPX resulted in the production of microparticles with enhanced dissolution rates. CONCLUSIONS: The ASES was operated under mild conditions and generated micron-sized spherical particles that could be of particular interest in formulations for pulmonary delivery. Particular advantages of the technique are that (1) nontoxic solvents are used, and (2) it is suitable for the processing of thermally labile compounds. The proposed process can create opportunities to improve current administration routes and exploit novel delivery systems for drug formulations incorporating CDs.

2-Hydroxypropyl-beta-cyclodextrin↗

PubMed2003

Inactivation of bacteria and spores by pulse electric field and high pressure CO2 at low temperature.

The common methods for inactivation of bacteria involve heating or exposure to toxic chemicals. These methods are not suitable for heat-sensitive materials, food, and pharmaceutical products. Recently, a complete inactivation of many microorganisms was achieved with high-pressure carbon dioxide at ambient temperature and in the absence of organic solvent and irradiation. The inactivation of spores with CO(2) required long residence time and high temperatures, such as 60 degrees C. In this study the synergistic effect of pulsed electric field (PEF) in combination with high-pressure CO(2) for inactivation was investigated. The bacteria Escherichia coli, Staphylococcus aureus, and Bacillus cereus were suspended in glycerol solution and treated in the first step with PEF (up to 25 KV/cm) and then with high-pressure CO(2) not higher than 40 degrees C and 200 bar. The inactivation efficiency was determined by counting the colony formation units of control and sample. Samples of the cells subjected to PEF treatment alone and in combination with CO(2) treatment were examined by scanning electron microscopy to determine the effect of the processes on the cell wall. Experimental results indicate that the viability decreased with increasing electrical field strength and number of pulses. A further batch treatment with supercritical CO(2) lead to complete inactivation of bacterial species and decreased the count of the spores by at least three orders of magnitude, the inactivation being enhanced by an increase of contact time between CO(2) and the sample. A synergistic effect between the pulsed electric field and the high-pressure CO(2) was evident in all the species treated. The new low temperature process is an alternative for pasteurization of thermally labile compounds such as protein and plasma and minimizes denaturation of important nutrient compounds in the liquid media.

Bacillus cereus↗

PubMed2003

Generation of fine powders of recombinant human deoxyribonuclease using the aerosol solvent extraction system.

PURPOSE: To investigate the feasibility of using the Aerosol Solvent Extraction System (ASES) to produce fine powders of recombinant human deoxyribonuclease (rhDNase), lysozyme-lactose and rhDNase-lactose powders from aqueous based solutions. METHODS: The ASES technique using high pressure carbon dioxide modified with ethanol or ethanol and triethylamine was used for the generation of rhDNase powders and protein-lactose powders from aqueous based solutions. Particle size, morphology, size distributions, crystallinity, and powder aerosol performance were measured. The biochemical integrity of the processed rhDNase was assessed by testing the monomer content and the degree of deamidation. RESULTS: RhDNase precipitated as spherical particles in the size range between 50 and 500 nm. The primary nano-sized particles were agglomerated to micron-sized clumps of particles during the precipitation process. The median particle size and the fine particle fraction were functions of the operating temperature and the nozzle system used. RhDNase was substantially denatured in the ASES process using carbon dioxide modified with ethanol as anti-solvent. However almost complete recovery of the monomer was achieved using carbon dioxide modified with ethanol-triethylamine as an anti-solvent. Lysozyme-lactose and rhDNase-lactose powders were also precipitated as agglomerated spheres using the ASES process. The powders were amorphous except for those with lactose content higher than 45%. CONCLUSIONS: Micron-sized particles of rhDNase suitable for inhalation delivery were generated from aqueous based solutions using the modified ASES technique. The biochemical integrity of the rhDNase powder is a function of the antisolvent and the operating temperature.

Administration, Inhalation↗

PubMed2003

Application of dense gas techniques for the production of fine particles.

The feasibility of using dense gas techniques such as rapid expansion of supercritical solutions (RESS) and aerosol solvent extraction system (ASES) for micronization of pharmaceutical compounds is demonstrated. The chiral nonsteroidal anti-inflammatory racemic ibuprofen is soluble in carbon dioxide at 35 degrees C and pressures above 90 bar. The particle size decreased to less than 2 microm while the degree of crystallinity was slightly decreased when processed by RESS. The dissolution rate of the ibuprofen (a poorly water-soluble compound) was significantly enhanced after processing by RESS. The nonsteroidal anti-inflammatory drug Cu2(indomethacin)4L2(Cu-Indo); (L = dimethylformamide [DMF]), which possessed very low solubility in supercritical CO2, was successfully micronized by ASES at 25 degrees C and 68.9 bar using DMF as the solvent and CO2 as the antisolvent. The concentration of solute dramatically influenced the precipitate characteristics. The particles obtained from the ASES process were changed from bipyramidal to spherical, with particle size less than 5 microm, as the concentration increased from 5 to 100 mg/g. A further increase in solute concentration to 200 mg/g resulted in large porous spheres, between 20 and 50 micron, when processing Cu-Indo by the ASES method. The dissolution rate of the micronized Cu-Indo was significantly higher than the commercial product.

Aerosols↗