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Biomedical subjects

Joseph Wong

Publications and source records attributed to Joseph Wong.

10 recordsLinked to original sources

Solid-phase extraction and HPLC analysis of methylparaben and propylparaben in a concentrated antibiotic suspension.

An accurate and precise solid-phase extraction coupled with high performance liquid chromatography (SPE/HPLC) method developed for the quantification of antimicrobial preservatives (methylparaben and propylparaben) in oxytetracycline injectable suspension is described in this article. The SPE technique was necessary to quantify the preservatives since the high concentration of the drug and excipients was masking low levels of preservatives, making quantification difficult. This developed HPLC method was stability-indicating and found to be linear between 1.3 to 2.4 mg/mL for methylparaben and 0.15 to 0.27 mg/mL for propylparaben in this concentrated antibiotic suspension formulation. The extraction recoveries were 98.8-101.6%. System precision and sample extraction precision (RSD) were less than 1%.

Anti-Bacterial Agents↗

Infections and Kawasaki disease: implications for coronary artery outcome.

OBJECTIVE: We sought to determine the effect of coincident infection, at time of diagnosis of Kawasaki disease (KD), on treatment response and coronary artery outcome. METHODS: A single-center, retrospective study of 129 consecutive patients diagnosed with typical KD between January 1997 and December 1998 was performed. Standardized clinical assessments, laboratory, microbiology, and imaging test results plus treatment regimens were reviewed. Coronary arteries were visualized by using echocardiography, and coronary artery lesions (CALs) were reported as body surface area-adjusted z scores. Infection-positive and -negative groups were identified, and clinical, laboratory, and treatment data were analyzed. The effect of infections and other outcome variables on CAL development was determined by multivariate regression analysis. RESULTS: (1) Concurrent infections: 33% of children with typical KD had > or =1 confirmed infection at KD diagnosis. (2) Treatment response: the presence of infection did not alter the response to treatment with intravenous immunoglobulin, with resolution of fever in 83% of children after 1 dose of intravenous immunoglobulin together with aspirin administration regardless of presence or absence of infection. (3) Coronary outcome: in total, 31% of the patients developed CALs. Both the proven-infection and no-proven-infection groups had a similar CAL frequency. (4) Multivariate regression analysis: proven infection did not increase the risk of coronary artery involvement even after adjusting for other factors impacting on coronary artery outcomes. CONCLUSIONS: Infections are common at diagnosis of KD. A broad spectrum of infectious agents was found. Infections at diagnosis of KD did not affect the patients' response to treatment and coronary artery outcome when compared with those patients without infections.

Adolescent↗

Targeting efficiency of galactosylated liposomes to hepatocytes in vivo: effect of lipid composition.

PURPOSE: To investigate the effects of the lipid composition of galactosylated liposomes on their targeted delivery to hepatocytes. METHODS: Several types of liposomes with a particle size of about 90 nm were prepared using distearoyl-L-phosphatidylcholine (DSPC), cholesterol (Chol) and cholesten-5-yloxy-N-(4-((1-imino-2-D- thiogalactosylethyl)amino)butyl)formamide (Gal-C4-Chol), and labeled with [3H]cholesterol hexadecyl ether. Their tissue disposition was investigated in mice following intravenous injection. The binding and internalization characteristics were also studied in HepG2 cells. RESULTS: Compared with [H]DSPC/Chol (60:40) liposomes, [3H]DSPC/Chol/Gal-C4-Chol (60:35:5) liposomes exhibit extensive hepatic uptake. Separation of the liver cells showed that galactosylated liposomes are preferentially taken up by hepatocytes, whereas those lacking Gal-C4-Chol distribute equally to hepatocytes and nonparenchymal cells (NPC). Increasing the molar ratio of DSPC to 90% resulted in enhanced NPC uptake of both liposomes, suggesting their uptake via a mechanism other than asialoglycoprotein receptors. DSPC Chol/Gal-C4-Chol (60:35:5) and DSPC/Chol/Gal-C4-Chol (90:5:5) liposomes exhibited similar binding to the surface of HepG2 cells, but the former were taken up faster by the cells. CONCLUSIONS: The recognition of galactosylated liposomes by the asialoglycoprotein receptors is dependent on the lipid composition. Cholesterol-rich galactosylated liposomes, exhibiting less non-specific interaction and greater receptor-mediated uptake, are better for targeting drugs to hepatocytes in vivo.

Animals↗

The clinical use of angiotensin-converting enzyme inhibitors.

Through an integrative understanding of cardiovascular pathophysiologic characteristics at the multiorgan level, significant achievements in cardiovascular therapeutics have been achieved and enabled the rationale design and development of drugs such as the angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs). In this article, we present a detailed review of the physiologic features of the renin-angiotensin-aldosterone system (RAAS), ACE inhibitors and ARB clinical pharmacologic characteristics, and specific diseases in which they are considered to be the standard of the care as supported by important clinical trial data. It is envisioned that an updated and detailed understanding of ACE inhibitors and ARBs will facilitate their successful use in the treatment of heart failure, myocardial infarction, hypertension, renal failure, and diabetic nephropathy.

Angiotensin Receptor Antagonists↗

Effect of terminal sterilization by irradiation on amber Type I and Type III glass containers containing veterinary oxytetracycline suspension.

The purpose of this study is to determine the effect of terminal sterilization by gamma irradiation on 500-mL amber Type I and Type III glass containers (bottles) containing oxytetracycline (OTC) (25% W/V) suspension formulated using 20% (W/V) phospholipids syrup. The formulation was developed for veterinary parenteral administration. The results of terminal sterilization were used to assess the acceptability for this suspension product. OTC is light-sensitive and needs to be stored in amber glass containers. Amber Type I and Type III glass containers were considered for this formulation during development. Type I is a highly resistant, borosilicate glass (oxidized glass). Type III, which is soda-lime glass (reduced glass, see Materials and Methods), may also be used for parenteral products. The amber Type I and Type III glass containers, containing the suspension, were irradiated at 20-40 kGy for 150 min. In order to determine the sterility of the suspension, ampoules of the biological indicator, Bacillus pumilus, were placed in a number of bottles of the suspension. The bottles with the biological indicators were then positioned among the rest of the production bottles as per a radiation dose-mapping study conducted at the sterilization facility. Potency determination and stability evaluations for OTC were performed using high pressure liquid chromatography (HPLC). The results indicate that the gamma irradiation dose of 20-40 kGy for 150 min was able to inactivate 10(6) Bacillus pumilus spores in ampoules. After gamma sterilization, OTC concentration, pH, particle size, endotoxins, and sterility were evaluated. The assay results were comparable for the suspension in amber Type I and Type III glass containers. Sterility and pyrogenicity were measured by the USP Membrane Filtration Method and USP Bacterial Endotoxins Test, respectively. The suspension in the amber Type III glass container was also chemically (HPLC) and physically (suspension mean particle size, viscosity, density, and syringeability) stable for at least 12 months at room temperature. However, amber Type I glass darkened following irradiation, leading to a substantial reduction in glass transparency. The appearance of amber Type III glass was acceptable. Thus, the "reduced" glass, such as soda-lime, was found to be much less susceptible to darkening than the highly oxidized borosilicate amber. Due to the potential aesthetic concerns with Type I glass, the amber Type III glass container was selected for this suspension formulation.

Chromatography, High Pressure Liquid↗

Suspension for intravenous injection: image analysis of scanning electron micrographs of particles to determine size and volume.

The purpose of this study is to determine the size and volume of large particles in a drug suspension by performing an image analysis of digital micrographs obtained by field emission, low voltage scanning electron microscopy (FE-LVSEM). The data obtained by this method are then used to select the appropriate imaginary component of the complete refractive index necessary for the software computation of particle size distribution measured using laser light diffraction. The application of FE-LVSEM involves four major elements: 1) the use of Anodisc inorganic aluminum oxide membrane filters for the image analysis of drug crystal particles > or = 350 nm having been isolated from suspension in order to determine the area, length, width, and other particle measurements; 2) the use of either a Thornley Everhart secondary electron detector or a MCP detector in the secondary electron mode directly above the specimen so as to produce a shadow-free digital image; 3) recording digital images as viewed normal to the crystal surface and at 45 degrees so as to image the edge of the crystal at a known angle; and 4) determination of drug particle volume from both views and the conversion of those volumes to an equivalent spherical volume.

Drug Stability↗

Itraconazole suspension for intravenous injection: determination of the real component of complete refractive index for particle sizing by static light scattering.

The purpose of this study is to assess the impact of real refractive indices, using different itraconazole suspensions, on the associated particle size distributions. Instrumental particle size measurement remains the practical option for determining the particle size distribution of a suspension. In this study, the suspension particle size distribution was measured by static light scattering, which requires knowledge of both the real and imaginary components of the complete refractive index. The real refractive indices of micronized itraconazole raw material, as well as vacuum-dried itraconazole suspension samples obtained from different formulations, polymorphs, manufacturing methods and particle size distributions, were determined using the Becke line method. Identical samples were analyzed by two contract laboratories in order to assess consistency. For the static light scattering equipment used in this study, the complete relative refractive index (RRI = n(particte) / n(dispersant) - ik) input required for software calculation is denoted by a refractive index kernel (RRI input) comprising a relative real component and an imaginary component. The reported real refractive indices for the itraconazole raw material as well as vacuum dried itraconazole suspension samples were different, ranging from 1.608 to 1.65 (selected kernel range of 120A010I to 124A010I). The imaginary component of itraconazole suspension was determined in a previous study to be 010I. The average real refractive index was calculated to be 1.62 (122A010I). The particle size distributions obtained using 120A010I and 124A010I were in good agreement with one generated using 122A010I. Therefore, itraconazole suspensions that were produced using different manufacturing methods/formulations or exhibited different particle size distributions/polymorphic forms may use 122A010I in determining particle size distribution. The particle size distributions determined using RRI input outside the range of 120A010I to 124A010I may not be reliable. However, it is recommended that similar investigations be conducted for other drug suspensions on a case-by-case basis.

Algorithms↗