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Biomedical subjects

Robert A Lodder

Publications and source records attributed to Robert A Lodder.

11 recordsLinked to original sources
PubMed2006

Near infrared spectrometry for the quantification of human dermal absorption of econazole nitrate and estradiol.

PURPOSE: The purpose of this study was to demonstrate the use of near-infrared (NIR) spectrometry for the in vitro quantification of econazole nitrate (EN) and estradiol (EST) in human skin. METHODS: NIR spectra were collected from EN and EST powders to verify the presence of NIR chromophores. One percent EN cream, a saturated solution of EN, or 0.25% EST solution was applied to human skin. NIR spectra were collected and one-point net analyte signal (NAS) multivariate calibration was used to predict the drug concentrations. NIR results were validated against known skin concentrations measured by high-pressure liquid chromatography (HPLC) analysis of solvent extracts. RESULTS: NIR spectroscopy measured dermal absorption from saturated solutions of EN on human skin with an r2=0.990, standard error of estimation (SEE)=2.46%, and a standard error of performance (SEP)=3.55%, EN cream on skin with an r2=0.987, SEE=2.30%, and SEP=2.66%, and 0.25% solutions of EST on skin with an r2=0.987, SEE=3.30%, and SEP=5.66%. Despite low permeation amounts of both drugs through the stratum corneum into human tissue, the NIR signal-to-noise ratio was greater than three, even for the lowest concentrations. CONCLUSION: NIR analyses paralleled the results obtained from HPLC, and thus could serve as a viable alternative for measuring the topical bioavailability/bioequivalence of different EN and EST formulations. Because these experiments were conducted in human tissue, this research suggests an all-optical in vivo method of measurement for dermal absorption could be developed.

Administration, Topical↗
PubMed2006

Acoustic-resonance spectrometry as a process analytical technology for the quantification of active pharmaceutical ingredient in semi-solids.

The purpose of this study was to demonstrate acoustic resonance spectrometry (ARS) as an alternative process analytical technology to near infrared (NIR) spectroscopy for the quantification of active pharmaceutical ingredient (API) in semi-solids such as creams, gels, ointments, and lotions. The ARS used for this research was an inexpensive instrument constructed from readily available parts. Acoustic-resonance spectra were collected with a frequency spectrum from 0 to 22.05 KHz. NIR data were collected from 1100 to 2500 nm. Using 1-point net analyte signal (NAS) calibration, NIR for the API (colloidal oatmeal [CO]) gave an r2 prediction accuracy of 0.971, and a standard error of performance (SEP) of 0.517%CO. ARS for the API resulted in an r2 of 0.983 and SEP of 0.317%CO. NAS calibration is compared with principal component regression. This research demonstrates that ARS can sometimes outperform NIR spectrometry and can be an effective analytical method for the quantification of API in semi-solids. ARS requires no sample preparation, provides larger penetration depths into lotions than optical techniques, and measures API concentrations faster and more accurately. These results suggest that ARS is a useful process analytical technology (PAT).

Acoustics↗
PubMed2006

Near-infrared spectrometry for the quantification of dermal absorption of econazole nitrate and 4-cyanophenol.

PURPOSE: The purpose of this study was to demonstrate the utility of near-infrared (NIR) spectroscopy for the in vitro quantification of econazole nitrate (EN) and 4-cyanophenol (4-CP) in hairless guinea pig skin. METHODS: NIR spectra were collected from each of the following: EN and 4-CP powders, EN and 4-CP in solution, and skin samples following topical exposure to either 4-CP in water or EN in propylene glycol and topical creams. To predict drug concentration from NIR spectra, principal component regression (PCR), interval PCR, and uninformative variable elimination PCR were each used with a leave-one-out cross-validation, and results were compared. NIR results were validated against known skin concentrations measured by high-pressure liquid chromatography (HPLC) analysis of solvent extracts. RESULTS: NIR results matched the HPLC results for the quantification of 4-CP and EN in skin exposed to saturated solutions and topical creams with an r2 > 0.90, a standard error of estimation < 7.0%, and a standard error of performance < 8.0%. CONCLUSION: This experiment demonstrated that NIR closely parallels results obtained from tissue extraction and HPLC analysis, proving its potential utility for the rapid and noninvasive determination of topical bioavailability/bioequivalence of EN and quantification of the model chemical 4-CP. Investigation of drugs in human skin is now justified.

Algorithms↗
PubMed2006

Acoustic-resonance spectrometry as a process analytical technology for rapid and accurate tablet identification.

This research was performed to test the hypothesis that acoustic-resonance spectrometry (ARS) is able to rapidly and accurately differentiate tablets of similar size and shape. The US Food and Drug Administration frequently orders recalls of tablets because of labeling problems (eg, the wrong tablet appears in a bottle). A high-throughput, nondestructive method of online analysis and label comparison before shipping could obviate the need for recall or disposal of a batch of mislabeled drugs, thus saving a company considerable expense and preventing a major safety risk. ARS is accurate and precise as well as inexpensive and nondestructive, and the sensor is constructed from readily available parts, suggesting utility as a process analytical technology (PAT). To test the classification ability of ARS, 5 common household tablets of similar size and shape were chosen for analysis (aspirin, ibuprofen, acetaminophen, vitamin C, and vitamin B12). The measures of successful tablet identification were intertablet distances in nonparametric multidimensional standard deviations (MSDs) greater than 3 and intratablet MSDs less than 3, as calculated from an extended bootstrap error-adjusted single sample technique. The average intertablet MSD was 65.64, while the average intratablet MSD from cross-validation was 1.91. Tablet mass (r (2) = 0.977), thickness (r (2) = 0.977), and density (r (2) = 0.900) were measured very accurately from the AR spectra, each with less than 10% error. Tablets were identified correctly with only 250 ms data collection time. These results demonstrate that ARS effectively identified and characterized the 5 types of tablets and could potentially serve as a rapid high-throughput online pharmaceutical sensor.

Drug Labeling↗
PubMed2003

From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part II.

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document will focus on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

Animals↗
PubMed2003

From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I.

Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document focuses on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.

Acute Disease↗
PubMed2003

Near-infrared spectroscopy for the determination of testosterone in thin-film composites.

More rapid, reproducible, and cost-effective methods to control product quality in the pharmaceutical industry continue to be a major emphasis, particularly with the FDA through its recent process analytical technologies (PAT) initiative. Many different methods have been used to determine the stability and content uniformity of a drug in various dosage forms; however, most of these methods include the destruction of the sample. Therefore, the development of nondestructive methods that allow the analysis of each individual dosage form has become the basis of much research. A new assay for the nondestructive determination of testosterone content in mucoadhesive bi-layer thin-film composites (TFCs) using near-infrared spectroscopy (NIR) was developed. Five sets of the circular films (n=5) with theoretical testosterone content of 0, 1, 2, 3, and 4 mg per 3/8th in. diameter disks were scanned in the near-infrared region of 1100-2500 nm to determine testosterone content. The NIR results were directly compared with those obtained using a previously developed ultraviolet assay for testosterone at 240 nm. Principal component regression (PCR) was performed to calibrate the NIR assay. This correlation produced r2=0.99 with a standard error of estimate (SEE)=0.18 mg, and a standard error of performance (SEP)=0.18 on cross validation with an equal number of samples (F test passed at P=0.05). Though the UV assay showed a slightly better r2 value, the NIR assay was much quicker, easier, and nondestructive. Therefore, the NIR assay may have significant potential for use in the quality control of pharmaceutical films containing drugs.

Acrylic Resins↗
PubMed2003

Near-infrared spectrometry of abdominal aortic aneurysm in the ApoE-/- mouse.

Abdominal aortic aneurysms (AAAs) occur in 5-7% of people over age 60 in the United States. Early intervention in the disease process could have a significant impact on the incidence of complications and on patient survival, but identifying incipient aneurysms can be difficult. ApoE knockout mice develop AAAs following infusion of angiotensin II (AngII) by osmotic minipump into the subcutaneous space of mice at doses ranging from 500 to 1000 ng kg(-1) min(-1) for 7-28 days. These mice are used as models of AAA development. This study tested the hypothesis that near-IR spectrometry and PCR can determine AngII dose (SEE = 26 ng kg(-1) min(-1), SEP = 37 ng kg(-1) min(-1), r2 = 0.99) and collagen/elastin (C/E) ratio (SEE = 0.38, SEP = 0.39, r2 = 0.85) in mouse aortas.

Angiotensin II↗
PubMed2002

Detection of lipid pool, thin fibrous cap, and inflammatory cells in human aortic atherosclerotic plaques by near-infrared spectroscopy.

BACKGROUND: A method is needed to identify nonstenotic, lipid-rich coronary plaques that are likely to cause acute coronary events. Near-infrared (NIR) spectroscopy can provide information on the chemical composition of tissue. We tested the hypothesis that NIR spectroscopy can identify plaque composition and features associated with plaque vulnerability in human aortic atherosclerotic plaques obtained at the time of autopsy. METHODS AND RESULTS: A total of 199 samples from 5 human aortic specimens were analyzed by NIR spectroscopy. Features of plaque vulnerability were defined by histology as presence of lipid pool, thin fibrous cap (<65 microm by ocular micrometry), and inflammatory cell infiltration. An InfraAlyzer 500 spectrophotometer was used. Spectral absorbance values were obtained as log (1/R) data from 1100 to 2200 nm at 10-nm intervals. Principal component regression was used for analysis. An algorithm was constructed with 50% of the samples used as a reference set; blinded predictions of plaque composition were then performed on the remaining samples. NIR spectroscopy sensitivity and specificity for histological features of plaque vulnerability were 90% and 93% for lipid pool, 77% and 93% for thin cap, and 84% and 89% for inflammatory cells, respectively. CONCLUSIONS: NIR spectroscopy can identify plaque composition and features associated with plaque vulnerability in postmortem human aortic specimens. These results support efforts to develop an NIR spectroscopy catheter system to detect vulnerable coronary plaques in living patients.

Algorithms↗
PubMed2002

Hyperspectral techniques in analysis of oral dosage forms.

Pharmaceutical oral dosage forms are used in this paper to test the sensitivity and spatial resolution of hyperspectral imaging instruments. The first experiment tested the hypothesis that a near-infrared (IR) tunable diode-based remote sensing system is capable of monitoring degradation of hard gelatin capsules at a relatively long distance (0.5 km). Spectra from the capsules were used to differentiate among capsules exposed to an atmosphere containing 150 ppb formaldehyde for 0, 2, 4, and 8 h. Robust median-based principal component regression with Bayesian inference was employed for outlier detection. The second experiment tested the hypothesis that near-IR imaging spectrometry of tablets permits the identification and composition of multiple individual tablets to be determined simultaneously. A near-IR camera was used to collect thousands of spectra simultaneously from a field of blister-packaged tablets. The number of tablets that a typical near-IR camera can currently analyze simultaneously was estimated to be approximately 1300. The bootstrap error-adjusted single-sample technique chemometric-imaging algorithm was used to draw probability-density contour plots that revealed tablet composition. The single-capsule analysis provides an indication of how far apart the sample and instrumentation can be and still maintain adequate signal-to-noise ratio (S/N), while the multiple-tablet imaging experiment gives an indication of how many samples can be analyzed simultaneously while maintaining an adequate S/N and pixel coverage on each sample.

Administration, Oral↗