Research Interests: Drug delivery, Pharmaceutical Chemistry, Adhesion, Quality Control, Dosage Form, and 15 moreSafety, Humans, Toxicity, United States, Drug Delivery Systems, Quality Attributes, Efficiency, European, Shear Strength, Shear, Food and Drug Administration, Transdermal Drug Delivery, Pharmaceutical preparations, Skin Absorption, and Pharmacology and pharmaceutical sciences
The United States Food and Drug Administration (FDA) has received numerous reports of serious adverse events, including death, in patients using fentanyl transdermal systems (FTS). To gain a better understanding of these problems, the... more
The United States Food and Drug Administration (FDA) has received numerous reports of serious adverse events, including death, in patients using fentanyl transdermal systems (FTS). To gain a better understanding of these problems, the current research focuses on the in vitro characterization of fentanyl reservoir (Duragesic) and matrix (Mylan) systems with respect to drug release and skin permeation under conditions of elevated temperature and compromised skin. In addition, different synthetic membrane barriers were evaluated to identify the one that best simulates fentanyl skin transport, and thus may be useful as a model for these systems in future studies. The results indicate that reservoir and matrix FTS are comparable when applied to intact skin at normal skin temperature but the kinetics of drug delivery are different in the two systems. At 40 degrees C, the permeation rate of fentanyl was twice that seen at 32 degrees C over the first 24 h in both systems; however, the total drug permeation in 72 h is significantly higher in the reservoir FTS. When applied to partially compromised skin, matrix FTS has a greater permeation enhancement effect than reservoir FTS. The intrinsic rate limiting membrane of the reservoir system served to limit drug permeation when the skin (barrier) permeability was compromised. Different ethylene vinyl acetate membranes were shown to have fentanyl permeability values encompassing the variability in human skin. Results using the in vitro model developed using synthetic membranes suggest that they mimic the effect of compromised skin on fentanyl permeability. Especially for highly potent drugs such as fentanyl, it is important that patients follow instructions regarding application of heat and use of the product on compromised skin.
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Multi-stage cascade impactors (CI) are accepted for the determination of metrics of the drug mass aerodynamic particle size distributions (APSD) of aerosols emitted from orally inhaled products (OIPs). This is particularly important for... more
Multi-stage cascade impactors (CI) are accepted for the determination of metrics of the drug mass aerodynamic particle size distributions (APSD) of aerosols emitted from orally inhaled products (OIPs). This is particularly important for products where the drug to excipient ratio or particle density may not be the same in each aerodynamic size fraction; examples of such products are carrier-containing dry powder inhalers (DPIs) and suspension pressurized metered-dose inhalers (pMDIs). CI measurements have been used as the "gold standard" for acceptance of alternative methods of APSD assessment, such as laser diffraction for nebulized solutions. Although these apparatus are labor-intensive, they are accepted in regulatory submissions and quality control assessments because the mass of active pharmaceutical ingredient(s) in the aerosol can be quantified by chemical assay and measured particle size is based on the aerodynamic diameter scale that is predictive of deposition in the respiratory tract. Two of the most important factors that modify the ideal operation of an impactor are "particle bounce," that is often accompanied by re-entrainment in the air flow passing the stage of interest, and electrostatic charge acquired by the particles during the preparation and aerosolization of the formulation when the inhaler is actuated. This article reviews how both factors can lead to biased APSD measurements, focusing on measurements involving pMDIs and DPIs, where these sources of error are most likely to be encountered. Recommendations are provided for the mitigation of both factors to assist the practitioner of these measurements.
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ABSTRACTThe multi-stage cascade impactor (CI) is the mainstay method for the determination of the aerodynamic particle size distribution (APSD) of aerosols emitted from orally inhaled products (OIPs). CIs are designed to operate at a... more
ABSTRACTThe multi-stage cascade impactor (CI) is the mainstay method for the determination of the aerodynamic particle size distribution (APSD) of aerosols emitted from orally inhaled products (OIPs). CIs are designed to operate at a constant flow rate throughout the measurement process. However, it is necessary to mimic an inhalation maneuver to disperse the powder into an aerosol when testing passive dry powder inhalers (DPIs), which constitute a significant portion of available products in this inhaler class. Methods in the pharmacopeial compendia intended for product quality assurance initiate sampling by applying a vacuum to the measurement apparatus using a timer-operated solenoid valve located downstream of the CI, resulting in a period when the flow rate through the impactor rapidly increases from zero towards the target flow rate. This article provides recommendations for achieving consistent APSD measurements, including selection of the CI, pre-separator, and flow control equipment, as well as reviewing considerations that relate to the shape of the flow rate-sampling time profile. Evidence from comparisons of different DPIs delivering the same active pharmaceutical ingredients (APIs) is indicative that the compendial method for APSD measurement is insensitive as a predictor of pharmacokinetic outcomes. Although inappropriate for product quality testing, guidance is therefore provided towards adopting a more clinically realistic methodology, including the use of an anatomically appropriate inlet and mimicking patient inhalation at the DPI while operating the CI at constant flow rate. Many of these recommendations are applicable to the testing of other OIP classes.
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Multiple factors may influence the performance of a metered dose inhaler (MDI) when used with a valved holding chamber (VHC or "spacer"). Andersen Cascade Impactor measurements were conducted for three... more
Multiple factors may influence the performance of a metered dose inhaler (MDI) when used with a valved holding chamber (VHC or "spacer"). Andersen Cascade Impactor measurements were conducted for three MDI products and two different VHCs using a specially designed system that accommodated variable delay times between MDI actuation and introduction of the aerosol into the impactor, and allowed reduced flow through the VHC while the impactor was operated at 28.3 L/min. Deposited drug mass and aerodynamic particle size distribution were determined using validated high-performance liquid chromatography (HPLC) methods. A two-level, three-factor full-factorial design of experiments (DOE) design was applied to assess the influences of VHC type, flow rate, and inhalation delay on a total of seven performance characteristics for each MDI product. An experiment without a VHC was added to assess the influence of VHC presence. DOE study shows the presence and type of VHC are the major influences on emitted dose and respirable fraction. Following the VHC effect, the inhalation delay has the most significant influence on most MDI performance metrics-emitted dose, respirable particle dose and fraction (aerosols between 1.1 and 4.7 μm), and fine particle dose and fraction (aerosols under 4.7 μm). This study illustrates the use of DOE analysis to effectively assess the effects of patient handling parameters (flow rate and inhalation delay) on the performance of MDI drugs when used with a VHC. The results of this study will inform Food and Drug Administration reviewers, the pharmaceutical industry, and healthcare practitioners as to safe and effective use of MDI products when used in conjunction with spacer devices.
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The full-resolution next generation impactor (NGI) and three abbreviated impactor systems were used to obtain the apparent aerodynamic particle size distribution (APSD) and other quality measures for marketed dry powder inhalers (DPIs)... more
The full-resolution next generation impactor (NGI) and three abbreviated impactor systems were used to obtain the apparent aerodynamic particle size distribution (APSD) and other quality measures for marketed dry powder inhalers (DPIs) using the compendial method and efficient data analysis (EDA). APSD for the active pharmaceutical ingredient (API) in Spiriva(®) Handihaler(®), Foradil(®) Aerolizer(®), and Relenza(®) Diskhaler(®) was obtained using a full-resolution NGI at 39, 60, and 90 L/min, respectively. Two reduced NGI (rNGI) configurations, the filter-only configuration (rNGI-f) and the modified-cup configuration (rNGI-mc), and the fast-screening impactor (FSI) with appropriate inserts to provide a 5-μm cut size were evaluated. The fine particle dose (FPD) obtained using the FSI for Spiriva was statistically similar to that obtained using the full NGI. However, the FPD for both Foradil and Relenza obtained using the FSI was significantly different from that obtained using the f...
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Research Interests: Medicine()
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Samples prepared by shaking, priming (four actuations each) and spraying each in an upright position onto inverted aluminum-coated glass microscope slides positioned approximately 6 inches from the spray nozzle. The samples were then... more
Samples prepared by shaking, priming (four actuations each) and spraying each in an upright position onto inverted aluminum-coated glass microscope slides positioned approximately 6 inches from the spray nozzle. The samples were then immediately turned upright and allowed to dry. • Raman images processed to calculate PSD of active pharmaceutical ingredient (API) from 1) all API particles 2) excipient-free API particles 3) API particles adhered to other excipients. • The sizes of all PS microsphere size standards and API particles were blinded to ChemImage. Measurements and Analysis A particle size study was performed using six polystyrene (PS) microsphere size standards in order to determine the accuracy of sizing micron dimension particles using RCI and optical microscopy. To minimize systematic overestimation of particle diameter, we prepared close packed hexagonal arrays of highly uniform microspheres and measured multiple PS microspheres in an row and divided by the total number...
Droplet velocity is an important parameter which can significantly influence inhalation drug delivery performance. Together with the droplet size, this parameter determines the efficiency of the deposition of MDI products at different... more
Droplet velocity is an important parameter which can significantly influence inhalation drug delivery performance. Together with the droplet size, this parameter determines the efficiency of the deposition of MDI products at different sites within the lungs. In this study, phase Doppler anemometry (PDA) was used to investigate the instantaneous droplet velocity emitted from MDIs as well as the corresponding droplet size distribution. The nine commercial MDI products surveyed showed significantly different droplet velocities, indicating that droplet velocity could be used as a discriminating parameter for in vitro testing of MDI products. The droplet velocity for all tested MDI products decreased when the testing distance was increased from 3 cm to 6 cm from the front of mouthpiece, with CFC formulations showing a larger decrease than HFA formulations. The mean droplet diameters of the nine MDIs were also significantly different from one-another. Droplet size measurements made using ...
Research Interests: Chemistry, Pharmaceutical Chemistry, Medicine, Pharmaceutics, Lasers, and 12 moreMotion, Particle Size, Pharmaceutical Formulation Technology, Time Factors, Doppler effect, Metered Dose Inhalers, Chlorofluorocarbons, Materials Testing, Drug Carriers, Drug Compounding, Equipment Design, and Pharmacology and pharmaceutical sciences
To determine aerosol deposition during the inhalation drug delivery, it is important to understand the combination of velocity and droplet size together. In this study, phase Doppler anemometry (PDA) was used to simultaneously... more
To determine aerosol deposition during the inhalation drug delivery, it is important to understand the combination of velocity and droplet size together. In this study, phase Doppler anemometry (PDA) was used to simultaneously characterize the aerosol velocity and droplet size distribution (DSD) of three nasal spray pumps filled with water. Thirteen sampling positions were located in the horizontal cross-sectional area of the nasal spray plumes at a distance of 3cm from the pump orifice. The results showed droplet velocities near the center of the spray plume were higher and more consistent than those near the edge. The pumps examined showed significant differences in their aerosol velocity at the center of the spray plume, which suggest that this metric might be used as a discriminating parameter for in vitro testing of nasal sprays. Droplet size measurements performed using PDA were compared with results from laser light scattering measurements. The ability of PDA to provide simul...
Research Interests: Chemistry, Water, Evaluation, Pharmaceutical Chemistry, Medicine, and 13 moreAerosols, Pharmaceutics, In Vitro, Light, Drug Delivery Systems, Droplet, Velocity, Particle Size, Size, Phase-Doppler Anemometry, Intranasal Administration, Laser Doppler Flowmetry, and Pharmacology and pharmaceutical sciences
A liquid chromatographic method was developed for determination of chlorhexidine and its degradation products in unformulated drug substance. A nonlinear gradient from 80% 0.1M ammonium acetate buffer, pH 5.0, to 20% buffer over 90 min... more
A liquid chromatographic method was developed for determination of chlorhexidine and its degradation products in unformulated drug substance. A nonlinear gradient from 80% 0.1M ammonium acetate buffer, pH 5.0, to 20% buffer over 90 min (balance is acetonitrile) is applied to a 3 microns octadecylsilane bonded-phase column. The drug and some of its degradation products are determined at 230 nm. Of 11 previously identified degradation products, 9 are determined with good precision (relative standard deviation of peak area is < 2%).
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We report the identification of 11 impurities in variously stressed chlorhexidine digluconate (CHG) solutions. The structural assignment of each CHG impurity involved tentative identification from HPLC-MS data followed by synthesis of the... more
We report the identification of 11 impurities in variously stressed chlorhexidine digluconate (CHG) solutions. The structural assignment of each CHG impurity involved tentative identification from HPLC-MS data followed by synthesis of the appropriate standard, isolation of the impurity from the CHG solution by flash chromatography, and comparison of HPLC-MS, HPLC-UV, and NMR data of the impurity with the standard. Six of the synthetic impurity standards represent new compounds. Degradation studies of CHG solutions systematically stressed by heat, light, and low pH are reported with identification and approximate quantification of resulting impurities. Degradation mechanisms were proposed for each set of stress conditions applied to CHG solutions. Parallels were noted between the way CHG degrades in the thermospray interface of the HPLC-MS and the way CHG degrades with shelf time. Similarities were noted in the synthetic starting materials of CHG and the final degradation products.
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Research Interests: Nanoparticle, Scanning Electron Microscopy, Morphology, Titanium, Nanoparticles, and 12 moreTransmission Electron Microscopy, Humans, Permeability, Nanostructure, Clinical Sciences, Surface Structure, X ray diffraction, Penetration, Structure activity Relationship, Cosmetic Science, Drug Stability, and Ultraviolet Rays
The responses of hepatic and adipose tissue malic enzyme (ME), citrate cleavage enzyme (CCE), glucose-6-phosphate dehydrogenase (G6PD), and glyceride synthetase (GS) to exercise training and exhaustive exercies and the potential of a high... more
The responses of hepatic and adipose tissue malic enzyme (ME), citrate cleavage enzyme (CCE), glucose-6-phosphate dehydrogenase (G6PD), and glyceride synthetase (GS) to exercise training and exhaustive exercies and the potential of a high fat or high carbohydrate diet to modify these responses were studied in male Carworth rats. Characteristic elevation and depression of ME, CCE, and G6PD were decreased in skeletal muscle, liver, and adipose tissues of high carbohydrate-fed rats. A significant two-way diet-training interaction was indicated for hepatic ME and G6PD. This interaction resulted from an apparent training modulation of ME and C6PD responses to the high fat and high carbohydrate diets. Adipose tissue G6PD was significantly decreased by training. Exhaustive exercise performed immediately prior to sacrifice did not significantly alter ME or CCE activities in either liver or adipose tissues, but decreased adipose tissue G6PD in untrained rats. Exhaustion was also associated w...
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These studies evaluated the ability of common household food and drink products to mask the bitter taste of three selected anti-terrorism drugs. Three anti-terrorism drugs (doxycycline, ciprofloxacin hydrochloride, and potassium iodide)... more
These studies evaluated the ability of common household food and drink products to mask the bitter taste of three selected anti-terrorism drugs. Three anti-terrorism drugs (doxycycline, ciprofloxacin hydrochloride, and potassium iodide) were mixed with a variety of common household food and drinks, and healthy adult volunteers evaluated the resulting taste and aftertaste. In parallel, the ASTREE Electronic Tongue was used to evaluate taste combinations. Stability of the mixtures over time was monitored, as was the dosage uniformity across preparations. Foods and drinks were identified that satisfactorily masked the bitter flavor of each drug. Dose uniformity and stability were also acceptable over the range studied, although some combinations were significantly less stable than others. The electronic tongue was able to differentiate between tastes, but ranked masking agents in a different order than human volunteers. Doxycycline, potassium iodide, and ciprofloxacin, which are stockpiled in solid tablet form, can conveniently be prepared into more palatable formulations, using common household foods and drinks. The electronic tongue can be used to perform an initial screening for palatability.
Research Interests: Chemistry, Analytical Chemistry, Pharmaceutical Technology, Drug delivery, Medicine, and 15 moreHumans, Pharmaceutical, Female, Bioterrorism, Male, Potassium, Middle Aged, Adult, Doxycycline, Ciprofloxacin, Human Subjects, Potassium Iodide, Drug Stability, Biosensing Techniques, and Pharmacology and pharmaceutical sciences
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To understand and evaluate the stability and skin permeation profiles of fentanyl reservoir systems as a function of patch age. Drug release and skin permeation studies were performed using a modified USP apparatus 5 with a novel sample... more
To understand and evaluate the stability and skin permeation profiles of fentanyl reservoir systems as a function of patch age. Drug release and skin permeation studies were performed using a modified USP apparatus 5 with a novel sample preparation technique. The amount of fentanyl present in the EVA/adhesive layer (EAL) increased from about 17% of label claim (LC) at 5 months to 25% LC at 22 months. The increase in the drug concentration was mainly observed in the peripheral EAL. Simultaneously, the alcohol content of the patch decreased as a function of patch age. A significant effect of patch age on the drug content in the EAL and the drug release from the system was observed; however, skin permeation studies did not indicate an increase in drug delivery rate. Novel sample preparation technique with USP Apparatus 5 allowed determination of in vitro skin permeation rates for fentanyl transdermal patches with different designs. Permeation rates with cadaver skin as substrate were found not to change with patch age despite changing drug concentration in the EAL.
Research Interests: Drug delivery, Stability, Medicine, Sample Preparation, Dosage Form, and 15 moreHumans, Age, Reservoir, Pharmaceutical, Drug Delivery Systems, Skin, Solubility, Time Factors, Permeation, Drug Release, Equipment Design, Fentanyl, Alcohols, Skin Absorption, and Pharmacology and pharmaceutical sciences
Résumé/Abstract A liquid chromatographic method was developed for determination of chlorhexidine and its degradation products in unformulated drug substance. A nonlinear gradient from 80% 0.1 M ammonium acetate buffer, pH 5.0, to 20%... more
Résumé/Abstract A liquid chromatographic method was developed for determination of chlorhexidine and its degradation products in unformulated drug substance. A nonlinear gradient from 80% 0.1 M ammonium acetate buffer, pH 5.0, to 20% buffer over 90 min ( ...
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Aims: To determine if commercial sunscreens contain distinct nanoparticles and to evaluate analytical methods for their ability to detect and characterize nanoparticles in unmodified topical products using commercial sunscreens as a... more
Aims: To determine if commercial sunscreens contain distinct nanoparticles and to evaluate analytical methods for their ability to detect and characterize nanoparticles in unmodified topical products using commercial sunscreens as a model. Methods: A total of 20 methods were evaluated for their ability to detect and characterize nanoparticles in unmodified commercial sunscreens. Results: Variable-pressure scanning-electron microscopy, atomic-force microscopy, laser-scanning confocal microscopy and X-ray diffraction were found to be viable and complementary methods for detecting and characterizing nanoparticles in sunscreens. Conclusions: It was determined that several of the commercial sunscreens contained distinct nanoparticles. No one method was able to completely characterize nanoparticles in the unmodified products but the viable methods provided complementary information regarding the nanoparticles and how they were interacting with the sunscreen matrix.
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Research Interests: Mathematics, Medicine, Variability, Pharmaceutical Sciences, Calibration, and 11 moreDissolution, Solubility, Observer Variation, Pharmaceutical Formulation Technology, Time Factors, Tablets, Reproducibility of Results, Dissolution Test, Pharmaceutical preparations, Prednisone, and Pharmacology and pharmaceutical sciences
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Dissolution testing of pharmaceutical products is an important technique used extensively for both product development and quality control, but there are many variables that can affect dissolution results. In this study, the effect of the... more
Dissolution testing of pharmaceutical products is an important technique used extensively for both product development and quality control, but there are many variables that can affect dissolution results. In this study, the effect of the inner shape of standard 1-L dissolution vessels on drug dissolution results was investigated. The geometric dimensions and irregularities of commercially available vessels (obtained from four different manufacturers) were examined using a three-dimensional video-based measuring machine (VMM). The same analyst, dissolution test assembly, and experimental conditions were used for dissolution testing involving 10 mg of prednisone tablets (NCDA #2) with dissolution apparatus 2 (paddle). Mechanical calibration of the dissolution apparatus was performed prior to dissolution testing with each set of vessels. Geometric characteristics varied within and among the sets of vessels, but the overall averages and standard deviations of dissolution results (six vessels) showed no statistical significant differences among the vessel sets. However, some dissolution differences were noted when comparing individual vessels. With these types of comparisons, the vessel concentricity, sphericity, and radius of sphere were found to possibly influence the amount of prednisone dissolved, but flatness of vessel flange, cylindricity, and circularity showed no effect on dissolution results. The study shows that VMM is a technique that could be used to qualify dissolution vessels.
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Environmental vibration induced by laboratory equipment, building construction, or even by the analysts themselves is one of the more complicated factors affecting dissolution testing. It is difficult to control and/or calibrate by... more
Environmental vibration induced by laboratory equipment, building construction, or even by the analysts themselves is one of the more complicated factors affecting dissolution testing. It is difficult to control and/or calibrate by mechanical means or performance-based methods. In this study, dissolution apparatus vibration levels were measured in the frequency range from 10 to 270 Hz along all three axes using commercially available, single-axis accelerometers. The vibration distribution on the dissolution vessel plate was mapped, and acceleration was subsequently measured during dissolution runs involving NCDA#2 (10 mg prednisone) tablets using the paddle method. Several types of laboratory equipment were used to induce vibration during dissolution testing and vibration levels along the X-, Y-, and Z-axes of the vessel plate were measured in an attempt to establish possible correlation with dissolution results. In the frequency range studied, root mean square (RMS) acceleration values above 0.01 g, in either vertical or horizontal direction, typically affected dissolution results.
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Research Interests: Thermodynamics, Water, Magnesium, Near Infrared Spectroscopy, Pharmaceutical Sciences, and 11 moreCalibration, Regression Analysis, Thermogravimetry, Partial Least Squares Regression, Thermogravimetric Analysis, Reproducibility of Results, Sensitivity and Specificity, Reference Values, Magnesium Sulfate, Multivariate Calibration, and Pharmacology and pharmaceutical sciences
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Dissolution testing is of primary importance for optimization of drug formulation and quality control, but test results typically show large variability. Vibration is one of the factors that can increase variability of dissolution... more
Dissolution testing is of primary importance for optimization of drug formulation and quality control, but test results typically show large variability. Vibration is one of the factors that can increase variability of dissolution testing. In this study, a Distek USP Apparatus 2 was used to perform dissolution testing using disintegrating 10 mg prednisone tablets at 50 rpm in 500 mL of 37 degrees C degassed water medium. A controllable vertical random vibration was applied to the dissolution apparatus during the dissolution testing. Real-time vibration waveforms were recorded using accelerometers placed at various locations on the vessel plate and on the dissolution vessels. Preliminary results showed a strong correlation between induced vibration and dissolution results. The vibration measured on the vessel plate correlates well with that measured within nearby vessels. The observed dissolution profiles suggest that vibration affects the disintegration and dissolving processes by different mechanisms, leading to high or low results depending upon during which phase of the dissolution process the vibration occurs. This study also presents a method capable of measuring vibration in a meaningful manner and how to determine where best to measure it.
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Research Interests: Microscopy, Pharmaceutical Technology, Medicine, Substance Use, Pharmaceutical Sciences, and 9 moreUnited States, Artifacts, Particle Size, Pharmaceutical Formulation Technology, Particle Size Analysis, Drug Industry, Pharmaceutical preparations, United States Food and Drug Administration, and Pharmacology and pharmaceutical sciences
Research Interests: Chemistry, Pharmacokinetics, Comparative Study, Medicine, DISTRIBUTION, and 11 morePharmaceutical Sciences, Particle Size, Next Generation, Cholinergic Receptor, Metered Dose Inhalers, Distribution, Flow Rate, Muscarinic Receptor, Particle Size Distribution, Pharmaceutical preparations, and Pharmacology and pharmaceutical sciences
A release liner removal test is a valuable test for assessing the quality of a transdermal drug delivery system (i.e., TDDS, patch). This test measures the force required to remove the release liner from a patch. The objective of the... more
A release liner removal test is a valuable test for assessing the quality of a transdermal drug delivery system (i.e., TDDS, patch). This test measures the force required to remove the release liner from a patch. The objective of the present study was to establish sample preparation and instrument parameters for measuring release liner removal adhesion for TDDS. Ten TDDS were evaluated (six drugs for a total of 29 lots). Patches which had a rate-controlling membrane were run as-is, since they could not be cut to a precise width without sacrificing their structural integrity. Patches that were square or rectangular in shape were run as-is, and the width of these patches was determined using a digital caliper. Patches which were not square or rectangular in shape and did not have a rate-controlling membrane were cut to a precise width using a specimen cutter. Double-sided tape was used to adhere the liner side of the transdermal system to a clean stainless steel test panel. A release liner peel adhesion method for TDDS is proposed using a dwell time of approximately 3 min, a peel angle of 90 degrees , and a peel speed of 300 mm/min.
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Research Interests: Mathematics, Chemistry, Design, Monte Carlo Simulation, Modeling, and 15 moreMonte Carlo, Performance, Experimental Design, Medicine, Conception, In Vitro, Factorial Design, Performance Model, Drug Design, Drug Delivery Systems, Design of experiment, Gels, Mathematical Model, Error Propagation, and Monte Carlo Method
ABSTRACT The panel discussion and audience comments on laboratory safety during the 46th Midwest and 39th Great Lakes Joint Regional American Chemical Society (ACS) Meeting in St. Louis, Missouri, are summarized as a starting point for... more
ABSTRACT The panel discussion and audience comments on laboratory safety during the 46th Midwest and 39th Great Lakes Joint Regional American Chemical Society (ACS) Meeting in St. Louis, Missouri, are summarized as a starting point for further discussions on improving laboratory safety in college and university research and teaching laboratories. All attendees and panelists agreed that laboratory safety must be an on-going high priority and that there was strong merit in developing a banding approach to classifying the chemical hazard risk in laboratories based on the type and quantity of chemicals used in a laboratory, analogous to the Biosafety Level risk approach used by the Centers for Disease Control and Prevention (CDC) and National Institutes of Health (NIH) Office of Biotechnology Activities (OBA). The panel members and attendees believed that the U.S. Chemical Safety Board (CSB) should work with ACS, environmental health and safety professionals, chemistry faculty representatives, college and university administration representatives, and other professional societies to not only develop chemical hazard risk assessment guidance, but also to support improvement of management systems at all levels of academic institutions (and granting and regulatory agencies) to improve safety.
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As part of a method development for peel testing, an interlaboratory comparison among Food and Drug Administration-Center for Drug Evaluation and Research, Food and Drug Administration-Center for Devices and Radiological Health and... more
As part of a method development for peel testing, an interlaboratory comparison among Food and Drug Administration-Center for Drug Evaluation and Research, Food and Drug Administration-Center for Devices and Radiological Health and Southwest Research Institute was conducted using medical tapes. The aim was to determine which readily available substrate [stainless steel (SS), high density polyethylene (HDPE) or Vitro-Skin(R)] would best distinguish among various medical tapes. Five medical tapes (3M 1523, 3M 1525L, 3M 1776, Mepiform(R) and Mediderm(R) 3505) were evaluated on four different substrates (SS, HDPE, Vitro-Skin, and human cadaver skin) using the following peel parameters: approximately 3 min dwell time, 90 degrees peel angle, and 300 mm/min peel rate. No substrate mimics cadaver skin for all five tapes. SS had the best ability to distinguish among the medical tapes. Overall, for quality control purposes (yielding good discrimination and precision), SS would be the optimal substrate.
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The electrochemistry of a series of N, N-diethyldithiocarbamate (DTC) complexes of molybdenum (VI),-(V), and-(IV) has been studied in dimethyl sulfoxide, dimethylformamide, and acetonitrile at platinum electrodes. The specific complexes... more
The electrochemistry of a series of N, N-diethyldithiocarbamate (DTC) complexes of molybdenum (VI),-(V), and-(IV) has been studied in dimethyl sulfoxide, dimethylformamide, and acetonitrile at platinum electrodes. The specific complexes that have been ...
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Samples of magnesium stearate monohydrate and dihydrate were used to prepare standard mixtures of known pseudopolymorphic composition. Near infrared spectra (NIR) of the standard mixtures were measured to develop multivariate calibration... more
Samples of magnesium stearate monohydrate and dihydrate were used to prepare standard mixtures of known pseudopolymorphic composition. Near infrared spectra (NIR) of the standard mixtures were measured to develop multivariate calibration models for the ...
Research Interests: Thermodynamics, Water, Magnesium, Near Infrared Spectroscopy, Pharmaceutical Sciences, and 11 moreCalibration, Regression Analysis, Thermogravimetry, Partial Least Squares Regression, Thermogravimetric Analysis, Reproducibility of Results, Sensitivity and Specificity, Reference Values, Magnesium Sulfate, Multivariate Calibration, and Pharmacology and pharmaceutical sciences
Research Interests: Evaluation, Pharmacokinetics, Drug delivery, Experimental Design, DISTRIBUTION, and 15 moreAerosols, In Vitro, Regression Analysis, Drug Delivery Systems, Droplet, Design of experiment, Model development, European, Particle Size, Distribution, Droplet Size Distribution, Excipients, Physical Properties, Production performance, and Pharmacology and pharmaceutical sciences
... Correspondence: Anna M. Wokovich ... A preliminary study was conducted to establish experimental parameters such as dwell time, peel speed, and peel angle that would be applicable to TDDSs,10 and, thus, factors were considered that... more
... Correspondence: Anna M. Wokovich ... A preliminary study was conducted to establish experimental parameters such as dwell time, peel speed, and peel angle that would be applicable to TDDSs,10 and, thus, factors were considered that may be important for peeling TDDSs, but ...
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There has been some apprehension expressed in the scientific literature that nanometer-sized titanium dioxide (TiO(2)) and other nanoparticles, if able to penetrate the skin, may cause cytotoxicity. In light of a lack of data regarding... more
There has been some apprehension expressed in the scientific literature that nanometer-sized titanium dioxide (TiO(2)) and other nanoparticles, if able to penetrate the skin, may cause cytotoxicity. In light of a lack of data regarding dermal penetration of titanium dioxide from sunscreen formulations, the Food and Drug Administration Center for Drug Evaluation and Research initiated a study in collaboration with the National Center for Toxicology Research using minipigs to determine whether nanoscale TiO(2) in sunscreen products can penetrate intact skin. Four sunscreen products were manufactured. The particle size distribution of three TiO(2) raw materials, a sunscreen blank (no TiO(2)) and three sunscreen formulations containing uncoated nanometer-sized TiO(2), coated nanometer-sized TiO(2) or sub-micron TiO(2) were analyzed using scanning electron microscopy (SEM), laser scanning confocal microscopy (LSCM), and X-ray diffraction (XRD) to determine whether the formulation process caused a change in the size distributions (e.g., agglomeration or deagglomeration) of the TiO(2). SEM and XRD of the formulated sunscreens containing nanometer TiO(2) show the TiO(2) particles to have the same size as that observed for the raw materials. This suggests that the formulation process did not affect the size or shape of the TiO(2) particles. Because of the resolution limit of optical microscopy, nanoparticles could not be accurately sized using LSCM, which allows for detection but not sizing of the particles. LSCM allows observation of dispersion profiles throughout the sample; therefore, LSCM can be used to verify that results observed from SEM experiments are not solely surface effects.
Research Interests: Materials Science, Nanoparticle, Scanning Electron Microscopy, Titanium, Nanoparticles, and 14 moreDrug development, Scanning Transmission Electron Microscopy, Confocal Microscopy, Pharmaceutical Chemistry, Medicine, Quantitative analysis, Permeability, Titanium dioxide, Laser Scanning Confocal Microscopy, X ray diffraction, Particle Size, Quantitative Analysis, Skin Absorption, and Pharmacology and pharmaceutical sciences(Drug development, Scanning Transmission Electron Microscopy, Confocal Microscopy, Pharmaceutical Chemistry, Medicine, Quantitative analysis, Permeability, Titanium dioxide, Laser Scanning Confocal Microscopy, X ray diffraction, Particle Size, Quantitative Analysis, Skin Absorption, and Pharmacology and pharmaceutical sciences)
(Drug development, Scanning Transmission Electron Microscopy, Confocal Microscopy, Pharmaceutical Chemistry, Medicine, Quantitative analysis, Permeability, Titanium dioxide, Laser Scanning Confocal Microscopy, X ray diffraction, Particle Size, Quantitative Analysis, Skin Absorption, and Pharmacology and pharmaceutical sciences)
Complaints from healthcare providers that the adhesive on the Daytrana™ methylphenidate transdermal drug delivery system (TDDS) adhered to the release liner to such an extent that the release liner could not be removed prompted this... more
Complaints from healthcare providers that the adhesive on the Daytrana™ methylphenidate transdermal drug delivery system (TDDS) adhered to the release liner to such an extent that the release liner could not be removed prompted this study. Daytrana™ has a packaging system consisting of a moisture-permeable pouch contained within a sealed tray containing a desiccant; the tray is impermeable to ambient moisture. The objective of this project was to determine if the Daytrana™ packaging system influenced the difficulty in removing the release liner. Both a sealed tray and an open tray containing sealed pouches were placed into an environmental chamber at 25°C and 60% relative humidity for 30 days; afterwards, release liner removal testing using a peel angle of 90° and a peel speed of 300 mm/min was performed. TDDS from open chamber trays required less force to remove the release liner than did TDDS from closed chamber trays. For the 10 mg/9 h TDDS and the 15 mg/9 h TDDS (the dosages examined), there were substantial differences in release liner removal force between an old lot and a new lot for closed chamber trays but not for open chamber trays. The results demonstrate that for this particular TDDS, storage conditions such as humidity influence release liner adhesion. This project also demonstrates that, to ensure adequate product quality, adhesion needs to become an important design parameter, and the design of a TDDS should consider the ability to remove the release liner under anticipated storage conditions.