The mechanisms that control the dissolution rates of chemical compounds in liquids have long been of interest to pharmaceutical scientists. Generally, control of the dissolution rate can be classified as being by interfacial reaction rate... more
The mechanisms that control the dissolution rates of chemical compounds in liquids have long been of interest to pharmaceutical scientists. Generally, control of the dissolution rate can be classified as being by interfacial reaction rate or by the rate of mass transport. Little work has been done in the area of sparingly soluble compounds dissolving in nonpolar organic solvents. In this study the dissolution of three isomers of methylacetanilide was investigated in three nonpolar organic solvents (hexane, heptane, and cyclohexane). The dissolution apparatus used a flat plate into which the nondisintegrating tablet could be placed so that dissolution occurred only from one face of the tablet. Agitation was provided by a four-bladed stirrer whose outer edge was 2 cm from the tablet surface. Dissolution data were collected only for concentrations less than 5% of the saturation solubility of the given compound in the given solvent. All dissolution profiles were linear. Dissolution rates were obtained from the slopes of these plots. Plots of In (dissolution rate) versus In (stirring speed) were also linear and yielded slopes that were close to the value of 0.50 predicted by the convective diffusion model employed.
Research Interests:
Research Interests: Chemistry, Electron Microscopy, Cystic Fibrosis, Rheology, Biology, and 15 moreScanning Electron Microscopy, Medicine, Humans, Diffusion, Permeability, Pharmaceutical Sciences, Animals, Glycoproteins, Steady state, Solutions, Swine, Mucus, Isoniazid, Pyrazinamide, and Pharmacology and pharmaceutical sciences
The effects of pH, mixed solvent systems, and divalent metal ions on oxytetracycline (OTC) solubility and the interactions between OTC and metal ions in aqueous and mixed solvent systems were investigated. OTC solubility profiles were... more
The effects of pH, mixed solvent systems, and divalent metal ions on oxytetracycline (OTC) solubility and the interactions between OTC and metal ions in aqueous and mixed solvent systems were investigated. OTC solubility profiles were obtained for pH 4-9. The cosolvents studied were glycerin, propylene glycol, PEG 400, and 2-pyrrolidone with the following metal ions: magnesium, calcium, and zinc. OTC and its interactions with these metal ions were evaluated by solubility, NMR, circular dichroism (CD), and electron diffraction (ED) methods. At pH 5.6, no complexation occurred with these metal ions, but OTC zwitterion formed aggregates in aqueous solutions as shown by NMR spectra. The hydration of the metal ions was observed to affect OTC aggregation, with Mg+2 causing the greatest OTC aggregation. At pH 7.5, OTC aggregation and metal-OTC complexation were observed in solutions with Ca+2 and Mg+2. Zinc ion was found to decrease OTC solubility because of zincate formation, which caused anionic OTC to precipitate. Electron diffraction revealed a relationship between OTC and metal-OTC complex crystallinity and solubility behavior. The zinc-OTC complex exhibited the highest crystallinity and lowest solubility at pH 8.0. Various cosolvents generally enhanced OTC solubility, with 2-pyrrolidone having the best solubility power. In OTC-metal-2-pyrrolidone and OTC-Zn(+2)-PEG 400 systems, circular dichroism provided evidence for the formation of soluble ternary complexes.
Research Interests: Chemistry, Inorganic Chemistry, Electron Microscopy, Water, Interaction, and 14 moreScanning Electron Microscopy, Magnetic Resonance Spectroscopy, Medicine, Circular Dichroism, Ph, Crystallinity, Solubility, Anti-Bacterial Agents, Solutions, Chelating Agents, Oxytetracycline, Hydrogen-Ion Concentration, Solvents, and Pharmacology and pharmaceutical sciences
Research Interests: Chemistry, Ion Chromatography, Polymers, Medicine, Pharmaceutics, and 15 moreDrug, Solubility, Anions, Time Factors, Emulsions, Microsphere, Microspheres, Emulsion, Salts, Lactic Acid, Delayed-Action Preparations, Solvents, Pharmaceutical preparations, Quinidine, and Pharmacology and pharmaceutical sciences
Research Interests:
ABSTRACT We determined contraceptive effectiveness of a 1-inoculation, 1-year porcine zona pellucida (PZP) vaccine in free-roaming feral horses (Equus caballus) in Nevada. We captured, freeze-branded, treated, and subsequently released... more
ABSTRACT We determined contraceptive effectiveness of a 1-inoculation, 1-year porcine zona pellucida (PZP) vaccine in free-roaming feral horses (Equus caballus) in Nevada. We captured, freeze-branded, treated, and subsequently released 267 adult feral mares given (1) 2 inoculations (13-17 days apart) of vaccine emulsion consisting of aqueous PZP and Freund's Complete Adjuvant (FCA; injection 1) or Freund's Incomplete Adjuvant (FIA; injection 2), (2) same 2 inoculations as in (1) except also containing a carbomer adjuvant in inoculation 1, or (3) a single inoculation of an emulsion of PZP and FCA containing a second dose of PZP and carbomer adjuvant in controlled-release polymer microspheres. We administered inoculations in January 1996, and monitored the mares via fecal analysis for pregnancy and via ground survey for foal production through October 1997. We determined pregnancy via measurement of estrone sulfate and progesterone metabolites in fresh feces collected from the ground. Among 2-inoculation mares, reproductive success across 1 year was 12.8% (carbomer adjuvant absent) and 10.6% (carbomer adjuvant present). In mares given 1 injection containing microspheres, reproductive success was 11.3%. The concurrent rate in 72 untreated mares was 62.5%. This study revealed marked and equivalent 1-year contraceptive efficacy in 1- and 2-inoculation PZP vaccine, indicating that controlled-release technology can replace a second inoculation and thereby increase PZP vaccine cost effectiveness and potential for use in feral horse management.
Research Interests:
The aim of this study was to investigate the dissolution characteristics of an acetaminophen/theophylline (AT) cocrystal compared with its pure components and physical mixtures. Intrinsic dissolution studies were conducted by a... more
The aim of this study was to investigate the dissolution characteristics of an acetaminophen/theophylline (AT) cocrystal compared with its pure components and physical mixtures. Intrinsic dissolution studies were conducted by a rotating-disk method. Solubility studies were conducted by collecting transient samples at 5, 30, and 60 min and equilibrium samples after 72 h, both at 37 °C. The AT cocrystal had a faster dissolution rate than AT physical mixtures, and the dissolution profiles were congruent (1:1 mole ratio) under different pH conditions. Thus, the AT cocrystal dissolved congruently at short times and exhibited higher transient solubility compared with its two pure components. Equilibrium solubilities of theophylline from the cocrystal were lower than transient values due to theophylline hydrate precipitation but no precipitation of free acetaminophen occurred. The solubility behavior of acetaminophen and theophylline exhibited typical 1:1 complex formation in physical mixtures, cocrystal, and phase-solubility studies. The Levich equation was used to predict the dissolution behavior of the AT cocrystal as well as that of the single components.
Research Interests:
In this investigation, salt effects on monomeric solubility and distribution are separated from self-association for caffeine. For self-associating compounds, the Setschenow equation is inadequate because it does not separate salt effects... more
In this investigation, salt effects on monomeric solubility and distribution are separated from self-association for caffeine. For self-associating compounds, the Setschenow equation is inadequate because it does not separate salt effects into their different contributions. Solubilities of caffeine, theophylline, and theobromine were determined in water and salt solutions at 25 degrees C. Caffeine, theophylline, and theobromine solubilities decreased with added Na(2)SO(4) or NaCl (i.e., salting-out) and increased with added NaClO(4) or NaSCN (i.e., salting-in). Caffeine distribution coefficients (D(W/O)) also decreased with added Na(2)SO(4) or NaCl and increased with added NaClO(4) or NaSCN. To separate salt-caffeine effects from salt effects on caffeine self-interaction, salting parameters (k(s)) were calculated from D(W/O) at infinite dilution instead of solubilities with the Setschenow equation. Caffeine k(s) values were smaller than the Setschenow constants (K) indicating that, for caffeine, K is not simply a salting-in/out parameter. Distribution data were used to characterize caffeine self-association using either a dimerization model (k(d), dimerization constant) or an isodesmic model (k(iso), stepwise association constant). Caffeine self-association constants (k(d) or k(iso)) decreased with NaClO(4) or NaSCN and increased with Na(2)SO(4) or NaCl.
Research Interests:
Research Interests: Chemistry, Biomedical Engineering, Chromatography, Dosage Form, In Vitro, and 13 moreControlled release, Biodegradable, FORMULATION, Proteins, Polyester, Particle Size, Microsphere, Microspheres, Emulsion, Bovine Serum Albumin, Active Ingredient, Serum albumin, and Pharmacology and pharmaceutical sciences
Basics and Applications of Solid-State Kinetics: A Pharmaceutical Perspective**The authors dedicate this review to the memory of Dr. David J.W. Grant who passed away on December 9, 2005. Dr. Grant was an internationally known authority at the University of Minnesota on the solid-state properties ...more
Most solid-state kinetic principles were derived from those for homogenous phases in the past century. Rate laws describing solid-state degradation are more complex than those in homogenous phases. Solid-state kinetic reactions can be... more
Most solid-state kinetic principles were derived from those for homogenous phases in the past century. Rate laws describing solid-state degradation are more complex than those in homogenous phases. Solid-state kinetic reactions can be mechanistically classified as nucleation, geometrical contraction, diffusion, and reaction order models. Experimentally, solid-state kinetics is studied either isothermally or nonisothermally. Many mathematical methods have been developed to interpret experimental data for both heating protocols. These methods generally fall into one of two categories: model-fitting and model-free. Controversies have arisen with regard to interpreting solid-state kinetic results, which include variable activation energy, calculation methods, and kinetic compensation effects. Solid-state kinetic studies have appeared in the pharmaceutical literature over many years; some of the more recent ones are discussed in this review.
Research Interests:
In the past there has been varying degrees of clinical interest in dissolving renal calculi by some type of in situ irrigation technique. The physical-chemical rationale for the selection of the best irrigation solutions has been based on... more
In the past there has been varying degrees of clinical interest in dissolving renal calculi by some type of in situ irrigation technique. The physical-chemical rationale for the selection of the best irrigation solutions has been based on the equilibrium solubility of calcium oxalate or other stone minerals in the particular medium without regard to other possible factors which may govern the dissolution process.
Research Interests:
Zein is a hydrophobic corn protein, rich in leucine, proline and alanine, that has has previously been investigated as a potential excipient in pharmaceutical manufacturing. We have investigated the diffusion through or from... more
Zein is a hydrophobic corn protein, rich in leucine, proline and alanine, that has has previously been investigated as a potential excipient in pharmaceutical manufacturing. We have investigated the diffusion through or from zein-containing systems and proposed aqueous channels formed by hydration and swelling as the dominant diffusional pathway. In this study, the swelling properties of zein membranes under various conditions and effect of swelling on membrane permeability were investigated. Conditions such as ionic strength and the effect of charged or neutral permeants altered the swelling behavior of zein. Although some permeants (which are highly bound to zein) interact through electrostatic interaction, van der Waals, hydrophobic, and hydrogen bonding interactions, they did not alter membrane swelling behavior significantly. Zein membranes were also cast from different solvent systems but membrane swelling was not affected by casting solvent and the aqueous channels produced in water are independent of membrane preparation. There was no significant permeation difference between different sides of the zein membrane (air or petri dish side). Thus, it appears that zein's permeability largely depends on swelling behavior that is affected by the aqueous ionic content in which it is immersed.
Research Interests:
Research Interests:
Research Interests:
Zein is a hydrophobic corn protein, rich in leucine, proline, and alanine, that has been investigated as an excipient in pharmaceutical formulations, maybe used as a biodegradable/biocompatible material for controlled release... more
Zein is a hydrophobic corn protein, rich in leucine, proline, and alanine, that has been investigated as an excipient in pharmaceutical formulations, maybe used as a biodegradable/biocompatible material for controlled release formulations. Zein's swelling behaviors under different conditions (e.g., pH, ionic strength, and permeant's charge) were investigated in a previous study and it showed that swelling indeed influenced zein's permeation. The diffusional behavior of model drugs through or from zein systems was investigated. Diffusional parameters such as effective diffusion coefficients, porosities, and tortuosities were calculated from release and membrane diffusion profiles for zein matrices and membranes. In addition, an alternative method of calculating porosity and tortuosity was proposed. The diffusional properties of zein systems appear to be primarily through aqueous channels that form during hydration and swelling in aqueous media. Permeation and release results show that the amount of diffused or released drug depends on permeant solubility and matrix/membrane permeability parameters (i.e., porosity and tortuosity). Calculated diffusional parameters for zein matrices and membranes support the aqueous channel model. Zein membranes and matrices hydrate and swell to form aqueous channels that are the dominant diffusional pathways.
Research Interests:
Research Interests:
Research Interests:
Research Interests: Chemistry, Water, Polymers, Medicine, Diffusion, and 14 moreTemperature, Sorption, Article, Mathematical Model, Diffusion Coefficient, Glass Transition Temperature, Theoretical Models, Fourier transform infrared spectroscopy, AAPS PharmSciTech, Acrylic Resins, Plasticizer, Acrylate, Pharmacology and pharmaceutical sciences, and Methacrylates
Research Interests:
Research Interests:
Research Interests:
Three classical particle dissolution rate expressions are commonly used to interpret particle dissolution rate phenomena. Our analysis shows that an assumption used in the derivation of the traditional cube-root law may not be accurate... more
Three classical particle dissolution rate expressions are commonly used to interpret particle dissolution rate phenomena. Our analysis shows that an assumption used in the derivation of the traditional cube-root law may not be accurate under all conditions for diffusion-controlled particle dissolution. Mathematical analysis shows that the three classical particle dissolution rate expressions are approximate solutions to a general diffusion layer model. The cube-root law is most appropriate when particle size is much larger than the diffusion layer thickness, the two-thirds-root expression applies when the particle size is much smaller than the diffusion layer thickness. The square-root expression is intermediate between these two models. A general solution to the diffusion layer model for monodispersed spherical particles dissolution was derived for sink and nonsink conditions. Constant diffusion layer thickness was assumed in the derivation. Simulated dissolution data showed that the ratio between particle size and diffusion layer thickness (a0/h) is an important factor in controlling the shape of particle dissolution profiles. A new semiempirical general particle dissolution equation is also discussed which encompasses the three classical particle dissolution expressions. The success of the general equation in explaining limitations of traditional particle dissolution expressions demonstrates the usefulness of the general diffusion layer model.
Research Interests: Mathematics, Chemistry, Pharmaceutical Chemistry, Medicine, Diffusion, and 12 morePharmaceutical Sciences, Spectrophotometry, Dissolution, Solubility, Difusion, Mathematical Model, Particle Size, Microspheres, Dissolution Testing, Benzocaine, Pharmacology and pharmaceutical sciences, and HPLC Chromatography
Research Interests:
Development of a physiologically-relevant in vitro system to study exhaled bioaerosols DEVELOPMENT OF A PHYSIOLOGICALLY-RELEVANT IN VITRO SYSTEM TO STUDY EXHALED BIOAEROSOLS Title and Department ____________________________________ Date DEVELOPMENT OF A PHYSIOLOGICALLY-RELEVANT IN VITRO SYSTEM TO...more
Airborne infectious diseases remain a major global health threat. The primary vector for their transmission is coarse and fine droplets, known as bioaerosols, exhaled from infected individuals during natural respiratory maneuvers, such as... more
Airborne infectious diseases remain a major global health threat. The primary vector for their transmission is coarse and fine droplets, known as bioaerosols, exhaled from infected individuals during natural respiratory maneuvers, such as breathing, coughing and sneezing. Unfortunately, our current knowledge of the mechanisms by which these exhaled bioaerosols are formed in the lungs is in its infancy. In particular, progress in this field has been hindered by the complex structure of the respiratory fluid and the resulting lack of understanding of the biophysical properties of the fluid. In this thesis, a series of in vitro mimetics of conducting airway mucus were developed to enable in depth studies of mucus properties and bioaerosol formation from mucus-like surfaces. These mucus mimetics overcome major limitations of currently available models by matching the primary chemical composition and key physical properties of the mimetic to that of native tracheal mucus. Three mimetics ...
Research Interests:
ABSTRACT Previously, we reported that the entrapment of suramin in dipalmitoylphosphatidylcholine (DPPC, C16) multilamellar liposomes ranged from 25% to 65% and the addition of 30-50 mol% cholesterol (CHL) greatly reduced entrapment.... more
ABSTRACT Previously, we reported that the entrapment of suramin in dipalmitoylphosphatidylcholine (DPPC, C16) multilamellar liposomes ranged from 25% to 65% and the addition of 30-50 mol% cholesterol (CHL) greatly reduced entrapment. Entrapment of small molecules similar to suramin, disodium 1,5-naphthalenedisulfonic acid (5.5%) and sodium 3-amino-2,7-naphthalenedisulfonic acid (1.2%), were very low. In the present study, the entrapment and interaction of suramin with dilauroylphosphatidylcholine (DLPC, C12), dimyristoylphosphatidylcholine (DMPC, C14), and distearoylphosphatidylcholine (DSPC, C18) liposomes was investigated. DLPC and DMPC showed 2-3-fold higher entrapment percentages (95.1% and 74.2%, respectively) than DPPC (37%). However, the entrapment with DSPC (29%) was about 25% lower than DPPC. Adding 50 mol% cholesterol greatly reduced suramin entrapment for all phospholipids. The entrapment of polysulfonated dyes such as Evans blue, Direct blue 1, or Trypan blue, which are structurally similar to suramin, was found to be in the same order of DLPC > DMPC > DPPC > DSPC. Differential scanning calorimetry of aqueous dispersions of DLPC and DMPC with suramin showed more apparent interaction than for DPPC and DSPC. These results suggest that a large portion of the associated suramin and other polysulfonated compounds results from binding to the surface of the phospholipid bilayer or intercalation into the liposomal bilayer. The phospholipid chain length effect on entrapment may be due to the lower net van der Waals interaction between hydrocarbon chains for shorter acyl chains which also increases the bilayer intermolecular spacing. Such effects could then increase the ability of suramin to interact with individual phospholipid molecules.
Research Interests:
Research Interests:
In the past there has been varying degrees of clinical interest in dissolving renal calculi by some type of in situ irrigation technique. The physical-chemical rationale for the selection of the best irrigation solutions has been based on... more
In the past there has been varying degrees of clinical interest in dissolving renal calculi by some type of in situ irrigation technique. The physical-chemical rationale for the selection of the best irrigation solutions has been based on the equilibrium solubility of calcium oxalate or other stone minerals in the particular medium without regard to other possible factors which may govern the dissolution process.
Research Interests:
Robert E. Becker, M.D., C.M.a,b, Nigel H. Greig, Ph.D.b, Lon S. Schneider, M.D., M.S.e, Clive Ballard, MB ChB, MRCPsych, M.D.f, Dag Aarsland, M.D., Ph.D.g, Debomoy K. Lahiri, Ph.D.h, Douglas Flanagan, Ph.D.i, Ramprakash Govindarajan,... more
Robert E. Becker, M.D., C.M.a,b, Nigel H. Greig, Ph.D.b, Lon S. Schneider, M.D., M.S.e, Clive Ballard, MB ChB, MRCPsych, M.D.f, Dag Aarsland, M.D., Ph.D.g, Debomoy K. Lahiri, Ph.D.h, Douglas Flanagan, Ph.D.i, Ramprakash Govindarajan, Ph.D.k, Mary Sano, Ph.D.j, Dimitrios Kapogiannis, M.D.d, and Luigi Ferrucci, M.D.c aAristea Translational Medicine Corporation, Park City, UT 84098 bDrug Design and Development Section, National Institute on Aging, Baltimore MD, 21224, USA cLongitudinal Study Section, Translational Gerontology Branch, National Institute on Aging, Baltimore MD, 21224, USA
Concussion (mild) and other moderate traumatic brain injury (TBI) and Alzheimer's disease (AD) share overlapping neuropathologies, including neuronal pre-programmed cell death (PPCD), and clinical impairments and disabilities.... more
Concussion (mild) and other moderate traumatic brain injury (TBI) and Alzheimer's disease (AD) share overlapping neuropathologies, including neuronal pre-programmed cell death (PPCD), and clinical impairments and disabilities. Multiple clinical trials targeting mechanisms based on the Amyloid Hypothesis of AD have so far failed, indicating that it is prudent for new drug developments to also pursue mechanisms independent of the Amyloid Hypothesis. To address these issue, we have proposed the use of an animal model of concussion/TBI as a supplement to AD transgenic mice to provide an indication of an AD drug candidate's potential for preventing PPCD and resulting progression towards dementia in AD. We searched PubMed/Medline and the references of identified articles for background on the neuropathological progression of AD and its implications for drug target identification, for AD clinical trial criteria used to assess disease modification outcomes, for plasma biomarkers ass...
Research Interests:
... Annual Progress Report 0 John L. tach Douglas R. Flanagan Lloyd E, Matheson, Jr. ELECTE JULO0I1987E July 1985 U ... 13¶. PERSONAL AUTHORl Lach, John L., Douglas R. Flanagan, and Lloyd E. Matheson, Jr. I11. SUPPLEMENTARY NOTATION... more
... Annual Progress Report 0 John L. tach Douglas R. Flanagan Lloyd E, Matheson, Jr. ELECTE JULO0I1987E July 1985 U ... 13¶. PERSONAL AUTHORl Lach, John L., Douglas R. Flanagan, and Lloyd E. Matheson, Jr. I11. SUPPLEMENTARY NOTATION '17 COSATI CODES 18I. ...
Research Interests:
Research Interests:
Research Interests:
New methods for the efficient and effective administration of vaccines are required particularly with the advent of new synthetic subunit vaccines. This chapter describes the approaches of several research groups to administer vaccines... more
New methods for the efficient and effective administration of vaccines are required particularly with the advent of new synthetic subunit vaccines. This chapter describes the approaches of several research groups to administer vaccines using biodegradable polymer carriers. Delivery systems composed of synthetic poly[esters] and poly[iminocarbonates] and natural (crosslinked serum albumin) biodegradable polymers are described. The antibody levels in response to these systems are presented, and possible mechanisms responsible for the observed effects are discussed. The important questions that need to be answered before this technology can be successfully applied are also discussed.
Research Interests:
To investigate the effects of inorganic salts in the external phase of an oil-in-water (O/W) emulsion method during microsphere preparation. An O/W emulsion method was used to prepare poly(D,L-lactic acid) microspheres containing... more
To investigate the effects of inorganic salts in the external phase of an oil-in-water (O/W) emulsion method during microsphere preparation. An O/W emulsion method was used to prepare poly(D,L-lactic acid) microspheres containing quinidine sulfate. Different inorganic salts were used in the external phase during microsphere preparation. Microsphere drug loading was determined by UV and the drug salt anions inside the microspheres were determined by ion chromatography. New drug salts were formed during encapsulation in the microspheres when salts with non-common anions to the drug salt were used. Drug loading increased when NaClO4 or NaSCN were used. The fraction of drug as the new salt in microspheres increased non-linearly with the salt concentration in the external phase, however, the fraction of drug as the new encapsulated salt was linearly related to drug loading. Drug loading decreased and new salt fraction increased with increasing organic solvent volume or with decreasing co...
Research Interests:
Research Interests:
... 7, 1994 Report Accelerated Degradation of Poly(e-caprolactone) by Organic Amines Wen-Jen Lin,1 Douglas R. Flanagan,1'3 and Robert J. Linhardt2 Received January 21, 1994; accepted March 4, 1994 The solid-state... more
... 7, 1994 Report Accelerated Degradation of Poly(e-caprolactone) by Organic Amines Wen-Jen Lin,1 Douglas R. Flanagan,1'3 and Robert J. Linhardt2 Received January 21, 1994; accepted March 4, 1994 The solid-state degradation ... V. Crescenzi, G. Manzini, G. Calzolari, and С. ...
Research Interests:
Research Interests:
... Annual Progress Report 0 John L. tach Douglas R. Flanagan Lloyd E, Matheson, Jr. ELECTE JULO0I1987E July 1985 U ... 13¶. PERSONAL AUTHORl Lach, John L., Douglas R. Flanagan, and Lloyd E. Matheson, Jr. I11. SUPPLEMENTARY NOTATION... more
... Annual Progress Report 0 John L. tach Douglas R. Flanagan Lloyd E, Matheson, Jr. ELECTE JULO0I1987E July 1985 U ... 13¶. PERSONAL AUTHORl Lach, John L., Douglas R. Flanagan, and Lloyd E. Matheson, Jr. I11. SUPPLEMENTARY NOTATION '17 COSATI CODES 18I. ...
Research Interests:
Research Interests:
There are many methods for analyzing solid-state kinetic data. They are generally grouped into two categories, model-fitting and isoconversional (model-free) methods. Historically, model-fitting methods were widely used because of their... more
There are many methods for analyzing solid-state kinetic data. They are generally grouped into two categories, model-fitting and isoconversional (model-free) methods. Historically, model-fitting methods were widely used because of their ability to directly determine the kinetic triplet (i.e., frequency factor [A], activation energy [E(a)], and model). However, these methods suffer from several problems among which is their inability to uniquely determine the reaction model. This has led to the decline of these methods in favor of isoconversional methods that evaluate kinetics without modelistic assumptions. This work proposes an approach that combines the power of isoconversional methods with model-fitting methods. It is based on using isoconversional methods instead of traditional statistical fitting methods to select the reaction model. Once a reaction model has been selected, the activation energy and frequency factor can be determined for that model. This approach was investigated for simulated and real experimental data for desolvation reactions of sulfameter solvates.
Research Interests:
Research Interests:
In this study of equids, we investigated the antibody response and the effect on the estrous cycle following a single inoculation of porcine zonae pellucidae (pZP) employing controlled-release methodology. We also investigated the use of... more
In this study of equids, we investigated the antibody response and the effect on the estrous cycle following a single inoculation of porcine zonae pellucidae (pZP) employing controlled-release methodology. We also investigated the use of two different water-soluble adjuvants as an alternative to oil-based adjuvants. Twenty-seven domestic mares were inoculated with various formulations of pZP and adjuvant. We showed that the anti-pZP antibodies generated as a result of the inoculations persisted for at least 43 weeks (length of the study). Of the various formulations used in the study, pZP and QS-21 water-soluble adjuvant, administered in combination with an emulsified preparation of pZP and Freund’s Complete Adjuvant generated a significantly (P < 0.05) higher titer of anti-pZP antibodies when compared with other formulations employing the water-soluble adjuvant, Carbopol. Hormone analyses for cyclicity indicated a high incidence and extended duration of persistent corpora lutea ...
Research Interests: Physiology, Reproduction, Biology, Immunohistochemistry, Saponins, and 15 moreMedicine, Antibodies, Pregnancy, Progesterone, Female, Animals, Immunization, Horses, Clinical Sciences, Time Factors, Swine, Acrylic Resins, Zona Pellucida, Enzyme Linked Immunosorbent Assay, and Paediatrics and reproductive medicine
Research Interests:
This work investigates the effect of various salts on the rate of a reaction involving a neutral species (benzocaine alkaline hydrolysis). Benzocaine hydrolysis kinetics in NaOH solutions in the presence of different salts were studied at... more
This work investigates the effect of various salts on the rate of a reaction involving a neutral species (benzocaine alkaline hydrolysis). Benzocaine hydrolysis kinetics in NaOH solutions in the presence of different salts were studied at 25 degrees C. Benzocaine solubility in salt solutions was also determined. Solubility data were used to estimate salt effects on benzocaine activity coefficients, and pH was used to estimate salt effects on hydroxide activity coefficients. Salts either increased or decreased benzocaine solubility. For example, solubility increased with 1.0 M tetraethylammonium chloride (TEAC) approximately 3-fold, whereas solubility decreased approximately 35% with 0.33 M Na2SO4. Salt effects on hydrolysis rates were more complex and depended on the relative magnitudes of the salt effects on the activity coefficients of benzocaine, hydroxide ion, and the transition state. As a result, some salts increased the hydrolysis rate constant, whereas others decreased it. For example, the pseudo-first-order rate constant decreased approximately 45% (to 0.0584 h(-1)) with 1 M TEAC, whereas it increased approximately 8% (to 0.116 h(-1)) with 0.33 M Na2SO4. Different salt effects on degradation kinetics can be demonstrated for a neutral compound reacting with an ion. These salt effects depend on varying effects on activity coefficients of reacting and intermediate species.
Research Interests:
The effects of pH and PEG 400 on the stoichiometry, conformation, and stability of the magnesium-oxytetracycline (Mg+2-OTC) complex were evaluated. Circular dichroism (CD) and HPLC were used to investigate Mg+2-OTC complex formation and... more
The effects of pH and PEG 400 on the stoichiometry, conformation, and stability of the magnesium-oxytetracycline (Mg+2-OTC) complex were evaluated. Circular dichroism (CD) and HPLC were used to investigate Mg+2-OTC complex formation and determine the stability of the complexes formed. The stoichiometry of the complex was determined to be a 1:1 molar ratio of Mg+2 to OTC regardless of changes in pH, in the range 7-10, and regardless of the percentage of polyethylene glycol (PEG) 400 in solution. CD showed that the conformation assumed by Mg+2-OTC complex is sensitive to changes in pH, however, little to no effect was found when the PEG 400 concentration was varied. PEG 400 was found to effect the magnitude of complexation as evident by the dependence of CD peak intensity on the cosolvent concentration in solution. The Job&#39;s method confirmed that the formation of this complex increased with increasing PEG 400 concentration and was most favored at pH 8. HPLC analyses of OTC solutions at pH 9 revealed the formation of multiple degradation products after storage at 50 degrees C. The incidence and magnitude of OTC degradation products were reduced in the presence of Mg+2 and PEG 400. Despite the HPLC results of maintained OTC stability in magnesium-complexed solutions over time, visual inspection showed these solutions to have darkened, indicating that an oxidative process is responsible for initial degradation of OTC. Therefore, the need for additional measures (i.e., antioxidants) was established to ensure the long-term stability of OTC in solution.
Research Interests: Algorithms, Stability, Magnesium, Circular Dichroism, Temperature, and 11 moreHigh Pressure Liquid Chromatography, Shell Half-Life, Anti-Bacterial Agents, Surface Active Agents, Oxytetracycline, Drug Compounding, Drug Stability, Hydrogen-Ion Concentration, Polyethylene Glycols, Solvents, and Pharmacology and pharmaceutical sciences
A novel method for the preparation of solvent-free poly(ε-caprolactone) (PCL) microspheres from PCL/poly(ethylene glycol) (PEG) blends was developed and demonstrated. The particle size of the PCL spheres are in the range of 1 to 20μm... more
A novel method for the preparation of solvent-free poly(ε-caprolactone) (PCL) microspheres from PCL/poly(ethylene glycol) (PEG) blends was developed and demonstrated. The particle size of the PCL spheres are in the range of 1 to 20μm (mostly in the range 5–10μm). The influences of the molecular weight of PCL, the molecular weight of PEG, the type of emulsifier, the concentration of
Research Interests:
ABSTRACT We determined contraceptive effectiveness of a 1-inoculation, 1-year porcine zona pellucida (PZP) vaccine in free-roaming feral horses (Equus caballus) in Nevada. We captured, freeze-branded, treated, and subsequently released... more
ABSTRACT We determined contraceptive effectiveness of a 1-inoculation, 1-year porcine zona pellucida (PZP) vaccine in free-roaming feral horses (Equus caballus) in Nevada. We captured, freeze-branded, treated, and subsequently released 267 adult feral mares given (1) 2 inoculations (13-17 days apart) of vaccine emulsion consisting of aqueous PZP and Freund&#39;s Complete Adjuvant (FCA; injection 1) or Freund&#39;s Incomplete Adjuvant (FIA; injection 2), (2) same 2 inoculations as in (1) except also containing a carbomer adjuvant in inoculation 1, or (3) a single inoculation of an emulsion of PZP and FCA containing a second dose of PZP and carbomer adjuvant in controlled-release polymer microspheres. We administered inoculations in January 1996, and monitored the mares via fecal analysis for pregnancy and via ground survey for foal production through October 1997. We determined pregnancy via measurement of estrone sulfate and progesterone metabolites in fresh feces collected from the ground. Among 2-inoculation mares, reproductive success across 1 year was 12.8% (carbomer adjuvant absent) and 10.6% (carbomer adjuvant present). In mares given 1 injection containing microspheres, reproductive success was 11.3%. The concurrent rate in 72 untreated mares was 62.5%. This study revealed marked and equivalent 1-year contraceptive efficacy in 1- and 2-inoculation PZP vaccine, indicating that controlled-release technology can replace a second inoculation and thereby increase PZP vaccine cost effectiveness and potential for use in feral horse management.
Research Interests:
In this investigation, salt effects on monomeric solubility and distribution are separated from self-association for caffeine. For self-associating compounds, the Setschenow equation is inadequate because it does not separate salt effects... more
In this investigation, salt effects on monomeric solubility and distribution are separated from self-association for caffeine. For self-associating compounds, the Setschenow equation is inadequate because it does not separate salt effects into their different contributions. Solubilities of caffeine, theophylline, and theobromine were determined in water and salt solutions at 25 degrees C. Caffeine, theophylline, and theobromine solubilities decreased with added Na(2)SO(4) or NaCl (i.e., salting-out) and increased with added NaClO(4) or NaSCN (i.e., salting-in). Caffeine distribution coefficients (D(W/O)) also decreased with added Na(2)SO(4) or NaCl and increased with added NaClO(4) or NaSCN. To separate salt-caffeine effects from salt effects on caffeine self-interaction, salting parameters (k(s)) were calculated from D(W/O) at infinite dilution instead of solubilities with the Setschenow equation. Caffeine k(s) values were smaller than the Setschenow constants (K) indicating that, for caffeine, K is not simply a salting-in/out parameter. Distribution data were used to characterize caffeine self-association using either a dimerization model (k(d), dimerization constant) or an isodesmic model (k(iso), stepwise association constant). Caffeine self-association constants (k(d) or k(iso)) decreased with NaClO(4) or NaSCN and increased with Na(2)SO(4) or NaCl.