Pharmacy and Pharmaceutical Sciences Commons^™

Development Of Novel Ahr Antagonists, Hyosung Lee

University of Kentucky Doctoral Dissertations

Aryl hydrocarbon receptor (AHR) is a sensor protein, activated by aromatic chemical species for transcriptionally regulating xenobiotic metabolizing enzymes. AHR is also known to be involved in a variety of pathogenesis such as cancer, diabetes mellitus, cirrhosis, asthma, etc. The AHR signaling induced by xenobiotics has been intensively studied whereas its physiological role in the absence of xenobiotics is poorly understood. Despite a number of ligands of AHR have been reported thus far, further applications are still hampered by the lack of specificity and/or the partially agonistic activity. Thus, a pure AHR antagonist is needed for deciphering the AHR cryptic …

Predicting The Drug Release Kinetics Of Matrix Tablets, Boris Baeumer, Lipika Chatterjee, Peter Hinow, Thomas Rades, Ami E. Radunskaya, Ian Tucker

Pomona Faculty Publications and Research

In this paper we develop two mathematical models to predict the release kinetics of a water soluble drug from a polymer/excipient matrix tablet. The first of our models consists of a random walk on a weighted graph, where the vertices of the graph represent particles of a drug, excipient and polymer, respectively. The graph itself is the contact graph of a multidisperse random sphere packing. The second model describes the dissolution and the subsequent diffusion of the active drug out of a porous matrix using a system of a partial differential equations. The predictions of both models show good qualitative …

An Analysis Of Drug Dissolution Rates In The Usp 24 Type 2 Apparatus, David Mcdonnell, Brendan Redmond, Deirdre M. D'Arcy, Anne Marie Healy, Owen Corrigan

Articles

This paper applies boundary layer theory to the process of drug dissolution in the USP 24, Type 2 Apparatus. The mass transfer rate from the top flat surface of a compact in various positions within the device is evaluated by means of a Pohlhausen integral method.

Liquid Chromatography-Tandem Mass Spectrometry For The Determination Of Methylprednisolone In Rat Plasma And Liver After Intravenous Administration Of Its Liver-Targeted Dextran Prodrug, Shuang-Qing Zhang, Helen R. Thorsheim, Suman Penugonda, Venkateswaran C. Pillai, Quentin R. Smith, Reza Mehvar

Pharmacy Faculty Articles and Research

A specific and sensitive liquid chromatography (LC)-tandem mass spectrometric method for quantitative determination of methylprednisolone (MP) in rat plasma and liver was developed and validated using triamcinolone acetonide as an internal standard. Liquid-liquid extraction using tert-butyl methyl ether was used to extract the drug and the internal standard from plasma and liver. The separation of MP was performed on a C(18) column with a mobile phase of acetonitrile:0.5% formic acid aqueous solution (85:15, v/v) over 4 min. The assay was based on the selected reaction monitoring transitions at m/z 375 -> 161 for MP in plasma, 375 -> 357 for …

Treatment Of Industrial Wastewater Containing Active Pharmaceutical Ingredients With A Membrane Bioreactor, With The Aim Of Reducing Resource Consumption, Pádraig Colm Ó'Maolcatha

Theses

The biodegradation of a selected active pharmaceutical ingredient (API) during wastewater treatment in a membrane bioreactor (MBR) was examined experimentally. A comparison study was conducted by operating a conventional activated sludge (CAS) pilot plant in parallel to the MBR. The MBR was operated under varying conditions of pH (pH6 and pH8), MLSS (6g/L and l0g/L) and SRT (20 days and 30 days) according to a full factorial design of experiments. In the CAS, pH and SRT were altered as above but MLSS was maintained at 3-4g/L. Comparable average API removal results of 95.5% and 95.7% were obtained for the MBR …

Synthesis Of Multifunctional Nanogels Using A Protected Macromonomer Approach, Neetu Singh, L. Andrew Lyon

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Nanoparticles possessing multiple functionalities provide synthetic handles for varied surface chemistries, making them useful for a range of applications such as biotargeting and drug delivery. However, the combination of interfering functionalities on the same particle is often challenging. We have employed a synthetic scheme involving chemical protection/deprotection to combine interfering functional groups on the same hydrogel nanoparticle. The synthesis of amine-containing poly(N-isopropylacrylamide) nanogels was carried out via free radical precipitation polymerization by incorporating a Fmoc-protected amine poly(ethylene glycol) (PEG) macromonomer. The Fmoc group was then removed to obtain free amines, which were shown to be available for conjugation. We further …

Bringing In The Green: Pharma Stands To Win Hearts, Minds, And Tax Credits By Launching An Eco Bandwagon, Porcher L. Taylor Iii, David E. Kitchen

School of Professional and Continuing Studies Faculty Publications

A green mind-set can lead to a black bottom line. Becoming nvironmentally friendly can help boost brand image and ROi -- and pharma can get there with a few easy steps.

First, with about 90,000 sales representatives on the road, the industry could lead a revolution in transportation if it bought hybrid cars. By replacing the current fleet, the benefits would be substantial. Each hybrid is cheaper to maintain, more fuel-efficient, and leaves a far smaller greenhouse-gas footprint on the environment. Imagine extrapolating these benefits to thousands of ca rs: That's an environmentally friendly signature that shows leadership in the …

Analysis Of Residual Solvents In Pharmaceuticals By Comprehensive Two-Dimensional Gas Chromatography, Cristina Marie Crimi

Seton Hall University Dissertations and Theses (ETDs)

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Efficacy Of Cognitive Therapy And Pharmacotherapy In Depression: A Meta-Analysis, Daniel B. Michel

Loma Linda University Electronic Theses, Dissertations & Projects

A meta-analysis comparing the long-term effectiveness of cognitive behavioral therapy (CBT) and pharmacotherapy in preventing relapse following treatment discontinuation was performed using published studies of depressed participants. Twenty-three articles met inclusionary criteria and were included in the analyses. Weighted effect sizes and moderators, treatment type, were calculated using statistical analysis software. Initially, fixed effects models were applied to the data, but due to significant between-group heterogeneity that could not be fully explained by treatment type, mixed effect models were used to account for the residual heterogeneity. Results indicated that overall, depressed individuals treated to remission with CBT evidence decreased relapse …

Intellectual Property Management In Health And Agricultural Innovation: A Handbook Of Best Practices, Vol. 2, Anatole Krattiger, Richard T. Mahoney, Lita Nelsen, Jennifer A. Thomson, Alan B. Bennett, Kanikaram Satyanarayana, Gregory D. Graff, Carlos Fernandez, Stanley Kowalski

Law Faculty Scholarship

Prepared by and for policy-makers, leaders of public sector research establishments, technology transfer professionals, licensing executives, and scientists, this online resource offers up-to-date information and strategies for utilizing the power of both intellectual property and the public domain. Emphasis is placed on advancing innovation in health and agriculture, though many of the principles outlined here are broadly applicable across technology fields. Eschewing ideological debates and general proclamations, the authors always keep their eye on the practical side of IP management. The site is based on a comprehensive Handbook and Executive Guide that provide substantive discussions and analysis of the opportunities …

Intellectual Property Management In Health And Agricultural Innovation: Executive Guide, Anatole Krattiger, Richard T. Mahoney, Lita Nelsen, Jennifer A. Thomson, Alan B. Bennett, Kanikaram Satyanarayana, Gregory D. Graff, Carlos Fernandez, Stanley Kowalski

Law Faculty Scholarship

Prepared by and for policy-makers, leaders of public sector research establishments, technology transfer professionals, licensing executives, and scientists, this online resource offers up-to-date information and strategies for utilizing the power of both intellectual property and the public domain. Emphasis is placed on advancing innovation in health and agriculture, though many of the principles outlined here are broadly applicable across technology fields. Eschewing ideological debates and general proclamations, the authors always keep their eye on the practical side of IP management. The site is based on a comprehensive Handbook and Executive Guide that provide substantive discussions and analysis of the opportunities …

Intellectual Property Management In Health And Agricultural Innovation: A Handbook Of Best Practices, Vol. 1, Anatole Krattiger, Richard T. Mahoney, Lita Nelsen, Jennifer A. Thomson, Alan B. Bennett, Kanikaram Satyanarayana, Gregory D. Graff, Carlos Fernandez, Stanley Kowalski

Law Faculty Scholarship

Prepared by and for policy-makers, leaders of public sector research establishments, technology transfer professionals, licensing executives, and scientists, this online resource offers up-to-date information and strategies for utilizing the power of both intellectual property and the public domain. Emphasis is placed on advancing innovation in health and agriculture, though many of the principles outlined here are broadly applicable across technology fields. Eschewing ideological debates and general proclamations, the authors always keep their eye on the practical side of IP management. The site is based on a comprehensive Handbook and Executive Guide that provide substantive discussions and analysis of the opportunities …

Preparation Of Silica-Coated Lanthanum-Strontium Manganite Particles With Designable Curie Point, For Application In Hyperthermia Treatments, Vuk Uskoković, Aljoša Košak, Miha Drofenik

Pharmacy Faculty Articles and Research

Silica-coated lanthanum–strontium manganite particles with La_0.76Sr_0.24MnO_3+δ stoichiometric formula, exhibiting Curie temperature at ∼40°C, were prepared by using a traditional solid-state method of synthesis of magnetic ceramic particles, followed by milling and a low-temperature coating procedure in an aqueous alcoholic alkali medium. The properties of the obtained material establish it as a potential candidate for self-regulated power-absorbing and temperature-controlling materials in hyperthermia treatments. Moreover, core-comprising LaSr–manganites with different stoichiometries, ranging from La_0.5Sr_0.5MnO_3+δ to LaMnO_3+δ, were synthesized, with magnetic and structural properties examined thereof. Herein reported findings can potentially be …

Interdependency Of Pharmacokinetic Parameters: A Chicken-And-Egg Problem? Not!, Reza Mehvar

Pharmacy Faculty Articles and Research

Pharmacokinetic (PK) software packages are widely used by scientists in different disciplines to estimate PK parameters. However, their use without a clear understanding of physiological parameters affecting the PK parameters and how different PK parameters are related to each other may result in erroneous interpretation of data. Often, mathematical relationships used for the estimation of PK parameters obscure the true physiological relationships among these parameters, prompting a discussion of which parameter came first and giving the appearance of the-chicken-and-the-egg dilemma. In this article, the author attempts to show how different PK parameters are related to physiological parameters and each other …

26Al-Containing Acidic And Basic Sodium Aluminum Phosphate Preparation And Use In Studies Of Oral Aluminum Bioavailability From Foods Utilizing 26Al As An Aluminum Tracer, Robert A. Yokel, Aaron A. Urbas, Robert A. Lodder, John P. Selegue, Rebecca L. Florence

Pharmaceutical Sciences Faculty Publications

We synthesized ²⁶Al-containing acidic and basic (alkaline) sodium aluminum phosphates (SALPs) which are FDA-approved leavening and emulsifying agents, respectively, and used them to determine the oral bioavailability of aluminum incorporated in selected foods. We selected applicable methods from published syntheses (patents) and scaled them down (∼3000- and 850-fold) to prepare ∼300–400 mg of each SALP. The ²⁶Al was incorporated at the beginning of the syntheses to maximize ²⁶Al and ²⁷Al equilibration and incorporate the ²⁶Al in the naturally-occurring Al-containing chemical species of the products. Near infrared spectroscopy (NIR) and X-ray powder diffraction (XRD) were used …

Chemical And Biochemical Modification Of Surfaces For Control Of Wettability, Adsorption, And Drug Delivery, Susan C. D'Andrea

Seton Hall University Dissertations and Theses (ETDs)

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A Comparison Of Esomeprazole And Lansoprazole For Control Of Intragastric Ph In Patients With Symptoms Of Gastro-Oesophageal Reflux Disease, D. A. Johnson, T. Stacy, M. Ryan, T. Wootton, J. Willia, K. Hornbuckle, W. Brooks, M. Doviak

Mathematics & Statistics Faculty Publications

Background: Intragastric acid suppression is the most direct measure of the pharmacodynamic efficacy of proton pump inhibitors, which are the most effective drugs for acid-related diseases.

Aim: To compare the effectiveness of once and twice daily dosing of lansoprazole and esomeprazole in controlling intragastric acidity ( target gastric pH > 4.0) over a 24-hour period.

Methods: In an open-label, two-way crossover study, 45 Helicobacter pylori-negative patients with gastro-oesophageal reflux disease were randomized to receive one of two regimens: 30 mg lansoprazole or esomeprazole 40 mg once daily. Intragastric pH was assessed by 24-hour pH monitoring on day 5 of each regimen. …

Symptoms Of Gastro-Oesophageal Reflux Disease And The Severity Of Obstructive Sleep Apnoea Syndrome Are Not Related In Sleep Disorders Center Patients, H.-N. Kim, R. D. Vorona, M. P. Winn, M. Doviak, D. A. Johnson, J. Catesby Ware

Mathematics & Statistics Faculty Publications

Background: Studies suggest obstructive sleep apnea syndrome (OSAS) frequently manifests in patients with gastroesophageal reflux disease (GERD) and that there may be a causal relationship.

Aim: To determine the relationship between OSAS and symptoms of GERD.

Methods: Consecutive patients referred to the Sleep Disorders Center (SDC) 18 years and older with polysomnographically defined OSAS were evaluated prospectively for GERD using a validated symptoms questionnaire. The GERD and OSAS relationship was assessed by 1) determining frequency of GERD in patients with and without OSAS; 2) ascertaining the relationship between OSAS severity categories and presence of GERD; 3) examining GERD score in …

Analysis Of Loratadine By Potentiometry And Reverse-Phase High Performance Liquid Chromatography, Kian Yong Puen

Student Works (2000-2009)

A non-aqueous titration method was developed to assay Loratadine bulk active and a High Performance Liquid Chromatography (HPLC) method was developed to determine Loratadine's manufacturing impurity. The HPLC method was also suitable for simultaneously assay and related substance determination of Loratadine pharmaceutical preparations. In the tritation method, glacial acetic acid was chosen as an amphiprotic solvent. Loratadine ionised in glacial acetic acid; the conjugated base of acetic acid (Ac·), was then titrated with standardised perchloric acid. The method was validated found to be precise, linear and robust. Reverse-phase HPLC method using a Novapak Cl8 column with a CH3CN: I0mM K2HPO4 …

Chemical Constituents Of Desmos Dumosus, Roxb., Mazdida Sulaiman

Student Works (2000-2009)

The chemical content of the 'leaves and bark of Des mos dumosus has been carried out in this study. The leaves yielded nine isoquinoline type of alkaloids and two flavones. The isoquinoline alkaloids isolated were pronuciferine 37, stepharine 39, nomuciferine 40, (-) - 3 - hydroxynomuciferine 41, norlirioferine 42, asimilobine 43, liriodenine 44, lysicamine 45 and O - methylmoschatoline 46. The flavones were 5 - hydroxy - 6,7 - dimethoxyflavone 47 and 5 - hydroxy - 7,8 - dimethoxyflavone 48. The same flavones, 47 and 48 and the alkaloids 45 and 46 were also present in the bark of this …

Sistem Maklumat Perubatan Tradisional Melayu, Omar Rosfazila

Student Works (2000-2009)

Sistem Maklumat Perubatan Tradisional Melayu adalah merupakan satu sistem makumat berkomputer yang dibangunkan di halaman web. Ia bertujuan untuk membantu pengguna mencapai maklumat mengenai (ubatan tradisional serta tumbuhan berubat yang) diamalkan oleh orang Melayu. Sistem ini akan menceritakan serba sedikit tentang sejarah penggunaan perubatan tradisional. Pengguna sistem juga dijangka dapat mengemukan pertanyaan dan memberi sebarang komen yang berkaitan dengan sistem. Bantuan kepada pengguna sistem tentang cara menggunakan sistem turut dipaparkan dalam pembangunan system ini nanti. Sistem ini juga membolehkan pihak pentadbir membuat pengemaskinian maklumat mengikut kesesuaian semasa dan pembaharuan. Ia adalah sejajar dengan matlamat untuk memastikan penyimpanan maklwnat yang lebih …

Sistem Inventori Farmasi, Embong Jamilah

Student Works (2000-2009)

Pada hari ini kemajuan Teknologi Maklumat semakin pesat berkembang. Organisasi kerajaan mahupun swasta menggunakan sistem komputer untuk: melicinkan lagi kerja yang dilakukan tiap hari Sistem lnventori Farmasi diperkenalkan bagi memudahkan kerja penyimpanan maklumat di kedai-kedai farmasi supaya kerja yaang dijalankan berjalan dengan lancar. Laporan ini bertujuan memberi penerangan serta gambaran tentang projek yang dijalankan ini. Kajian literasi memberi penerangan bagaimana kajian yang dilakukan sebelum dan sewaktu projek dijalankan. la juga menggambarkan tentang proses pembangunan perisian di mana ia diceritakan secara terperinci dalam bab analisis sistem rekabentuk, pengkodan dan pengujian. Akhir sekali, tentang operasi dan penilaian terhadap sistem di mana diberi …

Protein Adducts Of Iso[4]Levuglandin E2, A Product Of The Isoprostane Pathway, In Oxidized Low Density Lipoprotein, Robert G. Salomon, Wei Sha, Cynthia Brame, Kamaljit Kaur, Ganesamoorthy Subbanagounder, June O'Neil, Henry F. Hoff, L. Jackson Roberts Ii

Pharmacy Faculty Articles and Research

Levuglandin (LG) E₂, a cytotoxic seco prostanoic acid co-generated with prostaglandins by nonenzymatic rearrangements of the cyclooxygenase-derived endoperoxide, prostaglandin H₂, avidly binds to proteins. That LGE₂-protein adducts can also be generated nonenzymatically is demonstrated by their production during free radical-induced oxidation of low density lipoprotein (LDL). Like oxidized LDL, LGE₂-LDL, but not native LDL, undergoes receptor-mediated uptake and impaired processing by macrophage cells. Since radical-induced lipid oxidation produces isomers of prostaglandins, isoprostanes (isoPs), via endoperoxide intermediates, we postulated previously that a similar family of LG isomers, isoLGs, is cogenerated with isoPs. Now …

Aluminum And Phosphorus Separation: Application To Preparation Of Target From Brain Tissue For 26Al Determination By Accelerator Mass Spectrometry, Russell D. Brauer, J. David Robertson, Pankaj Sharma, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Acid digested brain containing 4 mg added ²⁷Al was ashed at 1000°C to prepare an Al₂O₃ target for accelerator mass spectrometry (AMS) analysis of ²⁶Al. A glass-like material usually resulted which was thought to be aluminum (Al) oxyphosphate. The separation of Al and phosphate was investigated. Al, but not phosphate, was bound by a cation exchange resin (AG 50-X8). Hydrofluoric acid eluted the Al from the resin. Removal of phosphate from acid digested brain by this method produced an amorphous material after ashing that was easier to recover from the porcelain crucible and had a …

Optimisation Studies In A Batch Pharmaceutical Company, Sarah Fitzgerald

Theses

This thesis outlines a collaborative project between industry and academia based on a short term research contract.

In the past in Eli Lilly, process optimisation in a multi-purpose, modular building had been mainly confined to equipment commissioning and new product development. It was necessary to embark upon an exercise to develop an optimisation programme m order to meet the increased requirements and demands of the building. Increased market demands, through the introduction of over-the-counter (OTC) drugs, and the demand for cycle time reduction through the expiry of existing patents, made the need for optimisation inevitable.

The purpose of this thesis …

Characterisation And Optimisation Of Gypsum Crystallization, Catherine H. Shannon

Theses

Gypsum is produced as a by-product during the citric acid production process at ADM Ringaskiddy. The particle size and filterability of the gypsum has a critical bearing on the overall citric acid production rate. Prior to August 1996, research in the area of gypsum crystal optimisation at ADM had concentrated on the application of vortex mixing to perform the gypsum formation reaction. While the gypsum crystals produced with vortex mixing were found to be desirably clear of microcrystalline gypsum, the crystals were considerably smaller and more difficult to filter and wash. This research project sought to retain the advantages conferred …

Rapamycin-Induced Inhibition Of P34(Cdc2) Kinase Activation Is Associated With G1/S-Phase Growth Arrest In T Lymphocytes, W. G. Morice, Gregory J. Brunn, Gregory Wiederrecht, John Siekierka, R. T. Abraham

Department of Chemistry and Biochemistry Faculty Scholarship and Creative Works

The macrolide rapamycin (RAP) is a potent inhibitor of interleukin-2 (IL- 2)-induced T-cell proliferation. Current models suggest that RAP, when complexed to its intracellular receptor, FK506-binding protein, interferes with an IL-2 receptor-coupled signaling pathway required for cell-cycle progression from G1- to S-phase. Here we show that RAP treatment inhibits the growth of an IL-2-dependent cytotoxic T-cell line, CTLL-2, in late G1- phase, just prior to entry of the cells into S-phase. In contrast, RAP- treated CTLL-2 cells retained the ability to respond to IL-2 with enhanced cytolytic activity, indicating that RAP was not a general suppressant of cellular responsiveness to …

Comparison Of Selected Radiopharmaceutical Chromatographic Quality Control Procedures, Lawrence Ray Andreatta

University of the Pacific Theses and Dissertations

The purpose of this study was to compare the accuracy and reproducibility of two commercially available chromatography kits with Instant Thin Layer Chromatography-Silica Gel (ITLC-SG) and Whatman Chromatography Paper. The two commercial kits evaluated were the- MAC Klt- produced-General Radioisotopes Products, and the TECH Kit by Ackerman Nuclear.

The Synthesis Of Various Substituted 3-Amino-7-Hydroxy-2,2-Dimethyltetralins And Their Opioid-Related Activities, David Alan Lippman

University of the Pacific Theses and Dissertations

A series of aminotetralones and aminotetralins were synthesized from the common intermediate F, 3-amino-2,2-dimethyl-7-methoxy- 1-tetralone. The final compounds derived from F were simple substituted and/or reduced analogues. The products would allow a progressive structure activity relationship to be drawn based on pharmacological testing.

The common intermediate F was synthesized utilizing a six step procedure starting with p-methoxyphenylacetic acid. The overall yield from the precursor to the F:HC1 was 25%. Compound F was either O-demethylated to form 3-amino-2,2-dimethyl-7-hydroxy-l-tetralone (I) or was dimethylated on the amine and subsequently O-demethylated to yield the 3-dimethylamino-7-hydroxy-2,2-dimethyl-l-tetralone (J). The last major modification was the reduction of …

Synthesis Of Dihydroisoquinolines And Tetrahydroisoquinolines, John J. Schlager

Chemistry & Biochemistry Theses & Dissertations

Dihydroisoquinolines and tetrahydroisoquinolines are compounds which possess a variety of pharmacological activities. New easier methods of synthetic manipulations of these structures is of constant interest in the pharmaceutical industry.

This paper describes a new three step method of preparing 1-alkyl- and 1-aryl-tetrahydroisoquinolines from a tetrahydroisoquinoline. The synthesis involves the N-chlorination of tetrahydroisoquinoline followed by dehydrohalogenation with potassium superoxide. The reaction products are the dihydroisoquinolines. Overall yields range from 85-96%. The unsubstituted, 1-methyl-, and 1-phenyl-J,4-dihydroisoquinolines have been formed. Organometallation of the unsubstituted dihydroisoquinoline provides the 1-substituted tetrahydroisoquinoline. The 1-benzyl-, 1-n-butyl-, 1-ethyl-, 1-methyl-, and 1-phenyl-1,2,J,4-tetrahydroisoquinolines were prepared. The use of Grignard and …