Medicine and Health Sciences Commons^™

Preparation, Characterization And Pharmacokinetics Of Tolfenamic Acid-Loaded Solid Lipid Nanoparticles, Wei Xu, Zhaoyou Deng, Yifei Xiang, Dujuan Zhu

Faculty and Student Publications

The clinical use of nonsteroidal anti-inflammatory drugs is limited by their poor water solubility, unstable absorption, and low bioavailability. Solid lipid nanoparticles (SLNs) exhibit high biocompatibility and the ability to improve the bioavailability of drugs with low water solubility. Therefore, in this study, a tolfenamic acid solid lipid nanoparticle (TA-SLN) suspension was prepared by a hot melt–emulsification ultrasonication method to improve the sustained release and bioavailability of TA. The encapsulation efficiency (EE), loading capacity (LC), particle size, polydispersity index (PDI), and zeta potential of the TA-SLN suspension were 82.50 ± 0.63%, 25.13 ± 0.28%, 492 ± 6.51 nm, 0.309 ± …

Application Of Physiologically Based Pharmacokinetic (Pbpk) Modeling To Study The Impact Of Roux-En-Y Gastric Bypass (Rygb) Surgery On The Bioavailability Of Oral Antibiotics, Suvarchala Kiranmai Avvari

Selected Full-Text Dissertations 2020-

Understanding the mechanisms that govern drug absorption and elimination is a critical component in pharmaceutical research and development, as the oral route remains the most common method of drug administration. The utilization of in silico physiologically based pharmacokinetic modeling and simulation (PBPK M&S) has enabled the extrapolation of modeling and simulation in special populations where concerns regarding alteration in overall drug exposure may arise, such as following gastrointestinal surgery. Roux-en-Y Gastric bypass (RYGB), or partial resection of the gastrointestinal tract, leads to multiple physiological alterations that affect drug absorption. The inability to generalize and predict changes in oral drug bioavailability …

Selecting An Anti-Malarial Clinical Candidate From Two Potent Dihydroisoquinolones, Yizhe Chen, Fangyi Zhu, Jared T. Hammill, Gloria Holbrook, Lei Yang, Burgess Freeman, Karen L. White, David M. Shackleford, Kathleen G. O'Loughlin, Susan A. Charman, Jon C. Mirsalis, R. Kiplin Guy

Pharmaceutical Sciences Faculty Publications

BACKGROUND: The ongoing global malaria eradication campaign requires development of potent, safe, and cost-effective drugs lacking cross-resistance with existing chemotherapies. One critical step in drug development is selecting a suitable clinical candidate from late leads. The process used to select the clinical candidate SJ733 from two potent dihydroisoquinolone (DHIQ) late leads, SJ733 and SJ311, based on their physicochemical, pharmacokinetic (PK), and toxicity profiles is described.

METHODS: The compounds were tested to define their physicochemical properties including kinetic and thermodynamic solubility, partition coefficient, permeability, ionization constant, and binding to plasma proteins. Metabolic stability was assessed in both microsomes and hepatocytes derived …

Ex Vivo Dermis Microdialysis: A Tool For Bioequivalence Testing Of Topical Dermatological Drug Product (Demonstration Of Proof Of Concept And Testing), Mohammad Asif Ali

Selected Full-Text Dissertations 2020-

Clinical response to most topical dermatological drug products (TDDP) depends on the availability of the drug in the dermis. Dermal Microdialysis (dMD) is a sampling technique that permits measuring the concentration of a drug over time, in vivo, directly into the target tissue, the dermis. The pharmacokinetic parameters obtained from such studies may help to optimize the development of TDDP and potentially can be applied to the assessment of TDDP bioequivalence. However, these studies require several hours or even days of continuous sampling that makes it often stressful and unpractical for human subjects as well as animals. The goal of …

Investigation Of Percutaneous Drug Pharmacokinetics In Yucatan Mini-Pig Utilizing Microdialysis: Development Of An In Vitro - In Vivo Relationship With Metronidazole Topical Dermatological Drug Products, Benjamin Alexander Kuzma

Selected Full-Text Dissertations 2020-

The use of dermal microdialysis (dMD) to evaluate bioavailability (BA) and bioequivalence (BE) of topical dermatological drug products (TDDP) has shown promising results; however, studies conducted thus far have been inconclusive conceivably due to large inter- and intra-subject variability, in addition to the inability of short experiments to completely characterize the dermis pharmacokinetics (PK). By using multiple test sites on the same subject, and replicate probes at each test site, it is feasible to compare the dermal pharmacokinetics (dPK) of a drug from different products in parallel on the same subject, which in turn will help to control variability. Moreover, …

Development Of Topical Oil/Peg Creams Of Voriconazole, Abhishek Shivashankar Shettar

Electronic Theses and Dissertations

Voriconazole (VRC) was selected as a model drug for preparation of Oil/PEG cream consisting of PEG 2000, PEG 400 and propylene glycol after performing drug-excipient compatibility studies. Twin screw processor with a 10 mm co-rotating twin screw configuration was used for preparation of oil/PEG creams. Creams prepared using twin-screw processor were characterized for the following: Differential Scanning Calorimetry (DSC), pH, Solvent activity (as)), viscosity, drug content uniformity, in vitro drug release testing (IVRT) and in vitro permeation testing (IVPT) using human cadaver skin. Creams are heterogenous biphasic semi-solid preparations consisting of oil and aqueous phases, wherein one phase is dispersed …

The Role Of Aryl Hydrocarbon Receptor (Ahr) In Drug-Drug Interaction And The Expression Of Ahr In Pichia Pastoris, Yujuan Zheng

University of the Pacific Theses and Dissertations

The aryl hydrocarbon receptor is a ligand-activated transcription factor that is involved in many important functions in the body. To study the role and function of AHR, an abundant amount of in vitro expressed and purified protein is needed. A baculovirus insect expression system is commonly employed to express AHR, however, there are several drawbacks with this method, such as mutation potential and high cost. A better in overexpression system is needed and we hypothesize that Pichia pastoris, a yeast expression system, could stably express AHR and ARNT (aryl hydrocarbon receptor nuclear translocator) in sufficient amount with reasonable cost. Codon …

Effect Of Sulfobutyl Ether Β-Cyclodextrins On Oral And Dermal Pharmacokinetics Of Drugs, Vijay Kumar Shankar

Electronic Theses and Dissertations

Silymarin is an extract of Milk Thistle, major constituents are taxifolin, silychristin, silydianin, silybin A, silybin B, isosilybin A and isosilybin B. The in vitro, preclinical and clinical studies have demonstrated silymarin possesses hepatoprotective, anticancer, hypocholesterolemic, cardioprotective effect and dermatological beneficial effect (treatment of UV induced erythema, melanoma, non-melanoma skin cancer, rosacea, melasma, vitiligo and psoriasis) both individually and collectively. Solubility enhancement of silymarin constituent is utmost important to increase bioavailability and to improve drug developability property. The solubility of silymarin in water was enhanced by SBE-β-CD by conventional and heating method, heating method was found to be more efficient …

Challenges In The Pharmacokinetics Of Therapeutic Proteins, Wararat Limothai

Theses and Dissertations (ETD)

Due to the complex structure and complicated disposition pattern of therapeutic macromolecules, their pharmacokinetic interpretation has many challenges. Two of these challenges were investigated in this dissertation: 1) the error of classical bioavailability assessment observed during subcutaneous (SC) administration of therapeutic macromolecules that undergo target-mediated drug disposition (TMDD) and 2) the ontogeny of the neonatal Fc receptor (FcRn) expression along with its effect on the pharmacokinetics of monoclonal antibodies (mAbs) during development.

TMDD often well describes the pharmacokinetics of therapeutic proteins that have high specificity and affinity of binding to their target receptors. The target receptors can be saturated by …

Influence Of Novel Techniques On Solubility, Mechanical Properties And Permeability Via Hot Melt Extrusion Technology, Eman A. Ashour

Electronic Theses and Dissertations

Hot melt extrusion (HME) was evaluated as a continuous processing technology for the manufacture of solid dispersions. The aim of the current research project was to study the effect of pressurized carbon dioxide (P-CO2) on the physico-mechanical properties of three different grades of cellulose polymers, Klucel™ ELF, EF and LF hydroxypropylcellulose (HPC) resulting from hot melt extrusion techniques, and to assess the plasticization effect of P-CO2 on the tested polymers. The physico-mechanical properties as well as the tablet characteristics of the extrudates with and without injection of P-CO2 and with non-extruded polymers were examined. P-CO2 acted as plasticizer for Klucel™ …

Evaluating The Bioavailability Of Carbamazepine Using A Novel Snedds Formulation, Gina M. Mattes, Zachary A. Wallace, Derrick L. Chapman, Jinwon Byun, Rebecca A. Kyper, Elisha R. Injeti

The Research and Scholarship Symposium (2013-2019)

Carbamazepine (CBZ) is an anticonvulsant drug primarily used to treat epilepsy, bipolar disorder, trigeminal and glossopharyngeal neuralgia. CBZ is a lipophilic, poorly soluble drug that belongs to the class-2 category according to the Biopharmaceutics Classification System. As a class-2 drug, the plasma concentration of CBZ is limited by its ability to diffuse across biological membranes. To increase its bioavailability, different methods such as crystal modifications, particle size reduction, amorphization, cyclodextrin complexation, pH modification, and self-emulsification were explored. Of these methods, Self Nano Emulsifying Drug Delivery Systems (SNEDDS) have shown to reduce particle size of CBZ molecules and improve its solubility. …

Tobramycin Disposition In The Lung Following Airway Administration, Min Li

Theses and Dissertations

Tobramycin disposition following airway administration was evaluated by meta-analysis of human data in the literature and, experimentally, using a realistic ex vivo model, the isolated perfused rat lung preparation (IPRL). Pulmonary bioavailability of inhaled tobramycin in published studies was re-evaluated separately for CF and healthy adults, with the drug’s intrinsic pharmacokinetic (PK) parameters obtained from intravenous (IV) studies in the literature. While large variations in tobramycin’s clearance precluded accurate assessment of its bioavailability, the results were indicative of substantial pulmonary absorption, in spite of its hydrophilic and poly cationic properties. To explore its disposition kinetics and mechanisms following airway administration, …

Evaluating The Bioavailability Of Carbamazepine Using A Novel Snedds Formulation, Jinwon Byun, Derrick L. Chapman, Rebecca A. Kyper, Gina M. Mattes, Zachary A. Wallace, Elisha R. Injeti

Pharmacy and Nursing Student Research and Evidence-Based Medicine Poster Session

Central to the mechanism of how drugs work are the concepts of solubility and bioavailability. Drugs enter the body via absorption into the bloodstream, arrive at the target location, and bind to receptors to cause an effect. Drugs need to be soluble enough to pass through the cell membrane to enter and exit the bloodstream. Higher solubility generally correlates to higher bioavailability. Additionally, the smaller the particle size, the easier the drug will pass through the membrane into the blood plasma. Researchers have designed a system to categorize solubility class: Class I being high permeability and high solubility, Class II …

Assessment Of The Feasibility Of Co-Administration Of Phenolic Dietary Compounds With Phenylephrine To Increase Its Bioavailability, Zhenxian Zhang

Theses and Dissertations

R-(-)-Phenylephrine (PE) is the most commonly used nonprescription oral nasal decongestant in the United States. It is a selective α1-adrenergic receptor agonist and has many years of safe usage. However, the efficacy of PE is controversial, due to its extensive pre-systemic metabolism, which leads to low and variable oral bioavailability (38 ± 9%, mean ± SD). Sulfation plays a very important role in pre-systemic metabolism of PE. The sulfation of PE occurs at its phenolic group, which is the preferred structural feature of many sulfotransferase (SULT) substrates. Compounds with phenolic groups have similar structures to PE, which may share the …

The Antiinflammatory Action And Pharmacokinetics Of A Novel Glucosamine-Based Di-Peptide Aminosugar, Mohammad H. Gilzad-Kohan, Kamaljit Kaur, Fakhreddin Jamali

Pharmacy Faculty Articles and Research

Purpose. We have previously shown favorable in vitro gut permeability for three novel dipeptide esters of glucosamine (GlcN) likely facilitated by the peptide transporter 1 (PepT1). Herein, we report the development of a novel assay for the determination of bioavailability of the peptide ester of interest, the anti-inflammatory properties of a glycine-valine ester derivative of GlcN (GVG) as well as its pharmacokinetics under healthy and inflammatory conditions.

Methods. A pre-column derivatization (with 9-fluorenylmethoxycarbonyl) HPLC assay was developed to study bioavailability of GVG, GlcN or cleaved GlcN in the rats that were cannulated in their right jugular vein for …

Biopharmaceutical Approaches For Improved Drug Delivery Across Ocular Barriers, Ketan Hippalgaonkar

Electronic Theses and Dissertations

The eye is protected from the external environment by various physiological and anatomical barriers. These barriers through there protective actions drastically diminish the ocular bioavailability of drugs. The corneal epithelium acts as a major barrier towards the permeation of hydrophilic agents, whereas poor aqueous solubility presents a formulation challenge for lipophilic compounds. Additionally, P-glycoprotein (P-gp) expressed on the retinal pigmented epithelium (RPE P-gp) limits the penetration of substrates, in therapeutically relevant concentrations, into the back-of-the-eye.

In the present research, use of penetration enhancers (chitosan, benzalkonium chloride (BAK) and ethylenediaminetetraacetic acid (EDTA)) and formulation approaches (cyclodextrins and solid lipid nanoparticles (SLNs)) …

Synthesis Of A Water Soluble Resveratrol Derivative As A Potential Anti-Cancer Drug., Augustine Essel

Electronic Theses and Dissertations

Research on development of water soluble anti-cancer drugs is one of the great challenges of modern medicinal chemistry. Resveratrol (Res) is one of the many phytoalexins producing stilbenoids present in several medicinal plants, grape skin, peanuts, and red wine. It has been found to exhibit anti-cancer, anti-inflammatory, and anti-oxidant properties. Water solubility and bioavailability are some of the setbacks of this interesting compound. In view of this, effort has been made to synthesize amino acid derivative of resveratrol to improve its bioavailability and solubility in water. Methyl 4-{-[(1E)-2-(3, 5-dihydroxyphenyl)-ethenyl] - phenoxy} butyrate (7), a novel ester intermediate, has been synthesized …