4,780 results match your criteria AAPS PharmSciTech[Journal]


Measurement of IL-17AA and IL-17FF as Pharmacodynamic Biomarkers to Demonstrate Target Engagement in the Phase I Study of MCAF5352A.

AAPS J 2018 Dec 13;21(1). Epub 2018 Dec 13.

Department of OMNI Biomarker Development, Genentech Inc, South San Francisco, California, USA.

The interleukin (IL)-17 pathway has been implicated in the pathophysiology of many autoimmune diseases. MCAF5352A is a humanized monoclonal antibody which targets both IL-17A and IL-17F, thereby inhibiting the activity of IL-17 dimers (IL-17AA, IL-17AF, and IL-17FF). The pharmacokinetic profile of MCAF5352A has been characterized in both a Phase Ia single ascending dose study and a Phase Ib multiple ascending dose study. Read More

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December 2018

Antipsychotic-induced metabolic alterations: recounting the mechanistic insights, therapeutic targets and pharmacological alternatives.

Eur J Pharmacol 2018 Dec 7. Epub 2018 Dec 7.

Pharmacology Research Laboratory, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study (UGC-CAS), Panjab University, Chandigarh-160014, India. Electronic address:

Atypical antipsychotics (AAPs) are the drug of choice in the management of mental illnesses by virtue of their advantage over typical antipsychotics i.e. least tendency of producing extrapyramidal motor symptoms (EPS) or pseudoparkinsonism. Read More

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December 2018

PBPK and its Virtual Populations: the Impact of Physiology on Pediatric Pharmacokinetic Predictions of Tramadol.

AAPS J 2018 Nov 29;21(1). Epub 2018 Nov 29.

Faculty of Pharmaceutical Sciences, Laboratory of Medical Biochemistry and Clinical Analysis, Ottergemsesteenweg 460, 9000, Ghent, Belgium.

In pediatric PBPK models, age-related changes in the body are known to occur. Given the sparsity of and the variability associated with relevant physiological parameters, different PBPK software providers may vary in their system's data. In this work, three commercially available PBPK software packages (PK-Sim®, Simcyp®, and Gastroplus®) were investigated regarding their differences in system-related information, possibly affecting clearance prediction. Read More

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November 2018

International Stakeholder Community of Pain Experts and Leaders Call for an Urgent Action on Forced Opioid Tapering.

Authors:
Beth D Darnall David Juurlink Robert D Kerns Sean Mackey Brent Van Dorsten Keith Humphreys Julio A Gonzalez-Sotomayor Andrea Furlan Adam J Gordon Debra B Gordon Diane E Hoffman Joel Katz Stefan G Kertesz Sally Satel Richard A Lawhern Kate M Nicholson Rosemary C Polomano Owen D Williamson Heath McAnally Ming-Chih Kao Stephan Schug Robert Twillman Terri A Lewis Richard L Stieg Kate Lorig Theresa Mallick-Searle Robert W West Sarah Gray Steven R Ariens Jennifer Sharpe Potter Penney Cowan Chad D Kollas Danial Laird Barby Ingle J Julian Grove Marian Wilson Kashelle Lockman Fiona Hodson Carol S Palackdharry Roger B Fillingim Jeffrey Fudin Jennifer Barnhouse Ajay Manhapra Steven R Henson Bruce Singer Marie Ljosenvoor Marlisa Griffith Jason N Doctor Kimeron Hardin Cathleen London Jon Mankowski Andrea Anderson Linda Ellsworth Lisa Davis Budzinski Becky Brandt Greg Harkootley Debbie Nickels Heck Mark J Zobrosky Celeste Cheek Megan Wilson Cynthia E Laux Geralyn Datz Justin Dunaway Eileen Schonfeld Melissa Cady Thérèse LeDantec-Boswell Meredith Craigie John Sturgeon Pamela Flood Melita Giummarra Jessica Whelan Beverly E Thorn Richard L Martin Michael E Schatman Maurice D Gregory Joshua Kirz Patti Robinson James G Marx Jessica R Stewart Phillip S Keck Scott E Hadland Jennifer L Murphy Mark A Lumley Kathleen S Brown Michael S Leong Mechele Fillman James W Broatch Aaron Perez Kristine Watford Kari Kruska Dokyoung Sophia You Stacy Ogbeide Amy Kukucka Susan Lawson James B Ray T Wade Martin James B Lakehomer Anne Burke Robert I Cohen Peter Grinspoon Marc S Rubenstein Stephani Sutherland Kristie Walters Travis Lovejoy

Pain Med 2018 Nov 29. Epub 2018 Nov 29.

Department of Psychiatry, Oregon Health & Science University, Portland, Oregon.

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November 2018
3 Reads
2.300 Impact Factor

The Assessment of Quality Attributes for Biosimilars: a Statistical Perspective on Current Practice and a Proposal.

AAPS J 2018 Nov 27;21(1). Epub 2018 Nov 27.

Novartis Pharma AG, 4056, Basel, Switzerland.

Establishing comparability of the originator and its biosimilar at the structural and functional level, by analyzing so-called quality attributes, is an important step in biosimilar development. The statistical assessment of quality attributes is currently in the focus of attention because both the FDA and the EMA are working on regulatory documents for advising companies on the use of statistical approaches for strengthening their comparability claim. In this paper, we first discuss "comparable" and "not comparable" settings and propose a shift away from the usual comparison of the mean values: we argue that two products can be considered comparable if the range of the originator fully covers the range of the biosimilar. Read More

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November 2018
2 Reads

Overlooked Issues on Pharmacokinetics Data Interpretation of Protein Drugs-a Case Example of Erythropoietin.

AAPS J 2018 Nov 26;21(1). Epub 2018 Nov 26.

Department of Pediatrics, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, USA.

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November 2018

Effect of the Plasticizer DEHP in Blood Collection Bags on Human Plasma Fraction Unbound Determination for Alpha-1-Acid Glycoprotein (AAG) Binding Drugs.

AAPS J 2018 Nov 16;21(1). Epub 2018 Nov 16.

Q2 Solutions, Bioanalytical and ADME Labs, 5225 Exploration Drive, Indianapolis, Indiana, 46241, USA.

Fraction unbound (f) is a critical drug distribution parameter commonly utilized for modeling efficacious dosage and safety margin predictions. An over-estimation of f for 13 chemically diverse small molecule drugs primarily bound to alpha-1-acid glycoprotein (AAG) in human plasma was discovered when in vitro results from our screening lab were compared to literature values. Di-(2-ethylhexyl) phthalate (DEHP), a plasticizer known to be used in the manufacture of blood collection bags, was extracted from plasma obtained through three common techniques that allowed contact with DEHP, and drug f values in plasma from each collection method were estimated using the HTDialysis protein binding methodology. Read More

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November 2018
2 Reads

Skin Penetration and Permeation Properties of Transcutol®-Neat or Diluted Mixtures.

AAPS PharmSciTech 2018 Nov 12;19(8):3512-3533. Epub 2018 Nov 12.

Pharmaceutical Division, Gattefossé North America, Paramus, New Jersey, 07652, USA.

A heightened interest in (trans)dermal delivery is in part driven by the need to improve the existing skin therapies and also the demand for alternative routes of administration, notably for pharmaceutical actives with undesirable oral absorption characteristics. The premise of delivering difficult actives to the skin or via the skin however is weighed down by the barrier function properties of the stratum corneum. Short of disrupting the skin by physical means, scientists have resorted to formulation with excipients known to enhance the skin penetration and permeation of drugs. Read More

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November 2018

Enhanced Understanding of Pharmaceutical Materials Through Advanced Characterisation and Analysis.

AAPS PharmSciTech 2018 Nov 8;19(8):3462-3480. Epub 2018 Nov 8.

Bristol-Myers Squibb, Reeds Lane, Moreton, Wirral, CH46 1QW, UK.

The impact of pharmaceutical materials properties on drug product quality and manufacturability is well recognised by the industry. An ongoing effort across industry and academia, the Manufacturing Classification System consortium, aims to gather the existing body of knowledge in a common framework to provide guidance on selection of appropriate manufacturing technologies for a given drug and/or guide optimization of the physical properties of the drug to facilitate manufacturing requirements for a given processing route. Simultaneously, material scientists endeavour to develop characterisation methods such as size, shape, surface area, density, flow and compactibility that enable a stronger understanding of materials powder properties. Read More

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November 2018
6 Reads

Approaches to Resolve False Reporting in Neutralizing Antibody Assays Caused by Reagent Leaching from Affinity Capture Elution Solid Phase.

AAPS J 2018 Nov 6;21(1). Epub 2018 Nov 6.

Pfizer Worldwide Research & Development, Biomedicine Design, 1 Burtt Rd., Andover, Massachusetts, 01810, USA.

Insufficient drug tolerance presents a major challenge in the development of neutralizing antibody (NAb) assays for biotherapeutics. Sample pre-treatment using solid-phase extraction with acid dissociation (SPEAD) is widely reported to improve drug tolerance. In this paper, a case study is presented in which SPEAD was used in conjunction with a competitive ligand binding NAb assay format. Read More

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November 2018
6 Reads

In Vitro and In Vivo Efficacy of the Monocarboxylate Transporter 1 Inhibitor AR-C155858 in the Murine 4T1 Breast Cancer Tumor Model.

AAPS J 2018 Nov 5;21(1). Epub 2018 Nov 5.

Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, State University of New York, 352 Kapoor Hall, Buffalo, New York, 14214, USA.

Monocarboxylate transporter 1 (MCT1), also known as a L-lactate transporter, is a potential therapeutic target in cancer. The objectives of this study were to evaluate efficacy and assess concentration-effect relationships of AR-C155858 (a selective and potent MCT1 inhibitor) in murine 4T1 breast cancer cells and in the 4T1 tumor xenograft model. Western blotting of 4T1 cells demonstrated triple negative breast cancer (TNBC) characteristics and overexpression of MCT1 and CD147 (a MCT1 accessory protein), but absence of MCT4 expression. Read More

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November 2018
1 Read

The importance of equal treatment: Medical students'opinions on affirmative action, equal treatment and discrimination.

Health Care Women Int 2018 Nov 5:1-19. Epub 2018 Nov 5.

a Gender Medicine Unit , Medical University of Innsbruck , Innsbruck , Austria.

We assessed medical students' opinion of affirmative action programs (AAPs), perception of gender equality and discrimination. 276 medical students (56.2% female) participated. Read More

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November 2018

Population Pharmacokinetics of AL-335 and Its Two Main Metabolites (ALS-022399, ALS-022227) in Monotherapy and in Combination with Odalasvir and/or Simeprevir.

AAPS J 2018 Oct 24;21(1). Epub 2018 Oct 24.

Janssen Research and Development, Global Clinical Pharmacology, Turnhoutseweg 30, B-2340, Beerse, Belgium.

The aim of the current study was to characterize the time course of plasma concentrations of AL-335 and its main metabolites (ALS-022399 and ALS-022227) after oral administration in healthy and hepatitis C virus (HCV)-infected subjects, in monotherapy as well as in combination with simeprevir and/or odalasvir. AL-335, ALS-022399, and ALS-022227 plasma concentrations from subjects receiving 800 mg of AL-335 orally once daily (qd) as monotherapy or in combination were pooled and analyzed using a nonlinear mixed effect modeling approach. The typical values (between subject variability) of AL-335 and ALS-022399 apparent linear clearances were 3300 L/h (33. Read More

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October 2018
1 Read

Characterizing the Pharmacokinetic Interaction Between Simeprevir and Odalasvir in Healthy Volunteers Using a Population Modeling Approach.

AAPS J 2018 Oct 22;20(6):111. Epub 2018 Oct 22.

Janssen Research and Development, Global Clinical Pharmacology, Turnhoutseweg 30, B-2340, Beerse, Belgium.

The aim of this study was to characterize the pharmacokinetic drug-drug interaction (DDI) between simeprevir (NS3/4A protease inhibitor) and odalasvir (NS5A inhibitor) after oral administration to support the design and dose selection of clinical studies with this combination for the treatment of chronic hepatitis C infection (HCV). Simeprevir and odalasvir plasma concentrations from 30 healthy subjects receiving these drugs in monotherapy as well as in combination were pooled and analyzed using a population pharmacokinetic modeling approach. Previous pharmacokinetic models developed to characterize the pharmacokinetics for each drug were used as starting point. Read More

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October 2018
5 Reads

Augmentation of Fluvastatin Cytotoxicity Against Prostate Carcinoma PC3 Cell Line Utilizing Alpha Lipoic-Ellagic Acid Nanostructured Lipid Carrier Formula.

Authors:
Usama A Fahmy

AAPS PharmSciTech 2018 Nov 22;19(8):3454-3461. Epub 2018 Oct 22.

Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, P.O. Box: 80200, Jeddah, 21589, Saudi Arabia.

Statins are commonly used in the middle-aged and elderly people for treatment of hyperlipidemia. Both alpha lipoic acid (ALA) and ellagic acid (EA) are natural antioxidants found in a normal diet. They can protect against cellular damage and induce cellular apoptosis in many types of cancer cells. Read More

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November 2018
19 Reads

Power of the Dissolution Test in Distinguishing a Change in Dosage Form Critical Quality Attributes.

Authors:
Vivian A Gray

AAPS PharmSciTech 2018 Nov 22;19(8):3328-3332. Epub 2018 Oct 22.

V. A. Gray Consulting, Inc., Hockessin, Delaware, USA.

For a dissolution method to be considered relevant to in vivo performance, the dissolution data profiles should show discrimination or meaningful change when there is a change in critical material attributes (CMAs) and critical product properties (CPPs). The dissolution test has been shown repeatedly to have the power to distinguish between significant changes in active pharmaceutical ingredient (API), formulation, and process that relate to the release mechanism of the in vivo performance. Examples will be discussed in the literature where the effects of formulation, drug substance, and manufacturing variables have been measured by dissolution testing. Read More

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November 2018
5 Reads

Conjugation to Ascorbic Acid Enhances Brain Availability of Losartan Carboxylic Acid and Protects Against Parkinsonism in Rats.

AAPS J 2018 Oct 22;20(6):110. Epub 2018 Oct 22.

Drug Development and Analysis Lab., School of Pharmaceutical Sciences, Siksha O Anusandhan Deemed to be University, Ghatikia, Kalinganagar, Bhubaneswar, Odisha, 751029, India.

Identification of renin-angiotensin system in the interplay of hypertension and neurodegeneration has paved the way for the repurposing of antihypertensive drugs against Parkinsonism. Losartan carboxylic acid (LCA), the potent AT1 blocker metabolite of losartan, suffers from poor bioavailability and brain access. Since ascorbate transporters have earlier shown enough flexibility as carriers, we have conjugated losartan carboxylic acid to ascorbic acid with the aim of achieving higher oral/brain availability. Read More

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October 2018
1 Read

Contribution of the plasma and lymph Degradome and Peptidome to the MHC Ligandome.

Immunogenetics 2018 Oct 20. Epub 2018 Oct 20.

Institute for Cell Biology, Department of Immunology, University of Tübingen, Auf der Morgenstelle 15, 72076, Tübingen, Germany.

Every biological fluid, blood, interstitial fluid and lymph, urine, saliva, lacrimal fluid, nipple aspirate, and spinal fluid, contains a peptidome-degradome derived from the cellular secretome along with byproducts of the metabolic/catabolic activities of each parenchymal organ. Clement et al. (J Proteomics 78:172-187, 2013), Clement et al. Read More

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October 2018
6 Reads

Summary report of second EUFEPS/AAPS conference on global harmonization in bioequivalence.

Eur J Pharm Sci 2019 Jan 18;127:24-28. Epub 2018 Oct 18.

Medicines Evaluation Board, the Netherlands.

The Global Bioequivalence Harmonization Initiative (GBHI) was launched by the Network on Bioavailability and Biopharmaceutics (BABP) under the auspices of European Federation for Pharmaceutical Sciences (EUFEPS) several years ago. Since 2015, EUFEPS in collaboration with the American Association of Pharmaceutical Scientists (AAPS) has organized three international conferences to support global harmonization of regulatory requirements for bioequivalence (BE) assessment. These conferences provided an open forum for pharmaceutical scientists from academia, industry and regulatory agencies to discuss various BE topics at issue. Read More

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January 2019
10 Reads

Minimizing Delay and Transmission Times with Long Lifetime in Code Dissemination Scheme for High Loss Ratio and Low Duty Cycle Wireless Sensor Networks.

Sensors (Basel) 2018 Oct 18;18(10). Epub 2018 Oct 18.

Department of Networks Engineering, School of Computer, National University of Defense Technology, Changsha 410073, China.

Software defined networks brings greater flexibility to networks and therefore generates new vitality. Thanks to the ability to update soft code to sensor nodes, wireless sensor networks (WSNs) brings profound changes to Internet of Things. However, it is a challenging issue to minimize delay and transmission times and maintain long lifetime when broadcasting data packets in high loss ratio and low duty cycle WSNs. Read More

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October 2018

Nucleic Acid-Based Therapeutics for Pulmonary Diseases.

AAPS PharmSciTech 2018 Nov 18;19(8):3670-3680. Epub 2018 Oct 18.

Department of Pharmacy, China Pharmaceutical University, No.639, Longmian Avenue, Nanjing, 211198, People's Republic of China.

Nucleic acid-based therapeutics present huge potential in the treatment of pulmonary diseases ranging from lung cancer to asthma and chronic pulmonary diseases, which are often fatal and widely prevalent. The susceptibility of nucleic acids to degradation and the complex structure of lungs retard the effective pulmonary delivery of nucleic acid drug. To overcome these barriers, different strategies have been exploited to increase the delivery efficiency using chemically synthesized nucleic acids, vector encapsulation, proper formulation, and administration route. Read More

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November 2018
7 Reads

Formulation, Characterization, and Pharmacokinetic Studies of 6-Gingerol-Loaded Nanostructured Lipid Carriers.

AAPS PharmSciTech 2018 Nov 15;19(8):3661-3669. Epub 2018 Oct 15.

Department of Pharmaceutics, School of Pharmacy, Center for Nano Drug/Gene Delivery and Tissue Engineering, Jiangsu University, No.301, Xuefu Road, Jingkou District, Zhenjiang City, 212013, Jiangsu Province, China.

In this study, an optimized nanostructured lipid carriers (NLCs) were developed and investigated for improving the solubility and oral availability of 6-Gingerol (6G), an active and abundant component of ginger with limited applications due to its poor water solubility plus oral biological availability. The NLCs consisted of a solid lipid (glyceryl monostearate), another liquid lipid (decanoyl/octanoyl-glycerides) and mixed surfactants (Tween 80 and Poloxamer 188), and was prepared by high pressure homogenization method. The optimal 6G-NLC formulation was evaluated through physical properties such as appearance, mean particle size, zeta potential, encapsulation efficiency, and in vitro drug release, alongside techniques viz. Read More

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November 2018
10 Reads

In Vivo Evaluation of Taste-Masked Fast-Disintegrating Sublingual Tablets of Epinephrine Microcrystals.

AAPS PharmSciTech 2018 Nov 15;19(8):3886-3894. Epub 2018 Oct 15.

College of Pharmacy, Nova Southeastern University, 3200 South University Drive, Fort Lauderdale, Florida, 33328, USA.

In community settings, IM injection of 0.3 mg epinephrine (Epi) using an auto-injector is the drug of choice for treatment of anaphylaxis. Previously, a taste-masking (TM) formulation of fast-disintegrating sublingual tablets (FDSTs) was developed in our lab. Read More

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November 2018
2 Reads

Green Synthesis of Carbon Nanotubes-Reinforced Molecularly Imprinted Polymer Composites for Drug Delivery of Fenbufen.

AAPS PharmSciTech 2018 Nov 15;19(8):3895-3906. Epub 2018 Oct 15.

Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical University, Tianjin, 300070, People's Republic of China.

The facile fabrication of single-walled carbon nanotubes (SWCNTs)-doping molecularly imprinted polymer (MIP) nanocomposite-based binary green porogen system, room-temperature ionic liquids (RTILs), and deep eutectic solvents (DESs) was developed for drug delivery system. With fenbufen (FB) as template molecule, 4-vinylpyridine (4-VP) was used as functional monomer, ethylene glycol dimethacrylate as cross-linking monomer, and 1-butyl-3-methylimidazoliumtetrafluoroborate and choline chloride/ethylene glycol as binary green solvent, in the presence of SWCNTs. The imprinting effect of the SWCNT-MIP composites was optimized by regulation of the amount of SWCNTs, ratio of RTILs and DES, and the composition of DES. Read More

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November 2018
3 Reads

Risk-Based Comparability Assessment for Monoclonal Antibodies During Drug Development: A Clinical Pharmacology Perspective.

AAPS J 2018 Oct 15;20(6):109. Epub 2018 Oct 15.

Global Clinical Pharmacology, Janssen Research & Development, LLC, 1400 McKean Road, Spring House, Pennsylvania, 19477, USA.

Due to complexities in the structure, function, and manufacturing process of antibody-based therapeutic proteins, comparability assessment for supporting manufacturing changes can sometimes be a challenging task. Regulatory guidance recommends a hierarchical risk-based approach, starting with Chemistry, Manufacturing, and Controls (CMC) analytical characterizations, followed by non-clinical and/or clinical studies to ensure that any potential changes in quality attributes have no adverse impact on efficacy and safety of the product. This review focuses on the changes in quality attributes which may potentially affect the pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of a monoclonal antibody (mAb) product, and provides general guidelines in designing non-clinical and clinical PK/PD studies to help support comparability assessments. Read More

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October 2018
4 Reads

Atypical Antipsychotics and the Human Skeletal Muscle Lipidome.

Metabolites 2018 Oct 13;8(4). Epub 2018 Oct 13.

Department of Pharmaceutical Science, Wayne State University, Detroit, MI 48202, USA.

Atypical antipsychotics (AAPs) are a class of medications associated with significant metabolic side effects, including insulin resistance. The aim of this study was to analyze the skeletal muscle lipidome of patients on AAPs, compared to mood stabilizers, to further understand the molecular changes underlying AAP treatment and side effects. Bipolar patients on AAPs or mood stabilizers underwent a fasting muscle biopsy and assessment of insulin sensitivity. Read More

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October 2018
6 Reads

Novel Random Triblock Copolymers for Sustained Delivery of Macromolecules for the Treatment of Ocular Diseases.

AAPS PharmSciTech 2018 Nov 10;19(8):3871-3885. Epub 2018 Oct 10.

Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, 2464 Charlotte St. HSB 5258, Kansas City, Missouri, 64108, USA.

The objective of this study is to design, develop, and synthesize novel random triblock (RTB) copolymers for sustained delivery of macromolecules. RTB copolymers have not been utilized for the delivery of macromolecules for ocular diseases. RTB copolymers comprising of polyethylene glycol, glycolide, and ɛ-caprolactone blocks were synthesized and assessed for their molecular weights and purity using H-NMR spectroscopy, gel permeation chromatography, FTIR (functionality), and XRD (crystallinity). Read More

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November 2018
1 Read

Nanoparticle-Based Delivery of CRISPR/Cas9 Genome-Editing Therapeutics.

AAPS J 2018 Oct 10;20(6):108. Epub 2018 Oct 10.

Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, 52242, USA.

The recent progress in harnessing the efficient and precise method of DNA editing provided by CRISPR/Cas9 is one of the most promising major advances in the field of gene therapy. However, the development of safe and optimally efficient delivery systems for CRISPR/Cas9 elements capable of achieving specific targeting of gene therapy to the location of interest without off-target effects is a primary challenge for clinical therapeutics. Nanoparticles (NPs) provide a promising means to meet such challenges. Read More

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October 2018
8 Reads

The First AAPS Cannon Student Scholarship Experience.

Plast Reconstr Surg 2018 Oct 9. Epub 2018 Oct 9.

Professor Emeritus, Department of Plastic Surgery Medical College of Wisconsin, Accreditation Field Representative Accreditation Council for Graduate Medical Education.

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October 2018
3 Reads
2.993 Impact Factor

Tissue Physiology of Cynomolgus Monkeys: Cross-Species Comparison and Implications for Translational Pharmacology.

AAPS J 2018 Oct 8;20(6):107. Epub 2018 Oct 8.

Preclinical and Translational Pharmacokinetics, Genentech Research and Early Development, South San Francisco, California, 94080, USA.

We previously performed a comparative assessment of tissue-level vascular physiological parameters in mice and rats, two of the most commonly utilized species in translational drug development. The present work extends this effort to non-human primates by measuring tissue- and organ-level vascular volumes (V), interstitial volumes (V), and blood flow rates (Q) in cynomolgus monkeys. These measurements were accomplished by red blood cell labeling, extracellular marker infusion, and rubidium chloride bolus distribution, respectively, the same methods used in previous rodent measurements. Read More

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October 2018

Radiolabeling of Preformed Niosomes with [Tc]: In Vitro Stability, Biodistribution, and In Vivo Performance.

AAPS PharmSciTech 2018 Nov 5;19(8):3859-3870. Epub 2018 Oct 5.

Department of Pharmaceutics and Nanotechnology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Nanocarriers radiolabeled with [Tc] can be used for diagnostic imaging and radionuclide therapy, as well as tracking their pharmacokinetic and biodistribution characteristics. Due to the advantages of niosomes as an ideal drug delivery system, in this study, the radiolabeling procedure of niosomes by [Tc]-HMPAO complexes was investigated and optimized. Glutathione (GSH)-loaded niosomes were prepared using a thin-film hydration method. Read More

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November 2018
1 Read

Lipomers (Lipid-polymer Hybrid Particles) of Vardenafil Hydrochloride: a Promising Dual Platform for Modifying the Drug Release Rate and Enhancing Its Oral Bioavailability.

AAPS PharmSciTech 2018 Nov 5;19(8):3650-3660. Epub 2018 Oct 5.

Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo, 11562, Egypt.

Vardenafil hydrochloride is commonly used for the curing of erectile dysfunction. VAR suffers certain limitations: (i) short elimination half-life (4-5 h), (ii) low aqueous solubility (0.11 mg/mL), (iii) susceptibility to extensive first-pass metabolism and drug efflux transporters (P-glycoprotein), and (iv) limited (15%) oral bioavailability. Read More

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November 2018
3 Reads

In-Line Film Coating Thickness Estimation of Minitablets in a Fluid-Bed Coating Equipment.

AAPS PharmSciTech 2018 Nov 2;19(8):3440-3453. Epub 2018 Oct 2.

Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana, Aškerčeva cesta 7, Ljubljana, SI-1000, Slovenia.

Film coating thickness of minitablets was estimated in-line during coating in a fluid-bed equipment by means of visual imaging. An existing, commercially available image acquisition system was used for image acquisition, while dedicated image analysis and data analysis methods were developed for this purpose. The methods were first tested against simulated minitablet's images and after that examined on a laboratory-scale fluid-bed Wurster coating process. Read More

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November 2018

Intranasal Surface-Modified Mosapride Citrate-Loaded Nanostructured Lipid Carriers (MOS-SMNLCs) for Treatment of Reflux Diseases: In vitro Optimization, Pharmacodynamics, and Pharmacokinetic Studies.

AAPS PharmSciTech 2018 Nov 2;19(8):3791-3808. Epub 2018 Oct 2.

Department of Surgery, Anesthesiology and Radiology, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt.

Gastroesophageal reflux disease (GERD) is an esophageal injury occurred when the stomach contents reflux abnormally into the esophagus. GERD complications include esophageal adenocarcinoma. Mosapride (MOS) is a safe prokinetic agent potentially used to treat GERD. Read More

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November 2018
2 Reads

Nano-lipid Complex of Rutin: Development, Characterisation and In Vivo Investigation of Hepatoprotective, Antioxidant Activity and Bioavailability Study in Rats.

AAPS PharmSciTech 2018 Nov 2;19(8):3631-3649. Epub 2018 Oct 2.

Department of Pharmaceutics, NGSM Institute of Pharmaceutical Sciences, Nitte (Deemed to be University), Deralakatte, Mangaluru, 575018, India.

The current study was aimed to develop an amphiphilic drug-lipid nano-complex of rutin:egg phosphatidylcholine (EPC) to enhance its poor absorption and bioavailability, and investigated the impact of the complex on hepatoprotective and antioxidant activity. Rutin nano-complexes were prepared by solvent evaporation, salting out and lyophilisation methods and compared for the complex formation. For the selected lyophilisation method, principal solvent DMSO, co-solvent (t-butyl alcohol) and rutin:EPC ratios (1:1, 1:2 and 1:3) were selected after optimisation. Read More

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November 2018
8 Reads

Investigating a Novel Hot Melt Extrusion-Based Drying Technique to Solidify an Amorphous Nanosuspension Using Design of Experiment Methodology.

AAPS PharmSciTech 2018 Nov 2;19(8):3778-3790. Epub 2018 Oct 2.

Natoli Institute for Industrial Pharmacy Research and Development at Arnold and Marie Schwartz College of Pharmacy and Health Sciences, Long Island University, Brooklyn, New York, 11201, USA.

The hot melt extrusion (HME) technology was explored and optimized to solidify an amorphous nanosuspension using Quality by Design (QbD) methodology. A design of experiments (DoE) approach was used to perform a set of 15 experiments, varying independent variables (feed rate, input temperature, and screw speed) within a design space. Redispersibility index (RDI), moisture content, and process yield constituted the critical quality attributes (CQAs) of the experimental design. Read More

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November 2018
14 Reads

Aggregate Elasticity and Tabletability of Molecular Solids: a Validation and Application of Powder Brillouin Light Scattering.

AAPS PharmSciTech 2018 Nov 2;19(8):3430-3439. Epub 2018 Oct 2.

Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, The University of Iowa, Iowa City, Iowa, 52242, USA.

Describing the elastic deformation of single-crystal molecular solids under stress requires a comprehensive determination of the fourth-rank stiffness tensor (C). Single crystals are, however, rarely utilized in industrial applications, and thus averaging techniques (e.g. Read More

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November 2018
2 Reads

Preparation and Characterization of an Oral Vaccine Formulation Using Electrosprayed Chitosan Microparticles.

AAPS PharmSciTech 2018 Nov 2;19(8):3770-3777. Epub 2018 Oct 2.

Department of Micro and Nanotechnology, Technical University of Denmark, Ørsteds Plads 345C, 2800, Kgs. Lyngby, Denmark.

Chitosan particles loaded with the antigen ovalbumin (OVA) and the adjuvant Quil-A were produced by electrospray, using mixtures of water/ethanol/acetic acid as a solvent. Three different chitosans designed as HMC70, HMC85, and HMC90 (called as 705010, 855010, and 905010) were tested and its efficacy to be used in oral vaccine delivery applications was investigated. The morphology, size, and zeta potential of the produced particles were investigated, together with the encapsulation efficiency and release of OVA from the three chitosan formulations. Read More

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November 2018
6 Reads

Enhanced Oral Bioavailability of Chlormadinone Acetate through a Self-Microemulsifying Drug Delivery System for a Potential Dose Reduction.

AAPS PharmSciTech 2018 Nov 2;19(8):3850-3858. Epub 2018 Oct 2.

Key Laboratory of Contraceptives and Devices Research (NPFPC), Shanghai Engineering Research Center of Reproductive Health Drug and Devices, Shanghai Institute of Planned Parenthood Research, 200032, Shanghai, People's Republic of China.

Chlormadinone acetate (CMA) is a derivative of the naturally secreted hormone progesterone and exhibits reliable contraceptive and non-contraceptive benefits. Although the marketed product of CMA as oral tablets under the trade name Belara® has been highly successful, there is still room for further improvements in oral bioavailability and a reduction in the clinical dose to decrease related adverse effects. In the current study, a CMA-based self-microemulsifying drug delivery system (SMEDDS) was developed using 32% ethyl oleate as an oil phase, 40% Tween-80 as a surfactant, and 12% Transcutol P combined with 16% PEG400 as a cosurfactant, resulting in spherical droplets with a z-average particle size of 38. Read More

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November 2018
13 Reads

Comparing a Statistical Model and Bayesian Approach to Establish the Design Space for the Coating of Ciprofloxacin HCl Beads at Different Scales of Production.

AAPS PharmSciTech 2018 Nov 2;19(8):3809-3828. Epub 2018 Oct 2.

School of Pharmacy, Department of Pharmaceutical Sciences, University of Maryland, Baltimore, 20 N Pine Street, Baltimore, MD, 21201, USA.

The primary objective of this study was to compare two methods for establishing a design space for critical process parameters that affect ethylcellulose film coating of multiparticulate beads and assess this design space validity across manufacturing scales. While there are many factors that can affect film coating, this study will focus on the effects processing conditions have on the quality and extent of film formation, as evaluated by their impact coating yield and drug release. Ciprofloxacin HCl layered beads were utilized as an active substrate core, ethylcellulose aqueous dispersion as a controlled release polymer, and triethyl citrate as a plasticizer. Read More

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November 2018
4 Reads

Intratumoral Injection Administration of Irinotecan-Loaded Microspheres: In Vitro and In Vivo Evaluation.

AAPS PharmSciTech 2018 Nov 2;19(8):3829-3838. Epub 2018 Oct 2.

School of Pharmaceutical Sciences, Shandong University, No.44 Wenhua Xi Road, Jinan, Shandong Province, People's Republic of China.

To reduce the toxic and side effects of intravenous chemotherapeutic drugs on the tumor-patients, the aims of this study were to design and study intratumor-administrated irinotecan-loaded PLGA microspheres (CPT-11-PLGA-MS) in vitro and in vivo according to the structure characteristics of CPT-11. PLGA microspheres containing irinotecan were prepared by emulsion solvent evaporation method and evaluated in terms of their morphology, particle size analysis, in vitro drug release, drug retention and leakage studies in vivo, and pharmacodynamics studies. The CPT-11-PLGA-MS were spherical with mean size of 9. Read More

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November 2018
1 Read

Nanocarrier-Based Combination Chemotherapy for Resistant Tumor: Development, Characterization, and Ex Vivo Cytotoxicity Assessment.

AAPS PharmSciTech 2018 Nov 2;19(8):3839-3849. Epub 2018 Oct 2.

Drug delivery Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Central University, Sagar, M.P., 470003, India.

A folic acid-conjugated paclitaxel (PTX)-doxorubicin (DOX)-loaded nanostructured lipid carrier(s) (FA-PTX-DOX NLCs) were prepared by using emulsion-evaporation method and extensively characterized for particle size, polydispersity index, zeta potential, and % entrapment efficiency which were found to be 196 ± 2.5 nm, 0.214 ± 0. Read More

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November 2018
8 Reads
1.780 Impact Factor

Interactions Between Biological Products and Product Packaging and Potential Approaches to Overcome Them.

AAPS PharmSciTech 2018 Nov 2;19(8):3681-3686. Epub 2018 Oct 2.

Department of Pharmaceutics & Drug Delivery, The University of Mississippi, University, Mississippi, 38677, USA.

Biological products such as protein-based biopharmaceuticals are playing an important role in the healthcare and pharmaceutical industry. The interaction between biological products and packaging materials has become the focus of many studies since it can reduce the effectiveness of biological products. These interactions are heavily influenced by the surface properties and physicochemical nature of the therapeutic agents and the packaging materials. Read More

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November 2018
3 Reads

Reverse Engineering the 1-Month Lupron Depot®.

AAPS J 2018 Oct 2;20(6):105. Epub 2018 Oct 2.

Department of Pharmaceutical Sciences, The Biointerfaces Institute, University of Michigan, 2800 Plymouth Rd., Ann Arbor, Michigan, 48109, USA.

The 1-month Lupron Depot® (LD) encapsulating water-soluble leuprolide in poly(lactic-co-glycolic acid) (PLGA) microspheres is a benchmark product upon which modern long-acting release products are often compared. Despite expiration of patent coverage, no generic product for the LD has been approved in the USA, likely due to the complexity of components and manufacturing processes involved in the product. Here, we describe the reverse engineering of the LD composition and important product attributes. Read More

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October 2018
5 Reads
3.800 Impact Factor

A Gyrolab Assay for the Quantitation of Free Complement Protein C5a in Human Plasma.

AAPS J 2018 Oct 2;20(6):106. Epub 2018 Oct 2.

Bioanalytical Development, Alexion Pharmaceuticals Inc., 100 College Ave, New Haven, Connecticut, USA.

Complement protein C5a is recognized as an important component of the alternative complement pathway. Its role is prominent enough to garner interest not only as a biomarker, but also as a potential therapeutic target. Bioanalytical challenges have been posed in proper quantitation of free C5a due to interference from its precursor, C5. Read More

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October 2018
19 Reads

Antioxidant and anti-diabetic effects of Auricularia auricular polysaccharides and their degradation by artificial gastrointestinal digestion - Bioactivity of Auricularia auricular polysaccharides and their hydrolysates.

Acta Sci Pol Technol Aliment 2018 Jul-Sep;17(3):277-288

College of Life Sciences, China Jiliang University, Xueyuan Street, Xiasha, Hangzhou, Zhejiang, China.

Background: Auricularia auricular polysaccharides (AAPs) derived from the dried fruit body of A. auricular are valuable compounds with many bioactivities. This research aimed to investigate the antioxidant and anti- diabetic activities of these polysaccharides and their artificial gastrointestinal fluid hydrolysates (AAPHs). Read More

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October 2018
1 Read

Impact of Natural Variations in Freeze-Drying Parameters on Product Temperature History: Application of Quasi Steady-State Heat and Mass Transfer and Simple Statistics.

AAPS PharmSciTech 2018 Oct 26;19(7):2828-2842. Epub 2018 Sep 26.

Genentech (A Member of the Roche Group), South San Francisco, California, USA.

Inter- and intra-batch variability in heat and mass transfer during the drying phase of lyophilization is well recognized. Heat transfer variability between individual vials in the same batch arise from both different positions in the vial array and from variations in the bottom contour of the vials, both effects contributing roughly equally to variations in the effective heat transfer coefficient of the vials, K. Both effects can be measured in the laboratory, and variations in average K values as a function of vial position in the array for lab and production can be calculated by use of the simple steady-state heat and mass transfer theory. Read More

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October 2018
7 Reads

Bioavailability Enhancement of Aripiprazole Via Silicosan Particles: Preparation, Characterization and In vivo Evaluation.

AAPS PharmSciTech 2018 Nov 26;19(8):3751-3762. Epub 2018 Sep 26.

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ahram Canadian University, 6th of October City, Cairo, Egypt.

The aim of this study was to design a novel carrier for enhancing the bioavailability of the poorly water-soluble drug, aripiprazole (ARP). Silicosan, the applied carrier, was obtained by chemical interaction between tetraethyl orthosilicate (TEOS) and chitosan HCl. Different ARP-loaded silicosan particles were successfully prepared in absence and presence of one of the following surfactants; Tween 80, Poloxamer 407 and cetyltrimethylammonium bromide (CTAB). Read More

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November 2018
5 Reads