Pharmaceutical Research

http://link.springer.com/journal/11095

List of Papers (Total 352)

Development of a Two-Dimensional Model for Predicting Transdermal Permeation with the Follicular Pathway: Demonstration with a Caffeine Study

Purpose The development of a new two-dimensional (2D) model to predict follicular permeation, with integration into a recently reported multi-scale model of transdermal permeation is presented. Methods The follicular pathway is modelled by diffusion in sebum. The mass transfer and partition properties of solutes in lipid, corneocytes, viable dermis, dermis and systemic...

Controlled Suspensions Enable Rapid Determinations of Intrinsic Dissolution Rate and Apparent Solubility of Poorly Water-Soluble Compounds

PurposeTo develop a small-scale set-up to rapidly and accurately determine the intrinsic dissolution rate (IDR) and apparent solubility of poorly water-soluble compounds.MethodsThe IDR and apparent solubility (Sapp) were measured in fasted state simulated intestinal fluid (FaSSIF) for six model compounds using wet-milled controlled suspensions (1.0% (w/w) PVP and 0.2% (w/w) SDS...

Endocytic Uptake, Transport and Macromolecular Interactions of Anionic PAMAM Dendrimers within Lung Tissue

Purpose Polyamidoamine (PAMAM) dendrimers are a promising class of nanocarrier with applications in both small and large molecule drug delivery. Here we report a comprehensive evaluation of the uptake and transport pathways that contribute to the lung disposition of dendrimers. Methods Anionic PAMAM dendrimers and control dextran probes were applied to an isolated perfused rat...

Reflections on the Future of Pharmaceutical Public-Private Partnerships: From Input to Impact

Public Private Partnerships (PPPs) are multiple stakeholder partnerships designed to improve research efficacy. We focus on PPPs in the biomedical/pharmaceutical field, which emerged as a logical result of the open innovation model. Originally, a typical PPP was based on an academic and an industrial pillar, with governmental or other third party funding as an incentive. Over...

Pharmacokinetic-Pharmacodynamic Relationship of Erenumab (AMG 334) and Capsaicin-Induced Dermal Blood Flow in Healthy and Migraine Subjects

PurposeCapsaicin-induced dermal blood flow (CIDBF) is a validated biomarker used to evaluate the target engagement of potential calcitonin gene-related peptide-blocking therapeutics for migraine. To characterize the pharmacokinetics (PK) and quantify the inhibitory effects of erenumab (AMG 334) on CIDBF, CIDBF data were pooled from a single- and a multiple-dose study in healthy...

Metformin – a Future Therapy for Neurodegenerative Diseases

Type 2 diabetes mellitus (T2DM) is a complex, chronic and progressive metabolic disease, which is characterized by relative insulin deficiency, insulin resistance, and high glucose levels in blood. Esteemed published articles and epidemiological data exhibit an increased risk of developing Alzheimer’s disease (AD) in diabetic pateints. Metformin is the most frequently used oral...

A Biocompatible Synthetic Lung Fluid Based on Human Respiratory Tract Lining Fluid Composition

Purpose To characterise a biorelevant simulated lung fluid (SLF) based on the composition of human respiratory tract lining fluid. SLF was compared to other media which have been utilized as lung fluid simulants in terms of fluid structure, biocompatibility and performance in inhalation biopharmaceutical assays. Methods The structure of SLF was investigated using cryo...

Morphometric Characterization of Rat and Human Alveolar Macrophage Cell Models and their Response to Amiodarone using High Content Image Analysis

PurposeProgress to the clinic may be delayed or prevented when vacuolated or “foamy” alveolar macrophages are observed during non-clinical inhalation toxicology assessment. The first step in developing methods to study this response in vitro is to characterize macrophage cell lines and their response to drug exposures.MethodsHuman (U937) and rat (NR8383) cell lines and primary...

Mesoporous Silica Nanoparticle-Coated Microneedle Arrays for Intradermal Antigen Delivery

PurposeTo develop a new intradermal antigen delivery system by coating microneedle arrays with lipid bilayer-coated, antigen-loaded mesoporous silica nanoparticles (LB-MSN-OVA).MethodsSynthesis of MSNs with 10-nm pores was performed and the nanoparticles were loaded with the model antigen ovalbumin (OVA), and coated with a lipid bilayer (LB-MSN-OVA). The uptake of LB-MSN-OVA by...

The Need for Restructuring the Disordered Science of Amorphous Drug Formulations

The alarming numbers of poorly soluble discovery compounds have centered the efforts towards finding strategies to improve the solubility. One of the attractive approaches to enhance solubility is via amorphization despite the stability issue associated with it. Although the number of amorphous-based research reports has increased tremendously after year 2000, little is known on...

A Trivalent Enzymatic System for Uricolytic Therapy of HPRT Deficiency and Lesch-Nyhan Disease

Purpose Because of the evolutionary loss of the uricolytic pathway, humans accumulate poorly soluble urate as the final product of purine catabolism. Restoration of uricolysis through enzyme therapy is a promising treatment for severe hyperuricemia caused by deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT). To this end, we studied the effect of PEG conjugation...

Photochemically Controlled Drug Dosing from a Polymeric Scaffold

Purpose To develop the first photoactive biomaterial coating capable of controlled drug dosing via inclusion of synthesised drug-3,5-dimethoxybenzoin (DMB) conjugates in a poly(2-methyoxyethyl acrylate) (pMEA) scaffold. Methods Flurbiprofen- and naproxen-DMB conjugates were prepared via esterification and characterised via NMR spectroscopy and mass spectrometry following...

Velocity Field Visualization in USP Dissolution Apparatus 3 Using Particle Image Velocimetry

Purpose The hydrodynamics in USP dissolution apparatus 3, at five different dip rates, was characterized by analyzing phase-averaged velocity fields obtained using Particle Image Velocimetry (PIV). Methods Phase locked 2 Component-PIV (2C–PIV) measurements were recorded on a typical dissolution apparatus 3 configuration with a black painted tablet fixed at the center of the...

Virtual Clinical Studies to Examine the Probability Distribution of the AUC at Target Tissues Using Physiologically-Based Pharmacokinetic Modeling: Application to Analyses of the Effect of Genetic Polymorphism of Enzymes and Transporters on Irinotecan Induced Side Effects

Purpose To establish a physiologically-based pharmacokinetic (PBPK) model for analyzing the factors associated with side effects of irinotecan by using a computer-based virtual clinical study (VCS) because many controversial associations between various genetic polymorphisms and side effects of irinotecan have been reported. Methods To optimize biochemical parameters of...

Formulation, Delivery and Stability of Bone Morphogenetic Proteins for Effective Bone Regeneration

Bone morphogenetic proteins (BMPs) are responsible for bone formation during embryogenesis and bone regeneration and remodeling. The osteoinductive action of BMPs, especially BMP-2 and BMP-7, has led to their use in a range of insurmountable treatments where intervention is required for effective bone regeneration. Introduction of BMP products to the market, however, was not...

Transmembrane Domain Single-Nucleotide Polymorphisms Impair Expression and Transport Activity of ABC Transporter ABCG2

Purpose To study the function and expression of nine naturally occurring single-nucleotide polymorphisms (G406R, F431L, S441N, P480L, F489L, M515R, L525R, A528T and T542A) that are predicted to reside in the transmembrane regions of the ABC transporter ABCG2. Methods The transport activity of the variants was tested in inside-out membrane vesicles from Sf9 insect and human...

Network Reconstruction Reveals that Valproic Acid Activates Neurogenic Transcriptional Programs in Adult Brain Following Traumatic Injury

Objectives To determine the mechanism of action of valproic acid (VPA) in the adult central nervous system (CNS) following traumatic brain injury (TBI) and hemorrhagic shock (HS). Methods Data were analyzed from different sources, including experiments in a porcine model, data from postmortem human brain, published studies, public and commercial databases. Results The...

A Review of Disintegration Mechanisms and Measurement Techniques

Pharmaceutical solid dosage forms (tablets or capsules) are the predominant form to administer active pharmaceutical ingredients (APIs) to the patient. Tablets are typically powder compacts consisting of several different excipients in addition to the API. Excipients are added to a formulation in order to achieve the desired fill weight of a dosage form, to improve the...

Determination of the Porosity of PLGA Microparticles by Tracking Their Sedimentation Velocity Using a Flow Imaging Microscope (FlowCAM)

Purpose To investigate whether particle sedimentation velocity tracking using a flow imaging microscope (FlowCAM) can be used to determine microparticle porosity. Methods Two different methods were explored. In the first method the sedimentation rate of microparticles was tracked in suspending media with different densities. The porosity was calculated from the average apparent...

In Vitro and In Vivo Modeling of Hydroxypropyl Methylcellulose (HPMC) Matrix Tablet Erosion Under Fasting and Postprandial Status

Purpose To develop a model linking in vitro and in vivo erosion of extended release tablets under fasting and postprandial status. Methods A nonlinear mixed-effects model was developed from the in vitro erosion profiles of four hydroxypropyl methylcellulose (HPMC) matrix tablets studied under a range of experimental conditions. The model was used to predict in vivo erosion of the...

Non-destructive Determination of Disintegration Time and Dissolution in Immediate Release Tablets by Terahertz Transmission Measurements

Purpose The aim of this study was to establish the suitability of terahertz (THz) transmission measurements to accurately measure and predict the critical quality attributes of disintegration time and the amount of active pharmaceutical ingredient (API) dissolved after 15, 20 and 25 min for commercial tablets processed at production scale. Methods Samples of 18 batches of...

Bioequivalence Methodologies for Topical Drug Products: In Vitro and Ex Vivo Studies with a Corticosteroid and an Anti-Fungal Drug

Objective To examine whether in vitro and ex vivo measurements of topical drug product performance correlate with in vivo outcomes, such that more efficient experimental approaches can be reliably and reproducibly used to establish (in)equivalence between formulations for skin application. Materials and Methods In vitro drug release through artificial membranes, and drug...