Pharmaceutical Research

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

List of Papers (Total 349)

Using the Lessons Learned From the Clinic to Improve the Preclinical Development of Antibody Drug Conjugates

The treatment options for cancer patients include surgery, chemotherapeutics, radiation therapy, antibody therapy and various combinations of these therapies. The challenge with each therapy is finding the balance between maximizing the anti-tumor efficacy while minimizing the dose limiting toxicities. Antibodies, unlike small molecule chemotherapeutics, selectively bind to cell...

Prediction of Disease Progression, Treatment Response and Dropout in Chronic Obstructive Pulmonary Disease (COPD)

Purpose Drug development in chronic obstructive pulmonary disease (COPD) has been characterised by unacceptably high failure rates. In addition to the poor sensitivity in forced expiratory volume in one second (FEV1), numerous causes are known to contribute to this phenomenon, which can be clustered into drug-, disease- and design-related factors. Here we present a model-based...

Bisoprolol and Bisoprolol-Valsartan Compatibility Studied by Differential Scanning Calorimetry, Nuclear Magnetic Resonance and X-Ray Powder Diffractometry

Purpose The objective of this study was to evaluate the thermal behavior of crystalline and amorphous bisoprolol fumarate and its compatibility with amorphous valsartan. This pharmacologically relevant drug combination is a potential candidate for fixed-dose combination formulation. Methods DSC and TMDSC were used to examine thermal behavior of bisoprolol fumarate. SSNMR and XRPD...

Computational Prediction of Drug Solubility in Fasted Simulated and Aspirated Human Intestinal Fluid

Purpose To develop predictive models of apparent solubility (Sapp) of lipophilic drugs in fasted state simulated intestinal fluid (FaSSIF) and aspirated human intestinal fluid (HIF). Methods Measured Sapp values in FaSSIF, HIF and phosphate buffer pH 6.5 (PhBpH6.5) for 86 lipophilic drugs were compiled and divided into training (Tr) and test (Te) sets. Projection to latent...

Mechanism of Mucosal Permeability Enhancement of CriticalSorb® (Solutol® HS15) Investigated In Vitro in Cell Cultures

Purpose CriticalSorb™, with the principal component Solutol® HS15, is a novel mucosal drug delivery system demonstrated to improve the bioavailability of selected biotherapeutics. The intention of this study is to elucidate mechanism(s) responsible for the enhancement of trans-mucosal absorption of biological drugs by Solutol® HS15. Methods Micelle size and CMC of Solutol® HS15...

Development of Thermostable Lyophilized Inactivated Polio Vaccine

Purpose The aim of current study was to develop a dried inactivated polio vaccine (IPV) formulation with minimal loss during the drying process and improved stability when compared with the conventional liquid IPV. Methods Extensive excipient screening was combined with the use of a Design of Experiment (DoE) approach in order to achieve optimal results with high probability...

High Therapeutic Efficiency of Magnetic Hyperthermia in Xenograft Models Achieved with Moderate Temperature Dosages in the Tumor Area

Purpose Tumor cells can be effectively inactivated by heating mediated by magnetic nanoparticles. However, optimized nanomaterials to supply thermal stress inside the tumor remain to be identified. The present study investigates the therapeutic effects of magnetic hyperthermia induced by superparamagnetic iron oxide nanoparticles on breast (MDA-MB-231) and pancreatic cancer (BxPC...

Pharmacokinetics and Efficacy of the Spleen Tyrosine Kinase Inhibitor R406 after Ocular Delivery for Retinoblastoma

Purpose Retinoblastoma is a childhood cancer of the retina. Clinical trials have shown that local delivery of broad spectrum chemotherapeutic agents is efficacious. Recent studies characterizing the genomic and epigenomic landscape of retinoblastoma identified spleen tyrosine kinase (SYK) as a promising candidate for targeted therapy. The purpose of this study was to conduct...

Tumor-Targeted Responsive Nanoparticle-Based Systems for Magnetic Resonance Imaging and Therapy

Purpose Design and synthesis of a tumor responsive nanoparticle-based system for imaging and treatment of various cancers. Methods Manganese oxide nanoparticles (Mn3O4 NPs) were synthesized and modified with LHRH targeting peptide or anti-melanoma antibodies (cancer targeting moieties) and a MMP2 cleavable peptide (a possible chemotactic factor). Nanostructured lipid carriers...

Evidence for the existence of powder sub-populations in micronized materials: Aerodynamic size-fractions of aerosolized powders possess distinct physicochemical properties.

Purpose To investigate the agglomeration behaviour of the fine (<5.0 μm) and coarse (>12.8 μm) particle fractions of salmeterol xinafoate (SX) and fluticasone propionate (FP) by isolating aerodynamic size fractions and characterising their physicochemical and re-dispersal properties. Methods Aerodynamic fractionation was conducted using the Next Generation Impactor (NGI). Re...

Quantitative Measurement of the Target-Mediated Internalization Kinetics of Biopharmaceuticals

PurposeMeasurement of internalization of biopharmaceuticals targeting cell surface proteins can greatly facilitate drug development. The objective of this study was to develop a reliable method for determination of internalization rate constant (kint) and to demonstrate its utility.MethodsThis method utilized confocal imaging to record the internalization kinetics of fluorescence...

Magnetic Resonance Microscopy for Assessment of Morphological Changes in Hydrating Hydroxypropylmethylcellulose Matrix Tablets In Situ–Is it Possible to Detect Phenomena Related to Drug Dissolution Within the Hydrated Matrices?

Purpose So far, the hydrated part of the HPMC matrix has commonly been denoted as a “gel” or “pseudogel” layer. No MRI-based results have been published regarding observation of internal phenomena related to drug dissolution inside swelling polymeric matrices during hydration. The purpose of the study was to detect such phenomena. Methods Multiparametric, spatially and temporally...

Investigations on the Viscoelastic Performance of Pressure Sensitive Adhesives in Drug-in-Adhesive Type Transdermal Films

Purpose We aimed to investigate the effect of solubility parameter and drug concentration on the rheological behaviour of drug-in-adhesive films intended for transdermal application. Methods Films were prepared over a range of drug concentrations (5%, 10% and 20% w/w) using ibuprofen, benzoic acid, nicotinic acid and lidocaine as model drugs in acrylic (Duro-Tak 87-4287 and Duro...

A Novel Suspension Formulation Enhances Intestinal Absorption of Macromolecules Via Transient and Reversible Transport Mechanisms

Purpose Medium chain fatty acid salts promote absorption by increasing paracellular permeability of the intestinal epithelium. Novel oily suspension (OS) formulation disperses a powder containing sodium caprylate and macromolecules such as octreotide or fluorescent dextran (FD). Formulation safety, macromolecule absorption and pharmacokinetic (PK)/pharmacodynamic (PD) were...

Improved Utilization of ADAS-Cog Assessment Data Through Item Response Theory Based Pharmacometric Modeling

Purpose This work investigates improved utilization of ADAS-cog data (the primary outcome in Alzheimer’s disease (AD) trials of mild and moderate AD) by combining pharmacometric modeling and item response theory (IRT). Methods A baseline IRT model characterizing the ADAS-cog was built based on data from 2,744 individuals. Pharmacometric methods were used to extend the baseline...

Does a Hot Drink Provide Faster Absorption of Paracetamol Than a Tablet? A Pharmacoscintigraphic Study in Healthy Male Volunteers

Purpose To investigate the hypothesis that paracetamol is absorbed faster from a hot drink than from a standard tablet using simultaneous scintigraphic imaging and pharmacokinetic sampling. Methods Twenty-five healthy male volunteers received both paracetamol formulations in a randomised manner. The formulation administered in the first treatment arm was radiolabelled to allow...

Bioactive Equivalence of Combinatorial Components Identified in Screening of an Herbal Medicine

Purpose To identify bioactive equivalent combinatorial components (BECCs) in herbal medicines. The exact composition of effective components in herbal medicines is often elusive due to the lack of adequate screening methodology. Herein, we propose a hypothesis that BECCs accounting for the whole efficacy of original herbal medicines could be discovered from a complex mixture of...

Spatial Characterization of Hot Melt Extruded Dispersion Systems Using Thermal Atomic Force Microscopy Methods: The Effects of Processing Parameters on Phase Separation

Purpose In this study we explore the use of nano-scale localized thermal analysis (LTA) and transition temperature microcopy (TTM) as a novel combined approach to studying phase separation in HME dispersions of cyclosporine A in Eudragit EPO. Methods Modulated temperature differential scanning calorimetry (MTDSC), attenuated total reflectance FTIR spectroscopy, nano-LTA and TTM...

Potential of a Cyclone Prototype Spacer to Improve In Vitro Dry Powder Delivery

Purpose Low inspiratory force in patients with lung disease is associated with poor deagglomeration and high throat deposition when using dry powder inhalers (DPIs). The potential of two reverse flow cyclone prototypes as spacers for commercial carrier-based DPIs was investigated. Methods Cyclohaler®, Accuhaler® and Easyhaler® were tested with and without the spacers between 30...

Dissolution Testing of Hardly Soluble Materials by Surface Sensitive Techniques: Clotrimazole from an Insoluble Matrix

PurposeThe low aqueous solubility of many drugs impedes detailed investigation as the detection limit of standard testing routines is limited. This is further complicated within application relevant thin films typical used in patches or stripes for buccal or topical routes.MethodsIn this work a model system is developed based on spin – casting technique allowing defined...

Long-Acting Atypical Antipsychotics: Characterization of the Local Tissue Response

PurposeLong-acting injectables (LAIs) are increasingly recognized as an effective therapeutic approach for treating chronic conditions. Many LAIs are formulated to create a poorly soluble depot from which the active agent is delivered over time. This long residing depot can cause localized chronic-active inflammation in the tissue, which has not been well defined in the...

Recent Advances in Lipid-Based Formulation Technology

IntroductionLipid-based formulations encompass a wide variety of delivery modes and technologies, ranging from immediate release to sustained release formulations, from liquids to semi-solids, from crystalline suspensions to lipid solutions, from systems containing small-molecule active pharmaceutical ingredients (APIs) to those containing more complex peptide-based molecules...