Pharmaceutical Research

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

List of Papers (Total 355)

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...

Development of Thermostable Lyophilized Inactivated Polio Vaccine

PurposeThe 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.MethodsExtensive excipient screening was combined with the use of a Design of Experiment (DoE) approach in order to achieve optimal results with high probability...

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...

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

PurposeMedium 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...

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...

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

PurposeIn 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.MethodsModulated temperature differential scanning calorimetry (MTDSC), attenuated total reflectance FTIR spectroscopy, nano-LTA and TTM were...

The Use of ROC Analysis for the Qualitative Prediction of Human Oral Bioavailability from Animal Data

Purpose To develop and evaluate a tool for the qualitative prediction of human oral bioavailability (Fhuman) from animal oral bioavailability (Fanimal) data employing ROC analysis and to identify the optimal thresholds for such predictions. Methods A dataset of 184 compounds with known Fhuman and Fanimal in at least one species (mouse, rat, dog and non-human primates (NHP)) was...

Human and Non-Human Primate Intestinal FcRn Expression and Immunoglobulin G Transcytosis

Purpose To evaluate transcytosis of immunoglobulin G (IgG) by the neonatal Fc receptor (FcRn) in adult primate intestine to determine whether this is a means for oral delivery of monoclonal antibodies (mAbs). Methods Relative regional expression of FcRn and localization in human intestinal mucosa by RT-PCR, ELISA & immunohistochemistry. Transcytosis of full-length mAbs (sandwich...

Validation of Anatomical Models to Study Aerosol Deposition in Human Nasal Cavities

Purpose Intranasal deposition of aerosols is often studied using in vitro nasal cavity models. However, the relevance of these models to predict in vivo human deposition has not been validated. This study compared in vivo nasal aerosol deposition and in vitro deposition in a human plastinated head model (NC1) and its replica constructed from CT-scan (NC2). Methods Two nebulizers...

Carbon Dioxide-Mediated Generation of Hybrid Nanoparticles for Improved Bioavailability of Protein Kinase Inhibitors

Purpose A versatile methodology is demonstrated for improving dissolution kinetics, gastrointestinal (GI) absorption, and bioavailability of protein kinase inhibitors (PKIs). Methods The approach is based on nanoparticle precipitation by sub- or supercritical CO2 together with a matrix-forming polymer, incorporating surfactants either during or after nanoparticle formation...

Development of Solid SEDDS, V: Compaction and Drug Release Properties of Tablets Prepared by Adsorbing Lipid-Based Formulations onto Neusilin® US2

Purpose To develop tablet formulations by adsorbing liquid self-emulsifying drug delivery systems (SEDDS) onto Neusilin®US2, a porous silicate. Methods Nine SEDDS were prepared by combining a medium chain monoglyceride, Capmul MCM EP, a medium chain triglyceride, Captex 355 EP/NF, or their mixtures with a surfactant Cremophor EL, and a model drug, probucol, was then dissolved...

Intranasal Treatment of Central Nervous System Dysfunction in Humans

One of the most challenging problems facing modern medicine is how to deliver a given drug to a specific target at the exclusion of other regions. For example, a variety of compounds have beneficial effects within the central nervous system (CNS), but unwanted side effects in the periphery. For such compounds, traditional oral or intravenous drug delivery fails to provide benefit...

Development of Solid SEDDS, IV: Effect of Adsorbed Lipid and Surfactant on Tableting Properties and Surface Structures of Different Silicates

PurposeTo compare six commonly available silicates for their suitability to develop tablets by adsorbing components of liquid lipid-based drug delivery systems.MethodsThe tabletability of Aerosil® 200, Sipernat® 22, Sylysia® 350, Zeopharm® 600, Neusilin® US2 and Neusilin® UFL2 were studied by compressing each silicate into tablets in the presence of 20% microcrystalline cellulose...

Computational Prediction of Drug Solubility in Lipid Based Formulation Excipients

PurposeTo investigate if drug solubility in pharmaceutical excipients used in lipid based formulations (LBFs) can be predicted from physicochemical properties.MethodsSolubility was measured for 30 structurally diverse drug molecules in soybean oil (SBO, long-chain triglyceride; TGLC), Captex355 (medium-chain triglyceride; TGMC), polysorbate 80 (PS80; surfactant) and PEG400 co...

Rapid Assessment of Homogeneity and Stability of Amorphous Solid Dispersions by Atomic Force Microscopy—From Bench to Batch

Purpose To verify the robustness and fundamental value of Atomic Force Microscopy (AFM) and AFM-based assays to rapidly examine the molecular homogeneity and physical stability of amorphous solid dispersions on Hot-Melt-Extrudates. Methods Amorphous solid dispersions were prepared with a Hot-Melt Extruder (HME) and profiled by Raman Microscopy and AFM following a sequential...

Uncertainty Estimates of Purity Measurements Based on Current Information: Toward a “Live Validation” of Purity Methods

Purpose To predict precision and other performance characteristics of chromatographic purity methods, which represent the most widely used form of analysis in the biopharmaceutical industry. Methods We have conducted a comprehensive survey of purity methods, and show that all performance characteristics fall within narrow measurement ranges. This observation was used to develop a...

Simulating Intravitreal Injections in Anatomically Accurate Models for Rabbit, Monkey, and Human Eyes

Purpose To develop models for rabbit, monkey, and human that enable prediction of the clearance after intravitreal (IVT) injections in one species from experimental results obtained in another species. Methods Anatomically accurate geometric models were constructed for rabbit, monkey, and human that enabled computational fluid dynamic simulation of clearance of an IVT injected...

Sustained Local Delivery of Structurally Diverse HIV-1 Microbicides Released from Sublimation Enthalpy Controlled Matrices

Purpose Use of coital-dependent products to prevent HIV-1 transmission has resulted in mixed success. We hypothesize that incorporation of antiviral drug candidates into a novel controlled delivery system will prolong their activity, making their use coital independent, thus increasing their chance of prophylactic success. Methods Tenofovir, emtricitabine, and C5A peptide HIV...