Pharmaceutical Research

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

List of Papers (Total 349)

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

Purpose To investigate if drug solubility in pharmaceutical excipients used in lipid based formulations (LBFs) can be predicted from physicochemical properties. Methods Solubility 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...

Hepatocyte Nuclear Factor 4 Alpha and Farnesoid X Receptor Co-regulates Gene Transcription in Mouse Livers on a Genome-Wide Scale

PurposeFarnesoid X receptor (Fxr) is a ligand-activated nuclear receptor critical for liver function. Reports indicate that the functions of Fxr in the liver may overlap with those of hepatocyte nuclear factor 4α (Hnf4α), but studies of their precise genome-wide interaction to regulate gene transcription in the liver are lacking. Thus, we compared the genome-wide binding of Fxr...

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...

Nanoparticles for Improved Local Retention after Intra-Articular Injection into the Knee Joint

PurposeTo evaluate using cationic polymeric nanoparticles that interact with hyaluronate to form ionically cross-linked hydrogels to increase the intra-articular retention time of osteoarthritis drugs in the synovial cavity.Methods In vitro tests included nanoparticle release from cross-linked hydrogels using syringe and membrane dissolution tests, viscosity measurement of...

Targeting of Liposomes via PSGL1 for Enhanced Tumor Accumulation

Purpose To improve the delivery of liposomes to tumors using P-selectin glycoprotein ligand 1 (PSGL1) mediated binding to selectin molecules, which are upregulated on tumorassociated endothelium. Methods PSGL1 was orientated and presented on the surface of liposomes to achieve optimal selectin binding using a novel streptavidin-protein G linker molecule. Loading of PSGL1...

Magnetic Resonance Microscopy for Assessment of Morphological Changes in Hydrating Hydroxypropylmethyl Cellulose Matrix Tablets In Situ

Purpose To resolve contradictions found in morphology of hydrating hydroxypropylmethyl cellulose (HPMC) matrix as studied using Magnetic Resonance Imaging (MRI) techniques. Until now, two approaches were used in the literature: either two or three regions that differ in physicochemical properties were identified. Methods Multiparametric, spatially and temporally resolved T2 MR...

Design of the Novel Protraction Mechanism of Insulin Degludec, an Ultra-long-Acting Basal Insulin

Purpose Basal insulins with improved kinetic properties can potentially be produced using acylation by fatty acids that enable soluble, high-molecular weight complexes to form post-injection. A series of insulins, acylated at B29 with fatty acids via glutamic acid spacers, were examined to deduce the structural requirements. Methods Self-association, molecular masses and...