Bioequivalence of Two Tiotropium Dry Powder Inhalers and the Utility of Realistic Impactor Testing.

Inhaled antimuscarinics are a cornerstone of the management of chronic obstructive pulmonary disease. This article details a series of five pharmacokinetic (PK) studies comparing a generic tiotropium dry powder inhaler (DPI) to Spiriva HandiHaler, the realistic methods used to support those studies, and the related - correlations (IVIVCs). All five PK studies were of open-label, single-dose, crossover design with test and reference treatments administered to healthy subjects.

Population Pharmacokinetics of Ibrutinib in Healthy Adults.

Background And Objectives: Ibrutinib is an antineoplastic agent that reduces B-cell proliferation by inhibiting Bruton's tyrosine kinase. We describes population pharmacokinetics of ibrutinib in healthy adults, and explores potential patient characteristics associated with ibrutinib pharmacokinetics.

Methods: A population pharmacokinetic modeling approach was applied to 39 healthy subjects.

The Influence of Oily Vehicle Composition and Vehicle-Membrane Interactions on the Diffusion of Model Permeants across Barrier Membranes.

In many instances, one or more components of a pharmaceutical or cosmetic formulation is an oil. The aims of this study were two-fold. First, to examine the potential of preferential uptake of one oily vehicle component over another into a model barrier membrane (silicone) from blended vehicles (comprising two from the common excipients isohexadecane (IHD), hexadecane (HD), isopropyl myristate (IPM), oleic acid (OA) and liquid paraffin).

Multivariate Analytical Approaches to Identify Key Molecular Properties of Vehicles, Permeants and Membranes That Affect Permeation through Membranes.

There has been considerable recent interest in employing computer models to investigate the relationship between the structure of a molecule and its dermal penetration. Molecular permeation across the epidermis has previously been demonstrated to be determined by a number of physicochemical properties, for example, the lipophilicity, molecular weight and hydrogen bonding ability of the permeant. However little attention has been paid to modeling the combined effects of permeant properties in tandem with the properties of vehicles used to deliver those permeants or to whether data obtained using synthetic membranes can be correlated with those obtained using human epidermis.

Establishing the importance of oil-membrane interactions on the transmembrane diffusion of physicochemically diverse compounds.

The diffusion process through a non-porous barrier membrane depends on the properties of the drug, vehicle and membrane. The aim of the current study was to investigate whether a series of oily vehicles might have the potential to interact to varying degrees with synthetic membranes and to determine whether any such interaction might affect the permeation of co-formulated permeants: methylparaben (MP); butylparaben (BP) or caffeine (CF). The oils (isopropyl myristate (IPM), isohexadecane (IHD), hexadecane (HD), oleic acid (OA) and liquid paraffin (LP)) and membranes (silicone, high density polyethylene and polyurethane) employed in the study were selected such that they displayed a range of different structural, and physicochemical properties.

Saliva versus Plasma Relative Bioavailability of Tolterodine in Humans: Validation of Class III Drugs of the Salivary Excretion Classification System.

Relative bioavailability study of tolterodine in healthy human volunteers was done using saliva and plasma matrices in order to investigate the robustness of using saliva instead of plasma as a surrogate for bioavailability and bioequivalence of class III drugs according to the salivary excretion classification system (SECS). Saliva and plasma samples were collected up to 16 h after 2 mg oral dose. Saliva and plasma pharmacokinetic parameters were calculated by non compartmental analysis using Kinetica program V5.