Development of Dexlansoprazole Delayed-Release Capsules, a Dual Delayed-Release Proton Pump Inhibitor.

Proton pump inhibitors (PPIs) are widely used for treating acid-related disorders. For an "ideal PPI," achieving maximal absorption and sustaining pharmacodynamic effects through the 24-h dosing cycle are critical features. Dexlansoprazole offers a relevant case study on how an improved PPI was developed capitalizing on the rational optimization of a precursor molecule-in this case, using lansoprazole as a starting point, leveraging its chemical properties on pharmacokinetics, and exploring optimized formulations.

Dissolution Testing in Drug Product Development: Workshop Summary Report.

This publication summarizes the proceedings and key outcomes of the first day ("Day 1") of the 3-day workshop on "Dissolution and Translational Modeling Strategies Enabling Patient-Centric Product Development." The overall aims of the workshop were to foster a productive dialog between industry and regulatory agencies and to discuss current strategies toward the development and implementation of clinically relevant dissolution specifications as an integral part of enhanced drug product understanding and effective drug product life-cycle management. The Day 1 podium presentations covered existing challenges and concerns for implementing highly valuable, yet often unique and novel experimental dissolution setups as quality control tools.

Industry's View on Using Quality Control, Biorelevant, and Clinically Relevant Dissolution Tests for Pharmaceutical Development, Registration, and Commercialization.

This article intends to summarize the current views of the IQ Consortium Dissolution Working Group, which comprises various industry companies, on the roles of dissolution testing throughout pharmaceutical product development, registration, commercialization, and beyond. Over the past 3 decades, dissolution testing has evolved from a routine and straightforward test as a component of end-product release into a comprehensive set of tools that the developer can deploy at various stages of the product life cycle. The definitions of commonly used dissolution approaches, how they relate to one another and how they may be applied in modern drug development, and life cycle management is described in this article.

Approaches for Establishing Clinically Relevant Dissolution Specifications for Immediate Release Solid Oral Dosage Forms.

This manuscript represents the perspective of the Dissolution Analytical Working Group of the IQ Consortium. The intent of this manuscript is to highlight the challenges of, and to provide a recommendation on, the development of clinically relevant dissolution specifications (CRS) for immediate release (IR) solid oral dosage forms. A roadmap toward the development of CRS for IR products containing active ingredients with a non-narrow therapeutic window is discussed, within the context of mechanistic dissolution understanding, supported by in-human pharmacokinetic (PK) data.

Chlorhexidine hexametaphosphate as a wound care material coating: antimicrobial efficacy, toxicity and effect on healing.

Aim: In this study, chlorhexidine hexametaphosphate (CHX-HMP) is investigated as a persistent antimicrobial coating for wound care materials.

Materials & Methods: CHX-HMP was used as a wound care material coating and compared with chlorhexidine digluconate materials with respect to antimicrobial efficacy, toxicity and wound closure.

Results: Antimicrobial efficacy at day 1, 3 and 7 was observed with experimental and commercial materials.

Functionalization of ethylene vinyl acetate with antimicrobial chlorhexidine hexametaphosphate nanoparticles.

Ethylene vinyl acetate (EVA) is in widespread use as a polymeric biomaterial with diverse applications such as intravitreal devices, catheters, artificial organs, and mouthguards. Many biomaterials are inherently prone to bacterial colonization, as the human body is host to a vast array of microbes. This can lead to infection at the biomaterial's site of implantation or application.

Registration rates, adequacy of registration, and a comparison of registered and published primary outcomes in randomized controlled trials published in surgery journals.

Objective: To determine the proportion of registered trials published in the surgical literature, to compare, in registered trials, the primary outcomes registered with those published and to determine whether outcome-reporting bias favored significant primary outcomes.

Background: Trial protocol registration before patient enrolment for randomized controlled trials (RCTs) is a perquisite for many journals in attempt to decrease publication and selective reporting bias. Analysis of the medical literature demonstrates poor registration rates with discrepancies between reported and registered primary outcomes.

Attenuation of G2 checkpoint function precedes human cell immortalization.

We have investigated the hypothesis that attenuation of the G2 checkpoint, which delays entry into mitosis in response to damage to DNA and protects against clastogenesis, may contribute to the genetic instability of immortal human cell lines. IMR-90 normal human fibroblasts displayed stringent G2 checkpoint response to gamma-radiation-induced DNA damage. Irradiation with 1.

Enhanced replicative bypass of platinum-DNA adducts in cisplatin-resistant human ovarian carcinoma cell lines.

We have examined the relationship between cis-diamminedichloroplatinum(II) (cisplatin) resistance and replicative bypass in the human ovarian carcinoma cell lines 2008, A2780, and their respective cisplatin-resistant derivatives C13* and A2780/DDP. Replicative bypass is defined as the ability of a replication complex to proceed past a DNA adduct known to block or stall the complex during synthesis. Previous studies in our laboratory have shown a 3-4-fold increase in the replicative bypass of platinum-DNA adducts in platinum-resistant murine leukemia cell lines [G.

Renal blood flow varies during normal activity in conscious unrestrained rats.

The extent to which renal blood flow (RBF) varied during normal daily activity and its dependence on renal nerve activity were studied in unrestrained rats. RBF (measured with a pulsed Doppler flow probe) and behavior pattern (observed with a video camera) were recorded during both phases of the light-dark cycle (n = 11). RBF was highest (100%) when the rat was fully relaxed and apparently asleep (9% time) but was significantly lower (P less than 0.

Comprehensive community-based mental health outreach services for suburban seniors.

An outreach program to deliver mental health services to mentally ill older adults has been developed in Baltimore County, Maryland. Incorporating prevention and early intervention strategies, this program targets persons aged 60 and over with late-onset or previously undiagnosed psychiatric histories. Services are provided through a novel one-third/one-third/one-third delivery schedule in senior centers, in community mental health centers, and in seniors' homes.

Effect of albumin on serum digoxin radioimmunoassays.

The use of certain commerically available radioimmunoassay kits for measurement of digoxin results in errors in the determined digoxin concentration of patients when these kits are used according to manufacturers' directions. One factor that is, in part, responsible for these errors is a difference between standards and samples with respect to albumin concentration. Three of the four kits investigated showed a significant inverse relationship between the albumin concentration in the sample and the binding of radiolabeled digoxin by its antibody when the albumin concentration was varied over an extended range.

Microbodies in experimentally altered cells.

A rapid and sustained increase in the number of microbodies in liver and kidney cells can be induced in male rats by ethyl chlorophenoxyisobutyrate (CPIB), a hypolipidemic drug. This phenomenon permits investigation of several aspects of microbody behavior in experimental conditions. Reversal experiments demonstrate that liver cells revert to normal between 2 and 3 weeks after withdrawal of CPIB and that one of the mechanisms for removal of excess microbodies is their incorporation into structures indistinguishable from lysosomes.