Biomedical subjects

Robert A Lionberger

Publications and source records attributed to Robert A Lionberger.

3 recordsLinked to original sources

PubMed2004

Applications of process analytical technology to crystallization processes.

Crystallizations of pharmaceutical active ingredients, particularly those that posses multiple polymorphic forms, are among the most critical and least understood pharmaceutical manufacturing processes. Many process and product failures can be traced to a poor understanding and control of crystallization processes. The Food and Drug Administration's process analytical technology (PAT) initiative is a collaborative effort with industry to introduce new and efficient manufacturing technologies into the pharmaceutical industry. PAT's are systems for design, analysis, and control of manufacturing processes. They aim to assure high quality through timely measurements of critical quality and performance attributes of raw materials, in-process materials, and final products. Implementation of PAT involves scientifically based process design and optimization, appropriate sensor technologies, statistical and information tools (chemometrics), and feedback process control strategies working together to produce quality products. This review introduces the concept of PAT and discusses its application to crystallization processes through review of several case studies. A variety of in situ analytical methods combined with chemometric tools for analysis of multivariate process information provide a basis for future improvements in modeling, simulation, and control of crystallization processes.

Amino Acids↗

PubMed2002

Viscosity of bimodal and polydisperse colloidal suspensions.

We present a theoretical framework for the viscosity of bimodal and polydisperse colloidal suspensions. For colloidal dispersions both interparticle forces between pairs of particles and many-particle effects such as depletion forces can have a significant effect on rheology. As hydrodynamic interactions are also important for colloidal systems, a theoretical description that includes hydrodynamic and thermodynamic interactions is required. An integral equation theory for multicomponent systems accounts for the contribution of thermodynamic interactions to the viscosity of dispersions. Introduction of small particles into a system of larger particles causes depletion forces between the large particles that increase the viscosity, while replacing large particles with an equal volume fraction of small particles increases the free volume in the system and decreases the viscosity. The integral equations model both of these effects in concentrated suspensions and provide a microscopic interpretation of free volume changes as changes in radial distribution functions. For a bimodal mixture they predict a dependence of the viscosity on size ratio, composition, and total volume fraction. Polydispersity is modeled by a small number of components whose sizes and weights are chosen to match the moments of the size distribution. This theory predicts a reduction in viscosity due to polydispersity and explains conflicting experimental measurement of the viscosity of hard-sphere colloids. Existing theoretical approaches that neglect the multiparticle correlations, included through the integral equations, yield qualitatively incorrect results for the change in the viscosity relative to monodisperse systems.

Journal Article↗

PubMedDate not supplied

Impact of P-glycoprotein-mediated intestinal efflux kinetics on oral bioavailability of P-glycoprotein substrates.

Studies of many P-glycoprotein (Pgp) substrates have demonstrated a significant effect of Pgp-mediated efflux on intestinal drug transport. However, most of these studies were designed to detect whether a particular drug is a Pgp substrate and thus were conducted at very low concentrations. We performed two simulations to evaluate the effect of Pgp-mediated efflux on oral drug absorption at various concentrations. In the first simulation, a steady-state model allowed us to predict whether the contribution of Pgp to oral drug absorption would be significant at clinically relevant concentrations. Our second simulation investigated the role of Pgp-mediated efflux in oral absorption with a dynamic compartmental absorption and transit model linked to a pharmacokinetic model. For high-solubility drugs, Pgp-mediated efflux altered the bioavailability only at drug concentrations corresponding to doses much lower than the usual clinical dose. The ratio of transporter-mediated transport to passive transport determined whether intestinal Pgp transporters would reduce the bioavailability of high-solubility drugs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗