Characterization of a Novel Particle in a Pharmaceutical Drug Product.

A previously unreported particle type was observed during routine visual vial inspection of a liquid drug product and suspected to be the result of vial delamination. Delamination is the corrosive attack on the interior surface of a glass container resulting in the release of thin flake-like glass particles, lamellae, into solution. It is a major concern for pharmaceutical companies, especially for parenteral solutions, and drug programs with a high risk for delamination are typically monitored for lamellae formation through long-term stability studies.

Observation and Mitigation of Lamellar Silica Particles Formed in Pharmaceutical Products Packaged in Glass Vials.

A new type of lamellae-like particles was observed in protein based liquid therapeutic protein drug product (DP) packaged in standard (STD) and delamination controlled (DC) Type IB glass vials stored at 2-8°C as early as two weeks after manufacture. These particles were determined to be remarkably different from lamellae in not only in their chemical composition, but in the mechanism by which these are formed. The lamellae-like particles were an ultra-thin (< 200 nm) film, appeared curled, sheet-like, folded with no defined edges identified as lamellar silica composed of silica and polysorbate 80 (PS 80).

Impact of Uncontrolled vs Controlled Rate Freeze-Thaw Technologies on Process Performance and Product Quality.

Most biomolecules, owing to their marginal stability in liquid state, susceptibility to microbial growth, and tendency to foam upon storage/shipment in the liquid state, often require an alternate method of long-term storage. Cryopreservation is preferred, as it addresses most of these issues associated with liquid storage. However, the stability of the protein in the frozen state depends on the methodology of freezing/thawing and physico-chemical characteristics of the protein.

Influence of chain length on the diffusion and electrophoresis of DNA adsorbed on heterogeneous supported lipid bilayers.

This manuscript describes the influence of chain length on the diffusion and electrophoresis of single stranded DNA (ssDNA) adsorbed on heterogeneous cationic supported lipid bilayers. These studies are motivated by the increasing interest in developing novel strategies for the separation of DNA. We studied ssDNA molecules with the number of bases (N) varying from 21 to 84.

Controlling DNA adsorption and diffusion on lipid bilayers by the formation of lipid domains.

We describe the influence of membrane heterogeneity on the adsorption and diffusion of DNA. Cellular membranes are believed to contain domains (lipid rafts) that influence processes ranging from signal transduction to the diffusion of membrane components. By analogy, we demonstrate that the formation of raft-like domains in supported lipid bilayers provides control over the adsorption and diffusion of DNA.

Enhancing protein stability by adsorption onto raftlike lipid domains.

We demonstrate that the stability of adsorbed proteins can be enhanced by controlling the heterogeneity of the surfaceby creating raftlike domains in a soft liposomal membrane. Recent work has shown that enzymes adsorbed onto highly curved nanoscale supports can be more stable than those adsorbed on flat surfaces with nominally the same chemical structure. This effect has been attributed to a decrease in lateral interenzyme interactions on a curved surface.

Lipid mobility controls the diffusion of small biopolymer adsorbates.

Recent studies on the diffusion of adsorbed polymers such as DNA on supported lipid bilayers have suggested that such strongly adsorbed polymers can be treated similarly to a polymer "in" a 2D fluid, but this conjecture has not been experimentally verified. To test this hypothesis and also to gain a better understanding of polymer dynamics in two dimensions, we designed an experimental protocol-the lateral transport of a short, single-stranded DNA oligonucleotide adsorbed on a supported cationic lipid bilayer. Fluorescence recovery after photobleaching (FRAP) analysis reveals that the diffusivity of the adsorbed DNA quantitatively tracks that of the underlying lipid, even though the bilayer mobility changes by 2 orders of magnitude with changes in temperature.

Statistical pattern matching facilitates the design of polyvalent inhibitors of anthrax and cholera toxins.

Numerous biological processes involve the recognition of a specific pattern of binding sites on a target protein or surface. Although ligands displayed by disordered scaffolds form stochastic rather than specific patterns, theoretical models predict that recognition will occur between patterns that are characterized by similar or "matched" statistics. Endowing synthetic biomimetic structures with statistical pattern matching capabilities may improve the specificity of sensors and resolution of separation processes.

Microfluidic separation of DNA.

DNA separation is important for numerous applications in biotechnology and medicine. Efforts to improve DNA separation in microdevices have led to advances in capillary electrophoresis and the development of novel separation strategies. Current research on microcapillary electrophoresis materials is focused on the development of separation matrices with low injection viscosities and wall-coating capabilities.