Recombinant Spider Silk Hydrogels for Sustained Release of Biologicals.

Therapeutic biologics (i.e., proteins) have been widely recognized for the treatment, prevention, and cure of a variety of human diseases and syndromes.

An in vitro digestion test that reflects rat intestinal conditions to probe the importance of formulation digestion vs first pass metabolism in Danazol bioavailability from lipid based formulations.

The impact of gastrointestinal (GI) processing and first pass metabolism on danazol oral bioavailability (BA) was evaluated after administration of self-emulsifying drug delivery systems (SEDDS) in the rat. Danazol absolute BA was determined following oral and intraduodenal (ID) administration of LFCS class IIIA medium chain (MC) formulations at high (SEDDSH-III) and low (SEDDSL-III) drug loading and a lipid free LFCS class IV formulation (SEDDS-IV). Experiments were conducted in the presence and absence of ABT (1-aminobenzotriazole) to evaluate the effect of first pass metabolism.

Non-linear increases in danazol exposure with dose in older vs. younger beagle dogs: the potential role of differences in bile salt concentration, thermodynamic activity, and formulation digestion.

Purpose: To explore the possibility that age-related changes in physiology may result in differences in drug bioavailability after oral administration of lipid based formulations of danazol.

Methods: Danazol absorption from lipid formulations with increasing drug load was examined in younger (9 months) and older (8 years) beagles. Age related changes to hepatic function were assessed via changes to systemic clearance and serum bile acid concentrations.

Lipid-based formulations and drug supersaturation: harnessing the unique benefits of the lipid digestion/absorption pathway.

Drugs with low aqueous solubility commonly show low and erratic absorption after oral administration. Myriad approaches have therefore been developed to promote drug solubilization in the gastrointestinal (GI) fluids. Here, we offer insight into the unique manner by which lipid-based formulations (LBFs) may enhance the absorption of poorly water-soluble drugs via co-stimulation of solubilization and supersaturation.

Toward the establishment of standardized in vitro tests for lipid-based formulations. 2. The effect of bile salt concentration and drug loading on the performance of type I, II, IIIA, IIIB, and IV formulations during in vitro digestion.

The LFCS Consortium was established to develop standardized in vitro tests for lipid-based formulations (LBFs) and to examine the utility of these tests to probe the fundamental mechanisms that underlie LBF performance. In this publication, the impact of bile salt (sodium taurodeoxycholate, NaTDC) concentration and drug loading on the ability of a range of representative LBFs to generate and sustain drug solubilization and supersaturation during in vitro digestion testing has been explored and a common driver of the potential for drug precipitation identified. Danazol was used as a model poorly water-soluble drug throughout.

Incomplete desorption of liquid excipients reduces the in vitro and in vivo performance of self-emulsifying drug delivery systems solidified by adsorption onto an inorganic mesoporous carrier.

The purpose of the current study was to provide a mechanistic basis for in vitro and in vivo performance differences between lipid-based formulations solidified by adsorption onto a high surface area material and their respective liquid (i.e., nonadsorbed) counterparts.

Lipid digestion as a trigger for supersaturation: evaluation of the impact of supersaturation stabilization on the in vitro and in vivo performance of self-emulsifying drug delivery systems.

The generation of supersaturation in the gastrointestinal (GI) tract is an increasingly popular means of promoting oral absorption for poorly water-soluble drugs. The current study examined the impact of changes to the quantities of medium-chain (MC) lipid (Captex 300:Capmul MCM), surfactant (Cremophor EL) and cosolvent (EtOH), and the addition of polymeric precipitation inhibitors (PPI), on supersaturation during the dispersion and digestion of MC self-emulsifying drug delivery systems (SEDDS) containing danazol. The data suggest that digestion acts as a "trigger" for enhanced supersaturation and that solubilization/precipitation behavior is correlated with the degree of supersaturation on dispersion (S(M)DISP) or digestion (S(M)DIGEST).

Real time evolution of liquid crystalline nanostructure during the digestion of formulation lipids using synchrotron small-angle X-ray scattering.

The role of the digestion of lipids in facilitating absorption of poorly water-soluble compounds, such as vitamins, is not only an important nutritional issue but is increasingly being recognized as an important determinant in the effectiveness of lipid-based drug formulations. It has been known for some time that lipids often form complex liquid crystalline structures during digestion and that this may impact drug solubilization and absorption. However, until recently we have been unable to detect and characterize those structures in real time and have been limited in establishing the interplay between composition, digestion, and nanostructure.