Impact of process stress on protein stability in highly-loaded solid protein/PEG formulations from small-scale melt extrusion.

As protein-based therapeutics often exhibit a limited stability in liquid formulations, there is a growing interest in the development of solid protein formulations due to improved protein stability in the solid state. We used small-scale (<3 g) ram and twin-screw extrusion for the solid stabilization of proteins (Lysozyme, BSA, and human insulin) in PEG-matrices. Protein stability after extrusion was systematically investigated using ss-DSC, ss-FTIR, CD spectroscopy, SEM-EDX, SEC, RP-HPLC, and in case of Lysozyme an activity assay.

High-Throughput Screening for Colloidal Stability of Peptide Formulations Using Dynamic and Static Light Scattering.

Selection of an appropriate formulation to stabilize therapeutic proteins against aggregation is one of the most challenging tasks in early-stage drug product development. The amount of aggregates is more difficult to quantify in the case of peptides due to their small molecular size. Here, we investigated the suitability of diffusion self-interaction parameters () and osmotic second virial coefficients () for high-throughput (HT) screening of peptide formulations regarding their aggregation risk.

Site specific solubility improvement using solid dispersions of HPMC-AS/HPC SSL--mixtures.

Many upcoming drug candidates are pH-dependent poorly soluble weak bases in the pH range of the gastrointestinal tract. This often leads to a high in vivo variability and bioavailability issues. Aiming to overcome these limitations, the design of solid dispersions for site specific dissolution improvement or maintenance of a potent supersaturation over the entire gastro-intestinal pH-range, is proposed to assure a reliable drug therapy.

Predicting in vivo absorption behavior of oral modified release dosage forms containing pH-dependent poorly soluble drugs using a novel pH-adjusted biphasic in vitro dissolution test.

The focus of in vitro dissolution testing during early development of modified release (MR) formulations is to provide predictive estimates of drug release in respect to in vivo performance of a drug product. However, there are enormous challenges in MR drug development to establish proper dissolution conditions for a predictive test. To overcome limitations of dissolution testing at constant pH, a modified USP apparatus 2 was developed, combining biphasic dissolution with a pH-gradient in the aqueous dissolution medium.

Hydrophilic solutes in modified carbon dioxide extraction-prediction of the extractability using molecular dynamic simulation.

Super- and subcritical carbon dioxide (CO2) extractions of crude drugs were simulated by molecular modelling to predict the extractability of different hydrophilic plant constituents under various extraction conditions. The CO2 extraction fluids were simulated either with pure CO2 or with solvent modified CO2 at different pressures and temperatures. Molecular modelling resulted in three different solubility parameters: the total solubility parameter delta and the partial solubility parameters delta(d) for the van der Waals and delta(EL) for the polar forces.