25 research outputs found
Score-Informed Audio Decomposition and Applications
codedemo: http://www.audiolabs-erlangen.de/resources/2013-ACMMM-AudioDecomp/codedemo: http://www.audiolabs-erlangen.de/resources/2013-ACMMM-AudioDecomp/codedemo: http://www.audiolabs-erlangen.de/resources/2013-ACMMM-AudioDecomp/codedemo: http://www.audiolabs-erlangen.de/resources/2013-ACMMM-AudioDecomp
Data for: Exploring the chemical space for freeze-drying excipients
Table overview over calculated molecular descriptors for freeze-drying excipients.Also contains experimental results:Tg', solid state upon freeze-drying an
Data for: Exploring the chemical space for freeze-drying excipients
Table overview over calculated molecular descriptors for freeze-drying excipients.Also contains experimental results:Tg', solid state upon freeze-drying andTHIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV
GTZ sectoral project, promotion of anaerobic technology for the treatment of municipal and industrial sewage and wastes.
Amino acids as co-amorphous stabilizers for poorly water-soluble drugs - Part 2:Molecular interactions
Dissolution properties of co-amorphous drug-amino acid formulations in buffer and biorelevant media
Co-amorphous formulations, particularly binary drug-amino acid mixtures, have been shown to provide enhanced dissolution for poorly-soluble drugs and improved physical stability of the amorphous state. However, to date the dissolution properties (mainly intrinsic dissolution rate) of the co-amorphous formulations have been tested only in buffers and their supersaturation ability remain unexplored. Consequently, dissolution studies in simulated intestinal fluids need to be conducted in order to better evaluate the potential of these systems in increasing the oral bioavailability of biopharmaceutics classification system class II drugs. In this study, solubility and dissolution properties of the co-amorphous simvastatin-lysine, gibenclamide-serine, glibenclamide-threonine and glibenclamide-serine-threonine were studied in phosphate buffer pH 7.2 and biorelevant media (fasted and fed state simulated intestinal fluids (FaSSIF and FeSSIF, respectively)). The co-amorphous formulations were found to provide a long-lasting supersaturation and improve the dissolution of the drugs compared to the crystalline and amorphous drugs alone in buffer. Similar improvement, but in lesser extent, was observed in biorelevant media suggesting that a dissolution advantage observed in aqueous buffers may overestimate the advantage in vivo. However, the results show that, in addition to stability advantage shown earlier, co-amorphous drug-amino acid formulations provide dissolution advantage over crystalline drugs in both aqueous and biorelevant conditions
Refining solubility and dissolution rate of amorphous drug formulations
INTRODUCTION: Poor aqueous solubility of active pharmaceutical ingredients (APIs) is one of the main challenges in the development of new small molecular drugs. Additionally, the proportion of poorly soluble drugs among new chemical entities is increasing. The transfer of a crystalline drug to its amorphous counterpart is often seen as a potential solution to increase the solubility. However, amorphous systems are physically unstable. Therefore, pharmaceutical formulations scientists need to find ways to stabilise amorphous forms. AREAS COVERED: The use of polymer-based solid dispersions is the most established technique for the stabilisation of amorphous forms, and this review will initially focus on new developments in this field. Additionally, newly discovered formulation approaches will be investigated, including approaches based on the physical restriction of crystallisation and crystal growth and on the interaction of APIs with small molecular compounds rather than polymers. Finally, in situ formation of an amorphous form might be an option to avoid storage problems altogether. EXPERT OPINION: The diversity of poorly soluble APIs formulated in an amorphous drug delivery system will require different approaches for their stabilisation. Thus, increased focus on emerging techniques can be expected and a rational approach to decide the correct formulation is needed.peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope.
aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=iedd20status: publishe
Multivariate Analysis of Phenol in Freeze-Dried and Spray-Dried Insulin Formulations by NIR and FTIR
Dehydration is a commonly used method to stabilise protein formulations. Upon dehydration, there is a significant risk the composition of the formulation will change especially if the protein formulation contains volatile compounds. Phenol is often used as excipient in insulin formulations, stabilising the insulin hexamer by changing the secondary structure. We have previously shown that it is possible to maintain this structural change after drying. The aim of this study was to evaluate the residual phenol content in spray-dried and freeze-dried insulin formulations by Fourier transform infrared (FTIR) spectroscopy and near infrared (NIR) spectroscopy using multivariate data analysis. A principal component analysis (PCA) and partial least squares (PLS) projections were used to analyse spectral data. After drying, there was a difference between the two drying methods in the phenol/insulin ratio and the water content of the dried samples. The spray-dried samples contained more water and less phenol compared with the freeze-dried samples. For the FTIR spectra, the best model used one PLS component to describe the phenol/insulin ratio in the powders, and was based on the second derivative pre-treated spectra in the 850–650 cm−1 region. The best PLS model based on the NIR spectra utilised three PLS components to describe the phenol/insulin ratio and was based on the standard normal variate transformed spectra in the 6,200–5,800 cm−1 region. The root mean square error of cross validation was 0.69% and 0.60% (w/w) for the models based on the FTIR and NIR spectra, respectively. In general, both methods were suitable for phenol quantification in dried phenol/insulin samples
Large-Scale Biophysical Evaluation of Protein PEGylation Effects: In Vitro Properties of 61 Protein Entities
PEGylation is the
most widely used method to chemically modify
protein biopharmaceuticals, but surprisingly limited public data is
available on the biophysical effects of protein PEGylation. Here we
report the first large-scale study, with site-specific mono-PEGylation
of 15 different proteins and characterization of 61 entities in total
using a common set of analytical methods. Predictions of molecular
size were typically accurate in comparison with actual size determined
by size-exclusion chromatography (SEC) or dynamic light scattering
(DLS). In contrast, there was no universal trend regarding the effect
of PEGylation on the thermal stability of a protein based on data
generated by circular dichroism (CD), differential scanning calorimetry
(DSC), or differential scanning fluorimetry (DSF). In addition, DSF
was validated as a fast and inexpensive screening method for thermal
unfolding studies of PEGylated proteins. Multivariate data analysis
revealed clear trends in biophysical properties upon PEGylation for
a subset of proteins, although no universal trends were found. Taken
together, these findings are important in the consideration of biophysical
methods and evaluation of second-generation biopharmaceutical drug
candidates