White Papers

Solubility²

 

Together with the Solubility Company Oy (Helsinki, Finland) we explored the potential of their revolutionary small-scale SPA™ technique for solubility measurements as input for the PC-SAFT parametrization of pharmaceuticals.

Download the white paper to see how good the combination is!

Formulation²

 

A negligibly small amout of material is sufficient for characterizing intermolecular interaction profiles of an API. The Solubility Company Oy (Helsinki, Finland) determined with their revolutionary small-scale SPA™ technique solubilities in organic solvents, serving as input for a PC-SAFT based predictive formulation screening at amofor.

Find out already at early stage what type of enabling formulation (e.g. lipid, ASD, co-amorphous) and even which excipient type is the best for your API, whithout the need of further experiments!

ASD shelf life​

The crystallization onset time in a metastable ASD is crucial for determining the shelf life of an ASD.

Many variable factors affect the true shelf life of an ASD, making a prediction for any storage humidity, temperature or API load almost rpedictable. Have a look at this white paper and learn more about our fast-track revolutionary approach to circumvent this issue!

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Peer-reviewed publications

Learn more about the potential of in-silico formulation approaches in formulation development in the recently published papers:

 

Predicting the solubility of amorphous and polymorphic forms

Based on few solubility measurements of the crystalline active in pure solvent(s), we are able to predict the solubility of different polymorphs and even of the amorphous form in solvents and solvent mixtures, as well as in water/solvent mixtures and also as function of pH. 

Publications:

K. Kiesow, F. Tumakaka, G. Sadowski, Experimental Investigation and Prediction of Oiling Out During Crystallization Processes, J. Cryst. Growth 310 (2008) 4163 – 4168

F. Ruether, G. Sadowski, Modeling the solubility of pharmaceuticals in pure solvents and solvent mixtures for drug process design. J. Pharmaceutical Sci98 (2009) 4205 – 4215

J. Cassens, F. Ruether, K. Leonhard, G. Sadowski, Solubility Calculation of Pharmaceutical Compounds using Quantum-Chemical Methods, Fluid Phase Equilibria 299 (2010) 161-170, DOI:10.1016/j.fluid.2010.09.025

J. Cassens, A. Prudic, F. Ruether, G. Sadowski, Solubility of pharmaceuticals and their salts as function of pH. Ind. Eng. Chem. Res. 52 (2013) 2721-2731, DOI: 10.1021/ie302064h

F. S. Laube, G. Sadowski, Predicting the extraction behavior of pharmaceuticals, Ind. Eng. Chem. Res. 53 (2014) 865 – 870, DOI: 10.1021/ie403284y

F. S. Laube, T. Klein, G. Sadowski, Partition coefficients of pharmaceuticals as functions of temperature and pH. Ind. Eng. Chem. Res. 54 (2015) 3968-3975, DOI: 10.1021/acs.iecr.5b00068

R. Paus; E. Hart; Y. Ji, G. Sadowski, Solubility and Caloric Properties of Cinnarizine, J. Chem. Eng. Data 60 (2015) 2256-2261, DOI: 10.1021/acs.jced.5b00075

R. Paus, Y. Ji, L. Vahle, G. Sadowski, Predicting the solubility advantage of amorphous pharmaceuticals – a novel thermodynamic approach, Molecular Pharmaceutics 12 (2015) 2823-2833, DOI: 10.1021/mp500824d

Providing the result of long-term stability tests within a few weeks or even days

Having already investigated more than 1.000 different amorphous solid dispersions we could proof that we are able to correctly predict the long-term stability at any temperature and humidity.  

Publications:

Prudic, Y. Ji, G. Sadowski, Phase behavior of API/polymer solid dispersions. Molecular Pharmaceutics 11 (2014) 2294-2304, DOI: 10.1021/mp400729x

Prudic, T. Kleetz, M. Korf, Y. Ji, G. Sadowski, Thermodynamic phase behavior of API/copolymer solid dispersions, Molecular Pharmaceutics 11 (2014) 4189-98, DOI:10.1021/mp500412d 

A. Prudic, A.-K. Lesniak, Y. Ji, G. Sadowski, Thermodynamic phase behavior of indomethacin/ PLGA formulations, European Journal of Pharmaceutics and Biopharmaceutics 93 (2015) 88-94, DOI: 10.1016/j.ejpb.2015.01.029

A. Prudic, Y. Ji, C. Luebbert, G. Sadowski, Influence of humidity on the phase behavior of API/polymer formulations, European Journal of Pharmaceutics and Biopharmaceutics 94 (2015) 352-362, DOI: 10.1016/j.ejpb.2015.06.009 

K. Lehmkemper, S. Kyeremateng, O. Heinzerling, M. Degenhardt, G. Sadowski, Long-term physical stability of PVP- and PVPVA-amorphous solid dispersions, Molecular Pharmaceutics 14 (2017) 157-171, DOI: 10.1021/acs.molpharmaceut.6b00763

C. Luebbert, F. Huxoll, G. Sadowski, Amorphous-amorphous phase separation in API/polymer formulations, Molecules 22 (2017) 296, DOI: 10.3390/molecules22020296

C. Luebbert, G.Sadowski, Moisture-induced phase separation and recrystallization in amorphous solid dispersions, International Journal of Pharmaceutics 532 (2017) 635-646, DOI: 10.1016/j.ijpharm.2017.08.121

K. Lehmkemper, S. Kyeremateng, O. Heinzerling, M. Degenhardt, G. Sadowski, Impact of polymer type and relative humidity on the long-term physical stability of amorphous solid dispersions, Molecular Pharmaceutics 14 (2017) 4374-4386, DOI: 10.1021/acs.molpharmaceut.7b00492

K. Lehmkemper, S. O. Kyeremateng, M. Degenhardt, G. Sadowski, Influence of Low-Molecular-Weight Excipients on the Phase Behavior of PVPVA64 Amorphous Solid Dispersions, Pharmaceutical Research 35 (2018) 25, DOI: 10.1007/s11095-017-2316-y

C. Luebbert, C. Klanke, G. Sadowski, Investigating phase separation in amorphous solid dispersions via Raman mapping, International Journal of Pharmaceutics 535 (2018) 245-252, DOI: 10.1016/j.ijpharm.2017.11.014

C.Luebbert, M. Wessner, G. Sadowski, Mutual impact of phase separation/crystallization and water sorption in amorphous solid dispersions, Molecular Pharmaceutics 15 (2018) 669-678, DOI: 10.1021/acs.molpharmaceut.7b01076

K. Lehmkemper, S. O. Kyeremateng, M. Bartels, M. Degenhardt, G. Sadowski, Physical Stability of API/Polymer-Blend Amorphous Solid Dispersions, European Journal of Pharmaceutics and Biopharmaceutics 124 (2018) 147-157, DOI: 10.1016/j.ejpb.2017.12.002

C. Luebbert, G. Sadowski, In-situ determination of crystallization kinetics in ASDs via water sorption experiments, European Journal of Pharmaceutics and Biopharmaceutics 127 (2018) 183-193, DOI: 10.1016/j.ejpb.2018.02.028

C. Luebbert, D. Real, G. Sadowski, Choosing appropriate solvents for ASD preparation, Molecular Pharmaceutics 11 (2018) 5397-5409, DOI: 10.1021/acs.molpharmaceut.8b00892

Analyzing the dissolution behavior of your active ingredient

Via thermodynamic modeling of a few dissolution experiments we analyse the dissolution behavior of active ingredients and formulations and propose possibilities to influence the dissolution kinetics. 

Publications:

Y. Ji, R. Paus, A. Prudic, C. Luebbert, G. Sadowski, A novel approach for analyzing the dissolution mechanism of solid dispersions, Pharmaceutical Research 32 (2015) 2559-2578, DOI: 10.1007/s11095-015-1644-z

R. Paus, Y. Ji, G. Sadowski, Dissolution of crystalline pharmaceuticals – experimental investigation and thermodynamic modeling, Ind. Eng. Chem. Res. 54 (2015) 731-742, DOI: 10.1021/ie503939w

Y. Ji, A.K. Lesniak, A. Prudic, R. Paus, G. Sadowski, Drug release kinetics and mechanism from PLGA formulations, AIChE J. 62 (2016) 4055-4065, DOI: 10.1002/aic.15282

Y. Ji, M. Lemberg, A. Prudic, R. Paus, G. Sadowski, Modeling and Analysis of Dissolution of paracetamol/Eudragit® formulations, Chem. Eng. Res. Des. 121 (2017) 22-31, DOI: 10.1016/j.cherd.2017.03.007

Choosing the right process conditions for ASD preparation

Whenever a solvent is used for ASD preparation, the quality of the resuling ASD might be significantly influenced by the choice of the solvent. Process conditions havely determine the formation of solvates, hydrates or polymorphs. We find feasible production process windows for crystallization, spray drying, hot-melt extrusion and drying processes. 

Publications:

C. Luebbert, D. Real, G. Sadowski, Choosing Appropriate Solvents for ASD Preparation, Molecular Pharmaceutics 15(11) (2018) 5397-5408, DOI: 10.1021/acs.molpharmaceut.8b00892

Generating and stabilizing the targeted solid form of your active ingredient  

We are able to predict the solubility of cocrystals in different solvents and solvent mixtures providing the best conditions for cocrystal preparation. We predict conditions at which hydrates or solvates of your active ingredient are ultimately formed or can be avoided.

Publications:

L. Lange, G. Sadowski, Thermodynamic modeling for efficient cocrystal formation, Crystal Growth & Design 15 (2015) 4406-4416, DOI: 10.1021/acs.cgd.5b00735

L. Lange, G. Sadowski, Polymorphs, hydrates, cocrystals and cocrystal hydrates: thermodynamic modeling of theophylline systems, Crystal Growth & Design 16 (2016) 4439-4449, DOI: 10.1021/acs.cgd.6b00554

L. Lange, K. Lehmkemper, G. Sadowski Predicting the aqueous solubility of pharmaceutical cocrystals as function of pH and temperature, Crystal Growth & Design 16 (2016) 2726-2740, DOI: 10.1021/acs.cgd.6b00024

L. Lange, S. Heisel, G. Sadowski,Predicting the solubility of pharmaceutical cocrystals in solvent/anti-solvent mixtures, Molecules 21 (2016) 593, DOI: 10.3390/molecules21050593

L. Lange, M. Schleinitz. G. Sadowski, Predicting the Effect of pH on Stability and Solubility of Polymorphs, Hydrates, and Cocrystals, Crystal Growth & Design 16 (2016) 4236-4147, DOI: 10.1021/acs.cgd.6b00664

H. Veith, M. Schleinitz, C. Schauerte, G. Sadowski, Thermodynamic approach for co-crystal screening, Crystal Growth and Design 19, 6 (2019), 3253-3264, DOI: 10.1021/acs.cgd.9b00103