Anke Prudic

Project

Solubility and bioavailability of pharmaceutical agents

Info

Area: downstream processing
Project Start: 1.03.2011
Supervisor(s): Prof. Dr. Oliver Kayser, Prof. Dr. Gabriele Sadowski, Dr. Yuanhui Ji
University: Dortmund

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Anke successfully defended her thesis in October 2015 and received her doctorate degree from TU Dortmund University. She now works as senior process engineer for a multinational company in NRW.

About the Project

Abstract

The low aqueous solubility of most active pharmaceutical ingredients (API) presenting in a crystalline state often results in a limited bioavailability. A possible strategy is to integrate the amorphous API into a polymer matrix (solid dispersion). One of the key challenges is the prediction of the long-term stability of such formulations. Therefore this research focuses on the preparation and phase behaviour of the amorphous solid dispersion and solubility of pharmaceutical in aqueous solutions by both experimental measurement and model description and prediction.

Description

Active pharmaceutical ingredients (API) are often complex molecules and for purity reasons in the crystalline state, which may result in a poor solubility in water. Because of this, they dissolve slowly in the body, which leads to a low bioavailability [1]. In order to circumvent this problem and to promote their therapeutic effect, several approaches have been proposed to increase the bioavailability of such compounds. One possible solution is to integrate the pharmaceutical compound into an amorphous carrier matrix consisting of a hydrophilic polymer. In this matrix, the pharmaceutical is integrated in its amorphous state rather than in the crystalline state. The resulting formulation is called a solid dispersion.

Several formulations for improving the solubility and dissolution behavior of pharmaceutical compounds are presented in the literature. However, the available amorphous solid dispersion is mainly prepared by a trial and error procedure for each case. To design an appropriate formulation, a theoretical approach is required to predict the solubility of pharmaceutical in various polymers. Moreover, a possible problem of this formulation is that phase separation might occur during storage. This supports recrystallization of the drug leading again to lower solubilities [2]. To prevent the recrystallization process of the pharmaceutical compound, it is required to study the phase behaviour of the amorphous solid dispersion.

In this project binary solid dispersions consisting of a model pharmaceutical and various polymers are experimentally investigated towards their phase behavior. The PC-SAFT equation of state [3] is applied to model the measured data. This research reduces the experimental effort and contributes to a faster screening of possible solubility-increasing concepts.

References

[1] C. Leuner and J. Dressman: "Improving drug solubility for oral delivery using solid dispersions" European Journal of Pharmaceutics and Biopharmaceutics 50 (2000) 47-60

[2] G. Van den Mooter et. al.: "Physical stabilisation of amorphous ketoconazole in solid dispersions with polyvinylpyrrolidone K25" European Journal of Pharmaceutical Sciences 12 (2001) 261-269

[3] J. Gross and G. Sadowski: "Perturbed-chain SAFT: An equation of state based on a perturbation theory for chain molecules" Industrial & Engineering Chemistry Research, vol. 40, pp. 1244-1260, Feb 21 2001

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Anke´s latest poster, April 2011
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