engleski

By the principles of green chemistry to a drug with improved properties

Currently, pharmaceutical industry is facing many challenges. Hazardous solvents are widely used, especially in synthesis of active pharmaceutical ingredients (APIs) and formulation processes. Because of their health, environmental and economic consequences, there is a huge effort nowadays for reducing their use and a strong appeal for using safer solvents. Furthermore, pharmaceutical industry is dealing with the development and production of novel and more effective dosage forms for oral absorption of already existing drugs. Many drugs suffer from the low aqueous solubility leading to inadequate therapeutic effect of drug product. This paper will reveal our vision to use the principles of green chemistry and chemical engineering methodology (Fig. 1) to design a more effective drug product without the use of any solvent. The ideal API candidate for this, we believe, is drug X with low aqueous solubility and consequently poor gastrointestinal absorption and low bioavailability. It is a relatively new drug on the market indicated for the cancer treatment. For the purpose of drug solubility enhancement, solid dispersions of drug X in the hydrophilic polymer carrier poly(vinyl pyrrolidone) (PVP), are to be made by using the principles of mechanochemistry and properly characterized by the solid state analytics that could explain physically the enhanced dissolution properties (Fig. 1). Solid dispersions were prepared in different ratios using a high-energy laboratory ball mill with adjustable frequency of up to 30 Hz and characterized properly by differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD) and Fourier-transform infrared spectroscopy (FTIR). The change in phase composition, decreased relative degree of crystallinity and shifts of the absorption bands for the interacting functional groups, might indicate hydrogen interactions between drug X and polymer, thus revealing promising properties of the solid dispersions prepared without the use of solvents. The results presented confirm that this particular drug can be activated mechanochemically in terms of improving its dissolution properties.

drug X ; drug solubility improvement ; solid dispersion ; green chemistry ; mechanochemical activation

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