Adsorption of carbamazepine onto crospovidone to prevent drug recrystallization

作者：Schulz Martin; Fussnegger Bernhard; Bodmeier Roland^*

来源：International Journal of Pharmaceutics, 2010, 391(1-2): 169-176.

DOI：10.1016/j.ijpharm.2010.03.015

• Crospovidone
• Drug adsorbates
• Recrystallization inhibition
• Poorly water-soluble drug
• Solvent deposition method

The adsorption mechanism of the poorly water-soluble drug carbamazepine onto crosslinked polyvinylpyrrolidone (crospovidone) was investigated by adsorption isotherms in different solvents and Fourier-transformation infrared spectroscopy (FTIR). The drug adsorption was a result of hydrogen bonds between carbamazepine's amine group and crospovidone's carbonyl group. Solvents with a hydrogen donor site competed with the drug for binding sites on crospovidone and thereby decreased the extent of drug adsorption. To optimize the drug-carrier ratio, adsorbates with different drug loadings were prepared by the solvent deposition method and analyzed for drug crystals using differential scanning calorimetry, X-ray diffraction, scanning electron microscopy and polarized light microscopy. Adsorbates with a drug loading of 9.1% or less did not show drug crystals. The drug release increased in the order of micronized drug < physical mixture < adsorbate. This was attributed to wetting and deagglomeration effects in both the physical mixture and the adsorbate and the molecularly dispersed state of the drug in the adsorbate. The findings allow for a more rationale design of immediate release formulations and of transdermal patches containing drug adsorbates onto crospovidone.

• 出版日期2010-5-31