Physical stability of ternary solid dispersions of itraconazole in polyethyleneglycol 6000/hydroxypropylmethylcellulose 2910 E5 blends

Int J Pharm. 2008 May 1;355(1-2):100-7. doi: 10.1016/j.ijpharm.2007.11.054. Epub 2007 Dec 4.

Abstract

In order to understand the influence of temperature and moisture, polymer blends of polyethyleneglycol 6000 (PEG 6000) and hydroxypropylmethylcellulose 2910 E5 (HPMC 2910 E5) and solid dispersions of itraconazole in these polymer blends were spray dried, further dried for 2 weeks and stored at three different conditions: 25 degrees C, 0% relative humidity (RH); 25 degrees C, 52% RH; 60 degrees C, 0% RH. MTDSC analysis of the polymer blends revealed that at 25 degrees C, 52% RH, PEG 6000 recrystallized to a high extent. At 60 degrees C, 0% RH the two polymers were miscible, probably due to the removal of bound water. In the ternary dispersions the polymers behaved similarly. The crystallinity degree of itraconazole in samples stored at 25 degrees C, 52% RH and at 60 degrees C, 0% RH was increased compared to the samples stored at 25 degrees C, 0% RH, probably due to the plasticizing effect of moisture at 25 degrees C, 52% RH and to an increased mobility at 60 degrees C, 0% RH. XPS analysis revealed a redistribution of itraconazole at the surface as itraconazole recrystallized from the blend. Dissolution tests revealed that a decrease in the itraconazole release was directly related to its crystallinity degree, no correlation was found with the crystallinity degree of PEG 6000.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / administration & dosage
  • Antifungal Agents / chemistry*
  • Calorimetry, Differential Scanning
  • Chemical Phenomena
  • Chemistry, Physical
  • Chromatography, High Pressure Liquid
  • Crystallization
  • Excipients
  • Hypromellose Derivatives
  • Itraconazole / administration & dosage
  • Itraconazole / chemistry*
  • Methylcellulose / analogs & derivatives
  • Polyethylene Glycols / chemistry
  • Polymers / chemistry
  • Solubility
  • Spectrometry, X-Ray Emission
  • Spectrophotometry, Ultraviolet
  • Temperature

Substances

  • Antifungal Agents
  • Excipients
  • Polymers
  • Itraconazole
  • Hypromellose Derivatives
  • Polyethylene Glycols
  • Methylcellulose