Effect of Hydrophobically-Modified Hydroxypropyl Methylcellulose on the Crystallization from Supersaturated Solutions of Indomethacin

Abstract

Hydrophobically-modified hydroxypropyl methylcellulose (HM-HPMC), possessing long-chain alkyl groups, is a new thickening agent for gel preparations. The solubility of indomethacin (IM) in supersaturated solutions increased with HM-HPMC concentration, but HM-HPMC did not solubilize IM crystals. This is not due to the suppression of the transformation of IM crystals from α to γ. HM-HPMC would thus appear to suppress the crystallization of IM from supersaturated solutions. Nucleation and crystal growth rates in a supersaturated solution of IM in the absence and presence of HM-HPMC were determined by measuring light transmittance under cooling. It became clear that HM-HPMC caused a slight stimulation of nucleation and a strong suppression of crystal growth. This activity of HM-HPMC was derived from the original polymer, HPMC, but was greater than that of HPMC itself. The suppression of crystal growth by HM-HPMC may thus be due to the hydrophobic interaction between hydrophobic regions, particularly long-chain alkyl groups, and IM molecules.