Role of excipients in hydrate formation kinetics of theophylline in wet masses studied by near-infrared spectroscopy

Eur J Pharm Sci. 2004 Sep;23(1):99-104. doi: 10.1016/j.ejps.2004.06.001.

Abstract

Hydrate formation is a phase transition, which can occur during wet granulation. This kind of processing-induced transformation (PIT) can influence the quality of a finished product. The aim of the study was to investigate the effect of excipients on the kinetics of hydrate formation in wet masses. Anhydrous theophylline was chosen as the hydrate-forming model drug compound and two excipients, silicified microcrystalline cellulose (SMCC) and alpha-lactose monohydrate, with different water absorbing properties, were used in formulation. An early stage of wet massing was studied with anhydrous theophylline and its 1:1 (w/w) mixtures with alpha-lactose monohydrate and SMCC with 0.1g/g of purified water. The changes in the state of water were monitored using near-infrared spectroscopy, and the conversion of the crystal structure was verified using X-ray powder diffraction (XRPD). SMCC decreased the hydrate formation rate by absorbing water, but did not inhibit it. The results suggest that alpha-lactose monohydrate slightly increased the hydrate formation rate in comparison with a mass comprising only anhydrous theophylline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchodilator Agents / chemistry*
  • Cellulose
  • Chemistry, Pharmaceutical
  • Excipients
  • Kinetics
  • Lactose
  • Solubility
  • Spectroscopy, Near-Infrared
  • Theophylline / chemistry*
  • X-Ray Diffraction

Substances

  • Bronchodilator Agents
  • Excipients
  • Cellulose
  • Theophylline
  • Lactose
  • microcrystalline cellulose