Forskning ved Københavns Universitet - Københavns Universitet


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

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Anna C Jørgensen
  • Sari Airaksinen
  • Milja Karjalainen
  • Pirjo Luukkonen
  • Rantanen, Jukka
  • Jouko Yliruusi

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.

TidsskriftEuropean Journal of Pharmaceutical Sciences
Udgave nummer1
Sider (fra-til)99-104
Antal sider6
StatusUdgivet - sep. 2004


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

ID: 140622518