Role of excipients in hydrate formation kinetics of theophylline in wet masses studied by near-infrared spectroscopy.
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.
Pharmaceutical Technology Division, Department of Pharmacy, University of Helsinki, P.O. Box 56, FIN-00014 Helsinki, Finland. acj@dfuni.dk
Anna C
AC
Jørgensen
Sari
S
Airaksinen
Milja
M
Karjalainen
Pirjo
P
Luukkonen
Jukka
J
Rantanen
Jouko
J
Yliruusi
D001993:Bronchodilator Agents / Q000737:chemistry*; D002482:Cellulose; D002626:Chemistry, Pharmaceutical; D005079:Excipients; D007700:Kinetics; D007785:Lactose; D012995:Solubility; D019265:Spectroscopy, Near-Infrared; D013806:Theophylline / Q000737:chemistry*; D014961:X-Ray Diffraction
D001993:Bronchodilator Agents; D005079:Excipients; D002482:Cellulose; D013806:Theophylline; D007785:Lactose; C109691:microcrystalline cellulose