International Journal of Pharmaceutics 180 (1999) 105 – 111
Degradation of hydroxypropylcellulose by Rhizomucor : effects
on release from theophylline – hydroxypropylcellulose tablets
C. Alvarez-Lorenzo, R. Duro, J.L. Go ´ mez-Amoza, R. Martı ´nez-Pacheco,
C. Souto, A. Concheiro *
Departamento de Farmacia y Tecnologı ´a Farmace ´utica, Facultad de Farmacia, Uniersidad de Santiago de Compostela,
15706 Santiago de Compostela, Spain
Received 9 October 1998; received in revised form 25 November 1998; accepted 7 December 1998
Abstract
The stability of several varieties of hydroxypropylcellulose was monitored during 3 years of storage (1) under the
conditions recommended by manufacturers and official pharmacopoeias (simple storage in closed containers) and (2)
at zero relative humidity. After 1 year, severe degradation of the varieties with lower initial pH and particle size stored
at ambient relative humidity was shown by changes in their molecular weight and in the pH and apparent viscosity
of 2% aqueous dispersions. Microbiological analyses showed the observed degradation to be attributable to the action
of fungi of the genus Rhizomucor. The changes in apparent viscosity significantly affected the release of theophylline
from direct compression tablets formulated with the degraded excipients. © 1999 Elsevier Science B.V. All rights
reserved.
Keywords: Hydrophilic matrices; Hydroxypropylcellulose; Microbiological contamination of excipients; Rhizomucor ;
Stability of cellulose ethers
1. Introduction
Cellulose ethers are hydrophilic polymers that
are widely used as pharmaceutical excipients
(Doelker, 1993). They are generally considered to
be stable in the solid state when kept in closed
containers under normal environmental condi-
tions (Handbook of Pharmaceutical Excipients,
1994) and the norms established by official phar-
macopoeias for their storage are accordingly not
particularly stringent: The United States Pharma-
copeia (1995) and the British Pharmacopoeia
* Corresponding author: Tel.: +34-981-594627; fax: +34-
981-547148.
E-mail address: ffancon@usc.es (A. Concheiro)
0378-5173/99/$ - see front matter © 1999 Elsevier Science B.V. All rights reserved.
PII:S0378-5173(98)00410-4