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Accelerated Stability Studies of Widely Used Pharmaceutical Substances Under Simulated Tropical Conditions
(1986; 119 pages) View the PDF document
Table of Contents
View the document1. Introduction
View the document2. Index of degradable substances
View the document3. Index of substances resistant to degradation
Open this folder and view contents4. Stability experiments on degradable substances
 

1. Introduction

Many pharmaceutical substances are known to deteriorate during distribution and storage particularly in hot, humid climates. Nonetheless, little precise information is available on the degradation characteristics of many long-established substances. More is known of the stability of recently introduced substances since relevant data must now be generated as a condition of registration to support proposed expiry dates. The results, however, are rarely published.

The World Health Organization has consequently commissioned a systematic survey of the stability of many widely used pharmaceutical substances. It has also developed simplified tests to detect or exclude gross degradation for the least stable substances.1

1 WHO Technical Report Series, No. 645, 1979 (WHO Expert Committee on Specifications for Pharmaceutical Preparations, twenty-seventh report, section 5.2)

The conditions under which this survey were carried out were carefully standardized. Light was excluded, while temperature and humidity were adjusted to simulate tropical conditions. All substances were initially exposed for 30 days to air at 50 °C and 100% humidity. If no degradation was demonstrable at this time, the temperature was raised to 70 °C for a further period of 3-7 days. The extent of degradation was assessed in most cases by thin-layer chromatography. A semi-quantitative method was used to determine the proportion of unaltered substance. The results of these tests have also been referred to in relevant monographs of the International Pharmacopoeia.2

2 The International Pharmacopoeia, third edition, volume 2, WHO, Geneva, 1981; volume 3 - in print.

"Standard degraded samples" were prepared under conditions described above that contained about 90% of the original substance and 10% of the degradation product. If necessary, final adjustments were made by mixing the degraded and original substances in appropriate proportion. The resulting mixture were then used to establish simple analytical procedures permitting demonstration of the absence of gross degradation. These procedures are incorporated in WHO's basic tests for pharmaceutical substances.1

1 Basic Tests for Pharmaceutical Substances, WHO, Geneva, 1986

The study was initiated and coordinated by Dr M. Pesez, a member of the WHO Expert Advisory Panel on The International Pharmacopoeia and Pharmaceutical Preparations. The World Health Organization gratefully acknowledges the contribution of Dr M. Pesez and of Messrs Roussel-Uclaf SA, Romainville, France which generously offered facilities within their analytical laboratories to effect the work.

Acknowledgements are also due to Professor A.W.M. Indemans, Director of the Laboratory of the Dutch Pharmaceutical Society, The Hague, Netherlands, who kindly performed stability studies on some substances subject to narcotic regulations, and to Mr B. Ohrner, Director of the WHO Collaborating Centre for Chemical Reference Substances, Solna, Sweden who has corroborated many of the results obtained.2

2 WHO Technical Report Series, No. 704, 1984 (WHO Expert Committee on Specifications for Pharmaceutical Preparations, twenty-ninth report).

 

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