The effect of mechanical comminution on drug stability
Waltersson, J.O.; Lundgren, P.
Acta Pharmaceutica Suecica 22(5): 291-300
1985
ISSN/ISBN: 0001-6675 PMID: 4091000 Document Number: 252823
Mechanical "activation" in the formulation of a drug has been reported to be deleterious to the stability of the finished product. The stability of two model drugs, acetylsalicylic acid and procaine penicillin G, was studied in suspension and in the solid state after exposure to ball milling for various times up to 20 hours. Increasing rate of degradation with increasing milling time up to limit values was found for both drugs in suspension, which was related to increasing solubility of the drugs. Furthermore, drug-excipient compatibility studies were performed on the milled model substances. At moderately elevated temperature and humidity, an increasing rate of degradation with increasing milling time was obtained in mixtures with Avicel PH 101 and Emcompress. It can therefore be concluded that exposure to a mechanical stress could have a negative effect on the stability of drugs susceptible to a hydrolytic degradation. The increase in degradation rate can be explained by changes in the physico-chemical properties of the drug substances.