Lactose contaminant as steroid degradation enhancer.
OBJECTIVE
By pharmaceutical processes and in the presence of solid excipients physical-chemical changes are known to occur, leading to increased rate of chemical degradation. The purpose of this work was to determine the critical aspects in the stability of a steroid in the presence of a commonly used excipient, lactose.


METHODS
A steroid was either mixed or wet granulated with lactose with different particle size.


RESULTS
Small lactose particles lead to a higher degree of degradation. Degradation was enhanced under warm humid conditions although the presence of water alone could not account for this effect. Lactose-phosphate, a known intrinsic contaminant in lactose is demonstrated to enhance the degradation of the steroid. Stability was improved in high purity lactose and deteriorated upon extra addition of phosphates. Since the exposure to the contaminant is a function of the surface area of the lactose, particle size differences of the excipient have a clear consequence. High shear granulated lactose granules exhibit a heterogeneous composition; large granules consist of small primary particles and vice versa. It is shown that the large granules, composed of the small primary lactose particles reveal the highest degree of degradation. Granule composition dictates the stability profile of the granules.


CONCLUSIONS
The lactose contaminant and granule composition dictates the stability profile of the granules and mixtures.
Nieuwmeyer
Florentine
F
Department of Pharmaceutics, Schering Plough Corporation, P.O. Box 20, 5340 BH, Oss, The Netherlands. fjsnieuwmeyer@yahoo.com
van der Voort Maarschalk
Kees
K
Vromans
Herman
H
D004340:Drug Contamination; D004355:Drug Stability; D005079:Excipients; D006863:Hydrogen-Ion Concentration; D007785:Lactose / Q000737:chemistry*; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000737:chemistry; D010316:Particle Size
D005079:Excipients; D007785:Lactose; D009640:Norethindrone; C097629:Org 30659