Publication

Lactose contaminant as steroid degradation enhancer

Nieuwmeyer, F., Maarschalk, K. V. D. V. & Vromans, H., Nov-2008, In : Pharmaceutical Research. 25, 11, p. 2666-2673 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

Purpose. 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.

Conclusion. The lactose contaminant and grandule composition dictates the stability profile of the granules and mixtures.

Original languageEnglish
Pages (from-to)2666-2673
Number of pages8
JournalPharmaceutical Research
Volume25
Issue number11
Publication statusPublished - Nov-2008

    Keywords

  • degradation, lactose, particle surface, phosphate, steroid, HIGH-SHEAR GRANULATION, SOLID-STATE STABILITY, PHARMACEUTICAL EXCIPIENTS, CHEMICAL-STABILITY, DOSAGE FORMS, FORMULATIONS, MOISTURE, PHOSPHATE, DECOMPOSITION, CRYSTALLINE

View graph of relations

ID: 4784304