Short-term changes in drug agglomeration within interactive mixtures following blending

Jim Andreou, Peter Stewart, David Morton

Research output: Contribution to journalArticleResearchpeer-review

8 Citations (Scopus)


The objective was to investigate the nature and extent of short-term dynamic changes to dissolution within specific interactive mixtures following blending. Two micronized drugs, nitrazepam and flunitrazepam, were formulated into lactose-based interactive mixtures containing a micronized surfactant. The dissolution rate of the drugs decreased significantly over a period of days after preparation. The dissolution was modelled using a multi-exponential equation, allowing estimation of agglomeration and dissolution rate. From this model, decreasing dissolution rates were consistent with increasing agglomeration. Particle-sizing studies provided evidence of an increase in drug agglomerates over the same timescale. This is the first study to report short-term dissolution changes immediately following secondary processing. Several hypotheses are proposed for increases in agglomeration, which potentially relate to changes in surface charge, particle rearrangements, recrystallisation at surfaces and the role of moisture, although the role of mechanical processing on agglomerate behaviour remains poorly understood. The observations from this study may have wider implications, for dissolution and for other powder-based drug delivery systems which include interactive mixtures with fine powders. This study emphasizes the need for improved understanding if we are to implement a a??Quality by Designa?? ethos to improve control and risk management over the performance and stability of these systems.
Original languageEnglish
Pages (from-to)1 - 11
Number of pages11
JournalInternational Journal of Pharmaceutics
Issue number1-2
Publication statusPublished - 2009

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