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Establishing the Design Space for Composite Soft Agglomerates in a Multi-dose Dry Powder Inhaler

Chamarthy SP, Bharatwaj B, Orekie C, Doughty D, Pandey P, Donovan B, Wylie J.

Respiratory Drug Delivery 2016. Volume 1, 2016: 211-222.

Abstract:

The design space for agglomerate based dry powder inhaler (DPI) formulations was explored by quantifying the impact of drug particle size and addition of ternary additives on aerosol performance. The impact of active pharmaceutical ingredient (API) particle size on aerosol performance was assessed using agglomerate formulations, prepared with different size fractions of a phosphodiesterase (PDE-4) inhibitor, while the influence of magnesium stearate as a ternary additive on aerosol performance was evaluated using agglomerate formulations of a corticosteroid. PDE-4 inhibitor agglomerates manufactured using smaller API particles yielded a higher fine particle fraction (FPF) compared to agglomerates prepared with larger diameter API particles. Only a marginal increase in the FPF (and fine particle dose) was observed for agglomerate formulations as a function of ternary excipient (magnesium stearate) concentration. Both these observations contradict literature evidence documented for carrier-based formulations. In carrier-based formulations, reduction in API size reduces the FPF while addition of a ternary excipient increases FPF significantly. Agglomerate formulations appear to exhibit different fundamental behavior to carrier-based systems.