Preparation and characterisation of novel spray-dried nano-structured para-aminosalicylic acid particulates for pulmonary delivery: impact of ammonium carbonate on morphology, chemical composition and solid state.

OBJECTIVES

The objective of this work was to spray dry p-aminosalicylic acid (PAS) and its ammonium salt and to investigate the impact of the pore-forming agent, ammonium carbonate (AC), on the morphological, aerodynamic and physicochemical properties of the resulting powders.

METHODS

Microparticles were prepared by spray drying from ethanol/water solvent systems. Their solid-state properties were evaluated by scanning electron microscopy, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis and in-vitro deposition, using the twin impinger.

KEY FINDINGS

The physicochemical properties of PAS were altered on spray drying with AC and a new solid state was produced. The solution composition impacted on the morphology of the resulting powders, which ranged from irregular crystal agglomerates to spherical crystal clusters and porous microparticles. The chemical composition, structure and morphology were dependent on process inlet temperature, low inlet temperatures resulting in a novel solid of stoichiometry; PAS : ammonia : water, 2 : 1 : 0.5. At higher temperatures pure PAS was obtained. In-vitro deposition studies showed an increase in emitted dose from spray dried drug, relative to the micronised PAS.

CONCLUSIONS

Under appropriate process conditions AC interacts with the acidic PAS, resulting in the formation of a novel solid-state drug phase. Spray-dried PAS powders have potential for pulmonary delivery.