Solid-state characterization of tobramycin powders for inhalation

F. Martinelli, D. Frascio, M. Di Cuia, A. G. Balducci, P. Colombo, F. Buttini, R. Bettini

Background: Tobramycin is an aminoglycoside broad-spectrum antibiotic, effective against Gram-negative bacteria, especially Pseudomonas infections in CF’s patients.

The pulmonary administration of powder formulations offers well known advantages with respect to liquid formulation.

When solid dosage forms are considered, the solid state characteristic of the active ingredient, i.e. polymorphism, represents an issue that should be addressed.

Methods: The spray-dried powder was produced starting from an ethanol-water mixture while three tobramycin raw material, namely Powder A, Powder B and jet-milled tobramycin Powder C were obtained from the market. They were characterized in terms of morphology by SEM, thermal behaviour by DSC and TGA, crystallinity by XRPD and water uptake by DVS.

Results: XRPD patterns showed that Powder A and C were crystalline, while SD powder and Powder B were amorphous. In the DSC profiles, Powder A showed two main endothermic peaks and one exothermic event between them. Interestingly, Powder C presented only the endotherm corresponding to the fusion of the high melting phase.

TGA pointed out a water content of 6.0%, 5.0%, 5.6% for Powder A, C and B, respectively. Spray-dried tobramycin showed the highest water content (9.8%). Isothermal DVS on spray-dried powder afforded a crystalline monohydrate phase presenting DSC and XRPD traces similar to those reported in literature.

Conclusions: The analysis on raw materials pointed out the existence of two solid phases of tobramycin. A monohydrate, already described in literature, can be obtained upon isothermal crystallization between 50% and 70% RH.

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