Clarithromycin Nanokristalle zur Hochdosisinhalation

Pneumonia remains a major global cause of morbidity and mortality, especially where access to care is limited. Standard oral / i.v. antibiotics often require high systemic doses to reach effective lung levels, increasing adverse effects, lowering adherence and fostering resistance. This work developed a high-dose inhalable dry-powder approach to deliver clarithromycin locally. Poorly soluble clarithromycin (BCS II) was converted to nanocrystals by wet media milling. Spray-dried hollow microparticles, so called "Trojan particles", in which nanocrystals are incorporated in a matrix shell are designed for deep-lung deposition while retaining good flow and dispersion. Hydroxypropyl methylcellulose (HPMC) served as a dual-function excipient, stabilising nanocrystals during milling and acting as the spray-drying matrix, enabling low excipient load. Adding a citric acid/NaOH buffer (pH 5) markedly improved nanocrystal redispersibility in simulated lung fluid. The optimised formulation achieved a fine particle fraction of 52.7%; further spray-drying optimisation did not improve this. In vitro, intrinsic dissolution rate increased 5.5-fold and saturation solubility ~10-fold versus micronised clarithromycin, indicating preserved nanonisation benefits after particle formation. Overall, nanonisation plus Trojan architecture and targeted matrix design represents a promising platform for high-dose inhalable anti-infectives; further biocompatibility, deposition and efficacy studies are needed, and the concept may extend to other poorly soluble drugs.