Temperature Cycling-Induced Formation of Crystalline Coatings

The surface of particles is the hotspot of interaction with their environment and is therefore a major target for particle engineering. Particles with tailored coatings are greatly desired for a range of different applications. Amorphous coatings applied via film coating or microencapsulation have frequently been described in the pharmaceutical context and usually result in homogeneous surfaces. In the present study we have been exploring the feasibility of coating core particles with crystalline substances, a matter that has rarely been investigated.

The expansion of the range of possible coating materials to include small organic molecules enables completely new product properties to be achieved. We present an approach based on temperature cycles performed in a tubular crystallizer to result in engineered crystalline coatings on excipient core particles. By manipulating the process settings and by the choice of coating substance we are able to tailor surface roughness, topography as well as surface chemistry.

Benefits of our approach are demonstrated by using resulting particles as carriers in dry-powder-inhaler formulations. Depending on the resulting surface chemistry and surface roughness, coated carrier particles show varying fitness for delivering the model API salbutamol sulphate to the lung.

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Materials

α-mannitol (Pearlitol 200SD, spray-dried form, Roquette, France), was selected as core material for crystalline coating and as a reference inhalation carrier. The coating substances urea (UR) and citric acid (CA) were purchased from Merck KGaA (Germany). Solvents (1-butanol 99.8 %, ethanol 99.8 % and acetone 99.8 %) were purchased from Carl Roth GmbH (Germany). Salbutamol sulphate (SBS) was purchased from Fagron GmbH & Co KG (Germany) and used as model drug after micronization with a 50 AS spiral-jet mill (Hosokawa, Alpine, Germany; injection pressure 8.0 bar and milling pressure 5.0 bar) to a mean particle size of 2.8 µm. β-mannitol (P160C) for inverse gas chromatography (IGC) measurements was donated from Roquette (France).

Sarah Zellnitz-Neugebauer, Magdalena Lanzinger, Hartmuth Schroettner, Majid Naderi, Meishan Guo, Amrit Paudel, Heidrun Gruber-Woelfler, Peter Neugebauer, Temperature Cycling-Induced Formation of Crystalline Coatings,
International Journal of Pharmaceutics, 2022, 122577, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2022.122577.