Dermal smartPearls – Optimized silica particles for commercial products & mechanistic considerations

• Published in: International journal of pharmaceutics Vol. 574; p. 118757
• Main Authors: Hespeler, David, Pyo, Sung Min, Müller, Rainer H.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 25.01.2020
• Subjects: Amorphous stability; Mesoporous silica; smartPearls; Solubility enhancer; Supersaturation; Amorphous stability; Supersaturation; Mesoporous silica; Solubility enhancer; smartPearls
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2019.118757

[Display omitted] The amorphous state of actives can be long-term stabilized by incorporation into mesoporous particles, thus the increase in the saturation solubility by amorphicity can be exploited to improve the bioavailability. In this study 5 different silica particles were investigated regarding loading capacity and long-term stability of the amorphous form. Five different silica were used ranging in pore mean size from 3 to 25 nm, pore volume 0.4 to 1.8 mL/g, and BET surface from 740 to 320 m2/g. As model active avobenzone was used, because it is a challenging molecule by its high crystallisation tendency. To be industrially feasible, a loading capacity of about 50% pore volume was investigated. The particles were loaded by an immersion evaporation method, being able to be used in industrial production. A theory of the active precipitation in the pores was developed based on the Ostwald-Miers range. The 25 nm pore-sized particles showed a crystalline fraction directly after loading, the 3 nm and 17 nm pore-sized particles after 1 month of storage. Long-term stability of 1 year had the silica with 6 nm and 10 nm pore size, thus being ideal for products. By nitrogen sorption studies, primarily filling of the pores from bottom to top was identified as loading mechanism. HPLC analysis showed some active remaining in the pores due to strong interaction with the pore surface, which needs to be considered when developing dermal products. Interestingly, the increase in saturation solubility Cs – determined in carrageenan gels – remained also for silica particles showing a minor partial crystalline avobenzone fraction. Thus, limited crystallinity does not impair the shelf-life and performance of dermal formulations.