Nanocrystals of Medium Soluble Actives: Novel Concept for Improved Dermal Delivery and Production Strategy

    Xuezhen Zhai, Jürgen Lademann, Cornelia M. Keck, Rainer H. Müller
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    TLDR Nanocrystals improve skin penetration and stability of caffeine, suggesting a new method for delivering similar substances through the skin.
    The 2014 document details a study on improving dermal delivery of medium soluble actives, using caffeine as a model compound, by formulating nanocrystals. The study found that nanocrystals can maintain a constant concentration gradient for better skin penetration and can accumulate in hair follicles. The production strategy involved low energy milling with stabilizers like Carbopol® 981 to prevent crystal growth. Nanocrystals around 660 nm were optimal for hair follicle accumulation, while those around 250 nm dissolved faster. The study concluded that nanocrystals increased the solubility of caffeine by 35% to 70%, depending on the particle size, and the most stable formulation remained stable for 60 days, indicating its suitability for in vivo testing. The method could potentially be applied to other medium soluble actives for dermal delivery.
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