Hespeler David, El Nomeiri Sanaa, Kaltenbach Jonas, Müller Rainer H
Pharmaceutical Technology, Institute of Pharmacy, Freie Universität Berlin, Kelchstraße 31, 12169 Berlin, Germany.
Department for Mathematics, Physics and Chemistry, Beuth Hochschule für Technik Berlin, Luxemburger Straße 10, 13353 Berlin, Germany.
Beilstein J Nanotechnol. 2019 Aug 8;10:1666-1678. doi: 10.3762/bjnano.10.162. eCollection 2019.
smartPearls are a dermal delivery system for poorly soluble active agents, consisting of nanoporous silica particles loaded with a long-term stable, amorphous active agent in its mesopores (2-50 nm). The amorphous state of the active agent is known to increase dermal bioavailability. For use in marketed products, optimal silica types were identified from commercially available, regulatory accepted silica. In addition, a scalable production process was demonstrated. The loading of the particles was performed by applying the immersion-evaporation method. The antioxidant rutin was used as a model active agent and ethanol was applied as the solvent. Various silica particles (Syloid, Davisil) differing in particle size (7-50 µm), pore diameter (3-25 nm) and pore volume (0.4-1.75 mL/g) were investigated regarding their ease of processing. The evaporation from the silica-ethanol suspensions was performed in a rotary evaporator. The finest powders were obtained with larger-sized silica. The maximum loading staying amorphous was achieved between 10% and 25% (w/w), depending on the silica type. A loading mechanism was also proposed. The most suitable processing occurred with the large-sized Syloid XDP 3050 silica with a 50 µm particle size and a pore diameter of 25 nm, resulting in 18% (w/w) maximum loading. Based on a 10% (w/w) loading and the amorphous solubility of the active agent, for a 100 kg dermal formulation, about 500 g of loaded particles were required. This corresponds to production of 5 kg of loaded smartPearls for a formulation batch size of a ton. The production of 5 kg (i.e., about 25 L of solvent removal) can be industrially realized in a commercial 50 L rotary evaporator.
智能微珠是一种用于难溶性活性剂的皮肤给药系统，由纳米多孔二氧化硅颗粒组成，其介孔（2-50纳米）中负载有长期稳定的无定形活性剂。已知活性剂的无定形状态可提高皮肤生物利用度。为用于上市产品，从市售的、监管认可的二氧化硅中确定了最佳的二氧化硅类型。此外，还展示了一种可扩展的生产工艺。颗粒的负载通过浸渍-蒸发法进行。抗氧化剂芦丁用作模型活性剂，乙醇用作溶剂。研究了各种粒径（7-50微米）、孔径（3-25纳米）和孔体积（0.4-1.75毫升/克）不同的二氧化硅颗粒（Syloid、Davisil）的加工难易程度。二氧化硅-乙醇悬浮液的蒸发在旋转蒸发仪中进行。使用较大尺寸的二氧化硅可获得最细的粉末。根据二氧化硅类型的不同，保持无定形的最大负载量在10%至25%（w/w）之间。还提出了一种负载机制。最适合加工的是粒径为50微米、孔径为25纳米的大尺寸Syloid XDP 3050二氧化硅，最大负载量为18%（w/w）。基于10%（w/w）的负载量和活性剂的无定形溶解度，对于100千克的皮肤制剂，大约需要500克负载颗粒。这相当于生产5千克负载智能微珠用于批量为1吨的制剂。5千克（即约25升溶剂去除量）的生产可以在工业上通过商用50升旋转蒸发仪实现。
