Nanoporous smartPearls for dermal application – Identification of optimal silica types and a scalable production process as prerequisites for marketed products

Abstract

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.

Design and Optimization of Pioglitazone Hydrochloride Self-Nanoemulsifying Drug Delivery System (SNEDDS) Incorporated into an Orally Disintegrating Tablet

“…For solidified SNEDDS, the slower release of PGZ from S-SNEDDS as compared to L-SNEDDS counterparts was attributed to the physical interaction of L-SNEDDS carrying the drug with the hydrophobic structures of silica particles within the adsorbent powder [46,47]. Upon adsorption, the lipid formulation becomes trapped in the intraparticular pores of the adsorbent particles and causes a reduction in the dissolution rate [48].…”

“…The order of decreasing surface area was as follows: Syloid ® 244FP (380 m 2 /g) > Neusilin US2 ® and Neusilin ® UFL2 (300 m 2 /g) > Aerosil ® PH200 (200 m 2 /g) [7,45]. Furthermore, it is important to mention that Aerosil (SiO 2 ) is associated with more hydrophobic surface properties, which resulted in a decreased moisture uptake, as compared to the mesoporous structure of Mg-Al-silicates i.e., Syloid that have higher adsorption capacities and improved moisture uptake, that in turn improves the dissolution rate of the corresponding formulation [27,46]. Accordingly, SYL was preferred over the other types of adsorbents and was utilized in a ratio of 1:0.5 (L-SNEDDS: SYL) to produce S-SNEDDS powders with good flow properties.…”

Design and Characterization of Phosphatidylcholine-Based Solid Dispersions of Aprepitant for Enhanced Solubility and Dissolution

“…According to the specifications of silica particles from Fuji Chemical Industry Co., Ltd. (Toyama, Japan) and Grace Co., Ltd., (Columbia, MD, USA) the specific surface area and pore diameter of Syloid ® were higher (380 m 2 /g and 17 nm, respectively) than those of Neusilin ® (300 m 2 /g and 5-6 nm, respectively). In addition, the particle size of Syloid ® was lower (3 µm) than that of Neusilin ® (44-177 µm) [56,57]. This suggests that the wide specific surface area and pore size of silica particles increase its wettability, thus increasing the solubilized amount of APR from the formulation.…”

Apolar Extracts of St. John’s Wort Alleviate the Effects of β-Amyloid Toxicity in Early Alzheimer’s Disease

“…The scCO 2 extract was first dissolved in heptane, and then silicon dioxide (SiO 2 , Syloid ® XDP3050, Grace GmbH, Worms, Germany) was added [63][64][65]. The solvent mixture was subjected to complete evaporation under rotation and vacuum using a rotary evaporator (Hei-VAP Core HL G3B XL, Heidolph Instruments, Schwabach, Germany).…”