Vanti Giulia, Grifoni Lucia, Bergonzi Maria Camilla, Antiga Emiliano, Montefusco Francesca, Caproni Marzia, Bilia Anna Rita
Department of Chemistry, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, FI, Italy.
Department of Health Sciences, Section of Dermatology, University of Florence, Viale Michelangiolo 41, 50125 Florence, Italy.
Int J Pharm. 2021 Sep 25;607:121036. doi: 10.1016/j.ijpharm.2021.121036. Epub 2021 Aug 23.
Cannabidiol (CBD) is a pleiotropic phytocannabinoid, recently investigated to treat many skin diseases. This study aimed to develop a CBD-loaded O/A microemulsion (CBD-ME) formulated as microemulgel (CBD-MEgel), suitable for local administration. The developed CBD-ME consisted of Solutol HS 15 (20%, surfactant), Transcutol P (9%, cosolvent), isopropyl myristate (5%, oil phase), water (66%) and 1% w/w CBD. Globules had polydispersity index less than 0.23 ± 0.02 and size of 35 ± 2 nm; these values did not change after loading CBD and gelling the formulation with Sepigel 305 obtaining a clear and homogeneous formulation with a pH of 6.56 ± 0.20, suitable for cutaneous application. Viscosity properties were investigated by the rotational digital viscometer, at both 21 ± 2 °C and 35 ± 2 °C. Viscosities of CBD-MEgel were 439,000 ± 4,243 mPa·s and 391,000 ± 1,414 mPa·s respectively. The release studies displayed that 90 ± 24 μg/cm of CBD were released in 24 h. The CBD permeability, evaluated using Franz diffusion cells and rabbit ear skin, was 3 ± 1 μg/cm. Skin-PAMPA gave a CBD effective permeability of (1.67 ± 0.16) ·10 cm/s and an absorbed dose of 115.30 ± 16.99 µg/cm after 24 h. Lastly, physical and chemical stability of both CBD-ME and CBD-MEgel were evaluated over a period of 3 months, showing optimal shelf-life at the storage conditions.
大麻二酚（CBD）是一种具有多种效应的植物大麻素，最近被研究用于治疗多种皮肤疾病。本研究旨在开发一种负载CBD的油包水（O/A）微乳（CBD-ME），并将其制成适合局部给药的微乳凝胶（CBD-MEgel）。所制备的CBD-ME由聚氧乙烯蓖麻油氢化蓖麻油15（20%，表面活性剂）、二乙二醇单乙醚（9%，助溶剂）、肉豆蔻酸异丙酯（5%，油相）、水（66%）和1% w/w的CBD组成。微球的多分散指数小于0.23±0.02，粒径为35±2 nm；在负载CBD并用Sepigel 305使制剂胶凝后，这些值没有变化，得到了一种澄清均匀的制剂，pH值为6.56±0.20，适合皮肤应用。使用旋转数字粘度计在21±2℃和35±2℃下研究了粘度特性。CBD-MEgel的粘度分别为439,000±4,243 mPa·s和391,000±1,414 mPa·s。释放研究表明，在24小时内释放出90±24μg/cm的CBD。使用Franz扩散池和兔耳皮肤评估的CBD渗透率为3±1μg/cm。皮肤平行人工膜渗透试验（Skin-PAMPA）显示，CBD的有效渗透率为(1.67±0.16)·10 cm/s，并在24小时后吸收剂量为115.30±16.99μg/cm。最后，对CBD-ME和CBD-MEgel的物理和化学稳定性进行了3个月的评估，结果表明在储存条件下具有最佳保质期。
