Exploring the affluent potential of glyceryl mono oleate – myristol liquid crystal nanoparticles mediated localized topical delivery of Tofacitinib: Study of systematic QbD, skin deposition and dermal pharmacokinetics assessment

This study aimed to design and characterize Tofacitinib (TF)-loaded lyotropic liquid crystalline nanoparticles (TF-LCNP) gel using quality by design-driven approach to enhance the skin delivery of TF. The present work investigated the impact of two different liquid lipids on different critical quality attributes of LCNP. The optimized lyotropic liquid crystals system was constructed with the glyceryl monooleate,myristol, Lutrol® and water system. The optimized TF – LCNP showed particle size of 74.82 ± 4.26 nm, polydispersity index of 0.124 ± 0.024, and entrapment efficiency of 68.29 ± 5.24 %.

Highlights

Systematic investigation of impact of oleic acid and myristol on the CQAs of LCNP.

GMO – myristol based LCNP were successfully optimized with QbD approach.

TF-LCNP showed 2.81 times higher skin retention compared to conventional cream.

TF-LCNP exhibited improved dermatokinetic parameters compared to conventional cream.

The TF-LCNP showed sustained release for 24 h and followed quasi-Fickian diffusion from non-swellable matrix diffusion with n value of 0.197. The ex vivo permeation studies exhibited that amount of TF permeated through LCNP gel and cream after 24 h were found to be 61.11 ± 1.5 µg/cm² and 37.7 ± 3.5 µg/cm^2, respectively. The penetration mechanism of TF-LCNP gel through skin layers followed the Korsmeyer- Peppas model (n-value of 1.687), indicated Case-II relaxational release of TF. The tape stripping studies showed that TF loaded LCNPs retained 3 fold and 2.81 fold greater TF in stratum corneum and viable skin layers than conventional cream. The coumarin – 6 loaded LCNP study using Fluorescence microscopy confirmed the penetration of TF-LCNP into the deeper layers of skin.

The dermal pharmacokinetic studies revealed that the LCNP showed a steady equilibrium state in 5–8 h in epidermis and dermis layers. The total amount of TF permeated with developed LCNP formulation was 3.42 times and 2.19 times higher in epidermis and dermis compared to the TF-cream. The developed formulation exhibited good spreadability and rheology and has not shown any significant changes in stability and scale-up studies. In a nutshell, the developed TF-LCNP strategy poses excellent potential in targeting the viable skin layer.

Read the article here

Article information: Srividya Gorantla, Ranendra N. Saha, Gautam Singhvi, Exploring the affluent potential of glyceryl mono oleate – myristol liquid crystal nanoparticles mediated localized topical delivery of Tofacitinib: Study of systematic QbD, skin deposition and dermal pharmacokinetics assessment, Journal of Molecular Liquids, 2021. https://doi.org/10.1016/j.molliq.2021.117053.

Watch the webinar about QbD and DoE Concepts here: