Topical Delivery of Apremilast Loaded Nanostructured Lipid Carrier Based Hydrogel for Psoriasis Therapy

Abstract

Background: Apremilast (APR) is an orally administered selective phosphodiesterase 4 inhibitor approved to treat plaque psoriasis and psoriatic arthritis and is available as an oral tablet formulation. However, its systemic side effects limit its application. The low solubility and permeability of apremilast make it difficult to administer it through the skin. Hence an attempt is made to incorporate apremilast into a suitable nanocarrier to facilitate its topical delivery.
 Aims: To formulate and characterize Apremilast loaded nanostructured lipid carriers for the management of psoriasis to reduce the systemic side effects.
 Methodology: Apremilast loaded Nanostructured Lipid carriers (NLC) were prepared by melt emulsification accompanied by probe sonication. The formulation was prepared using GMS, Sefsol 218, Tween 80 and Transcutol P as Solid Lipid, Liquid lipid, Surfactant and Penetration Enhancer. The NLC was incorporated into carbapol 934 dispersion to convert it into a gel. The NLC formulation was evaluated for size, Polydispersity Index, Zeta Potential, Entrapment efficiency, Transmission Electron Microscopy. After that, the NLC gel was examined for Spreadability, Extrudabilty, Viscosity, In vitro drug release, Ex vivo permeation, Skin deposition and In vivo studies.
 Results: The formulated Apremilast loaded showed particle size of less than 200 nm (i.e.170.32nm) with a narrow PDI of 0.267. Entrapment efficiency revealed that 89.26±01.22% of the drug was entrapped. Transmission electron microscopy images confirmed the spherical nature of the nanocarrier. The extended-release pattern of the formulated NLC for 24h was observed in the in vitro release studies and followed the Higuchi model(R2=0.9966). Ex vivo permeability showed a 6.14 fold increase in permeability and 74.05±0.25% deposition of apremilast loaded NLC gel compared to apremilast gel. The formulation was stable for three months without significant changes. In vivo skin studies showed that the prepared NLC did not have any skin irritation potential. The antipsoriatic activity demonstrated by the Apremilast loaded NLC gel in the imiquimod induced psoriasis model in mice was comparable to the standard treatment.
 Conclusion: Apremilast loaded NLC demonstrated enhanced permeation, improved skin retention and extended-release compared to conventional gel. The developed formulation can be an alternative for psoriasis therapy after clinical trials in the future.

Formulation characterization of lecithin organogel as topical drug delivery system for psoriasis: In‐vitro permeation and preclinical evaluation

“…Consequently, a safer delivery system is needed, one that may include hydrophobic drugs, increase skin permeability, and gel fast. Literature reports indicate two patents were filed for APM's topical composition (creams, gels, and ointments) (Abraham et al, 2017; Joharapurkar et al, 2019) and a few research works were published, including nanocrystal‐based gels (Parmar & Bansal, 2021), solid lipid nanoparticles (SLN) loaded hydrogel (Rapalli et al, 2021), and nanostructured lipid carrier (NLC) based gels (Sindhoor & Koland, 2021). However, these formulations have complex methodology and stability issues and are not cost‐effective.…”

Effect of Penetration Enhancers and Safety on the Transdermal Delivery of Apremilast in Skin

“…The effectiveness of this drug is limited by its side effects such as diarrhea, nausea, depression, and weight loss [ 18 ]. For this reason, the development of alternative administration forms, such as topical formulations, are attractive for local anti-inflammatory therapy; some research has covered this field with the development of nanocarriers incorporated into gels in some cases to improve the administration and bioavailability of APR [ 19 , 20 , 21 , 22 , 23 ].…”