Abstract
Objective: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are essential part of the administration of Rheumatoid Arthritis (RA). Methotrexate (MTX) is effective for tumor necrosis factor alpha (TNF-a) biologic agents, indicated only in minority of patients suffering from severe RA. MTX remains the "anchor drug" in the treatment of RA. For delivery improvement, novel pharmaceutical drug delivery system i.e. MTX-Cubosomes were developed.
 Methods: Poloxamer 407 and Glycerol monooleate (Monoelin, MO) used and the formulation were characterized as a sustained release drug delivery system for Methotrexate. Different ratios of Monolein, Poloxamer 407 and water were used to develop the different cubosomes using homogenization and emulsification method. Characterization of formulations for morphology was performed and also particle size distribution by Transmission Electron Microscopy (TEM).
 Results: Formulation showed the internal cubic structures of the vesicles. The particle size of the formulations was found to be ranging from 53.21 to 185.32 nm, zeta potential of the formulations varied from-18.20-36.10 mV. The cubosomal formulation exhibited good entrapment efficiency along with high drug loading. Compatibility with the excipients was also established. An in vitro release study was done using Franz Diffusion cell indicated sustained release of the formulation at a rate of 1.25 %/h. Cubosomes proved to be reliable system for sustained transdermal drug delivery system.
 Conclusion: Methotrexate cubosomes is a novel medication delivery framework and in this examination it has been developed and characterized. The formulations were found to be promising in terms of its characterization parameters like particle size, zeta potential, entrapment efficiency, loading capacity, release kinetics, and stability, suitable for topical delivery.
Highlights
Rheumatoid Arthritis (RA) is an autoimmune system sickness related with cutting edge incapacity, foundational inconveniences, early passing, and financial costs [1]
Poloxamer 407 and Glycerol monooleate (Monoelin, MO) used and the formulation were characterized as a sustained release drug delivery system for Methotrexate
The formulations were found to be promising in terms of its characterization parameters like particle size, zeta potential, entrapment efficiency, loading capacity, release kinetics, and stability, suitable for topical delivery
Summary
RA is an autoimmune system sickness related with cutting edge incapacity, foundational inconveniences, early passing, and financial costs [1]. RA is an affliction depicted by methods for intense and constant fundamental disease that incorporates the joints, and affects tissues and organs that comprise of veins, heart, skin, lungs, and muscles. The beginning and seriousness of infection are alterable and tricky. RA at first bears with weakness, musculoskeletal agony, and firmness and after certain weeks to months it develops to include joints. The little joints are influenced first, the little bones of the fingers than the bigger joints are influenced, winds up swollen, warm, and painful [2]. Morning firmness or stiffness is the signs and manifestations of RA and proposes enthusiastic illness. The influenced individual for the most part characterizes gradualness or challenge in development [3]
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