Abstract

DESIGN OF EXPERIMENT AVENUE FOR DEVELOPMENT AND VALIDATION OF RP-HPLC- PDA METHOD FOR DETERMINATION OF APREMILAST IN BULK TABLET FORMULATION

Palghadmal P. J.*, Bhawar S. B., Kolhe M. H.

ABSTRACT

Apremilast, an orally administered small molecule inhibitor of phosphodiesterase 4 (PDE4), has been licensed by the US Food and Drug Administration for the management of active psoriatic arthritis (March 21, 2014) and moderate to severe plaque psoriasis (September 23, 2014). It has got approval from Drug Controller General of India for marketing in India in 2017. The drug has drawn much attention from the practising dermatologists for its commendable safety profile and prescription convenience. Introduced initially as an orally administered small molecule in psoriasis patients, the drug has now been used in various other indications as evident by the recent surge in literature for its off-label uses. Being a relatively new drug in the treatment armamentarium of psoriasis and other inflammatory dermatoses; in this review, we will discuss various practical aspects of prescribing oral apremilast, based on the current and emerging literature. • Apremilast is an oral first-in-class phosphodiesterase 4 inhibitor that was approved by the FDA for the treatment of adults with active psoriatic arthritis and adults with moderate to severe plaque psoriasis. • The recommended daily dose is 30 mg twice daily and initial doses should be titrated over the course of about a week to reduce gastrointestinal adverse reactions. • Apremilast was shown to be moderately effective in clinical trials at reducing symptoms of psoriatic arthritis including tender and swollen joints and physical functioning (ACR20) in patients who have failed previous treatments. Concomitant treatment with methotrexate or other conventional systemic disease-modifying ant rheumatic drugs (DMARDs) was allowed. Results from 4 clinical trials showed NNTs ranging from 4 -10 with 30 mg twice daily dosing. • Apremilast was shown to be moderately effective in clinical trials at improving symptoms and quality of life for patients with plaque psoriasis. Results from two clinical trials showed statistically significant improvements in 75% improvement in Psoriasis Area and Severity Index (PASI-75) with 20 mg twice daily and 30 mg twice daily dosing. • Depression may develop or worsen during therapy; educate patients and use caution in patients with a history of depression or suicidality. The most common adverse reactions reported were diarrhoea, headache, nausea, and upper respiratory tract infection.

Keywords: Apremilast, phosphodiesterase, psoriatic arthritis, methotrexate.