A Review on Analytical Methods for estimation of Apremelast in Bulk, Pharmaceutical Formulation and in Biological Samples

Apremilast is approved by USFDA in 2014. It is used in treatment of psoriatic arthritis and other conditions like atopic dermatitis and plaque psoriasis. It is act as an anti-inflammatory agent. It is phthalimide derivative and belongs to class 4 category of BCS system. It is a phosphodiesterase-4 (PDE-4) inhibitor. Analytical methods plays an important role to describe physico-chemical properties of drug. Due to low solubility and low permeability analytical method development and formulation becomes challenging. Till date, there are no standard test methods available to analyze Apremilast. So, a review of the analytical methods for apremilast is carried out. Here we discussed latest analytical methods for estimation of apremilast in bulk, Pharmaceuticals dosage form and in biological samples. In that we study methods like HPLC, UV-Visible spectroscopy, HPTLC, UPLC and mostly used hyphenated technique LC-MS. This review will be helpful for the researcher who is working on apremilast.

Advances in Synthesis and Medicinal Applications of Compounds Derived from Phthalimide

Phthalimide derivatives have been presenting several promising biological activities in the literature, such as anti-inflammatory, analgesic, antitumor, antimicrobial and anticonvulsant. The most well-known and studied phthalimide derivative (isoindoline-1,3-dione) is thalidomide: this compound initially presented important sedative effects, but it is now known that thalidomide has effectiveness against a wide variety of diseases, including inflammation and cancer. This review approaches some of the recent and efficient chemical synthesis pathways to obtain phthalimide analogues and also presents a summary of the main biological activities of these derivatives found in the literature. Therefore, this review describes the chemical and therapeutic aspects of phthalimide derivatives.

DESIGN, SYNTHESIS AND BIOLOGICAL SCREENING OF AMINOACETYLENIC TETRAHYDROPHTHALIMIDE ANALOGUES AS NOVEL CYCLOOXYGENASE (COX) INHIBITORS

<p><strong>Objective: </strong>To design and synthesise a new amino acetylenic tetrahydro phthalimide derivative and investigate their selective inhibitory activity to COXs.</p><p><strong>Methods: </strong>Aminoacetylenic tetrahydro phthalimide derivatives were synthesised by alkylation of tetrahydro phthalimide with propargyl bromide afforded 2-(prop-2-yn-1-yl)-2,3,3a,4,7,7a-hexahydro-1H-isoindole-1,3-dione. The alkylated tetrahydro phthalimide was subjected to Mannich reaction afforded the desired amino acetylenic tetra phthalimide derivatives (AZ 1-6). The elemental analysis was indicated by the EuroEA elemental analyzer and biological characterization was via IR, ¹H-NMR, [13]C-NMR, DSC was determined with the aid of Bruker FT-IR and Varian 300 MHz spectrometer and DMSO-d₆ as a solvent, molecular docking was done using the Autodock Tool software (version 4.2). ChemBioDraw was used in the drawing of our schemes.</p><p><strong>Results</strong>:<strong> </strong>The IR, ¹H-NMR, ¹³C-NMR, DSC and elemental analysis were consistent with the assigned structures. The designers of the compounds as COXs inhibitor activity were based on the nationalisation of the important criteria that provide effective inhibitory binding with COXs–receptor. The results indicated that the synthesised compounds (AZ1-6) showed a close similarity in the binding affinity to both COXs and may be more specific to COX-1. AZ-5 showed the highest % of inhibition for COX-1 even better than aspirin. Which may suggest that the aryl group is required for COX-2 inhibition.</p><p><strong>Conclusion: </strong>For the first time, we indicate the requirement of aromaticity in COX-2 structural inhibitory activity. </p>