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Aim of the present study was to improve the solubility and dissolution rate of poorly water soluble, BCS class-II drug Ketoprofen (KETO) by solid-dispersion approach. Solid dispersions were prepared by using polyvinylpyrrolidone K30 (PVP K30) and d-mannitol in different drugs to carrier ratios. Dispersions with PVP K30 were prepared by kneading and solvent evaporation techniques, whereas solid dispersions containing d-mannitol were prepared by kneading and melting techniques. These formulations were characterized in the liquid state by phase-solubility studies and in the solid state by Differential Scanning Calorimetry (DSC), Fourier Transform Infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and Scanning Electron Microscopy (SEM). The aqueous solubility of KETO was favored by the presence of both carriers. The negative values of Gibbs free energy illustrate the spontaneous transfer from pure water to the aqueous polymer environment. Solid state characterization indicated KETO was present as fine particles in d-mannitol solid dispersions and entrapped in carrier matrix of PVP K30 solid dispersions. In contrast to the very slow dissolution rate of pure KETO, dispersions of drug in carriers considerably improved the dissolution rate. This can be attributed to increased wettability and dispersibility, as well as decreased crystallinity and increase in amorphous fraction of drug. Solid dispersions prepared with PVP K30 showed the highest improvement in dissolution rate of KETO. Even physical mixtures of KETO prepared with both carriers also showed better dissolution profiles than those of pure KETO.

1,3,5-Triazine and its derivatives have been the epicenter of chemotherapeutic molecules due to their effective biological activities, such as antibacterial, fungicidal, antimalarial, anticancer, antiviral, antimicrobial, anti-inflammatory, antiamoebic, and antitubercular activities. The present review represents a summarized report of the crucial biological activities possessed by substituted 1,3,5-triazine derivatives, with special attention to the most potent compounds.

A novel series of hybrid analogues of monastrol-1,3,5-triazine were designed and developed via one-pot synthesis using Bi(NO3)3 as a catalyst. Entire compounds were evaluated for their anticancer activity against HeLa (cervical cancer), MCF-7 (breast cancer), HL-60 (Human promyelocytic leukemia), HepG2 (Hepatocellular carcinoma) and MCF 12A (normal epithelial breast cell line) using MTT assay, where they showed highest inhibitory activity against MCF-7. The molecules were also found to be non-toxic to MCF 12A cells. These molecules showed considerable inhibitory percentage against Epidermal Growth Factor Receptor tyrosine kinase (EGFR-TK), in in-vitro assay. Molecular docking study was carried out on the analogs and reference compound (Erlotinib) into the ATP binding site of EGFR-TK domain (PDB ID:1M17) to elucidate vital structural residues necessary for bioactivity. The effect of most active compound 7l was also estimated in-vivo in DMBA induced mammary tumor in female Sprague-Dawley rats. The effect of anti-breast cancer effect of 7l was quantified on the basis of tumour incidence, body weight and tumor volume in DMBA-induced rats. Its effect on biochemical parameters, such as antioxidant status (SOD, CAT, GPX and GSH) and lipid peroxidation was also studied. The compound 7l showed inhibition of EGFR downstream signalling in the western blot analysis.

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