The reaction of 1,4-benzoquinone (BQ) with crizotinib (CZT); a novel drug used for treatment of non-small cell lung cancer) was investigated in different solvents of varying dielectric constants and polarity indexes. The reaction resulted in the formation of a red-colored product. Spectrophotometric investigations confirmed that the reaction proceeded through charge-transfer (CT) complex formation. The molar absorptivity of the complex was found to be linearly correlated with the dielectric constant and polarity index of the solvent; the correlation coefficients were 0.9425 and 0.8340, respectively. The stoichiometric ratio of BQ:CZT was found to be 2:1 and the association constant of the complex was found to be 0.26 x 103 l mol1. The kinetics of the reaction was studied; the order of the reaction, rate and rate constant were determined. Computational molecular modeling for the complex between BQ and CZT was conducted, the sites of interaction on CZT molecule were determined, and the mechanism of the reaction was postulated. The reaction was employed as a basis in the development of a novel 96-microwell assay for CZT. The assay limits of detection and quantitation were 5.2 and 15.6 µg ml1, respectively. The assay was validated as per the guidelines of the International Conference on Harmonization (ICH) and successfully applied to the analysis of CZT in its bulk and capsules with good accuracy and precision. The assay has high throughput and consumes minimum volume of organic solvent thus it reduces the exposures of the analysts to the toxic effects of organic solvents, and significantly reduces the analysis cost.

Two new, sensitive, and selective spectrofluorometric methods were developed for the determination of gemifloxacin mesylate (GFX) in tablets and spiked human plasma. Method A was based on measurement of the enhanced fluorescence spectral behaviour of GFX in a sodium dodecyl sulphate (SDS) micellar system. In aqueous solution of acetate buffer pH 5.5, the fluorescence intensity of GFX was greatly enhanced about tenfold in the presence of SDS. The fluorescence intensity was measured at 402 nm after excitation at 274 nm. Method B was based on Hantzsch condensation reaction between the primary amino group of GFX with acetylacetone and formaldehyde in acetate buffer of pH 3.5 yielding a highly yellow fluorescent derivative. The reaction of GFX with acetylacetone-formaldehyde system solution resulted in bathochromic shift of both emission (476 nm) and excitation (420 nm) wavelengths. The fluorescence intensity was directly proportional to the concentration over the range 10–1000 ng/ml and 100–2000 ng/ml for method A and B, respectively. The proposed methods were applied successfully for determination of GFX in its tablets and spiked plasma. Therefore, these methods can be considered of real interest for reliable and practical quality control analysis of GFX.

Two new, sensitive, and selective spectrofluorometric methods were developed for the determination of gemifloxacin mesylate (GFX) in tablets and spiked human plasma. Method A was based on measurement of the enhanced fluorescence spectral behaviour of GFX in a sodium dodecyl sulphate (SDS) micellar system. In aqueous solution of acetate buffer pH 5.5, the fluorescence intensity of GFX was greatly enhanced about tenfold in the presence of SDS. The fluorescence intensity was measured at 402 nm after excitation at 274 nm. Method B was based on Hantzsch condensation reaction between the primary amino group of GFX with acetylacetone and formaldehyde in acetate buffer of pH 3.5 yielding a highly yellow fluorescent derivative. The reaction of GFX with acetylacetone-formaldehyde system solution resulted in bathochromic shift of both emission (476 nm) and excitation (420 nm) wavelengths. The fluorescence intensity was directly proportional to the concentration over the range 10–1000 ng/ml and 100–2000 ng/ml for method A and B, respectively. The proposed methods were applied successfully for determination of GFX in its tablets and spiked plasma. Therefore, these methods can be considered of real interest for reliable and practical quality control analysis of GFX.

Two new, sensitive, and selective spectrofluorometric methods were developed for the determination of gemifloxacin mesylate (GFX) in tablets and spiked human plasma. Method A was based on measurement of the enhanced fluorescence spectral behaviour of GFX in a sodium dodecyl sulphate (SDS) micellar system. In aqueous solution of acetate buffer pH 5.5, the fluorescence intensity of GFX was greatly enhanced about tenfold in the presence of SDS. The fluorescence intensity was measured at 402 nm after excitation at 274 nm. Method B was based on Hantzsch condensation reaction between the primary amino group of GFX with acetylacetone and formaldehyde in acetate buffer of pH 3.5 yielding a highly yellow fluorescent derivative. The reaction of GFX with acetylacetone-formaldehyde system solution resulted in bathochromic shift of both emission (476 nm) and excitation (420 nm) wavelengths. The fluorescence intensity was directly proportional to the concentration over the range 10–1000 ng/ml and 100–2000 ng/ml for method A and B, respectively. The proposed methods were applied successfully for determination of GFX in its tablets and spiked plasma. Therefore, these methods can be considered of real interest for reliable and practical quality control analysis of GFX.

Novel, simple and sensitive high performance thin-layer chromatography (HPTLC) with fluorescence detection has been successfully developed and validated for determination of gemifloxacin mesylate (GFX) in plasma samples without prior pretreatment. Montelukast (MK) was used as internal standard. GFX and MK in plasma samples were separated using a mobile phase consisting of a mixture of ethyl acetate : methanol : 25% ammonia, (8:4.5:3, v/v/v). The emission intensity was measured using optical filter K400 after excitation at 342 nm. The Rf values for GFX and MK were 0.45  0.03 and 0.79  0.02, respectively. Under the optimum conditions, a linear relationship with good correlation coefficient (r = 0.9965, n = 6) was obtained in concentration range of 3–180 ng/band. The LOD and LOQ of the proposed method were 0.45 and 1.5 ng/band, respectively. The accuracy of the method was proved as the recovery % of GFX from spiked human plasma was 94.21–101.85%. The efficiency of the proposed method was confirmed by in-vivo application on human plasma in real patient samples. Moreover, the stability of GFX in plasma was carefully tested at different conditions and compared to others in aqueous solution.

Novel, simple and sensitive high performance thin-layer chromatography (HPTLC) with fluorescence detection has been successfully developed and validated for determination of gemifloxacin mesylate (GFX) in plasma samples without prior pretreatment. Montelukast (MK) was used as internal standard. GFX and MK in plasma samples were separated using a mobile phase consisting of a mixture of ethyl acetate : methanol : 25% ammonia, (8:4.5:3, v/v/v). The emission intensity was measured using optical filter K400 after excitation at 342 nm. The Rf values for GFX and MK were 0.45  0.03 and 0.79  0.02, respectively. Under the optimum conditions, a linear relationship with good correlation coefficient (r = 0.9965, n = 6) was obtained in concentration range of 3–180 ng/band. The LOD and LOQ of the proposed method were 0.45 and 1.5 ng/band, respectively. The accuracy of the method was proved as the recovery % of GFX from spiked human plasma was 94.21–101.85%. The efficiency of the proposed method was confirmed by in-vivo application on human plasma in real patient samples. Moreover, the stability of GFX in plasma was carefully tested at different conditions and compared to others in aqueous solution.

Novel, simple and sensitive high performance thin-layer chromatography (HPTLC) with fluorescence detection has been successfully developed and validated for determination of gemifloxacin mesylate (GFX) in plasma samples without prior pretreatment. Montelukast (MK) was used as internal standard. GFX and MK in plasma samples were separated using a mobile phase consisting of a mixture of ethyl acetate : methanol : 25% ammonia, (8:4.5:3, v/v/v). The emission intensity was measured using optical filter K400 after excitation at 342 nm. The Rf values for GFX and MK were 0.45  0.03 and 0.79  0.02, respectively. Under the optimum conditions, a linear relationship with good correlation coefficient (r = 0.9965, n = 6) was obtained in concentration range of 3–180 ng/band. The LOD and LOQ of the proposed method were 0.45 and 1.5 ng/band, respectively. The accuracy of the method was proved as the recovery % of GFX from spiked human plasma was 94.21–101.85%. The efficiency of the proposed method was confirmed by in-vivo application on human plasma in real patient samples. Moreover, the stability of GFX in plasma was carefully tested at different conditions and compared to others in aqueous solution.

The aim was to enhance the dissolution of lornoxicam (LOR) and to produce mini-tablets with an optimised system to provide a rapid-release multi-particulate formulation. LOR systems were prepared through co-evaporation with either polyethylene glycol 6000 or Pluronic® F-68 (PLU) and adsorption onto Neusilin® US2 alone or co-adsorption in the presence of different amounts of polysorbate 80. All systems were characterised by FT-IR, differential scanning calorimetry, X-ray diffraction, flowability and dissolution techniques. Mini-tablets were prepared using the system with the optimum dissolution profile and flowability. Tensile strengths, content uniformity and dissolution profiles of the mini-tablets were evaluated. The effects of different excipients and storage conditions on mini-tablet properties were also studied. The optimised rapid-release LOR mini-tablets were further evaluated for their in vivo pharmacokinetic profile. The co-evaporate of LOR with PLU showed significantly faster dissolution and superior flowability and was evaluated together with three directly compressible excipients (Cellactose® 80, StarLac® (STA) and Emcompress®) for mini-tablet formulation. The formulation with STA provided the optimum results in terms of tensile strength, content uniformity and rapid drug release following a 3-month stability study and was selected for further in vivo evaluation. The pharmacokinetic profile indicated the potential of the mini-tablets achieving rapid release and increased absorption of LOR.

An efficient synthesis of some new NSAIDs prodrugs viz., (S)-ethyl 2-[(S)-2-(4-isobutylphenyl)propanamido]-4-methylpentanoate (1), (S)-ethyl 2-[(R)-2-(4-isobutylphenyl)propanamido]-4-methylpentanoate (2), (S)-dimethyl 2-[2-(2,3-dimethylphenylamino)benzamido]-succinate (3) and (RS)-methyl-2-(2-(2,6-dichloro-3-methylphenylamino)benzamido)butanoate (4) with high purity were carried out by the amidation of RS-ibuprofen, mefenamic acid and meclofenamic acid with methyl ester and ethyl ester of amino acids L-leucine, L-aspartic acid and DL-2-aminobutyric acid. The products formed were confirmed by IR, 1H NMR, 13C NMR, HR MS (1-4) and single crystal X-ray crystallography analysis (2-4). Compound (2) crystallizes in orthorhombic space group P212121 with unit cell dimensions a = 5.1931 (2) Å, b = 10.0031 Å, c = 41.0764 (11) Å,  =  =  = 90°, V = 2133.80 (12) Å3, Z = 4. Compound (3) crystallizes in hexagonal space group P65 with unit cell dimensions a = 11.4965 (3) Å, b = 11.4965 (3) Å, c = 26.5323 (12) Å,  =  = 90°,  = 120°, V = 3036.94 (18) Å3, Z = 6. Compound (4) crystallizes in triclinic space group Pi with unit cell dimensions a = 8.7969 (3) Å, b = 10.6307 (3) Å, c = 11.8469 (4) Å,  = 76.724 (3)°,  = 89.066 (3)°,  = 66.169 (2)°, V = 982.70 (5) Å3, Z = 2.

A structure-based medicinal chemistry strategy was applied to design new naproxen derivatives that show growth inhibitory activity against human colon tumor cells through a cyclooxygenase (COX)-independent mechanism. In vitro testing of the synthesized compounds against the human HT-29 colon tumor cell line revealed enhanced growth inhibitory activity compared to the parent naproxen with 3a showing IC50 of 11.4 µM (two orders of magnitude more potent than naproxen). Selectivity of 3a was investigated against a panel of three tumor and one normal colon cell lines and showed up to six times less toxicity against normal colonocytes. Compound 3a was shown to induce dose-dependent apoptosis of HT116 colon tumor cells as evidenced by measuring the activity of caspases-3 and 7. None of the synthesized compounds showed activity against COX-1 or COX-2 isozymes, confirming a COX-independent mechanism of action. Compound 3k was found to have no ulcerogenic effect in rats as indicated by electron microscope scanning of the stomach after oral administration. A pharmacophore model was developed for elucidating structure–activity relationships and subsequent chemical optimization for this series of compounds as colorectal cancer chemopreventive drugs.