Fenoprofen and ketoprofen amides as potential antitumor agents.

Following numerous experimental observations that various non-steroidal anti-inflammatory drugs have antitumor potentials, a series of fenoprofenamides (1a-g) and ketoprofenamides (2a-c) was tested on proliferation of different human tumor cell lines and normal human fibroblasts in vitro. Fenoprofen and ketoprofen showed modest antiproliferative activity, whereas the growth inhibitory activity of the tested amides clearly demonstrates that the substituents linked by an amide bond are essential for the significantly stronger cytostatic activity, probably because of a greater lipophilicity and/or better cell uptake. Additionally, it was shown that the most active derivatives (1d and 2a) induced cell cycle arrest at the G1 phase, as well as apoptosis.

Dissolution of celecoxib from mucoadhesive disks based on polyaspartamide derivatives.

A series of mucoadhesive disks with celecoxib as a model drug of very low aqueous solubility were prepared and characterized. Two polymers of polyaspartamide type, poly[alpha,beta-(N-2-hydroxyethyl-DL-aspartamide)] (PHEA, 1) and its thiolated analogue poly[alpha,beta-(N-2-hydroxyethyl-DL-aspartamide)]-poly[alpha,beta-(N-2-thioethyl-DL-aspartamide)] copolymer (PHTA, 2a,b), and two commercially available polymers Carbopol 934P and hydroxypropylmethyl cellulose 4000 were used as excipients. Disks containing a mixture of equivalent amounts of thiomer 2b and Carbopol 934P as an excipient exhibited the highest dissolution rate.

Investigation of antimicrobial activity of Pelargonium radula (Cav.) L'Hérit.

Antimicrobial activities of two ethanolic extracts, made from fresh and dried leaves of Pelargonium radula (Cav.) L'Hérit, were tested against fourteen species of bacteria and fifteen species of fungi. The well-diffusion method indicated the strongest activity against Pseudomonas aeruginosa. The broth dilution method revealed that the most sensitive microorganisms were Bacillus pumilus, Bacillus subtilis, Escherichia coli and Serratia marcescens. Extract prepared from fresh leaves showed significantly higher antimicrobial activity than the extract prepared from dried leaves.

Antimicrobial activity of flavonoids from Pelargonium radula (Cav.) L'Hérit.

Flavonoids from Pelargonium radula (Cav.) L'Hérit were purified by column chromatography. Two fractions were obtained: F1 (main flavonoid isoquercitrin) and F2 (main flavonoid rutin). In vitro antimicrobial activity of F1 and F2 were tested against eleven species of bacteria and eleven species of fungi. Both fractions demonstrated strong inhibitory activity against Staphylococcus aureus, Proteus rettgeri, Candida tropicalis and Microsporum gypseum. Staphylococcus sp. (coagulase-negative) and Candida lusitaniae were strongly inhibited only by fraction F1 and Fusarium graminearum only by fraction F2.

Synthesis of fenoprofen and gemfibrozil styrene-maleic acid copolymer conjugates.

Two types of polymer-drug conjugates were synthesized starting from styrene-maleic acid anhydride copolymer (SMA). Fenoprofen and gemfibrozil were chosen as model drugs because of their short plasma half lives. Both drugs were first converted to their 2-aminoethylamides, which possess free amino groups capable of reacting with SMA anhydride rings. By modifying the degree and type of substitution, lipophilic and hydrophilic conjugates were obtained. Drug loading in the conjugates was between 17 and 47%.

Piroxicam benzoate--synthesis, HPLC determination, and hydrolysis.

An improved method of piroxicam benzoate synthesis was described, and an isocratic reversed-phase high-performance liquid chromatography method for its determination was developed and fully validated. The method was found to be specific, precise (relative standard deviation 0.3%), accurate (mean recovery 99.9%), and robust. Limit of detection was estimated at 0.055 microg mL(-1) and limit of quantification at 0.185 microg mL(-1). The kinetics of piroxicam benzoate hydrolysis in aqueous buffer solutions (pH 1.1 and 10), simulated gastric and intestinal fluids was studied. The hydrolysis followed first-order kinetics. The following rate constants were obtained at pH 10: k = 1.8 x 10(-3) hr(-1) at 37 degrees C and k = 3.4 x 10(-2) hr(-1) at 60 degrees C. In acidic media, no significant hydrolysis was observed after 24 hr. During the 24-hr period in simulated intestinal fluid, only 10.9% of the starting ester was hydrolyzed.

Solid-state investigation of piroxicam benzoate.

Solid-state properties of piroxicam benzoate, an ester prodrug of piroxicam, were investigated. Samples were prepared by recrystallization from various organic solvents (toluene, ethanol, methanol, ethyl acetate and acetone). Recrystallized samples were characterized by means of FTIR, DSC, TGA, SEM and XRPD. DSC, TGA and XRPD methods confirmed that piroxicam benzoate crystallized in two pseudopolymorphic forms, A and B. Pseudopolymorphic form A was obtained by recrystallization from ethanol and methanol by slow cooling at room temperature and by rapid cooling in an ice-cold bath, and also from toluene by rapid cooling in an ice-cold bath. Pseudopolymorphic form B was obtained by recrystallization from toluene by slow cooling at room temperature.