Il Farmaco

The p-[N,N-bis(2-chloroethyl)amino]phenylacetic acid esters of hecogenin and aza-homo-hecogenin have been prepared and their antineoplastic activity was evaluated against two basic drug screening systems in rodents, P388 lymphocytic and L1210 lymphoid murine leukemias. Among the compounds tested, the p-[N,N-bis(2-chloroethyl)amino]phenylacetic acid ester of aza-homo-hecogenin was appeared to possess a significant higher antileukemic effect. These results support that the alkylating esters of hecogenin produce important antitumor activity as well as, indicate that the aza-homo-hecogenin ester exhibits significantly higher activity due to lactam group (-NHCO-) modification...

The chiral separation of racemic tamsulosin hydrochloride (TH) was carried out using cyclodextrin (CD)-mediated capillary electrophoresis (CE) with DAD at 200 nm. The best separation of enantiomers of the studied compound was achieved at 20 kV with 30 cm x 50 microm I.D. polyacrylamide (PAA)-coated fused-silica capillary (effective length 20 cm) and running buffer with sulfated-beta-CD (S-beta-CD) as chiral selector. Other selected native or derivatized CDs were also tested: beta-CD (5, 15 mmol l(-1)), carboxymethyl-beta-CD (5, 30 mmol l(-1)), dimethyl-beta-CD (15 mmol l(-1)) and hydroxypropyl-beta-CD (5, 30 mmol l(-1))...

A differential pulse voltammetric method was described for the determination of domperidone. The method was based on the anodic oxidation of domperidone on a glassy carbon electrode at +0.64 V vs. SCE in Britton-Robinson buffer solution of pH 2.3. The reversibility of the oxidation was tested by cyclic voltammetry; the electrode process is irreversible and diffusion-adsorption controlled. Calibrations are linear over the range 1.0 x 10(-6)-2.0 x 10(-5) M of domperidone with a detection limit of 4.0 x 10(-7) M...

Four sensitive methods are described for the direct determination of telmisartan (TELM) and hydrochlorothiazide (HCT) in combined dosage forms without prior separation. The first method is a first derivative spectophotometry (1D) using a zero- crossing technique of measurement at 241.6 and 227.6 nm for TELM and HCT, respectively. The second method is the first derivative of ratio spectrophotometry (1DD) where the amplitudes were measured at 242.7 nm for TELM and 274.9 nm for HCT. The third method is based on TLC separation of the two drugs followed by the densitometric measurements of their spots at 295 and 225 nm for TELM and HCT, respectively...

A new, simple, rapid and accurate spectrophotometric method is proposed for determination of sodium diclofenac (SD) in pharmaceutical preparations based on its reaction with concentrated nitric acid (63% w/v). The reaction product is a yellowish compound with maximum absorbance at 380 nm. The corresponding calibration curve is linear over the range of 1-30 mg l(-1), while the limit of detection is 0.46 mg l(-1).

This study describes an orthogonal experimental design to optimize the formulation of 5-fluorouracil (5-FU) loaded poly D,L (lactide-co-glycolide) (PLGA) nanoparticles (5FU-NP) by a nanoprecipitation-solvent displacement technique. The type of surfactant, amount of acetone and molecular weight of the polymer with three levels of each factor were selected and arranged in an L18(3(5)) orthogonal experimental table. From the statistical analysis of the data polynominal equations were generated. Optimized formulations have the particle size ranging from 160 to 250 nm...

QSAR modeling was performed on 58 (S) N-[(1-ethyl-2-pyrrolidinyl) methyl]-6-methoxy benzamides as dopamine (DA) D2 receptor antagonists to identify the structural requirements for DA D2 receptor binding affinity. The study pointed out that the presence of hydrophobic substituents at R3 position and electron-donating groups at R5 position increased the biological activity. Substitutions at phenyl ring favored the binding affinity of these benzamides. Ethyl group and iodine at R3 position were advantageous to the activity whereas nitro group at phenyl ring hindered the antagonistic activity...

A method based on micellar electrokinetic capillary chromatography (MEKC) was developed for determination of minoxidil in Rogaine and competing products. The original intent of the work was to offer an orthogonal means to HPLC for testing illicit imitations of Rogaine. However, because the patent has since expired, we offer the procedure as a confirmatory measure to HPLC for assay of generic minoxidil products. The MEKC procedure complements an earlier method based on free solution capillary electrophoresis (FSCE), designed to the same end...

Piroxicam is a nonsteroidal anti-inflammatory drug that is characterized by low solubility-high permeability. The present study was designed to improve the dissolution rate of piroxicam at the physiological pH's through its increased solubility by preparing semi-solid dispersions of drug using Gelucires and Labrasol. These excipients are essentially characterized by their melting points and HLB (hydrophilic-lipophilic balance) values. The dissolution tests of the preparations were performed in the media with different pH's...

Endothelin-1 (ET-1), a peptide of 21 amino acid residues, is the most potent vasoconstrictor substance known and now it is understood to be one of a family of three mammalian vasoactive peptides that also includes ET-2 and ET-3. The endothelins (ETs) affect multiple organ systems and seem to be involved in the pathogenesis of many diseases such as hypertension, pulmonary hypertension, atherosclerosis, apoptosis inhibition and angiogenesis. The ETs exert their effects via activation of two distinct G-protein coupled receptor subtypes termed ET(A) and ET(B)...

Metronidazole (MTZ), a drug used for the treatment of protozoal infections caused by protozoa and anaerobic microorganisms, was conjugated to linear or branched poly(ethylene glycol) of 5,000, 10,000 and 20,000 Da. An ester linkage between polymer and drug was used in the coupling to yield a polymeric prodrug. The modification allowed overcoming the known MTZ solubility problem leading us to obtain a bioconjugate more suitable for parental administration. The conjugates of various molecular weight polymers have been tested in vitro toward chemical degradation and digestive enzymes...

An equimolar reaction of 2-diazo-1, 2-diarylethanones with N-(2-thienylidene)imines affords 1-substituted-3, 3-diaryl-4-(2-thienyl)-2-azetidinones in excellent yields. The products have been characterized on the basis of satisfactory analytical and spectral (IR, 1H and 13C NMR, MS) data. The mechanism of formation of the products is shown. The antimicrobial activity of the compounds against some Gram(+) and Gram(-) bacteria, and fungi is reported.

Endothelins (ETs) are the most ubiquitous, highly potent and unusually long-lasting peptidic constrictors of human vessels known. Elevated levels of the plasma concentration of ETs were observed in several diseases such as hypertension, acute myocardial infarction, congestive heart failure, renal failure, pulmonary hypertension, and atherosclerosis. ETs exert their activities via specific seven-transmembrane, G protein-coupled receptors. To date two receptor subtypes, endothelin A (ET(A)) and endothelin B (ET(B)), have been identified and cloned...

Novel phenyl branched cyclopropyl nucleoside analogues were designed and synthesized as potential antiviral agents. Cyclopropanation was performed via classical Simmons-Smith reaction using Zn(Et)2 and CH2I2. Coupling of the mesylates 11 and 12 with natural bases (A,C,T,U) and desilylation afforded a series of novel cyclopropyl nucleosides 21-28. The synthesized compounds were evaluated for their antiviral and antitumor activity against various viruses such as HIV, HSV-1, HSV-2 and HCMV.

A rapid, simple and sensitive high-performance liquid chromatography (HPLC) method has been developed for quantification of amlodipine in plasma. The assay enables the measurement of amlodipine for therapeutic drug monitoring with a minimum detectable limit of 0.2 ng ml(-1). The method involves simple, one-step extraction procedure and analytical recovery was about 97%. The separation was performed on an analytical 125 x 4.6 mm i.d. Nucleosil C8 column. The wavelength was set at 239 nm. The mobile phase was a mixture of 0...

A new synthetic route to obtain the carboxylate analog of mannose 6-phosphate (M6-P) is presented. The effects of the M6-P, the carboxylate and two other analogs (the phosphonate and the alpha,beta ethylenic carboxylate) on the proliferation of human keratinocytes and dermal fibroblasts as well as on the proliferation of a murine fibroblast cell line, 3T3-J2 are tested. We observed that M6-P is a potent inhibitor of proliferation of both fibroblasts and keratinocytes. Among its analogs, the phosphonate showed a similar effect on human dermal fibroblasts but not on keratinocytes...

Two simple and sensitive extractive spectrophotometric methods have been described for the assay of levofloxacin (LVFX) either in pure form or in pharmaceutical formulations. The developed methods involve formation of colored chloroform extractable ion-pair complexes (1:1 and 1:2 drug/dye) of levofloxacin with bromophenol blue (BPB) and bromocresol green (BCG) in aqueous acidic medium. The extracted complexes showed absorbance maxima at 424 and 428 nm for LVFX-BPB and LVFX-BCG, respectively. Beer's law is obeyed in the concentration ranges 1...

Three methods are developed for the simultaneous determination of diprophylline (DP), phenobarbitone (PH) and papaverine hydrochloride (PP). The chromatographic method depends on a high performance liquid chromatographic (HPLC) separation on a reversed-phase C18 column with a mobile phase consisting of 0.02 M potassium dihydrogen phosphate, pH 3.5--acetonitrile (55:45 v/v). Quantitation was achieved with UV detection at 210 nm based on peak area. The other two chemometric methods applied were principal component regression (PCR) and partial least squares (PLS-1)...

The use of a UV double divisor-ratio spectra derivative calibration for the simultaneous analysis of synthetic samples and commercial tablet preparations without prior separation is proposed. The method was successfully applied to quantify three ternary mixtures, chlorpheniramine maleate and caffeine combined with paracetamol or acetylsalicylic acid and a mixture of acetylsalicylic acid combined with paracetamol and caffeine, using the information in the absorption spectra of appropriate solutions. Beer's law was obeyed in the concentration range of 0...

This study was carried out to develop a membrane-controlled transdermal formulation (TF) of nicotine by using sustained release dosage design (SRDD). TFs were prepared with polyethylene membrane as a rate-controlling barrier; a carbomer was used as the gel reservoir with or without propylene glycol (PG). The in vitro target flux (0.0535 mg cm(-2) h(-1)) was calculated according to SRDD calculations. Nicotine permeation through the membrane with or without transfer adhesive was also studied using diffusion cells...