Showing papers in "Farmaco in 2002"

Synthesis and anti-inflammatory activity of 1-acylthiosemicarbazides, 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazole-3-thiones.

Abstract: Sixteen 1-(2-naphthyloxyacetyl)-4-substituted-3-thiosemicarbazide, 2-(2-naphthyloxymethyl)-5-substitutedamino-1,3,4-oxadiazole, 2-(2-naphthyloxymethyl)-5-substitutedamino-1,3,4-thiadiazole and 5-(2-naphthyloxymethyl)-4-substituted-1,2,4-triazole-3thione derivatives have been prepared and evaluated as orally active anti-inflammatory agents with reduced side-effects. The structures of the compounds were confirmed by IR and 1H NMR spectral data and microanalysis. The anti-inflammatory and ulcerogenic activities of the compounds were compared with naproxen, indomethacin and phenylbutazone. In carrageenan-induced foot pad edema assay, 2-(2-naphthyloxymethyl)-5-methylamino-1,3,4-oxadiazole, 5-(2-naphthyloxymethyl)-4-methyl-1,2,4-triazole-3-thione and 5-(2-naphthyloxymethyl)-4-ethyl-1,2,4-triazole-3-thione showed an interesting anti-inflammatory activity. In the air-pouch test, 1,3,4-oxadiazole and 1,2,4-triazole-3-thione derivatives reduced total number of leukocytes of the exudate that indicates excellent inhibition of prostaglandin production. Side effects of the compounds were examined on gastric mucosa, liver and stomach and none of the compounds showed significant side effects compared with reference nonsteroidal anti-inflammatory drugs (NSAIDs).

Synthesis of halogen derivatives of benzo[h]chromene and benzo[a]anthracene with promising antimicrobial activities.

Abstract: The synthesis of novel 7-(4-halophenyl)-8,9-dihydro-7H-12-oxa-9,11-diaza-benzo[a]anthracene derivatives has been reported. The key intermediate 3-amino-9-chloro-1-(4-halophenyl)-1H-benzo[h]chromene-2-carbonitrile (3) was obtained by treating 4-halobenzylidenmalononitriles (1a-c) and ethyl 4-halobenzylidenmalonates (1d-f) with 4-chloro-1-naphthol (2) in ethanolic piperidine solution. Antimicrobial activity was shown for most of the synthesized compounds.

Synthesis and antimicrobial activity of some new hydrazones of 4-fluorobenzoic acid hydrazide and 3-acetyl-2,5-disubstituted-1,3,4-oxadiazolines

Abstract: A series of hydrazide hydrazones and 1,3,4-oxadiazolines of 4-fluorobenzoic acid hydrazide were prepared and evaluated as potential antimicrobial agents and were tested for their antibacterial and antifungal activities against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans. From these compounds, 4-fluorobenzoic acid[(5-nitro-2-furanyl)methylene]hydrazide (1a) showed equal activity with ceftriaxone against S. aureus. In addition, the MIC values of compounds 1c, 1d and 2a for the same strain were in the range of those reported for ceftriaxone according to NCCLS 1997.

Structure–activity relationships of some 3-substituted-4-hydroxycoumarins as HIV-1 protease inhibitors

Abstract: The screening of the HIV-1 protease (PR) inhibitory activity (IC-50) of various substituted 3-phenyl-4-hydroxycoumarins, 3-benzyl-4-hydroxycoumarins, 3-phenoxy-4-hydroxy-coumarins, 3-benzenesulfonyl-4-hydroxycoumarins and 3-(7-coumarinyloxy)-4-hydroxycoumarins was performed. The data indicate the importance of substituents at positions 5 and 7 of the coumarin ring on the inhibitory potency of the HIV-1-PR.

Synthesis and antiviral activity evaluation of some new 6-substituted 3-(1-adamantyl)-1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles.

Abstract: A number of novel 3,6-disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole derivatives, containing the adamantyl moiety, were synthesized and examined in various viral test systems No antiviral effects were noted with any of the compounds at subtoxic concentrations in cell culture

The medicinal chemistry of multidrug resistance (MDR) reversing drugs.

Abstract: Multidrug resistance (MDR) is a kind of resistance of cancer cells to multiple classes of chemotherapic drugs that can be structurally and mechanistically unrelated. Classical MDR regards altered membrane transport that results in lower cell concentrations of cytotoxic drug and is related to the over expression of a variety of proteins that act as ATP-dependent extrusion pumps. P-glycoprotein (Pgp) and multidrug resistance protein (MRP1) are the most important and widely studied members of the family that belongs to the ABC superfamily of transporters. It is apparent that, besides their role in cancer cell resistance, these proteins have multiple physiological functions as well, since they are expressed also in many important non-tumoural tissues and are largely present in prokaryotic organisms. A number of drugs have been identified which are able to reverse the effects of Pgp, MRPI and sister proteins, on multidrug resistance. The first MDR modulators discovered and studied in clinical trials were endowed with definite pharmacological actions so that the doses required to overcome MDR were associated with unacceptably high side effects. As a consequence, much attention has been focused on developing more potent and selective modulators with proper potency, selectivity and pharmacokinetics that can be used at lower doses. Several novel MDR reversing agents (also known as chemosensitisers) are currently undergoing clinical evaluation for the treatment of resistant tumours. This review is concerned with the medicinal chemistry of MDR reversers, with particular attention to the drugs that are presently in development.

HPLC assay of acetylsalicylic acid, paracetamol, caffeine and phenobarbital in tablets.

Abstract: This paper present a HPLC method for simultaneous determination of acetylsalicylic acid, paracetamol, caffeine and phenobarbital in tablets, using chromatographic system consisting a Bio Rad 18 01 solvent pump, Rheodine 71 25 injector and Bio Rad 18 01 UV-Vis Detector. Separation was achieved using Bio SiL HL C18, 5 microm, 250 x 4.6 mm column. Mixture of acetonitrile-water (25:75 v/v) adjusted to pH 2.5 with phosphoric acid was used as a mobile phase at a flow rate of 2.0 ml min(-1). UV detection was at 207 nm range 0.01 AUFS. Under the same conditions it was possible to determine the level of salicylic acid. The chromatographic parameters such as retention times, capacity factor, peak asymmetry, selectivity factor and resolution factor was determined. The validation parameters: linearity (r > 0.998), intra-day precision (RSD: 0.36-1.89%) and inter-day precision (RSD: 0.58-2.18%), sensitivity (LOD: 9 x 10(-5)-1.7 x 10(-4) mg ml(-1) and LOQ: 2.5 x 10(-4)-5.6 x 10(-4) mg ml(-1)), accuracy (recoveries: 98.35-99.14%) and reproducibility (recovery values: 98.74-102.08% for acetylsalicylic acid, 99.93-102.11% for paracetamol, 98.25-102.12% for caffeine and 98.15-102.3% for phenobarbital) (RSD: 1.21-1.85%) were found to be satisfactory. The proposed HPLC method has been applied for the determination of acetylsalicylic acid, paracetamol, caffeine and phenobarbital in Malophenum tablets. The obtained RSD values were within 0.99-1.21%. The developed method is rapid and sensitive and therefore suitable for routine control of these drugs in dosage form.

Synthesis, characterization and evaluation of antituberculosis activity of some hydrazones.

Abstract: Several new hydrazone derivatives were prepared by the reaction of some active hydrogen compounds with the diazonium salts of 4-amino-3,5-di/1,3,5-trimethylpyrazoles at 0-5 degrees C. Structures of the new substances were confirmed using UV, IR, 1H NMR, 13C NMR and EI-mass spectral data. In vitro antituberculosis activity of these compounds were tested on Mycobacterium tuberculosis H37Rv at 6.25 microg/ml. Both hydrazone products, ethyl 2-[(3,5-dimethylpyrazole-4-yl)hydrazono]-3-oxobutyrate (3d) and methyl 2-[(3,5-dimethylpyrazole-4-yl)hydrazono]4-methoxy-3-oxobutyrate (3e) showed 29 and 28% inhibition against M. tuberculosis, respectively.

Synthesis and antimicrobial activity of some 1,3,4-oxadiazole derivatives

Abstract: Six new 5-(1-/2-naphthyloxymethyl)-1,3,4-oxadiazole-2(3 H )-thione, 2-amino-5-(1-/2-naphthyloxymethyl)-1,3,4-oxadiazole, 5-(1-/2-naphthyloxymethyl)-1,3,4-oxadiazole-2(3 H )-one derivatives have been synthesized from 1-and/or 2-naphthol. The structures of the compounds were confirmed by IR and 1 H NMR spectral data and microanalysis. The antimicrobial properties of the compounds were investigated against Staphylococcus aureus , Escherichia coli and Pseudomonas aeruginosa , Candida albicans , C . krusei and C. parapsilosis using microbroth dilution method. 2-Amino-5-(2-naphthyloxymethyl)-1,3,4-oxadiazole and 5-(2-naphthyloxymethyl)-1,3,4-oxadiazole-2(3 H )-one show significantly (32 μg/ml), compounds 5-(1-/2-naphthyloxymethyl)-1,3,4-oxadiazole-2(3 H )-thione, 2-amino-5-(1-naphthyloxymethyl)-1,3,4-oxadiazole and 5-(1-naphthyloxymethyl)-1,3,4-oxadiazole-2(3 H )-one moderately (64 μg/ml) active against C. krusei. All the compounds were active against S. aureus , E. coli , P. aeruginosa , C. albicans , and C. parapsilosis at 64–256 μg/ml concentration.

Optimization strategies for HPLC enantioseparation of racemic drugs using polysaccharides and macrocyclic glycopeptide antibiotic chiral stationary phases

Abstract: The chiral resolution by high performance liquid chromatography (HPLC) is controlled by a number of parameters. The optimization of HPLC parameters is an important issue in chiral resolution. This review discusses the optimization of HPLC conditions for the chiral resolution of racemic drugs on polysaccharides and macrocyclic glycopeptide antibiotic chiral stationary phases (CSPs). The most important parameters discussed are composition of mobile phase, pH of mobile phase, flow rate, temperature and effect of other parameters.

Synthesis antimicrobial and antifungal activity of some new 3 substituted derivatives of 4-(2,4-dichlorophenyl)-5-adamantyl-1H-1,2,4-triazole.

Abstract: The synthesis of a series of substituted hydrazones and thiazolidinones is described, starting from N-[4-(2,4-dichlorophenyl)-5-adamantyl-1H-1,2,4-triazol-3-ylmercaptoacetyl)hydrazine. The new compounds were tested for antimicrobial and antifungal activity and some of them exhibited moderate activity against Candida albicans.

Synthesis and antituberculosis activity of new N-phenyl-N'-[4-(5-alkyl/arylamino-1,3,4-thiadiazole-2-yl)phenyl]thioureas.

Abstract: In this study, eight original N-phenyl-N'-[4-(5-alkyl/arylamino-1,3,4-thiadiazole-2-yl)phenyl]thiourea derivatives were synthesized and tested for antituberculosis activity. Antituberculosis activities of the synthesized compounds were screened in vitro using BACTEC 460 Radiometric System against Mycobacterium tuberculosis H37Rv at 6.25 microg/ml. The highest inhibition observed with the synthesized compounds is 67% for N-phenyl-N'-[4-(5-cyclohexylamino-1,3,4-thiadiazole-2-yl)phenyl]thiourea.

Identification and mapping of small-molecule binding sites in proteins: computational tools for structure-based drug design

Abstract: The number of protein structures is currently increasing at an impressive rate. The growing wealth of data calls for methods to efficiently exploit structural information for medicinal and pharmaceutical purposes. Given the three-dimensional (3D) structure of a validated protein target, the identification of functionally relevant binding sites and the analysis ('mapping') of these sites with respect to molecular recognition properties are important initial tasks in structure-based drug design. To address these tasks, a variety of computational tools have been developed. Approaches to identify binding pockets include geometric analyses of protein surfaces, comparisons of protein structures, similarity searches in databases of protein cavities, and docking scans to reveal areas of high ligand complementarity. In the context of binding-site analysis, powerful data mining tools help to retrieve experimental information about related protein-ligand complexes. To identify interaction hot spots, various potential functions and knowledge-based approaches are available for mapping binding regions. The results may subsequently be used to guide virtual screenings for new ligands via pharmacophore searches or docking simulations.

Synthesis and preliminary anticancer activity of new 1,4-dihydro-3-(3-hydroxy-2-naphthyl)-4-substituted-5H-1,2,4-triazoline-5-thiones.

Abstract: 1,4-Dihydro-3-(3-hydroxy-2-naphthyl)-4-substituted-5H-L2,4-triazolinc-5-thiones were synthesized. The structures of original eight compounds were confirmed by elemental analysis, 1H NMR and mass spectral methods. One of the compounds (3a) was tested in vitro for its anticancer activity against 52 human tumor cell lines.

Synthesis and anti-hIV activity of 1-(2,6-difluorophenyl)-1H,3H-thiazolo[3,4-a]benzimidazole structurally-related 1,2-substituted benzimidazoles.

Abstract: The synthesis of 1,2-substituted benzimidazoles is reported. These novel derivatives share chemical similarities with 1-aryl-1H,3H-thiazolo[3,4-a]benzimidazoles, a class of HIV-1 NNRTIs studied widely. All compounds prepared were tested in MT-4 cells to explore their potential anti-HIV activity and were found to be less potent than 1-(2,6-difluorophenyl)-1H,3H-thiazolo[3,4-a]benzimidazole (TBZ).

Fluorimetric determination of some thiol compounds in their dosage forms.

Abstract: A simple fluorimetric procedure was adopted for determination of three pharmaceutical compounds containing thiol groups namely, captopril, d-penicillamine and N-acetylcysteine. In this method, the drugs are treated with 1,2-naphthoquinone-4-sulfonic acid. The latter is reduced to 1,2-dihydroxynaphthalene-4-sulfonic acid which has a maximum fluorescence intensity at 480/318 nm (λEm/Ex). The method is sensitive to 0.5–4.5 μg ml−1 with minimum detectability 0.05 μg ml−1 (S/N=2), and has been applied to determine these three thiols in their dosage forms. The results obtained are compared favourably with those obtained by their pharmacopeial methods.

Characterization and solubility study of solid dispersions of flunarizine and polyvinylpyrrolidone.

Abstract: Flunarizine is a selective calcium entry blocker poorly water-soluble. In this report, the interactions of this drug with polyvinylpyrrolidone in solid dispersions, prepared according to the dissolution method using methanol as the solvent, have been investigated. For purposes of comparison physical mixtures were prepared by simple mixture and homogeneization of the two pulverized components. Combinations of flunarizine/polyvinylpyrrolidone of the following percentage proportions were prepared: 10/90, 20/80, 30/70, 40/60, 50/50, 60/40 and 80/20 (mean particle size of 0.175 mm). The physicochemical properties of solid dispersions were investigated with X-ray diffraction, infrared spectroscopy, differential scanning calorimetry and solubility in equilibrium. X-ray patterns and differential scanning calorimetry have shown that polyvinylpyrrolidone inhibits the crystallization of flunarizine when percentages drug/polymer are 10/90, 20/80 and 30/70. The infrared spectra suggest that there was no chemical interaction between flunarizine and polyvinylpyrrolidone. Equilibrium solubility studies showed that drug solubility was enhanced as the polymer content increased. In general, the solubility increase was greater in solid dispersions than in physical mixtures and the solubility in equilibrium for solid dispersions and physical mixtures at the same drug/polymer proportion showed significant differences ( P

Synthesis and antimicrobial activities of N-substituted imides.

Abstract: In the field of our research programs concerning novel antimicrobial agents, a series of N-substituted imides was synthesized. These compounds were obtained by cyclization of amido-acids in acetic anhydride/sodium acetate or hexamethyldisilazane/zinc bromide for the hydroxy-aromatic derivatives. The hydroxy-alkyl maleimides were directly prepared by condensation of the corresponding amino-alcohol with maleic anhydride in boiling toluene. Most of N-substituted maleimides showed an interesting antimicrobial activity towards bacteria from the ATCC collection (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853) but the MIC values for P. aeruginosa were always high (128 microg/ml). The imides with alkyl substituents showed higher activities than aromatic analogues with MIC values in the range of 8-32 microg/ml. Comparatively, succinimides were practically inactive.

Chromatographic determination of clotrimazole, ketoconazole and fluconazole in pharmaceutical formulations

Abstract: High-performance liquid chromatographic technique has been developed for the determination or some azolcsantifungals namely, clotrimazole (CZ), ketoconazole (KZ) and fluconazole (FZ), in pure forms and in pharmaceutical formulations. The proposed HPLC-method can be successfully applied as a stability indicating method for the determination of CZ in presence of its acid degradation products; viz (2-chlorophenyl) -diphenyl methanol and imidazole. The analyzed drugs were separated on a reversed-phase column [Bondapak™ C18 (10 μm, 25 cm×4.6 mm, i.d.)] using a mobile phase containing acetonitrilc+25 mM trishydroxymeihyl aminomethane in phosphate butter (pH 7)=55:45 (v/v), with UV-detection at 260 nm. The differences in the retention times (tR) of the three azoles permit their use as internal standard for each other. In addition, a coupled TLC-densitometric method has been also applied as a stability indicating method to separate and quantify CZ alone or in presence of byproducts impurities and/or its acid degradation products. The TLC-fractionation was performed on a precoatcd silica gel F254 plates using a solvent system consisting of chloroform+acetone+ammonia (25%) (7:1:0.1, by volumes), CZ was well separated from its acid degradation products and quantified by densitometric scanning at 260 nm.

Synthesis of some 1,2,4-triazolo[3,2-b]-1,3-thiazine-7-ones with potential analgesic and antiinflammatory activities.

Abstract: Starting from 3-substituted-1,2,4-triazole-5-thiones (la-h), eight new 5-carbomethoxy-2-substituted-7H-1,2,4-triazolo[3,2-b]-1,3-thiazine-7-ones (2a-h) were synthesized and characterized by spectral and elementary analysis. The obtained compounds were submitted to preliminary pharmacological assay to evaluate their antiinflammatory and analgesic activities as well as gastrointestinal irritation liability and acute toxicity. Among the compounds studied, compounds 2c, 2d, 2e and 2h showed most remarkable antiinflammatory activity in the carrageenan and serotonin induced edema and in the inhibition of castor oil-induced diarrhea tests. The analgesic activity of these active compounds correlated with their antiinflammatory activities in the inhibition of acetic acid-induced writhing test. In gastric ulceration studies, the compounds were found safety at low dose levels (10 and 20 mg/kg).

Novel synthesis and antifungal activity of pyrrole and pyrrolo[2,3-d]pyrimidine derivatives containing sulfonamido moieties.

Abstract: Several sulfonamides containing pyrroles ( 2a – c , 6a – d , 8a – d) , pyrrolo[2,3-d] pyrimidines ( 3a – c ), acetanilides ( 11a – c ) and tetrahydrobenzothiophenes ( 13a – c ) were synthesized starting from N 4 -chloroacetylsulfanilamides ( 1a – d ). The structures of synthesized compounds were elucidated by elemental analyses and spectral data. Compounds 2b , 3b , 6b , 8b and 8d exhibited a remarkable antifungal activity compared with the standard fungicide mycostatine.

Progress in 5H[1]benzopyrano[4,3-d]pyrimidin-5-amine series: 2-methoxy derivatives effective as antiplatelet agents with analgesic activity.

Abstract: A series of 2-methoxy-5H[1]benzopyrano[4,3-d]pyrimidin-5-amines were prepared and screened for their in vitro antiplatelet activity inducing the aggregation by ADP, arachidonic acid (AA) and collagen. In vivo experiments were performed in order to evaluate their antiphlogistic, analgesic and antipyretic activities. Title compounds showed antiplatelet activity in aggregation AA or collagen-induced, and a good analgesic activity without any gastric toxicity. Comparison with a number of analogue benzopyrano[4,3-d]pyrimidine derivatives and some SAR consideration were reported.

Synthesis and anti-HIV activity of 2,3-diaryl-1,3-thiazolidin-4-(thi)one derivatives

Abstract: Several 2,3-diaryl-1,3-thiazolidine-4-thione derivatives and 2,3-diaryl-1,3-thiazolidin-4-ones bearing a methyl group at C-5 position have been synthesized and tested as anti-HIV agents. The results of the in vitro tests showed that some of them proved to be effective inhibitors of HIV-1 replication.

Solid-supported reagents for multi-step organic synthesis: preparation and application.

Abstract: Since the early days of combinatorial chemistry solid-phase organic synthesis has been the method of choice for the production of large libraries Solution-phase synthesis is again gaining importance especially for the synthesis of parallel arrays of smaller, focussed libraries containing single compounds with high degrees of purity In the field of solution-phase library generation, the use of solid-supported reagents, catalysts and scavengers is emerging as a leading strategy, combining the advantages of both solid-phase organic synthesis (eg allowing the employment of an excess of reagent without the need for additional purification steps) and solution-phase chemistry (eg the ease of monitoring the progress of the reactions by applying LC-MS, TLC or standard NMR techniques) An account of some of the most recent advances in this area of research will be presented

New benzimidazole derivatives as antimycobacterial agents

Abstract: A set of 2-alkylsulfanyl derivatives of 5-methylbenzimidazole was synthesized and evaluated for antimycobacterial activity. The structures of the compounds were confirmed by 1H NMR and IR data, and their purity by elemental analysis. Antimycobacterial activities against Mycobacterium tuberculosis and nontuberculous mycobacteria were expressed as the minimum inhibitory concentration. The substances exhibited significant antimycobacterial activity, in particular against both strains of Mycobacterium kansasii. The effect of the most active compound in the set, 3,5-dinitro derivative 3t, exceeded that of the standard isoniazide against M. kansasii and Mycobacterium avium.

Antimycobacterial activity of 5-arylidene derivatives of hydantoin.

Abstract: The synthesis of various 5-arylidene-2-thiohydantoins and results of the primary assay in vitro for their antimycobacterial activity is reported. Eight of those compounds exhibited >90% inhibition of Mycobacterium tuberculosis growth and for them the minimum inhibitory concentrations, cytotoxicity (IC 50 ) and the selectivity index values were determined. The most active structure, (5 Z )-5-(1,1′-biphenyl-4-ylmethylene)-2-thioxoimidazolidin-4-one, showed MIC=0.78 μg/ml. For all compounds log P and log D (pH 6.5) values were calculated.

Synthesis, characterization of novel coupling products and 4-arylhydrazono-2-pyrazoline-5-ones as potential antimycobacterial agents.

Abstract: Novel coupling products 7a-d and 4-arylhydrazono-2-pyrazoline-5-ones 8a-e were synthesized and evaluated for antimycobacterial activity against Mycobacterium tuberculosis H37Rv and Mycobacterium avium. Compound 7b was found to be the most potent derivatives of the 7a-d series by an MIC value of 6.25 microg/ml.

Antituberculosis agents. V. Synthesis, evaluation of in vitro antituberculosis activity and cytotoxicity of some 2-(5-nitro-2-furyl)-1,3,4- thiadiazole derivatives

Abstract: A new series of 2-(5-nitro-2-furyl)-1,3,4-thiadiazole-2-sulfide, sulfoxide and sulfones were synthesized and evaluated for in vitro antituberculosis activity against Mycobacterium tuberculosis strain H 37 Rv using the radiometric BACTEC 460-TB methodology. Active compounds were also screened by serial dilution to assess toxicity to a VERO cell line. The results indicate that some compounds exhibited a good antituberculosis activity and the ethylthio analogue ( 5b ) was the most active compound (MIC=0.78 μg ml −1 ). Also, the cytotoxic effects indicate that compound 5b was the least toxic compound.

Simultaneous determination of metronidazole and miconazole in pharmaceutical dosage forms by RP-HPLC.

Abstract: A reversed-phase high performance liquid chromatography (RP-HPLC) method with UV detection is described for the simultaneous determination of metronidazole and miconazole in pharmaceutical dosage forms. Chromatography was carried out on a C18 reversed-phase column, using a mixture of methanol–water (40+60, v/v) as a mobile phase, at a flow rate of 1.0 ml min−1. Sulfamethoxazole was used as an internal standard and detection was performed using a diode array detector at 254 nm. The method produced linear responses in the concentration ranges 10–70 and 1–20 μg ml−1 with detection limits 0.33 and 0.27 μg ml−1 for metronidazole and micanozole, respectively. This procedure was found to be convenient and reproducible for analysis of these drugs in ovule dosage forms.

Influence of irradiation sterilization on poly(lactide-co-glycolide) microspheres containing anti-inflammatory drugs.

Abstract: -Irradiation is finding increasing use in the sterilization of pharmaceutical products. However, irradiation might also affect the performance of drug delivery systems. In this study, the influence of -irradiation on the physicochemical properties of two commonly used non-steroidal anti-inflammatory drugs (NSAIDs) [naproxen sodium (NS) and diclofenac sodium (DS)] was investigated. The drugs were incorporated in poly(lactide-co-glycolide) (PLGA, 50:50; molecular weight 34 000 or 88 000 Da) microspheres. The biodegradable microspheres were irradiated at doses of 5, 15, 25 kGy using a 60 Co source. Drug loading of irradiated and non-irradiated microspheres with both 34 000 and 88 000 Da polymers were essentially the same. A significant difference was noticed in the particle sizes of the irradiated as compared to the non-irradiated formulations. Notably, in release studies, the amount of active substance released from PLGA microspheres showed an increase with increasing irradiation dose. In DSC, the glass transition temperatures (Tg) of microspheres exhibited a slow increase with irradiation dose. © 2002 Elsevier Science S.A. All rights reserved.