Development and physical characterization of chloramphenicol loaded biodegradable nanoparticles for prolonged release.

The objectives of our study were to prepare a biodegradable nanoparticulate system of chloramphenicol (CHL) and to evaluate its ability to prolong in vitro release of CHL compared to free drug suspension (FDS). CHL-loaded polylactide-co-glycolide nanoparticles (CHL-PLGA-NPs) were prepared by an emulsion/solvent evaporation method using ethyl acetate and polyvinyl alcohol. CHL-PLGA-NPs were characterized by particle size, zeta potential, infrared spectra, drug entrapment efficiency and in vitro release kinetics measurement. Sonication was done with an ultrasound pulse sonicator at 70 W, 30 kHz for 60 s to produce stable NPs of mean size range from 277 nm to 433 nm. Drug to polymer ratio (D:P) was selected as formulation variable and significantly influenced entrapment efficiency (approximately 30% to 66%) and release (p < 0.05). Entrapment of CHL in biodegradable NPs significantly prolonged drug release compared to FDS and thus implies potential antibiotic delivery system for ocular application.

A validated UV spectrophotometric method for determination of duloxetine hydrochloride.

A simple, sensitive and accurate UV spectrophotometric method was developed for the assay of duloxetine hydrochloride in raw material and capsules. Validation of the method yielded good results concerning range, linearity, precision and accuracy. The absorbance was measured at 290 nm for duloxetine capsule solution. The linearity range was found to be 5-50 microg/mL for the drug. It was found that the excipients in the commercial formulation did not interfere with the methods.

A validated UV spectrophotometric method for estimation of nebivolol hydrochloride in bulk and pharmaceutical formulation.

A simple, sensitive and accurate UV spectrophotometric method was developed for the assay of nebivolol hydrochloride in raw material and tablets. Validation of the method yielded good results concerning range, linearity, precision and accuracy. The absorbance was measured at 282 nm for nebivolol hydrochloride tablet solution. The linearity range was found to be 5-50 microg/mL for the drug. It was found that the excipients present in the commercial formulation did not interfere with the method.

Anomalous magnetic properties of mechanically milled cobalt oxide nanoparticles.

Defect induced magnetic properties of CoO nanoparticles produced via mechanical ball milling have been assessed by detailed magnetic measurements. A progressive decrease in the particle size and a concomitant increase in the induced strain have been observed with the milling times. The mechanically milled nanoparticles of CoO exhibit anomalous magnetic properties such as FM hysteresis when compared with the unmilled CoO sample. The presence of weak ferromagnetism, with a highest value of magnetization of 0.532 emu/g at 10 K in the 100 h milled sample, is attributed to the uncompensated surface spins resulting from induced surface defects via mechanical milling. The ZFC coercive force, measured at 10 K, increases with milling time reaching a maximum value of 1066 Oe for the 100 h milled sample. The temperature dependent field-cooled (FC) and zero-field-cooled (ZFC) magnetic measurements indicate a presence of an exchange bias field arising from uncompensated moments generated by mechanical strain and the antiferromagnetic (AFM) core. The exchange bias field measured at 10 K reaches a value 210 Oe for the 50 h milled sample and decreases upon prolonged milling. The exchange bias field vanishes at a temperature approximately 200 K, a temperature much lower than the Neel temperature of CoO (TN approximately 291 K). The observed anomalous magnetic behavior of CoO could be interpreted in terms of the exchanged bias FM-AFM model.

Preparation and in vitro dissolution of isoniazid from ethylcellulose microcapsules.

Microcapsules of isoniazid were prepared by phase separation coacervation process induced by non-solvent addition and using ethylcellulose (EC) as coating polymer. When polyisobutylene (PIB)--a protective colloid was present at sufficient concentration, film coated drug particles were formed. At 0-6% PIB concentration, the microcapsules were aggregated. Increase of colloid concentration produced microcapsules of less aggregation and higher drug content because coating became progressively thinner. PIB concentration also controlled the particle size and the release rate of drug from microcapsules. Wall thickness and EC loss were calculated from drug content. Microcapsules coated with EC were prepared with 7-9% PIB. Scanning Electron Microscopy was used to study the nature of aggregation and coating behaviour. The in vitro dissolution study confirmed the first order release pattern and also the Higuchi Matrix model.

Statistical optimization of transdermal drug delivery system of terbutaline sulfate by factorial analysis.

A matrix type of transdermal drug delivery system of terbutaline sulfate was designed and developed by full 3(2) factorial method using polyvinyl alcohol (PVA) of medium molecular weight and polyvinyl pyrrolidone (PVP K-30) as matrix forming polymer and propylene glycol as plasticizer. Patches were designed to deliver 62 micrograms/cm2/hr of the drug into the systemic circulation. These were evaluated for in vitro skin permeation study through excised guinea pig skin. The permeation followed Higuchi kinetics, as its coefficients of correlation (r = 0.965-0.978) predominates over other permeation kinetics. Various physico-chemical parameters of the patches were investigated. Statistical optimization of in vitro permeation rate of the drug from the films were evaluated using two way analysis of variance (ANOVA), regression analysis.

Development of amphotericin B loaded nanoparticles.

Amphotericin B loaded nanoparticles were successfully prepared by in-situ emulsion polymerization technique using Ethylcyanoacrylate monomer. Scanning Electron Micrographs (SEM) of the nanoparticles showed that the particles were spherical and discrete. Average particle size analysis of two samples were found to be within the range of 475.3 +/- 91.68 to 479.75 +/- 105.49 nm. Thus the particles formed were within the colloidal range. With increase in monomer concentration, the percentages of drug adsorbed on the surface of nanoparticles were also increased. At the optimum concentration of Ethylcyanoacrylate (21.6 microliters/ml), 72.1% of Amphotericin B was adsorbed.

Development and evaluation of an ideal formulation of glibenclamide by solid dispersion techniques.

An attempt was taken to develop an ideal formulation of Glibenclamide. Considering the physico-chemical nature of the drug the solid dispersion system was utilised using hydrophilic and hydrophobic carriers and formulations were made by fusion as well as solvent evaporation/co-precipitation techniques. The resulting formulations were evaluated in respect of physical nature, yield, assay content and stability. The in vitro release profiles of the formulations were compared with the marketed tablet and simple physical mixtures having same composition of drug and excipients. The effects of various carriers as well as manufacturing procedures on the in vitro release rate of drug were also studied. It is observed that a suitable blend of different batches of solid dispersions containing hydrophilic and hydrophobic carriers will give an optimum formulation with quick onset and prolonged duration of action.

Computer supported studies on design and evaluation of solid dispersions of carbamazepine.

The main advantages of solid dispersions (the drug could be maintained in a bioavailable form, dosage reduction and cleaner manufacturing conditions) provide scope for the continued interest in field. Additionally, their use in providing a sustained or controlled release of drugs has only been tentatively examined. In the present study, Carbamazepine has been used to develop a dosage form which will provide a booster amount followed by sustained release of the drug for effective control of epileptic seizures while keeping the serum level of the drug at minimum. Enteric polymers CAP and CAT have been used to retard the release till the formulation reaches the intestine. Either individually or combined fractions of the formulations may be used in the therapy of epilepsy.

Product development studies for stabilization of oral liquid enzyme preparations containing diastase and papain.

A product development study was undertaken with a view to stabilize acid sensitive amylolytic enzyme diastase and alkali sensitive proteolytic enzyme papain. An unique high technology method was adopted for both enzymes with enteric coating and non-enteric film forming materials respectively to achieve site specificity of action, better stability and to protect diastase from the adverse acid pH of the stomach. Feasibility of incorporating various excipients like thickening agents, surfactants, preservatives, etc., to produce stable elegant oral liquid suspension was also studied. Release studies of the enzymes both in simulated gastric and simulated intestinal juices showed steady and consistent release. The proteolytic and amylolytic activities were assessed by standard pharmacopoeial methods. The stability of the product during the studies was satisfactory. Reduction in addition of overages of costly enzymes met the project technically feasible and economically viable.

Assessment of antibacterial activity of smaller chain tripeptides and tetrapeptides.

Our objective is to investigate the smaller chain tripeptides and tetrapeptides with the efforts mainly directed towards the identification of compounds presenting a high bactericidal activity. In this connection, 5 peptides, Met-Arg-Tyr (MRY), Met-Val-Tyr (MVY), Met-Ile-Cys-Tyr (MICY), Phe-Trp-Lys-Tyr (FWKY) and Met-Trp-Lys-Tyr (MWKY) were synthesized by solid phase peptide synthesis. The column eluted pure synthesized compounds were tested for in-vitro antibacterial disc diffusion assay using 2 g positive S. aureus, B.subtilis and 1 g negative E.coli bacterial strains at different concentrations predicted by pH and inhibitory concentration findings. 2 of the tetrapeptides, Phe-Trp-Lys-Tyr (FWKY) and Met-Trp-Lys-Tyr (MWKY) were found to be highly efficient against all the gram positive and microbial strains tested. Maximum activity was observed at a concentration of 300 µg/ml (499.17 µM) for the tetrapeptide Phe-Trp-Lys-Tyr (FWKY) against B. subtilis and at a concentration of 450 µg/ml (748.75 µM) against E. coli with the corresponding zonal inhibition diameter readings (17 mm; 16 mm). The tetrapeptide Met-Trp-Lys-Tyr (MWKY) was found to have high potency against S. aureus at a concentration of 450 µg/ml (769.23 µM) with the corresponding zonal inhibition diameter as 13 mm. The experimental results are analysed statistically by t-test at 5% and 1% level of significance. Our tetrapeptides have shown antibacterial action against both gram positive and gram negative strains and are considered safer as par with commercial antibiotics available today. Further clinical studies will make sure to position our potent small chain tetrapeptides in the arsenal of new broad spectrum anti-gram positive and anti-gram negative agent.

Antimicrobial glycopeptides: synthesis and antibacterial activity of N-linked and O-linked smaller chain glycopeptides.

Our objective is to synthesize the smaller chain N-linked and O-linked glycopeptides using sugars belong to mono, di and polysaccharides, with the efforts mainly directed towards the identification of antibacterial compounds. 7 glycopeptides, viz., Arg-Asn-Mannose, Arg-Asn-Lactose, His-Asn-Mannose, His-Asn-Lactose (N-glycopeptides), Arg-Ser-Lactose, Arg-Thr-Lactose, Arg-Thr-Starch (O-glycopeptides) were prepared by dicyclohexyl carbodimide (DCC) coupling for amino acids using microwave oven (50W power; 15 min) and activated and coupled with respective sugar moieties using microwave oven at 120 W for 20-25 min. The column eluted compounds were tested for disc diffusion assay using 3 gram positive S. aureus, B. subtilis, S. caprae and 3 gram negative E. coli, P. aeruginosa and S. sonnei strains at different concentrations predicted by pH and inhibitory concentrations. One of the test glycopeptide, His-Asn-Lactose was found to be very effective against all the microbial strains tested and 3 other Test Compounds, viz., His-Asn-Mannose, Arg-Thr-Lactose and Arg-Thr-Starch are also proved to be effective against 2 gram positive and 2 gram negative strains tested. Maximum activity was observed at a concentration of 450 µg/ml (747.51 µM) for the N-glycopeptide His-Asn-Lactose with the corresponding zonal inhibition diameters (15 mm; 19 mm; 14 mm; 18 mm; 16 mm; 17 mm) against S. aureus, B. subtilis, S. caprae, E. coli, P. aeruginosa, S. sonnei. This is the first evidence based report that our N-glycopeptide, His-Asn-Lactose tested, has shown antibacterial action against both gram positive and gram negative strains. Further in vivo testing and clinical studies will make sure to position our potent small chain N-glycopeptide in the arsenal of new broad spectrum anti-gram positive and negative agent.

Antidiabetic Activity of the Ethanol Extract of Capparis sepiaria L Leaves.

Capparis sepiaria L, a profusely branched hedge plant, is used in Indian traditional medicine. Capparis sepiaria leaves were extracted with ethanol and concentrated to dryness. The LD(50) value was determined as 894.43 mg/kg body weight by acute toxicity study. The ethanol extract was investigated for possible hypoglycemic effect produced by single oral administration at various dose levels 100, 200 and 300 mg/kg in the streptozotocin induced diabetic rats and compared against normal saline control and the standard glibenclamide. A maximum fall of plasma glucose level 9.40%; 13.57%; 15.25% and 18.80% was observed after 12 h of treatment when administered with ethanol extract of Capparis sepiaria at 100, 200 and 300 mg/kg, and glibenclamide 10 mg/kg dose, respectively. The findings from the study suggest that the Capparis sepiaria leaves may be prescribed as an adjunct to traditional formulation and drug treatment for controlling diabetes mellitus.

Comparative anti - microbial evaluation studies of the extracts and isolates of leaves & bark of wrightia tomentosa.

The Butanol and Ethanol extract of the leaves and bark of Wrightia tomentosa along with its seven pure component isolates (BLF(28), BLF(29*), BBF(29), ELF(3), ELF7, ELF(17*), EBF(7) ) after fractionation by column chromatography were evaluated for antimicrobial activity against Gram positive (S. aureus, S. fecalis, S.albus and B.subtilis) and Gram negative (Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris & Klebsiella aerogenes) bacteria and the fungi Candida albicans by disc diffusion method. The extracts and isolates showed different degree of activity against pathogenic microbes. The results obtained were compared with standard drugs Ciprofloxacin (10µg) and Clotrimazole (10µg). The isolates of butanol bark extract (BBF(29)) followed by leaf extract(BLF(29*)) were considerably more effective than the ethanol leaf and bark extract in inhibiting all the microbial strains.

Pharmacognostical studies on leaves of commiphora caudata (wight & arn) engl.

Commiphora caudata (Wight & Arn) is a potential medicinal plant used for its antispasmodic activity, cytotoxic activity and hypothermic activity. Owing to its medicinal importance, macroscopic and microscopic characters of leaves of Commiphora caudata were studied.

Design and biopharmaceutical evaluation of nitrofurantoin-loaded Eudragit RS100 micropellets.

Nitrofurantoin, a synthetic bactericidal drug, was encapsulated with Eudragit RS 100 polymer by a coacervation phase separation technique using variable proportions of polyisobutylene (0% to 3%) as a protective colloid. The micropellets were evaluated by scanning electron microscopy (SEM), particle size distribution, wall thickness, and loss of wall polymer were determined. The in vitro release experiments were carried out over the entire pH range of the gastrointestinal tract, the data obtained from the dissolution profiles were compared in the light of different kinetic models, and the regression coefficients were compared. The in vivo studies were performed on female human volunteers. A linear correlation was obtained from in vitro-in vivo studies.

Product development studies on the tablet formulation of ibuprofen to improve bioavailability.

To improve the bioavailability of ibuprofen, a thorough preformulation trial was undertaken. As a part of these studies, particle size of the drug, solubility-pH profile, and pH-partition coefficient profile were studied. The probability of improving solubility by solid dispersion technique was also investigated. The effects of different binding agents and incorporation of various proportions of sodium lauryl sulfate on the release rate of ibuprofen were also studied. The in vitro release profiles of the developed tablets showed superiority over the popular marketed tablets.