Protein administration is often associated with practical problems due to it biological degradation in a very short time. Pegylation modification with monopolyethylene glycol (mPEG) is one of the ways to enhance thermal stability and solubility in organic solvents. mPEG can be applied to the development of diagnostics, targeting or imaging agents, and can be used in kinetic analysis or receptor binding studies. The mechanism of the immune system can also be deduced using these modified compounds. Pegylation can also be applied to other system like liposomes to enhance effectiveness of the delivery system. Site directed attachment and noncovalent attachment of mPEG open up the entire new spectrum of possibilities. Molecular weight changes and charge of the mPEG attached also provide new possibilities, thus opportunities for producing longer acting and cost effective end products. Realization of new thrilling horizon in the field of drug delivery system with polyethylene glycol is in the offing.

Multidrug resistance is a condition in which cells exhibit resistance to drugs to which they have never been exposed to previously. The main factor contributing to this is the overexpression of an energy-dependant multidrug transporter, P-glycoprotein. P-glycoprotein is also involved in the normal physiological functions. P-glycoprotein is widely distributed in the body and found in organs like lower gastrointestinal tract, kidney, liver, pancreas, testes and most importantly, the blood-brain barrier. Although, many mechanisms have been promulgated which involve P-glycoprotein in multidrug resistance, there is no satisfactory mechanism that reconciles the entire phenomenon related to multidrug resistance. Efforts have also been taken to isolate, characterize and spectroscopically analyze P-glycoprotein. Based on the available data, there are many agents, which are proven to be the substrates of P-glycoprotein. Moreover, there also are inhibitors to Pglycoprotein that enhance the intracellular levels of many drugs that are effluxed by P-glycoprotein.

Solid dispersions of glipizide were prepared using water-soluble carriers such as polyvinylpyrrolidone and polyethylene glycol by common solvent method in an attempt to increase the dissolution rate of glipizide, a practically insoluble drug in water. Differential scanning calorimetry, xray difiractometry and in vitro dissolution studies were used to characterize the solid dispersions. No chemical interaction was found between glipizide and polyvinylpyrrolidone/polyethylene glycol. The results from Differential scanning calorimetry and x-ray diffractometry studies show that polyvinylpyrrolidone/polyethylene glycol inhibits the crystallization of glipizide. The solid dispersions prepared in this study were found to have higher dissolution rates compared to intact glipizide and physical mixtures of polyvinylpyrrolidone/polyethylene glycol and glipizide. It was found that the optimum weight ratio for glipizide:carrier is 1:5 for polyvinylpyrrolidone and 1:7 for polyethylene glycol.

The hydrochloride salts of N-Mannich bases of ibuprofenamide, which in turn was prepared using either morpholine or piperidine as the amine component. The characterization of the N-Mannich bases was done by element analysis, IR spectroscopy and NMR spectroscopy. Physico-chemical properties such as solubility, dissolution-rate and partition-coefficient were determined. The hydrochloride salt of N-Mannich bases of ibuprofenamide prepared using morpholine was found to be water soluble whereas the one prepared using piperidine was found to be water insoluble. The dissolution rate studies showed that dissolution rate of N-Mannich base of ibuprofenamide was pH-independent whereas that of piperidine was pH-dependent.

The kinetics of decomposition of N-Mannich base derivatives of ibuprofenamide was studied to assess their utility as a prodrug for ibuprofen. These kinetic studies were performed in aqueous buffers at different pH values, in simulated gastric and intestinal fluids and in human plasma at 37o. Kinetic studies in aqueous buffers at different pH showed that these derivatives undergone pH dependent hydrolysis. The pH-rate profile for these compounds had a sigmoidal shape. These N-Mannich bases were hydrolyzed to ibuprofenamide but in no case ibuprofen was released. Kinetic studies performed in simulated gastric and intestinal fluid showed that there was not much effect of gastric and intestinal constituents on the release rate. But the kinetic studies performed in human plasma showed that some amount of ibuprofenarnide was converted to ibuprofen which might be due to the presence of proteolytic enzymes in human plasma.

The aim of the present study was to design nimodipine tablets with fast in vitro release rates using nimodipine-modified gum karaya co-grinding mixtures. Co-grinding mixtures of nimodipine and gum karaya were also prepared to highlight the efficiency of modified gum karaya. Physical mixtures of nimodipine with both the carriers were prepared for comparison. All the solid mixtures were characterized by differential scanning calorimetry and X-ray diffraction studies. Solubility studies and in vitro release rate studies were performed for all the solid mixtures to explain the results. Nimodipine tablets were formulated employing nimodipine-gum karaya/modified gum karaya co-grinding mixtures and their corresponding physical mixtures. The compressed tablets were evaluated for various tablet characteristics including in vitro dissolution rate studies. The best results from the dissolution test were obtained for tablets containing nimodipine-modified gum karaya co-grinding mixtures.

A sensitive and rapid extractive spectrophotometric method was developed for the assay of ceterizine hydrochloride in bulk drug, pharmaceutical preparations, urine and blood samples. The method was based on the formation of a chloroform soluble ion-pair complex between ceterizine hydrochloride with thymol blue in an acidic buffer. The complex showed absorption maximum at 413 nm with molar absorptivity of 4.2 X 103l/cm.mol. The system obeyed Beer's law in the concentration range of 3-60 μg/ml (r=0.9992). The results obtained by the proposed method were compared statistically by means of Student t-test and by the F- test with those of the reported method. The two were shown to be in good agreement. No interference was observed from common pharmaceutical excipients.

Entrapment efficiency and particle size distribution are important properties affecting pharmacokinetics of liposomes upon intravenous administration. Several factors such as composition of lipids, methods of preparation etc affect these properties of liposomes. A 24 complete factorial design with replicated center point was used to quantitate the effect of four factors viz. concentration of cholesterol, phospholipid composition, concentration of stearyl arnine and shaking time on the entrapment efficiency of pentoxifylline and particle size distribution of liposomes prepared by thin film hydration method. A mathematical model containing only significant factors affecting each response was predicted using multiple linear regression and ANOVA. Stearyl amine had negative effect on the entrapment efficiency i.e. increase in concentration of stearyl amine did not cause increase in the entrapment efficiency. Particle size distribution was affected by shaking time and phospholipid composition. In addition to main factors, two way and three way interactions also had a significant effect on all the measured responses. A new formulation based on combination of factors between the experimental levels was prepared and evaluated for allresponses. Experimental values were found to be in good agreement with the predicted values.

The human cyclooxygenase-2 inhibition activity for two series of compounds, namely the substituted 1,2-diarylimidazoles and the heteroaryl modified 1,2-diarylimidazoles is quantitatively analysed in relation to their physicochemical parameters and van der Waals volume, Vw, Significant correlations are obtained between the cyclooxygenase-2 inhibition activity and hydrophobic constant, π, molar refraction parameter and some indicator variables reflecting important structural binary variations in the first series of compounds. In the second series of compounds, however, the structural parameter Vw, along with indicator variables is found to play a significant role. Based on present findings, the strategy of substituent selection and possible modes of action of both series of compounds are discussed.

5-Hydroxytryptamine is an important neurotransmitter and hormone/paracrine agent mediating various enteric functions. The precise physiological and pathophysiological role of nitric oxide in 5- hydroxytryptamine-induced diarrhea remains unclear. Evidence is accumulating on the importance of nitric oxide in 5-hydroxytryptamine-induced secretion, but its role in fluid accumulation and electrolyte transport in jejunum and colon is not well established. This study therefore investigated in vivo, the effect of a nitric oxide synthase inhibitor and a nitric oxide precursor on intestinal fluid and electrolyte secretion induced by 5-hydroxytryptamine. Subcutaneous administration of 5-hydroxytryptamine (2-8 mg/kg) produced a dose-related increase in the intestinal fluid and electrolyte secretion in jejunum and in colon of the anaesthetized rats. 5-Hydroxytryptamineinduced (6.0 mg/kg, s.c.) jejunal and colonic fluid and electrolyte accumulation was inhibited by No-nitro-L-arginine (10-40 mg/kg, i.p.).The inhibitory effect of No-nitro-L-arginine was reversed by L-arginine (600-1 500 mg /kg, i.p.) dose-dependently but not by D-arginine (900 mg/kg, i.p.).These results demonstrate that, 5- hydroxytryptamine-induced fluid and electrolyte secretion in the jejunum and colon may involve nitric oxide.

The dried pulverised stem bark of Euphorbia poissoni, family Euphorbiaceae, was exhaustively and successively extracted with diethylether, chloroform and methanol using Soxhlet extractor. The methanol extract was fractionated into two: alkaloid extract and alkaloid free methanol extract. The extracts were screened for antimicrobial activity. The methanol and alkaloid free methanol extracts both showed antibacterial activity. The alkaloid free methanol extract was fractionated using preparative TLC (coated with silica gel 245 HF), developed with benzene:ethylacetate (9:l) to obtain 8 fractions. The fractions were screened for antibacterial activity and fractions, F1, F3, F4 and F5 showed activity. The chemical classes of the fractions and extracts were identified. Major constituents of the plant are alkaloids, tannins, saponins, glycosides, flavonoids and carbohydrates. Steroidal glycosides are the antibacterial agent of the plant.

Three simple visible spectropbotometric methods have been developed for the estimation of clarithromycin from tablet formulation. The first developed method is based on formation of orange-red coloured complex of drug with concentrated hydrochloric acid and acetone. The coloured complex shows absorbance maxima at 485 nm and obeys Beer's law in concentration range of 50-500 μg/ml. Second and third developed methods are based on formation of chloroform extractable complex of drug with bromocresol green and bromopbenol blue, respectively, both of which show abaorixince maxima at 414 nm and linearity in concentration range of 0-60 μg/ml of drug. Results of analysis for all the methods were validated statistically and by recoveiy studies.

A sensitive spectrophotometric method is presented for determining amiodarone and ondansetron. The drugs are extracted from formulations with chloroform from an alkaline medium and reacted with citric acid-acetic anhydride reagent to produce a bluish-violet colour having absorption maximum at 580 nm. Beer's law is obeyed between 2-12 μg/ml for amiodarone and ondansetron. The results agree within ± 1 .0% with official method.

Two simple and sensitive visible spectrophotometric methods for the analysis of some anesthetic drugs in pure and available pharmaceutical preparations have been developed. The first method is based on the formation of colored ion-pair complexes by the drugs, ketamine hydrochloride, lignocaine hydrochloride, bupivacaine hydrochloride and tetracaine hydrochloride with bromothymol blue. The ion-pair complexes formed are quantitatively extracted into dichloromethane and absorbance is measured at 420 nm. The second method is based on the coupling of the diazotized drugs benzocaine and procaine hydrochloride with a new and highly sensitive coupling agent, monosodium salt of 4-amino-5 hydroxynaphthalene-2,7-disulfonc acid. The absorbance of the red azo-dye is measured at 530 nm. These methods are quantitatively evaluated and found to be precise and accurate. Beer's law is obeyed in the concentration range 1-1 5 μg/ml and 0.1-7μg/ml for first and second methods, respectively.

A new water-soluble derivative of erythromycin, erythromycin nicotinate, was prepared and the physicochemical properties and biological activities were evaluated. The derivative has also good solubility in organic solvents. The partition coefficient value indicates its possible good penetration in vivo. Antimicrobial potency is 856 μg/mg and in vitro antibacterial spectrum is similar to that of erythromycin base. The LD50 value of the new derivative in mice by intraperitoneal route is 612 mg/kg. The present study indicates that the new derivative is a potential alternative to the existing water soluble derivatives.

Two simple spectrophotometric methods (A and B) have been developed for the determination of itraconazole in pure and in its pharmaceutical formulations. Method A is based on the formation of blood red colored complex with ferric chloride and 1,10-phenanthroline having absorption maximum at 520 nm, where as in method B, itraconazole forms a green colored complex with ferric chloride and MBTH reagent exhibiting maximum absorption at 630 nm .The chromogens obey Beer's law in the concentration ranges of 1.2 to 7.5 μg/ml and 2.5 t o 20 μg/ml for methods A and B, respectively. The results obtained are reproducible and are statistically validated

The presence of flavanoids, steroids and saponins was detected in the preliminary phytochemical investigation of different leaf extracts of Pergularia extensa. The ethanolic extract and petroleum ether extracts of dried leaves have shown significant analgesic activity, where as ethanolic, butanolic and petroleum ether extracts of dried leaves showed significant antipyretic activity in rats.

Two methods have been developed for estimation of sparfloxacin in tablets. Method A is based on the reduction of ferric ions to ferrous ions by the drug, which further in presence of potassium dichromate as oxidizing agent produces green chromogen measured at 680 nm against reagent blank. The chromoger obeyed linearity over 1.5 to 5.5μg/ml. Method B is based on similar reaction using ferric nitrate and potassium ferricyanide which produces blue chromogen measured at 720 nm against reagent blank. The chromogen obeyed linearity over 1.5 to 4.0 μg/ml.

Ethyl acetate and methanol extracts of five medicinal plants have been screened for in vivo antiinflammatory activity in albino rats. Methanol extract of Aegle marmelosand ethyl acetate extract Atalantla monophylla showed significant antiinflammatory activity at a dose of 100 mg/kg.

A colorimetric method has been developed for the determination of rofecoxib. Rofecoxib produces a yellow color chromogen in alkaline solution (pH 10-12), which exhibits a λmax at 355 nm. The system followed Beer-Lambert's Law in the concentration range of 5-40 μg/ml. The method is simple, economic, convenient, reproducible, precise and free from interference by excipients.

With a view to map out the synthesis and antimicrobial activity of series of 2-(3',5'-dibromo-2'- hydroxyphenyI)-3-aryl-5H/methyl/carboxymethyl-4-thiazolidinones (Ill-a-ss) have been prepared by the cyclocondensation of N-substituted-(3,5-dibromo-2-hydroxy benzylidene)-anilines (ll) with a-substituted mercaptoacetic acids and evaluated for their in vitro growth inhibiting activity against several microbes. Some of the compounds show significant antimicrobial activity.

A simple, sensitive spectrophotometric method has been developed for the determination of lamivudine and stavudine In pure and its pharmaceutical formulations. Lamivudine and stavudine give green coloured chromogens with 3-methyl-2-benzothiozolinone hydrazone hydrocloride and ferric chloride with absorption maximum at 660 nm and 630 nm, respectively. The chromogens obey Beer's law in the concentration ranges of 2.5 to 40 μg/ml and 2.5 to 12.5 μg/ml, respectively for lamivudine and stavudine.