Carbopol 940 and theobroma oil were used to formulate melt extrusion bioadhesive tablets of diclofenac. Different batches of the tablets were formulated using different quantities of Carbopol 940 granules containing diclofenac and theobroma oil in a plastic mould by pour moulding. The bioadhesion of the tablets were measured by determining the bioadhesive strength generated when the tablet interacted with the mucus on everted hog jejunum on a tensiometer adapted for that purpose. The tablets were evaluated using weight uniformity, resistance to rupture and liquefaction time. Release of diclofenac from the tablets was studied in simulated intestinal fluid (Ph 7.2) without pancreatin. The tablets had low liquefaction times and were highly bioadhesive. Result of the study indicated that theobroma oil could be used to formulate melt extrusion bioadhesive tablets of diclofenac. All the tablets evaluated conformed to pharmacopoeial specifications.

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A simple fast and precise reverse phase high performance liquid chromatographic method was developed for the determination of telmisartan from tablet dosage forms. A hypersil C18 BDS (250 mmx4.6 mm) from Thermo. In isocratic mode, mobile phase acetonitrile: methanoI (60:40) was used. The flow rate was 1.2 ml/min, and eluent monitored at 245 nm.

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The main objective of the present study is to improve the dissolution rate of naproxen using carrierssuch as PVP, PEG4000, PEG6000, PEG2000, methylcellulose and β-cyclodextrin with a view to develop fast release formulations of naproxen. Solid dispersions of naproxen were prepared by solvent evaporation method and the dispersions were evaluated for drug content uniformity, dissolution rate, moisture absorption, thin layer chromatography and X-ray diffraction analysis. The particle shape and topography were studied using scanning electron microscopy. A marked increase in dissolution rate was observed with all solid dispersions. Among the carriers studied, naproxen-β-cyclodextrin gave the highest improvement in dissolution rate. All the solid dispersions except naproxen-PVP were found to be non-hygroscopic. Naproxen was found to be in an amorphous form in solid dispersions. Selected dispersions of naproxen-β-cyclodextrin and naproxen-methylcellulose were formulated into capsules with usual additives and evaluated for drug release characteristics.

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A sustained release system for lansoprazole designed to increase its residence time in the stomach without contact with the mucosa was achieved through the preparation of floating micropellets by emulsion solvent diffusion technique. Floating micropellets of 1:1, 1:2 and 1:3 drug to carrier ratios were prepared using hydroxypropylmethylcellulose, methylcellulose and chitosan as a carrier. The yield of the micropellets was up to 82%. All floating micro pellet formulations showed good flow properties expect formulation contain hydroxypropylmethylcellulose as coating material and packability. Drug loaded micropellets were found to float on simulated gastric fluid and simulsted intestinal fluid for more than 12 h. The drug release studies were carried out in simulated gastric and intestinal fluid without enzymes at 37° for a period of 12 h. The Drug to chitosan ratio 1:1 showed good incorporation efficiency and high percentage in vitro release of lansoprazolc from micropeliets. The morphology and particle size analysis were analyzed by scanning electron microscopy and optical microscopy. The range of particle size is in between 327 to 431 pm. This method is simple, giving better yield and reproducible. The prepared lansoprazole floating micropellets can be used for sustained release in gastric media for more than 12 h, there by improving the oral bioavailability of lansoprazole by increasing gastric residence time because this helps to retained in stomach for a longer period.

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The volatile constituents of the whole herb of Coleus amboininus Lour (Labiatae) were analyzed by GC-MS following isolation by hydrodistillation. Ten compounds were identified among which carvacrol (50.7 %) γ-caryophyllene (13.1 %) and patchoulane (8.7%) were dominant.

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A systematic study of the colour reaction formed between iron (llI) and thiocyanate reagent has been carried out by using micro-scale spectrophotometric method. The optimized data resulted conditions in obtaining unusual highest sensitivity with molar absorption of 2.9565x104I/mol.cm at wavelength of maximum absorption 480 nm in 0.2-1.4 N nitric acid medium containing 60% acetone and 25,000 fold molar excess of the thiocyanate reagent. Beer's law is valid for 0.1-4.0 ppm of iron (llI). Sandell's sensitivity is 0.002 μg/cm2. Effects of reagent concentration, order of addition, stability, acidity, types of solvents and diverse ions are reported. It has been found to give accurate results of iron estimations in pharmaceutical preparations and mustard seeds. The proposed optimized method has highest sensitivity, unusual stability and simplicity in operation, without involving cumbersome extractive procedure. Further, the procedure has additional advantages of economy, safety and less time consuming with minimum waste disposal.

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Development of a colon specific delivery system bearing flurbiprofen using various azo-aromatic polymers and pH-sensitive polymers are discussed. The azo-aromatic polymers were synthesized and characterized for physical appearance, solubility, film forming properties and effect of colon microbial flora on the polymers. In vitro dissolution studies showed that flurbiprofen bearing hard gelatin capsules, coated with these polymers released drug only in simulated gastrointestinal fluid containing human fecal suspension, at pH 7.5. In vivo studies revealed that azo-aromatic and pH-sensitive polymer coating disintegrate only in colon following 10 h of oral administration. Hence these polymers can be successfully used to deliver drug at the colon.

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A simple, specific, accurate and precise reverse phase high performance liquid chromatographic method was developed for the simultaneous determination of losartan potassium and hydrochlorthiazide in tablet dosage forms. A Lichrospher 100 C-18, 5 μm column having 20x4.6 mm i.d. in isocratic mode, with mobile phase containing 20 mM KH2PO4 buffer (pH 3): acetonitri1e:tetrahydrofuran in 60:30:10 were used. The flow rate was 1.0 ml/min and effluent was monitored at 215 nm. The retention time of losartan potassium and hydrochlorthiazide were 7.94 min and 3.26 min, respectively. Linearity for losartan potassium and hydrochlorthiazide were in the range of 4-40 μg/ml and 1-10 μg/ml, respectively. Average percentage recoveries obtained for losartan and hydrochlorothiazide were 100.2% and 100.1%, respectively. In vitro evaluation of tablets containing losartan and hydrochlorothiazide was performed by evaluating tablets for thickness, diameter, hardness, tensile strength, disintegration and dissolution. Parameters for dissolution testing (dissolution medium and speed) were optimized. Dissolution testing was performed at 100 rpm in 0.1 N HCI as dissolution medium by paddle method. The proposed method is accurate, precise, specific and rapid for simultaneous estimation of losartan potassium and hydrochlorthiazide in tablets as well as for dissolution testing.

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A new simple, sensitive, specific and precise high performance thin layer chromatographic method has been developed for estimation of moxifloxacin in its tablet formulation (400 mg). In this method, standard solutions and sample solution of moxifloxacin were applied on precoated silica gel G60F254 TLC plate and developed using n- butanol:methanol:ammonia (4:4:2 v/v) as mobile phase: Moxifloxacin showed Rf value 0.50±0.03 and plate was scanned and quantified at 295 nm using Camag TLC Scanner 3. The method was validated in terms of linearity (400-1000 ng/spot), precision (intra-day variation 2.0 to 4.4%, inter-day variation 3.7 to 4.6%), accuracy (96.4 to 102.3%) and specificity. The limit of detection and limit of quantification for moxifloxacin were found to be 10 ng/spot and 50 ng/spot, respectively. The method is simple, sensitive, specific and precise and can be used for the routine quality control testing of marketed formulations.

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Recently, it has been shown that many drugs have better bioavailability by nasal route than by oral route. This has been attributed to rich vasculature and a highly permeable structure of the nasal mucosa coupled with avoidance of hepatic first-pass elimination, gut wall metabolism and/or destruction in the gastrointestinal tract. The nasal route could be particularly important for drugs used in crisis management such as for pain and for centrally acting drugs where the pathway from the nose to brain might provide a faster and more therapeutic effect. This article focuses on newer developments and strategies for nasal delivery along with nasal absorption mechanism.

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Conventional synthetic neuroleptic drugs used for the treatment of chronic cases of psychosis are associated with extra pyramidal side effects. Herbal neuroleptic drugs might prove to be devoid of these side effects. Monoherbal and polyherbal neuroleptic tablets of various combinations were prepared using Acorus calamus (I), Glycyrrhiza glabra (II) and Withania somnifera (Ill). Wet granulation technique was employed for tablet formulation (100 mg) and the tablets were film coated with hydroxy propyl methyl cellulose. The qualitative and quantitative estimation of various active constituents was done by high performance thin layer chromatography where elution media such as to1uene:ethyl acetate (93:7) for I, methanol: strong ammonia (200:3) for II and ethyl acetate: ethanol: water: ammonia (65:25:9:1) for Ill were used. The amount of β-asarone, glycyrrhizic acid and withaferin-A present in 100 mg of mono ingredient herbal tablets were found to be 2.81%, 2.95% and 0.69%, respectively. Tranquilizing effect, anxiolytic efficacy and catatonic response were measured in wistar rats. An optimum therapeutic efficacy of mono herbal formulations were confirmed by sleeping tranquilizing effects (P<0.001) using rotarod method and anxiolytic effects by thiopental sleeping time on Wistar rat model. No drug-induced catatonia was observed with the developed tablet formulations in rat model. The monoherbal tablet dosage form thus prepared may be a better alternative over synthetic drugs and polyherbal formulations during chronic treatment of psychosis and thereby expected to be a cost effective, safe and natural product for better psychiatric therapy.

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Development of novel therapies for Alzheimer's disease has now been given much attention, with an aim to search for more potent drugs for long term use through various approaches and hypothesis. Five distinct hypothesis/approaches for the therapies have been discussed in this review, namely, (1) cholinergic hypothesis, (2) hormone replacement approaches, (3) antiinflammatory approaches, (4) neurotrophic approaches and (5) an approach to inhibit formation of amyloid and neurofibrillary tangles. In the cholinergic hypothesis, acetylcholinestrase inhibitors have been more successful and potent compounds have been identified that include tacrine, physostigmine, donepezil and rivastigmine. Among these, tacrine and physostigmine have been associated with toxicity and bioavailability problems respectively and donepezil and rivastigmine have been launched in the market. Estrogen has shown efficacy in the treatment of Alzheimer's disease giving rise to the hormone replacement approach. Few antiinflammatory drugs such as ibuprofen, naproxen and rofecoxib have shown promise in long term therapy against Alzheimer's disease. Agents that stimulate neurotrophic effects such as citicoline, anapsos and AITS-C32 have shown progress in treatment of mental impairment and are at different stages of clinical trials. Few amino acid derivative, amine and urea analogs and hydorxy-hexamide have been shown to inhibit amyloid β synthesis or/and release.

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A transdermal drug delivery system of diclofenac sodium was developed for prolonged and controlled release of drug. The designed system essentially based on polymeric dispersion system. To achieve the desired release rate, different combinations of hydrophilic and hydrophobic polymers were used for the preparation of pseudolatex systems. The permeation kinetics of diclofenac sodium from transdermal system through hairless delipidized and lipidized mouse skin was done. The permeation profile and the related kinetic parameters of diclofenac sodium alone and in presence of an enhancer isopropyl myristate at different concentrations were studied. The observed permeation flux, permeation coefficient found to increase in presence of enhancer isopropyl myristate. The effect was found to be the maximum with isopropyl myristate at a concentration of 10 percent. The more pronounced enhancing effect of isopropyl myristate regarding permeability flux, permeation coefficient, diffusion coefficient was attributed with solubility parameter being nearer to the skin lipid solubility parameter and probably due to its passage across the skin barrier through the lipid pathway.

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Ethyl acetate extract and two crude fractions, solvent ether and ethyl acetate, of the rhizomes of Cyperus rotundus (Cyperaceae) were evaluated for hepatoprotective activity in rats by inducing liver damage by carbon tetrachloride. The ethyl acetate extract at an oral dose of 100 mg/kg exhibited a significant protective effect by lowering serum levels of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, alkaline phosphatase and total bilirubin. These biochemical observations were supplemented by histopathological examination of liver sections. Silymarin was used as positive control.

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Rofecoxib is novel cyclooxygenase-2 inhibitor, which is poorly soluble in aqueous media. The aim of present study was to improve the solubility and dissolution rate of drug by formulating its solid dispersions with various hydrophilic carriers (polyethylene glycol-6000, polyvinyl pyrrolidone K- 30, Eudragit E-100) and inclusion complex with β-cyclodextrin. Drug release profile was studied in 0.1 N HCI as dissolution media. Rofecoxib forms eutectic mixture with polyethylene glycol 6000 and glass solution with polyvinyl pyrrolidone K 30 and Eudragit E 100. Polyvinyl pyrrolidone K 30 was found to be more effective in increasing the drug dissolution, when compared with polyethylene glycol 6000 and Eudragit E 100.The theoretical prediction for the use of β-cyclodextrin as a dissolution enhancing agent was performed. The dissolution was obtained as high as 75% in rofecoxib:β-cyclodextrin molar ratio of 1:5 prepared by kneading method. For further dissolution enhancement the combination of two dissolution enhancing agent i.e. polyvinyl pyrrolidone K-30 and β-cyclodextrin were used. 32 factorial design was conducted to optimize the proportion of both the carriers.

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The technique of three variables at three levels (33) factorial design was used to derive simple reduced second order polynomial equation for constructing contour plots to obtain predetermined percent drug entrapment within liposomes of idoxuridine prepared by reverse phase evaporation method. Three independent variables selected were volume of organic phase (x1), volume of aqueous phase (x2), and drug/phosphatidyichoIine/cholesterol in molar ratio (x3). Based on factorial design, twenty-seven batches of idoxuridine liposomes were prepared. Prepared liposomal batches were evaluated for size, lamellarity, and percent drug entrapment. The percent drug entrapment (dependent variable) and the transformed values of independent variables were subjected to multiple regression to establish a second order polynomial equation (full model). To simplify the equation, F-statistic was applied to reduce polynomial equation (reduced model) by neglecting insignificant (p>0.05) terms. The coefficient value for independent variable; drug/phosphatldy/choline/cholesterol in molar ratio (x3) was found to be maximum (b3=17.96) and hence the variable x3 was considered to be a major contributing variable for percent drug entrapment within liposomes prepared by reverse phase evaporation method. The reduced polynomial equation was used to plot three two-dimensional contour plots at a fixed levels of -1, 0 and 1 of major contributing variable (x3) to obtain various combinations of values of two other independent variables (x1 and x2) at predetermined percent drug entrapment. The conformity of the established equation was checked by preparing three batches three times taking values of the independent variables from the contour plots for prefixed value of percent drug entrapment. Prefixed percent drug entrapment values were taken for designing the experiment and results obtained experimentally were compared using student 't' test and difference between experimentally obtained and theoretically calculated values of percent drug entrapment was found to be statistically insignificant (p>0.05). Hence, finding of this study establishes the role of the derived equation and plotted contour plots in predicting the values of independent variables for preparation and optimization of idoxuridine liposomes by reverse phase evaporation method having predetermined percent drug entrapment.

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Two simple, accurate, rapid and sensitive methods have been developed for the estimation of ethamsylate in dosage forms. Method A is based on the nitrosation of the drug followed by chelation of the o-nitroso derivative formed with Cu++ ions forming a stable purple coloured chromogen, which shows absorption maximum at about 525 nm while method B is based on the reduction of Fe+++ to Fe++ ions by ethamsylate which then reacts with potassium ferricyanide to produce a blue coloured complex that shows maximum absorption at about 750 nm against reagent blank. In both the methods Beer's law was obeyed in the concentration range of 2-20 μg/ml.

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Rosin, a natural resin, was used as an insoluble matrix forming material for studying the release of diltiazem HCI, which was taken as a model drug. The granules prepared were free flowing with good compressibility. The tablets prepared were flat faced, which retained their shape throughout. The method of preparation of matrix system and its concentration were found to have a pronounced effect on the release of diltiazem HCI. Various physical parameters of the granules and the tablets were evaluated. The release mechanisms and the release rate kinetics of the tablets were examined using different release models. The release was found to follow both the first order kinetics and Fickian diffusion. Marked differences in the release rate of the drug from different formulations were observed when % cumulative release was plotted against time. The drug delivery was analyzed using the paddle method according to USP XXIII. All the studies were done in distilled water.

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A gas chromatographic method was developed for the determination of clopidogrel in its tablet form. The method involves use of a DB-17 capillary column. Column is of 30 m length, 0.25 mm i.d. and 0.25 μ film thickness, and hydrogen as a carrier gas with the flow rate of 2.0 ml/min. Oven temperature was maintained at 250° for 8 min. Split type of injector and flame ionization detector was used. The retention time of clopidogrel and dioctyl phthalate (internal standard ) was 4.1 min and 3.2 min, respectively. Linearity for the clopidogrel was in the range of 0.5 to 5.0 mg/ml. Percentage recovery obtained was 99.89.The proposed method is accurate, precise and rapid for the estimation of clopidogrel.

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Malaria is recognized as a highly widespread infectious disease of world caused by sporozoa of genus Plasmodium. Most antimalarial drugs were developed on the basis of their action against asexual erythrocytic forms of malaria parasites, which are responsible for the clinical illness. More recently, chloroquine-resistant strains of P. vivax also have been reported. Practical, effective and safe drugs, insecticides and vaccines still are needed to combat malaria. The object of the present study was to develop a more effective, scientific-based herbal formulation by using traditional medicines. The screening was done by Peter's 4 day test by means of parasite counts. There was no parasitaemia from 15th day post infection in both drug treated animals. All animals were found infection free and healthy. The preliminary pharmacological studies revealed that the prepared formulation possesses promising antimalarial activity justifying its use for the management of malarial infections.

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A series of 19 antiinflammatory drugs 3,5-di-tert-butyl-4-hydroxy styrene derivatives were subjected to quantitative structure activity relationship analysis with an attempt to derive a correlation between the biological activity as dependent variable and various descriptors as independent variables by using Hansch approach. The QSAR analysis showed that, the anti-inflammatory activity of the analogues is significantly correlated with thermodynamic and sterimol parameters. The analysis resulted in the following 2-D equation suggest that, BA=(-0.588016) MR1+(0.2815) MR2+(-0.150769) Hdor1(- 1.322597), n=15, r=0.864, r2=0.764, f=7.336, t=2.709, STD=0.64, a lipophillic group, which is less bulkier at R1 and more bulkier at R2, is important in determining the anti-inflammatory activity along the axis of a parent skeleton, which can be used for predicting the affinity of related compound and for guiding the design of a new molecule.

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Two simple, sensitive, accurate and rapid spectrophotometric methods have been developed for the estimation of nicorandil in tablets. Method A is based on the reaction of nicorandil with sulphanilic acid reagent in presence of cyanogen bromide solution giving yellow chromogen, which show maximum absorbance at 460 nm against reagent blank while method B is based on the estimation of nicorandil in 0.1 N HCI at 262 nm. Beer's law was obeyed in the concentration range of 10-80 μg/ml in method A and 5-40 μg/ml in method B. Results of the analysis were validated statistically and by recovery studies.

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A reversed phase HPLC method is described for the determination of nevirapine in tablet dosage forms. Chromatography was carried out on an ODS column using a mixture of methanol and water (50:50 v/v) as the mobile phase at a flow rate of 0.9 ml/min. Cefixime was used as an internal standard and the detection was done at 230 nm. The retention time of the drug was 6.69 min. The method produced linear responses in the concentration range of 0.5 to 60 μg/ml of nevirapine. The method was found to be applicable for analysis of the drug in tablets. The results of the analysis were validated statistically.

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Two methods, kinetic and titrimetric, based on bromination reaction with bromine, are described for the assay of albendazole in bulk drug and in tablets. The kinetic method depends on the linear relationship between the concentration of the drug (μg/ml) and time (s) for bromination, as indicated by bleaching of methyl orange acid colour. The titrimetric method is based on the direct titration of the drug with standard bromate solution in the presence of excess of bromide and in hydrochloric acid medium using methyl orange as indicator. Kinetic method is applicable in the concentration range of 5 to 25 μg/ml, and using titrimetry, 3 to 20 mg of drug can be determined with a fair degree of accuracy and precision. Tablet excipients do not interfere in either method. Recoveries of drug added to commercial formulations were good. As indicated by t- and F- values, the methods are as accurate and precise as the reference method.

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A simple and economical dual wavelength spectrophotometric method has been developed for the simultaneous estimation of dextropropoxyphene hydrochloride and acetaminophen in combined dosage forms. The method was based on property of additivity of absorbances. The two wavelengths on acetaminophen curve were found out where it showed same absorbance, which were 216.6 and 262.9 nm. At 262.9 nm, acetaminophen showed some absorbance while dextropropoxyphene hydrochloride showed zero absorbance. Both the drugs gave absorbance at 216.6 nm. The method involved solving of an equation based on measurement of absorbances at two wavelengths 216.6 and 262.9 nm. The proposed method was found to be simple, economical, accurate and reproducible for the routine analysis of both drugs in capsule dosage forms.

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The present work describes a validated high performance thin layer chromatographic method for simultaneous estimation of lamivudine and stavudine in tablet formulation. Silica gel 60 F254 plate were used as stationary phase and toluene: n-hexane: tetrahydrofuran (7:1.5:1.5 v/v) as mobile phase. The wavelength selected for analysis was 253 nm. Amount of lamivudine and stavudine estimated as per peak height/area were found to be 149.9/147.5 mg and 30.2/30.6 mg, and the percentage recoveries for both the drugs were 99.4/98.8% and 99.3/100.0%, respectively.

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In the present study three dimensional quantitative structure activity relationship studies were performed on a series of 5,6-dihydropyran-2-ones as HIV protease inhibitors using CS Chem Office Version 6.0. Multiple linear regression analysis was performed to derive quantitative structure activity relationship models which were further evaluated internally as well as externally for the prediction of activity. The best quantitative structure activity relationship model was selected having a correlation coefficient (r) of 0.8285 and cross-validated correlation coefficient (Q2) of 0.5169. The study indicates that thermodynamic descriptors (torsion energy, total energy, molar refractivity and Vander Waals energy) and electronic descriptor (lowest unoccupied molecular orbital) play an important role for the HIV Protease binding affinities. The information generated from the present study may be useful in the design of more potent protease inhibitors as antiHlV agents.

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A simple, economical, fast and precise reverse phase high performance liquid chromatographic method has been developed for the simultaneous determination of zidovudine and lamivudine in from tablet dosage form. A BDS Hypersil C18 (5 micron 25 cmx4.6 mm) column from Thermo in isocratic mode with mobile phase o-phosphoric acid:methanol (70:30) buffered and adjusted to pH 5 by using triethylamine. The flow rate is 1.4 ml/min and effluent is monitored at 220 nm.

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Hepatoprotective activity of aqueous and petroleum ether (40-60°) extracts of stem bark of Diospyros cordifolia were screened on male Wistar rats against carbon tetrachloride-induced toxic hepatitis. Significant hepatoprotective activity was observed in the petroleum ether extract-treated animals. Biochemical tests representative of liver function such as serum total bilirubin, serum alanine aminotransaminase, aspartate aminotransaminase and alkaline phosphatase activities indicated hepatoprotective activity of the stem bark extracts. Histopathological studies revealed that hepatic lesions occurred In the carbon tetrachloride-treated group, which were reduced significantly by the stem bark extract treatment.

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Restenosis is a particular problem in small vessels following a successful percutaneous transluminal coronary angioplasty remains the main obstacle to this technique for myocardial revascularisation. The occurrence of restenosis, which is now known to be caused by both vessel remodelling and neointimal hyperplasia, might be reduced in the future by a combined mechanical and pharmacological approach. Despite intensive investigation in this area, no pharmacological therapy has yet been found to be useful in preventing restenosis after conventional balloon angioplasty. Though dramatic improvements in catheter and stent technology, in stent restenosis continue to hamper initial procedural success in patients undergoing coronary intervention. With the advent of drug eluting stents, opportunities for even greater long term success appears to be a reality.

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