Over the last decade, the field of chirality has witnessed revolutionary changes with increased emphasis placed on delineation of enantioselective pharmacology, pharmacokinetics and pharmacodynamics. Indeed, there are numerous examples in the literature, which confirm the benefits of recognizing chirality in a drug entity. Based on the current data, therefore, it is important not to ignore chirality of the molecule during the drug development process. lnspite of lack of special regulatory requirements, it appears to be prudent to evaluate very early in the development, the pharmacologic, pharmacokinetic, pharmacodynamic, and toxicologic profiles of the racemate and the individual enantiomers to justify the development of any one form of the chiral drug for human use. In this context, the present article emphasis the impact of chirality in the pharmacokinetic disposition of racemic drugs.

Diabetic nephropathy is one of the microvascular complications of diabetes. The pathophysiology involves an interaction between metabolic and hemodynamic factors. Metabolic factors include advanced glycation, increased formation of polyols and activation of protein kinase C (PKC). Hemodynamic factors include systemic hypertension, intraglomerular hypertension and the role of vasoactive hormones, such as angiotensin II. Clinical course progresses from microalbuminuria to overt proteinuria and then to renal failure. The disease cannot be cured, but can be prevented or limited in progression. The most important measures to be taken are maintenance of normoglycemia and normal blood pressure and protein diet restriction. Antihypertensive therapy has a major role in slowing the progression of diabetic nephropathy. Renal replacement therapy is available and the best method is kidney transplantation, if not contraindicated.

Combinatorial Chemistry is a relatively recent concept adapted very quickly into a time and cost effective technology, which imparted a totally new orientation to medicinal chemistry and drug discovery research. The conceptual and technical approaches that encompass combinatorial chemistry are reviewed in this article.

2-Acetylnaphtho [2,1-b] furan 1 was reacted with various aromatic aldehydes in presence of alkali, to produce corresponding chalcones 2a-i. These were converted into l-phenyl-3- (naphtho [2,l-b] fur-2yl-5- aryl-2-pyrazolines 3a-i and 1-(4-nitrophenyl)-3-(naphtho [2,1-b] fur-2yl-5-aryl-2-pyrazolines 4a-i by treatment with phenyl hydrazine and 4-nitrophenyl hydrazine respectively. The reaction of chalcones 2a-i with hydroxylamine hydrochloride in presence of sodium acetate in glacial acetic acid produced 3- (naphtho [2,1-b] fur-2yl)-5-aryI-2-isoxazole5a -i, whereas similar reaction in the presence of potassium hydroxide yielded 3-(naphtho [2,l-b] fur-2yl)-5-aryl-2-isoxazolines 6a and 6e. All the compounds have been characterized by elemental analysis and spectroscopic data. These novel biheterocyclic compounds have been screened for antibacterial, antifungal, anthelmintic and analgesic activities. The compound 4e showed promising antimicrobial activity, some of the compounds exhibited moderate antibacterial and antifungal activity. The only compound that showed maximum analgesic activity is 3d. Anthelmintic activity revealed the compounds 4e, 5b and 5i were as active as the standard drug.

Polyfructoscan, inulin was extracted from the dried roots of Saussurea Iappa. The crude inulin obtained was purified by fractional recrystallization using ethanol. lnulin was characterized by IR, NMR, DSC and X-ray diffraction studies. The fructose content in inulin isolated from Saussurea lappa roots was quantitatively estimated to be 95.89% w/w. lnulin in the insoluble form was found to significantly potentiate the delayed type hypersensitivity response to SRBC and also Increase the total WBC count.

Albumin and gelatin have been widely used alone and in combination with other colloids as drug carriers but so far, their combination with each other has not been reported. The present study reports a novel attempt to prepare complex coacervates of albumin and gelatin as carriers for the anticancer drug, 5- Fluorouracil (5 FU). Formaldehyde cross linked albumin-gelatin complex coacervates, prepared by the complex coacervation- phase separation method, were found to be nearly spherical and had 92.23±2.16% drug entrapment efficiency. These microacervates were evaluated for drug leaching, in vitro biodegradability and in vivo organ distribution studies. The microcoacervates were found to be more susceptible to pancreatin as compared to pepsin and exhibited diffusion controlled drug leaching in non sink, static conditions. In vivo organ distribution studies of the microcoacervates in healthy rats showed a statistically significant distribution of 5-FU in liver and kidneys (P<0.01) as compared to the free drug solution, indicating preferential uptake by the organs of the RES. Prolonged 5 FU levels in liver, lungs and kidneys also indicated sustained release of the drug from the microcoacervates.

5,6-Dihydro-3-alkyl-6-(5'-substituted-2'-phenylindol-3'-yl)-s-triazolo[3,4-b][1,3,4]thiadiazolea(2a-h)and 3-Substituted-6-(5'-substituted-3'phenylindol-2-yl)-s-triazolo [3,4-b][1,3,4] thiadiazole (3a-h) have been synthesised by the reaction of 5-alkyl-1-amino-2-mercapto [1,3,4] triazoles (1a-b) with 5-substituted-2-phenylindol-3-carboxaldehydes in dry DMF containing p-toluenesulphonic acid as catalyst and 5-substituted-3-phenylindol-2 carboxylic acids in the presence of phosphorousoxychloride respectively. The structures of the newly synthesised compounds were elucidated on the basis of analytical and spectral data. These compounds have been screened for antimicrobial, antiinflammatory and analgesic activities.

Rifampicin-chitosan matrices were prepared by direct compression method and wet granulation method to develop a sustained release form. The effects of methods of preparation on the drug release rate and release kinetics were investigated in this study. Moreover, the kinetics of rifampicin released from chitosan matrices, exposed to formaldehyde vapors for predetermined time intervals, were analysed using Ritger and Peppas exponential equation. The in vitro release kinetics of directly compressed matrices exhibited a non-Fickian transport model and matrices prepared by wet granulation method showed Fickian diffusion model. Increasing the exposure time to formaldehyde vapors decreased the release rate of rifampicin from chitosan matrices as a result of formation of greater structural strength and more tightly texture.

Quantitative structure protein binding relationships (QSPBR) have been derived for the binding of nine antipsychotic phenothiazine derivatives to human alpha-1-acid glycoprotein (AGP). Ninety eight topological indices for the phenothiazine derivatives were calculated using software Polly 2.3. Bivariate correlation matrix showed that most of the statistically significant correlations were obtained for topochemical indices. Four variables, complementary information contents, CICo, CIC1 and CIC2 and chain connectivity index, 6Xch, with correlations significant up to 0.01 level were considered to be the predictors of the model. Linear, multiple linear and non-linear regression analysis was performed on the retained variables. The complementary information content for 2nd order neighbourhood of vertices in a hydrogen filled graph, CIC2, was found to be the best single parameter that can be used in linear or quadratic fit to predict the binding affinities of phenothiazines to AGP.

Considering the importance of lipophilicity of contraceptive β-estradiol (ES) a significant contributor to its mechanism of action, interactions of the drug with total lipids of goat whole blood have been investigated using phospholipid binding, fatty acid composition and peroxidation phenomena as the parameters under investigation. The objective was to derive an insight into the pharmacodynamic behavior of the drug. Significant loss in phospholipid along with changes in fatty acid composition was observed after incubation of whole blood with ES at 150 pg/ml (effective contraceptive concentration in blood) in varying periods of time. This may be ascribed to binding affinity of ES with lipid constituents in blood. Lipid binding potential of the drug may have a role in its therapeutic effect. The effect of ES on lipid peroxidation phenomenon has been quantitatively measured and the results reveal that ES caused significant inhibition of lipid peroxidation which is in good agreement with its cardioprotectant action.

A simple, accurate, rapid and sensitive method has been developed for the estimation of melatonin and meloxicam using Folin-Ciocalteu reagent in the presence of 20% sodium carbonate solution. The blue coloured chromogen formed is measured at wavelength of maximum absorption 700 nm against reagent blank. The chromogen obeyed linearity over 1.5 to 15 μg/ml for melatonin and 1.5 to 22.5 μg/ml for meloxicam.

A comparative study of application of CLAL (Chromogenic Limulus Amebocyte Lysate) and rabbit pyrogen test on 35 samples of Water for injection was performed. With the pyrogen test, the accumulated temperature rise ranged from + 0.2o to + 1.3o passing all the samples by the rabbit pyrogen test. The endotoxin content varied from as low as 0 EU/ml (Endotoxin Unit per milliliter) to 0.15 EU/ml as tested by CLAL test suggesting that all samples had endotoxin levels below the prescribed levels of 0.25 EU/ml. No correlation could be established between the endotoxin content and temperature rise

Extracts of Cyperus rotundus Linn were investigated for antibacterial activity against Staphylococcus aureus (NCIM 2079), Escherichia coli (NCIM 2065), Bacillus Subtilis (NCIM 2063), Pseudomonas aeruginosna (NC1M 2036), and Proteus vulgaris (NCIM 2027) at 50 μg/disc using disc diffusion method. The acetone and ethanol extracts showed significant broad spectrum antibacterial activity. Our findings confirm the traditional therapeutic claims for this herb that it is useful against bacterial infection.

The effect of magnesium sulphate and sodium sulphate on the in vitro adsorption of rifampicin to activated charcoal (AC) was investigated. Solutions of rifampicin alone and rifampicin with 7.5 mg/ml cathartic solution were vortex mixed for 30 s with different quantities of AC, incubated for 30 min at 37o and analyzed for free rifampicin spectrophotometrically at 320 nm. Addition of sodium and magnesium sulphates significantly increased (P<0.05) the adsorption of rifampicin to activated charcoal. In all, the adsorption obeyed quantity-dependent kinetics.

Indigofera enneaphylla Linn. is a well known plant in Indian traditional medicine. On the basis of its traditional use and literature references, this plant was selected for evaluation of its wound healing potential. An alcoholic extract of aerial parts of lndigofera enneaphylla Linn. Was examined for its wound healing activity in the form of ointment in two types of wound models in rats the excision wound model and the incision wound model. The extract ointments showed significant response in both of the wound models as comparable to those of a standard drug, nitrofurazone, in terms of wound contracting ability, wound closure time and tensile strength.

Dissolution studies were carried out using the USP dissolution apparatus-I in the presence and absence of rat caecal contents and apparatus-II. The formulation taken for the analysis is Kinetal - 400 SR tablets, which contain 400mg of pentoxifylline, sampled at different storage periods (first month, first year, second year and last month of the shelf life). The studies indicates that there was no significant change (P>0.001) in dissolution pattern of the drug from, Kinetal-400 products on storage. USP dissolution apparatus-l showed quicker dissolution of products compared to apparatus-II. Adding rat caecal contents did not improve dissolution of products indicating that the tablet coating is unaffected by clonic bacterial enzymes.

Rifampicin release studies from modified pulsincap preparation were performed using different proportions of various hydrophilic polymers such as guar gum, carbopol 940, sodium alginate, hydroxy propyl methyl cellulose, methyl cellulose, gum karaya and poly vinyl alcohol. The in vitro dissolution studies revealed that the release exhibits a Fickian diffusion model. Increasing the hydrophilic polymer content resulted in a reduction in the release rate of rifampicin. Among all the polymers tested, guar gum showed better sustaining capacity even at low concentrations. This technique is more suited for preparing better controlled release formulations.

A reversed-phase HPLC (RP/HPLC) method using Lichrosphere RP select B, C8 column has been developed for the simultaneous determination of ipratropium bromide, methylparaben and propylparaben in formulations. The mobile phase consists of an aqueous solution containing heptane sulphonic acid sodium salt (pH 3.2) and 345 ml of acetonitrile, with detection at 210 nm. Recovery study values of 98-102% and a relative standard deviation of less than 1% for the assay showed that the method is accurate and precise.

Two spectrophotometric methods for the estimation of roxatidine acetate hydrochloride (RAH) in bulk drug and in its sustained release tablets have been developed. The method I is based on the formation of a yellow coloured ion pair with bromophenol blue whereas the method II is based on the reaction of RAH with hydroxylamine hydrochloride to get a hydroxamic acid which on further reaction with ferric chloride gives a reddish brown complex. Beer's law was followed in the concentration range of 2 to 15 μg/ml in method I and 50 to 300 μg/ml in method II.

A spectrophotometric method is described for the determination of several fluroquinolones as bulk drug and in dosage form by complexation of the drug with chloranilic acid. Job's method revealed a 1:1 complexation between the drug and chloranilic acid. Quantitative recoveries were obtained from bulk drug as well as from commercially available dosage forms.