Stratum corneum lipids form the major portion of skin constituents. Their synthesis and metabolism regulate the epidermal structural organization and barrier function. An alteration of their content is a good indicator of various skin diseases. The barrier function can be modified by employing epidermal lipid metabolic inhibitors. This approach can be advantageously utilized to increase the transcutaneous delivery of drugs. Hence, it is imperative to study the factors that influence the synthesis and metabolism of epidermal ceramide, cholesterol and fatty acids and their role in barrier homeostasis.

A series consisting of imidazo[1,5-a]quinoxalin-4-ones and imidazo[1,5-a]quinoxaline ureas, with a substituted phenyl ring in each class of these compounds, was reported to have high affinity for benzodiazepine receptor complex. In order to establish the exact relationship between activity and various quantifying parameters, these compounds were subjected to quantitative structure-activity relationship (QSAR) analysis. The study reveals that for in vitro radioligand displacement activities of substituted imidazo[1,5-a]quinoxalin-4-ones, a chloro group at R6, a relatively smaller group such as fluoro at R7 the less hydrophobic and more electron-donating groups, respectively, In para- and meta-positions of phenyl ring at R3 are necessary. In a related class of imidazo[1,5-a]quinoxaline ureas, the bulky group such as a pyrrolidine ring at R5, a less hydrophobic para-substituent on phenyl ring, a fluoro group at R7 and the unsubstituted R6-position are advantageous. In the piperazine urea sub-series, which was reported to possess biophasic efficacy, it emerged that a methoxy group at R3, a 3,5-dimethyl piperazine moiety at R5 and a fluoro group at R7 are essential, whereas R6 is required to be unsubstituted.

Colloidal drug carriers such as nanospheres are gaining importance by achieving reduced toxicity, enhanced efficacy and site-directed action. Hence, bovine serum albumin nanospheres were prepared by pH coacervation method. The potential antifungal agent amphotericin-B was incorporated into nanospheres at various concentrations. The drug-loaded batches were subjected to in vitro analysis and found to exhibit a bi-phasic release pattern. The batch with optimum drug-loading and satisfactory release profile was selected as ideal batch and it was used for in vivo targeting study in mice using HPLC analysis. The targeting efficiency of drug loaded nanospheres was compared with that of free drug in terms of percentage, increase in targeting to various organs like liver, lungs and spleen. The increase in targeting percentage was found to be 56.5%, 40.4% and 31.8% in lungs, liver and spleen respectively.

Transdermal free films of atenolol were made using sodium CMC as polymeric matrix and propylene glycol as the plasticizer. DMSO, PEG 400, Tween 20, Pluronic F127 and Brij 35 were used as permeation enhancers. The drug free films were evaluated for various mechanical properties. The drug diffusion studies were carried out using Keshary-Chein cell. A comparison of various permeation enhancers on permeation rate of atenolol was made. The effect of iontophoresis on permeation of atenolol was studied. lontophoresis increased the permeation rate of the drug to a greater extent compared to the permeation enhancers.

The absorbance maxima of phenylpropanolamine hydrochloride, chlorpheniramine maleate and dextromethorphan hydrobromide in 0.1 N hydrochloric acid are 257, 265 and 278 nm, respectively. This paper presents two methods based on first derivative spectrophotometry for simultaneous estimations of these three drugs in combinations in pharmaceutical formulations. The first derivative amplitudes at 264.4, 278.5 and 288.9 nm are utilized for simultaneous estimations. The first method utilizes correlative regression equations and the second method utilizes simultaneous equations to avoid complex interferences at selected wavelengths in derivative spectra. All three drugs obey Beer's law in the concentration range employed for analysis. Linearity was validated by Least Squares Method. The results of analysis have been validated statistically and by recovery studies. Both methods are simple, economical, accurate, reproducible and rapid.

Anti HIV and antibacterial activity of some 2,3-disubstitutedquinazolones, 2-substituted-[1,3,4]- thiadiazoloquinazolones and their bio-isostere-[1,3,4]-thiadiazolothienopyrimidones were determined. Among the compounds tested for antiHIV activity, the 2-methyl -[1,3,4]-thiadiazolo [2,3-b]-6,7,8,9-tetrahydrobenzo(b)thieno-[3,2-e]-pyrimidin-5(4H)-one (USP/VA-2) gave maximum protection against HIV-2 (ROD). The compounds 2-(4-methoxyphenylamino)-[l,3,4]-thiadiazolo-[2,3-b]-6,7-dimethylthieno-[3,2-e]-pyrimidin-5(4H)-one (USP/VA-1) and USP/VA-2 were exhibited comparable antibacterial activity with the standard amoxycill in against Escherichia coli.

Two new oxygenated heterocyclic constituents, named phyllanthusolactone and phyllanthodocosanyl ester, have been Isolated from the alocoholic extract of the root of Phyllanthus fraternus. The structures of the compounds have been established as 16-(18, 22, 22-trimethyl cyclohex-17-enyl)-4-methylhexadec-16-ol-3,17-diene-5,23-olide and 10-(12,16,16-trimethyl cyclohex-11-ene)-11- yl-3,7-dimethyldeca-2,4,6-triene-1-yl-n-docosan-13-one-18, 22-olide-1-oate, respectively on the basis of chemical reactions and spectral data.

The binding of a series of phenothiazine derivatives to bovine serum albumin was Investigated using fluorescene spectroscopic technique. In an attempt to elucidate the binding mechanism and to predict binding affinity, association constants for drug-protein binding have been correlated to physico-chemical parameters by fitting linear, multiple linear and quardratic equations to the data. The rationale of including molecular weight and molecular volume terms in the quantitative structure-activity correlations has been emphasized. It has been concluded that binding primarily involves hydrophobicity and molecular size of drug cations. However, the role of electrostatic forces as measured by ionization constant, pKa and molar conductance cannot be ignored. The association constants could be predicted with a fair degree of accuracy from physico-chemical properties of the drug molecules.

The aim of the study was to develop and evaluate mucoadhesive films of miconazole nitrate for the treatment of oral candidosis. Films were prepared by casting procedure using various polymer combinations and were evaluatted for their in vitro bioadhesive performance and release characteristics. The in vitroadhesion time and release behaviour were found to be a function of the type of polymer used. The formulation containing Carbopol 934P and Hydroxy porpyl cellulose-M combination was found to give the best results. Placebo films prepared on aluminium foil showed adequate comfort, non-irritancy and taste compliance, etc. when tested on healthy human volunteers.

Copolymers of methacrylic acid (MA) and 2-ethylhexyl acrylate (EHA) were synthesized by emulsion polymerization technique. These were characterized for their physicochemical properties and evaluated for their potential application in pharmaceutical film coating through free film studies and film coating tablets of diclofenac sodium. The copolymers were found to produce flexible, internally plasticized films with low water vapour permeability and adequate mechanical strength that remain insoluble below pH 5 but swell and become permeable to water at and above pH 5.The copolymers may find usefulness as film-forming agents in modified-release applications and as protective coatings against moisture. Preliminary acute oral toxicity studies in mice have indicated that these are quite safe.

Hydroxy propyl methyl cellulose (HPMC) K4M gels containing free (HCF), liposome encapsulated clobetasol propionate (HCL) and physical mixture of the drug and lipids (HCP) were prepared and subjected to in vitro drug diffusion studies using rat skin to determine diffusion parameters. Data obtained were analyzed to calculate the amount of the drug in the skin (Qm) and the quantity of the drug in the recipient fluid (Csf) and its ratio (Qm/Csf). In vivo skin blanching assay of these formulations in human volunteers showed low blanching scores for liposomal gel formulations indicating low absorption of the liposomal drug in to the blood stream resulting in it's accumulation in the skin. Out of all the formulations tested, liposomal gel prepared with drug, phosphatidyl choline and cholesterol in the ratio of 2:4:1 showed highest Qm/Csf ratio and minimum blanching score.

A simple and sensitive method has been developed for the estimation of terazosin in tablet formulations. The method is based on diazotisation of primary amine group of terazosin with sodium nitrite and hydrochloric acid followed by coupling with β-naphthol (in alkaline medium) to form a orange red dye, which has the characteristic light absorption in the visible region and having the absorption maximum at 560 nm. So the determination of the drug was based on the absorption at this wave length. Beer's law is obeyed in the concentration range of 1-10 μg/ml. The proposed method is precise, accurate and reproducible and it is extended to the analysis of terazosin in the tablet formulations.

The in vitro antifungal activity of Calendula officinalis flower extracts have been investigated against Aspergillus niger, Rhizopus japonicum, Candida albicans, Candida tropicallis and Rhodotorula glutinis. The extracts of Calendula officinalis showed high degree of activity against all test fungi. The inhibitory effects of extracts are very close and identical in magnitude and are comparable with that of standard abtibiotics used.

5 Amino salicylic acid (5-ASA) and several structurally-related analogs were tested for inhibitory role on nitrite-induced oxidation of hemoglobin in human blood-hemolysates. Results indicate a strong inhibitory role for 5-ASA in a concentration range of 0.2 to 0.8 mM. Although the inhibitory activity of 5-ASA was higher than other structural alalogs tested, the activity of curcumin was much higher at equimolar levels. PABA also showed some activity at similar concentrations although it was lower than that of 5-ASA. Benzoic acid showed marginal activity at lower concentrations. On the other hand, acetyl salicylic acid and salicylic acid increased the methemoglobin levels in hemolysate. The pro-oxidant activity was higher at higher concentrations for these compounds. Higher level of activity of 5-ASA is consistent with previous findings. As acetyl salicylic acid and 5-ASA are currently being prescribed, it is worth investigating their in vivo activity in order to establish novel and hitherto unexplored clinical applications.

One visible spectrophotometric and one HPLC method has been developed for the estimation of sertraline hydrochloride from tablet formulations. Developed visible spectrophotometric method is based on the formation of chloroform extractable coloured complex of drug with nitrosonaptho1. The coloured complex shows absorbance maxima at 441.5 nm. Beer's law was obeyed in the concentration of 20-100 μg/ml of scrtraline hydrochloride. Developed HPLC method was a reversed phase chromatoraphic method using Intertsil C18 column and methanol : acetate buffer (pH 2.8)::80:20 as mobile phase with detection at 220 nm. Caffeine was used as an internal standard and linearity was observed in the concentration range of 10-250 μg/ml of sertraline hydrochloride for HPLC method. Results of anlaysis for both the methods were validated statisically and by recovery studies.

Solid dispersions of itraconazole (ITR) in polyvinylpyrrolidone (PVP), hydroxy propyl methyl cellulose (HPMC), hydroxy propyl cellulose (HPC) and their tablet formulations were investigated with an objective of enhancing the dissolution rate of ITR from tablets. A marked enhancement in the dissolution rate of ITR was observed with all the solid dispersions. HPC gave the highest improvement (7.5 fold) in the dissolution rate of ITR at 10% concentration when compared to ITR itself. XRD indicated the presence of ITR in amorphous form in ITR-HPC solid dispersion and the crystallinity of ITR was much reduced in ITRHPMC and ITR-PVP solid dispersions. DSC indicated no interaction between ITR and PVP, HPMC and HPC. The solid dispersions could be formulated into tablets. These tablets, apart from fulfilling all official and other specifications, exhibited higher rates of dissolution and dissolution efficiency (DE) values.

Certain 5-phenyl-4-substituted amino-3-mercapto-(4H)-1,2,4-triazoles having different substitutions on the aromatic ring possessing the azomethine linkage were prepared and evaluated for their antimicrobial acivity. The compounds with a chloro, bromo, hydroxyl and a nitro group on the aromatic ring showed good antimicrobial activity.

The in vitro antioxidant activity of Cuscuta reflexa stem extract has been investigated by estimating degree of non-enzymatic hemoglobin glycosylation measured colorimetrically at 440 nm. The ethyl acetate fraction of ethanol extract showed higher activity than the other fractions. The antioxidant activity of extracts are very close and identical in magnitude and comparable to that of standard antioxidant compounds used.

Niosomes of sumatriptan succinate were prepared using lipid hydration method. The prepared niosomes were evaluated for entrapment efficiency, size analysis and in vitro release studies. Further, the niosomes were evaluated for nasal absorption using an ex vivo animal model. The entrapment efficiency was found to be 57.9 ± 0.96 %. The niosomes released 58.71% of sumatriptan succinate over a period of 6 h and 78.1% of the drug was absorbed from the nasal mucosa ex vivo.

Spherical matrices of nimesulide were prepared by using ethyl cellulose alone and a combination of ethyl cellulose and hydroxy propyl methyl cellulose by spherical agglomeration technique and the drug release from these matrices 20/40 and 40/60 size was studied for 8 h. It was found that the drug release from ethyl cellulose matrices was slow compared to that from the combined polymer matrices. The improved drug release from the combined polymer matrices appears to be due to improved solubility of the drug in the presence of hydroxy propyl methyl cellulose.