Antimicrobial Activity of Girardinia heterophylla

In the present study an attempt has been made to prepare the crude extracts of leaves and stem of ‘Girardinia heterophylla’ by using various solvents like petroleum ether, ethanol and double distilled water. The samples were given the code NGLS 1, NGLS 2, NGLS 3 and NGSS 1, NGSS 2 and NGSS 3 respectively. All the extracts were used to study their antimicrobial activity against gram positive bacteria e.g. Bacillus subtilis, gram negative bacteria e.g. E. coli and K. pneumonia and antifungal activity against Aspergillus niger. The results of the antimicrobial activity showed that all the crude extracts of the plant possesses antibacterial activity. Maximum antibacterial activity was shown by NGLS 2, NGLS 3 and NGSS 3 against K. pneumonia. The growth of fungus A. niger was also inhibited by all the crude extracts. Maximum inhibition was shown by NGSS 2 followed by NGSS 1.

Model Membrane from Shed Snake Skins

In this project we are interested in studying different kinds of shed snake skins in order to apply them as a model membrane for pharmaceutical purposes instead of human stratum corneum. Many types of shed snake skins as well as model drugs were studied by different techniques. The data will give deeper understanding about the interaction between drugs and model membranes and may allow us to choose the suitable model membrane for studying the effect of pharmaceutical products.

Effect of Alginate and Surfactant on Physical Properties of Oil Entrapped Alginate Bead Formulation of Curcumin

Oil entrapped floating alginate beads of curcumin were developed and characterized. Cremophor EL, Cremophor RH and Tween 80 were utilized to improve the solubility of the drug. The oil-loaded floating gel beads prepared by emulsion gelation method contained sodium alginate, mineral oil and surfactant. The drug content and % encapsulation declined as the ratio of surfactant was increased. The release of curcumin from 1% alginate beads was significantly more than for the 2% alginate beads. The drug released from the beads containing 25% of Tween 80 was about 70% while a higher drug release was observed with the beads containing Cremophor EL or Cremohor RH (approximately 90%). The developed floating beads of curcumin powder with surfactant provided a superior drug release than those without surfactant. Floating beads based on oil entrapment containing the drug solubilized in surfactants is a new delivery system to enhance the dissolution of poorly soluble drugs.

Formulation and Characterization of Drug Loaded Niosomal Gel for Anti-Inflammatory Activity

The main aim of the present research was to encapsulate mefenamic acid in niosomes andincorporate the prepared niosomes in the carbopol gel base for sustained therapeutic action. Mefenamic acid loaded niosomes were prepared by thin film hydration technique and evaluated for entrapment efficiency, vesicular size and zeta potential. The entrapment efficiency of the prepared niosomes was found to increase with decreasing the HLB values of surfactants and vesicle size was found to increase with increasing the cholesterol concentration. Niosomal vesicles with good entrapment efficiencies were incorporated in carbopol gel base to form the niosomal gel. The prepared niosomal gel was evaluated for pH, viscosity, spreadability, extrudability and skin permeation study across the rat skin. The results of permeation study revealed that the gel formulated with span 60 niosomes sustained the drug release for 12h. Further the in vivo study showed the good inhibition of inflammation by the gel prepared with span 60 niosomes.

Novel Solid Lipid Nanoparticles for Oral Delivery of Oxyresveratrol: Effect of the Formulation Parameters on the Physicochemical Properties and in vitro Release

Novel solid lipid nanoparticles (SLNs) were developed to improve oral bioavailability of oxyresveratrol (OXY). The SLNs were prepared by a high speed homogenization technique, at an effective speed and time, using Compritol® 888 ATO (5% w/w) as the solid lipid. The appropriate weight proportions (0.3% w/w) of OXY affected the physicochemical properties of blank SLNs. The effects of surfactant types on the properties of the formulations such as particle size and entrapment efficacy were also investigated. Conclusively, Tween 80 combined with soy lecithin was the most appropriate surfactant to stabilize OXY-loaded SLNs. The mean particle size of the optimized formulation was 134.40 ± 0.57 nm. In vitro drug release study, the selected S2 formulation showed a retarded release profile for OXY with no initial burst release compared to OXY suspension in the simulated gastrointestinal fluids. Therefore, these SLNs could provide a suitable system to develop for the oral OXY delivery.

Influence of Natural Gum on Curcumin Supersaturation in Gastrointestinal Fluids

Supersaturation of drugs in the gastrointestinal tract is one approach to increase the absorption of poorly water-soluble drugs. The stabilization of a supersaturated state was achieved by adding precipitation inhibitors that may act through a variety of mechanisms. In this study, the effect of the natural gums, acacia, gelatin, pectin and tragacanth on curcumin supersaturation in simulated gastric fluid (SGF) (pH 1.2), fasted state simulated gastric fluid (FaSSGF) (pH 1.6), and simulated intestinal fluid (SIF) (pH 6.8) was investigated. The results indicated that all natural gums significantly increased the curcumin solubility (about 1.2-6-fold) when compared to the absence of gum, and assisted in maintaining the supersaturated drug solution. Among the tested gums, pectin at 3% w/w was the best precipitation inhibitor with a significant increase in the degree of supersaturation about 3-fold in SGF, 2.4-fold in FaSSGF and 2-fold in SIF.

Development and Validation of a UPLC Method for the Determination of Albendazole Residues on Pharmaceutical Manufacturing Equipment Surfaces

In Pharmaceutical industries, it is very important to remove drug residues from the equipment and areas used. The cleaning procedure must be validated, so special attention must be devoted to the methods used for analysis of trace amounts of drugs. A rapid, sensitive and specific reverse phase ultra performance liquid chromatographic (UPLC) method was developed for the quantitative determination of Albendazole in cleaning validation swab samples. The method was validated using an ACQUITY HSS C18, 50 x 2.1mm, 1.8μ column with a isocratic mobile phase containing a mixture of 1.36g of Potassium dihydrogenphosphate in 1000mL MilliQ water, 2mL of triethylamine and pH adjusted to 2.3 ± 0.05 with ortho-phosphoric acid, Acetonitrile and Methanol (50:40:10 v/v). The flow rate of the mobile phase was 0.5 mL min-1 with a column temperature of 350C and detection wavelength at 254nm using PDA detector. The injection volume was 2µl. Cotton swabs, moisten with acetonitrile were used to remove any residue of drug from stainless steel, teflon, rubber and silicon plates which mimic the production equipment surface and the mean extraction-recovery was found to be 91.8. The selected chromatographic condition was found to effectively elute Albendazole with retention time of 0.67min. The proposed method was found to be linear over the range of 0.2 to 150µg/mL and correlation coefficient obtained is 0.9992. The proposed method was found to be accurate, precise, reproducible and specific and it can also be used for routine quality control analysis of these drugs in biological samples either alone or in combined pharmaceutical dosage forms.

New Drug Delivery System for Cancer Therapy

The paper presents a new drugs delivery system, based on the thin film technology. As a model antitumor drug, highly toxic doxorubicin is chosen. The system is based on the technology of obtaining zinc oxide composite of doxorubicin by deposition of nanosize ZnO films on the surface of doxorubicin coating on glass substrate using DC magnetron sputtering of zinc targets in Ar:O2 medium at room temperature. For doxorubicin zinc oxide compositions in the form of coatings and gels with 180-200nm thick ZnO films, higher (by a factor 2) in vivo (ascitic Ehrlich's carcinoma) antitumor activity is observed at low doses of doxorubicin in comparison with that of the initial preparation at therapeutic doses. The vector character of the doxorubicin zinc oxide composite transport to tumor tissues ensures the increase in antitumor activity as well as decrease of toxicity in comparison with the initial drug.

Development and Evaluation of Gastro Retentive Floating Tablets of Ayurvedic Vati Formulation

Floating tablets of Marichyadi Vati were developed with an aim to prolong its gastric residence time and increase the bioavailability of drug. Rapid gastrointestinal transit could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy of the administered dose. The tablets were prepared by wet granulation technique, using HPMC E50 LV act as Matrixing agent, Carbopol as floating enhancer, microcrystalline cellulose as binder, Sodium bi carbonate as effervescent agent with other excipients. The simplex lattice design was used for selection of variables for tablets formulation. Formulation was optimized on the basis of floating time and in vitro drug release. The results showed that the floating lag time for optimized formulation was found to be 61 second with about 97.32 % of total drug release within 3 hours. The vitro release profiles of drug from the formulation could be best expressed zero order with highest linearity r2 = 0.9943. It was concluded that the gastroretentive drug delivery system can be developed for Marichyadi Vati containing Piperine to increase the residence time of the drug in the stomach and thereby increasing bioavailability.

Development and Optimization of Colon Targeted Drug Delivery System of Ayurvedic Churna Formulation Using Eudragit L100 and Ethyl Cellulose as Coating Material

The purpose of this study was to prepare time and pH dependent release tablets of Ayurvedic Churna formulation and evaluate their advantages as colon targeted drug delivery system. The Vidangadi Churna was selected for this study which contains Embelin and Gallic acid. Embelin is used in Helminthiasis as therapeutic agent. Embelin is insoluble in water and unstable in gastric environment so it was formulated in time and pH dependent tablets coated with combination of two polymers Eudragit L100 and ethyl cellulose. The 150mg of core tablet of dried extract and lactose were prepared by wet granulation method. The compression coating was used in the polymer concentration of 150mg for both the layer as upper and lower coating tablet was investigated. The results showed that no release was found in 0.1 N HCl and pH 6.8 phosphate buffers for initial 5 hours and about 98.97% of the drug was released in pH 7.4 phosphate buffer in total 17 Hours. The in vitro release profiles of drug from the formulation could be best expressed first order kinetics as highest linearity (r2= 0.9943). The results of the present study have demonstrated that the time and pH dependent tablets system is a promising vehicle for preventing rapid hydrolysis in gastric environment and improving oral bioavailability of Embelin and Gallic acid for treatment of Helminthiasis.

Effect of Polyvinyl Pyrrolidone and Ethyl Cellulose Concentration on Release Profile and Kinetics of Glibenclamide Extended Release Dosage Form System

The aim of present work was to optimize the effect of Ethyl Cellulose (EC) and Polyvinyl Pyrrolidone (PVP) concentration in extended release solid dispersion of Glibenclamide using combination of hydrophilic and hydrophobic polymers such as Polyvinyl Pyrrolidone and Ethyl cellulose. The advantage of solid dispersion technique provides a unique approach to particle size reduction and increased rates of dissolution. The compatibility studies of the drug and polymers were studied by TLC and results suggested no interaction between drug and polymers. Solid dispersions of Glibenclamide were prepared by common solvent evaporation method using Polyvinyl Pyrrolidone and Ethyl cellulose. The results indicated that homogeneous or heterogeneous conditions during the preparation methods employed governed the internal structures of the polymer matrices while retaining the drug in an amorphous form. F2 formulation prepared by solid dispersion method, displayed extended drug release followed by Higuchi matrix model indicating diffusion release of GLB from polymer matrices.

QSAR Studies of Certain Novel Heterocycles Derived from Bis-1, 2, 4 Triazoles as Anti-Tumor Agents

In this paper we report the quantitative structure activity relationship of novel bis-triazole derivatives for predicting the activity profile. The full model encompassed a dataset of 46 Bis- triazoles. Tripos Sybyl X 2.0 program was used to conduct CoMSIA QSAR modeling. The Partial Least-Squares (PLS) analysis method was used to conduct statistical analysis and to derive a QSAR model based on the field values of CoMSIA descriptor. The compounds were divided into test and training set. The compounds were evaluated by various CoMSIA parameters to predict the best QSAR model. An optimum numbers of components were first determined separately by cross-validation regression for CoMSIA model, which were then applied in the final analysis. A series of parameters were used for the study and the best fit model was obtained using donor, partition coefficient and steric parameters. The CoMSIA models demonstrated good statistical results with regression coefficient (r2) and the cross-validated coefficient (q2) of 0.575 and 0.830 respectively. The standard error for the predicted model was 0.16322. In the CoMSIA model, the steric descriptors make a marginally larger contribution than the electrostatic descriptors. The finding that the steric descriptor is the largest contributor for the CoMSIA QSAR models is consistent with the observation that more than half of the binding site area is occupied by steric regions.

New Coating Materials Based On Mixtures of Shellac and Pectin for Pharmaceutical Products

Shellac is a natural polyester resin secreted by insects. Pectins are natural, non-toxic and water-soluble polysaccharides extracted from the peels of citrus fruits or the leftovers of apples. Both polymers are allowed for the use in the pharmaceutical industry and as a food additive. SSB Aquagold® is the aqueous solution of shellac and can be used for a coating process as an enteric or controlled drug release polymer. In this study, tablets containing 10 mg methylene blue as a model drug were prepared with a rotary press. Those tablets were coated with mixtures of shellac and one of the pectin different types (i.e. CU 201, CU 501, CU 701 and CU 020) mostly in a 2:1 ratio or with pure shellac in a small scale fluidized bed apparatus. A stable, simple and reproducible three-stage coating process was successfully developed. The drug contents of the coated tablets were determined using UV-VIS spectrophotometer. The characterization of the surface and the film thickness were performed with the scanning electron microscopy (SEM) and the light microscopy. Release studies were performed in a dissolution apparatus with a basket. Most of the formulations were enteric coated. The dissolution profiles showed a delayed or sustained release with a lagtime of at least 4 h. Dissolution profiles of coated tablets with pure shellac had a very long lagtime ranging from 13 to 17.9 h and the slopes were quite high. The duration of the lagtime and the slope of the dissolution profiles could be adjusted by adding the proper type of pectin to the shellac formulation and by variation of the coating amount. In order to apply a coating formulation as a colon delivery system, the prepared film should be resistant against gastric fluid for at least 2 h and against intestinal fluid for 4-6 h. The required delay time was gained with most of the shellac-pectin polymer mixtures. The release profiles were fitted with the modified model of the Korsmeyer-Peppas equation and the Hixson-Crowell model. A correlation coefficient (R²)> 0.99 was obtained by Korsmeyer-Peppas equation.

Impact of Altered Behavioral Condition on Markers of Oxidative Stress and Different Biochemical Parameters

Aim- Study was undertaken to investigate the effect of altered behavioral condition like depression on various oxidative stress markers and biochemical parameters in rats. Methods- Rats were subjected for short (21 days) and long term (84 days) social isolation; the rats displayed an increase in depression on force swim test relative to control. Various markers of oxidative stress like lipid per oxidation (LPO), reduced glutathione (GSH), Supers oxide dismutase (SOD), catalase (CAT) and biochemical parameters like SGOT, SGPT, and blood glucose were determined. Results- There was significant increase in the level of LPO and decrease in the levels of GSH, SOD and CAT after long term isolation. Biochemical parameters were significantly altered after social isolation. Conclusion- Increased oxidative stress in depression which may leads to alteration of biochemical parameters.

Protective Effect of Thymoquinone against Arsenic-Induced Testicular Toxicity in Rats

The protective effect of thymoquinone (TQ) was investigated in rats exposed to testicular injury induced by sodium arsenite (10mg/kg/day, orally, for two days). TQ treatment (10mg/kg/day, intraperitoneal injection) was applied for five days, starting three day before arsenic administration. TQ significantly attenuated the arsenic-induced decreases of serum testosterone, and testicular reduced glutathione level, and significantly decreased the elevations of testicular malondialdehyde and nitric oxide levels resulted from arsenic administration. Also, TQ ameliorated the arsenic-induced testicular tissue injury observed by histopathological examination. In addition, TQ decreased the arsenic-induced expression of inducible nitric oxide synthase and caspase-3 in testicular tissue. It was concluded that TQ may represent a potential candidate to protect against arsenic-induced testicular injury. 

In vitro and in vivo Anticholinesterase Activity of the Volatile Oil of the Aerial Parts of Ocimum basilicum L. and O. africanum Lour. Growing in Egypt

In this study, the in vitro anticholinesterase activity of the volatile oils of both O. basilicum and O. africanum was investigated and both samples showed significant activity. The major constituents of the two oils were isolated using several column chromatographies. Linalool, 1,8-cineol and eugenol were isolated from the volatile oil of O. basilicum and camphor was isolated from the volatile oil of O. africanum. The anticholinesterase activities of the isolated compounds were also evaluated where 1,8-cineol showed the highest inhibitory activity followed by camphor. To confirm these activities, learning and memory enhancing effects were tested in mice. Memory impairment was induced by scopolamine, a cholinergic muscarinic receptor antagonist. Anti-amnesic effects of both volatile oils and their terpenoids were investigated by the passive avoidance task in mice. We also examined their effects on brain acetylcholinesterase activity. Results showed that scopolamineinduced cognitive dysfunction was significantly attenuated by administration of the volatile oils and their terpenoids, eugenol and camphor, in the passive avoidance task and inhibited brain acetylcholinesterase activity. These results suggest that O. basilicum and O. africanum volatile oils can be good candidates for further studies on Alzheimer’s disease via their acetylcholinesterase inhibitory actions.

Extended Release System of Hypoglycemic Agent Containing Solid Dispersions: Strategies and Mechanisms

The main perspective of the present study aims at overcoming solubility problems by using the technique of solid dispersion. Repaglinide is a BCS Class II drug, having low aqueous solubility and therefore, low bioavailability. Solid dispersions of repaglinide with different carriers Polyvinyl Pyrrolidone (PVP) and Ethyl Cellulose (EC) in different ratios were prepared by suspending method and Dissolving methods. In vitro release studies revealed that the F7 formulation showed extended drug release. So, the dissolution profile of solid dispersion containing EC and PVP K30 (1: 3) was selected as the best formulation because of its extended drug release among all formulations. In conclusion, solid dispersions of Repaglinide in PVP have shown to be a promising approach to improve the bioavailability of Repaglinide.

Camel Thorn Has Hepatoprotective Activity against Carbon Tetrachloride or Acetaminophen Induced Hepatotoxicity, but Enhances the Cardiac Toxicity of Adriamycin in Rodents

In this study the administration of 660 mg/kg of the ethanolic extract of the Alhagigraecorum (Camel Thorn)to mice, showed a significant decrease in the level of transaminases in animals treated with a combination of CTE plus carbon tetrachloride (CCl4) or acetaminophen as compared to animals receiving CCl4 or acetaminophen alone. Histopatological investigation also confirmed that, camel thorn extract protects liver against damage-induced either by carbon tetrachloride or acetaminophen. On the other hand the cardiac toxicity produced by adriamycine was significantly increased in the presence of the ethanolic extract of camel thorn. Our study suggested that camel thorn can protect the liver against the injury produced by carbon tetrachloride or acetaminophen, with unexpected increase in the cardiac toxicity –induced by adriamycin in rodents.

A New Gateway for Rheumatoid Arthritis: COXIBs with an Improved Cardiovascular Profile

Today COXIBs are used in the treatment of arthritis and many other painful conditions in selected patients with high gastrointestinal risk and low cardiovascular (CV) risk. Previously, we have identified an unexpected mechanism of action of a traditional non-steroidal anti-inflammatory drug (NSAID) (diclofenac) and a specific inhibitor of cyclooxygenase-2 (COXIB) (lumiracoxib) demonstrating that they possess weak competitive antagonism at the thromboxane receptor (TP). We hypothesize that modifying the structure of a known COXIB so that it becomes also a more potent TP antagonist will preserve the anti-inflammatory and gastrointestinal safety typical of COXIBs and prevent the CV risk associated with long term therapy.

Preparation and in vivo Assessment of Nystatin-Loaded Solid Lipid Nanoparticles for Topical Delivery against Cutaneous Candidiasis

Solid lipid nanoparticles (SLNs) have gained great attention for the topical treatment of skin associated fungal infection as they facilitate the skin penetration of loaded drugs. Our work deals with the preparation of nystatin loaded solid lipid nanoparticles (NystSLNs) using the hot homogenization and ultrasonication method. The prepared NystSLNs were characterized in terms of entrapment efficiency, particle size, zeta potential, transmission electron microscopy, differential scanning calorimetry, rheological behavior and in vitro drug release. A stability study for 6 months was performed. A microbiological study was conducted in male rats infected with Candida albicans, by counting the colonies and examining the histopathological changes induced on the skin of infected rats. The results showed that SLNs dispersions are spherical in shape with particle size ranging from 83.26±11.33 to 955.04±1.09 nm. The entrapment efficiencies are ranging from 19.73±1.21 to 72.46±0.66% with zeta potential ranging from -18.9 to -38.8 mV and shear-thinning rheological Behavior. The stability studies done for 6 months showed that nystatin (Nyst) is a good candidate for topical SLN formulations. A least number of colony forming unit/ ml (cfu/ml) was recorded for the selected NystSLN compared to the drug solution and the commercial Nystatin® cream present in the market. It can be fulfilled from this work that SLNs provide a good skin targeting effect and may represent promising carrier for topical delivery of Nyst offering the sustained release and maintaining the localized effect, resulting in an effective treatment of cutaneous fungal infection.