DER PHARMACIA LETTRE 2009 : VOLUME ONE : ISSUE 2

Synthesis of some derived thiazolidin-4-one, azetidin-2-one and 1,3,4-oxadiazole ring systems from Isoninicotinic acid hydrazide: A novel class of potential anticonvulsant agents

A series of Isoninicotinic acid hydrazide (INH) incorporated derivatives of thiazolidin-4-one (2a-h,3a-h), azetidin-2-one (4a-h) and 1,3,4-oxadiazole (5a-h) has been synthesized using an appropriate synthetic route and characterized by elemental analysis and spectral data. The anticonvulsant activity of all the synthesized compounds was evaluated against maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. The neurotoxicity was assessed using the rota-rod method.All the test compounds were administered at doses of 30, 100 and 300 mg/kg body weight and the anticonvulsant activity was noted at 0.5 and 4h time intervals after the drug administration. All the compounds were active in MES and a majority of compounds were active in scPTZ test. All compounds were less neurotoxic than the standard drug phenytoin.

Design, hydrolysis and pharmacological evaluation of novel polymeric prodrugs of Etodolac

Etodolac (ED), 1,8-diethyl-1,3,4,9-tetrahydropyrano-[3,4-b]indole-1-acetic acid, is a non-steroidal anti-inflamatory and antirheumatic drug. A biocompatible and biodegradable polymer dextran was used as a carrier in the study for synthesizing macromolecular etodolac prodrugs. The synthesis involves condensation of acyl imidazole derivatives of etodolac with dextran of different molecular weights (10000 and 20000) to obtain etodolac-dextran prodrugs ED10 and ED20 respectively. The structures were confirmed by IR and NMR spectroscopy and the degree of substitution was obtained as 13.3 % and 16 % for ED10 and ED20 respectively. Hydrolysis kinetics of the synthesized prodrugs were studied in borate buffer solutions (pH 7.4 and pH 9.0) and simulated colonic fluid (SCF, pH 6.8). Much faster hydrolysis was observed in SCF than borate buffer solutions and the hydrolysis followed first order kinetics. The pharmacological evaluation showed an enhanced anti-inflammatory activity of 61 % and 65 % inhibition of ED10 and ED20 against 52 % of parent drug. The analgesic activity of the prodrugs was insignificant, whereas a remarkable reduction in ulcerogenicity was observed. The improved aqueous solubility, increased therapeutic efficiency and reduced gastrointestinal side effects of the prodrugs confirm the use of dextran as a promoiety for the delivery of etodolac in colon.

Formulation, Optimization and In-Vitro Evaluation of Ketoconazole Cream

Variations in the physico-chemical properties of ketoconazole have been studied, following polymorphic changes caused by fusion-cooling processes or by recrystallization in solvents commonly used in the pharmaceutical industry. Changes in physico-chemical properties were measured by differential scanning calorimetry (DSC), infrared, X-rays and HPLC. Results revealed changes in the peak temperature of the different recrystallization and changes in their X-ray diffraction patterns. Infrared spectra of the samples indicated no changes in the chemical structure of ketoconazole. HPLC results indicated a decrease in the solubility except in one case. No degradation products were detected. The validated methods were applied for quantitative determination of ketoconazole in commercial and simulated emulsion formulations. Quantitative first derivative UV spectrometric determinations were made using the zero – crossing method at 257 nm, with methanol as background solvent.

Design and characterisation of sustain release gastro retentive floating tablets of Diltiazem Hydrochloride

Gastroretentive drug delivery systems are the systems which are retained in the stomach for a longer period of time and thereby improve the bioavailability of drugs. Diltiazem Hydrochloride, is a Calcium channel blocker, an anti-hypertension and anti-anginal drug, Diltiazem Hydrochloride undergoes an extensive biotransformation, mainly through cytochrome P-450 CYP3A, which results in less than 4% of its oral dose being excreted unchanged in urine. Suffers from poor bioavailability (~30% to 40%) owing to an important first pass metabolism. It has an elimination half-life of 3.5 hrs and an absorption zone from the upper intestinal tract. Thus the present work is aimed to formulate floating tablets of Diltiazem Hydrochloride using an effervescent approach for gastroretentive drug delivery system.Floating tablets were prepared using direct compression technique using Hydrophilic polymer like HPMC K4M, HPMC K15M and hydrophobic polymer like Ethylcellulose as matrix materials in various quantities (%w/w), sodium bicarbonate, citric acid, magnesium stearate, talc and lactose in varying ratio to formulate the floating tablets. Observations of all formulations for physical characterization had shown that, all of them comply with the specification of official pharmacopoeias and/or standard reference. It was observed that tablets of batch F6 followed the results obtained, it was concluded that the formulation F6 is the best formulations as the extent of drug release was found to be around 99.81 % at the desired time 12 hrs.

Metal Based Drugs: Current Use and Future Potential

Besides the remarkable therapeutic success of anticancer drugs such as cisplatin, carboplatin and oxaliplatin, metallodrugs have also shown promising results in the treatment of diseases other than cancer. They have been developed to treat/cure a variety of ailments viz. diabetes, ulcer, rheumatoid arthritis, inflammatory and cardiovascular diseases etc. The enzymes in our body and many drugs of organic nature require traces of metal ion for proper functioning. Due to a wide variety of coordination spheres, ligands design, oxidation states and redox potential, coordination and organometallic complexes are supposed to alter the kinetic and thermodynamic properties of the complexes towards biological receptors. Thus, chelation causes drastic change in biological properties of ligands as well as metal moiety. Metal complexes are supposed to exert their effect by inhibition of enzymes, interaction with intracellular biomolecules, enhanced lipophilicity, alteration of cell membrane functions and arrest of cell cycle etc. The review includes the current use and future potential of some metal based drugs used/showed promising results in the treatment of diseases/conditions such as diabetes, ulcer, infection, mania and hypertension etc. which are being developed as therapeutic agents during the recent past.

Pharmacokinetics of 2-pyridyl acetic acid, a major betahistine metabolite in healthy Indian volunteers

Betahistine dihydrochloride is a vasodilator and most commonly used to treat the symptoms of M´eni`ere’s disease, vertigo and tinnitus. Due to the rapid metabolism of betahistine in humans, its estimation in human plasma is not possible. The only major metabolite detected in urine and plasma is 2-pyridyl acetic acid. The results of pharmacokinetic parameters in Indian volunteers have not been published before, and are presented and discussed for the first time in this article. A randomized, single dose, crossover bioequivalence study was conducted in healthy Indian volunteers to assess pharmacokinetics of 2-pyridyl acetic acid, by administering betahistine dihydrochloride tablet (24 mg) under fasting condition. 2-pyridyl acetic acid, was determined by a validated liquid chromatography/mass spectrometry method (LC-MS/MS) in human plasma with standard curve range 3.48 to 1279.12 ng/mL. The test betahistine dihydrochloride (24 mg) tablet formulationshowed bioequivalence with the respective reference betahistine dihydrochloride (24 mg) tablet formulation. However, on comparison of the pharmacokinetic parameters of the Indian volunteers with the results of previous study done on Chinese volunteers, Indian volunteers showed quite high Cmax (approximately twice) and AUC (approximately thrice) and also the deviation observed in both pharmacokinetic parameter was quite low as compared to Chinese volunteers.

New Strategy for Solubilization of poorly soluble drug- SEDDS

Self-emulsifying drug delivery systems (SEDDSs) have gained exposure for their ability to increase solubility and bioavailability of poorly soluble drugs. Self-emulsifying drug delivery systems (SEDDS) are mixtures of oils, surfactants, and cosurfactants, which are emulsified in aqueous media under conditions of gentle stirring and digestive motility that would be encountered in the gastrointestinal tract. We found that SEDDS could efficiently improve oral absorption of the sparingly soluble drugs by rapid self-emulsification and subsequently dispersion in the absorption sites.

Effect of Ocimum sanctum and Azadiracta indica on the formulation of antidandruff herbal shampoo powder

Now a day Herbal cosmetics are widely used when compared to synthetic cosmetics. In hair cosmetics, synthetic cosmetics lead to various side effects such as toxicity to eye, Over drying of hair and deposition of salt on hair shaft. Dandruff is a major problem in hair. In this study, the antidandruff herbal shampoo powder was formulated and evaluated various tests such as swelling index, foaming index, Antimicrobial activity and eye and skin irritation test etc. This study was designed to determine the antidandruff activity on the formulated herbal shampoo powder. The herbal shampoo powder was formulated using natural ingredients with Ocimum sanctum (Tulsi) and Azadiracta indica (Neem).Both are having antidandruff action. Thus the present study revealed that the antidandruff activity of Ocimum sactum and Azadiracta indica against strains of G + Organism, strains of G _ Organism and fungal organism such as candida albicans.

Emerging trends of drug used in treatment of liver cirrhosis

Cirrhosis is a condition in which the liver slowly deteriorates and malfunctions due to chronic injury. Scar tissue replaces healthy liver tissue, partially blocking the flow of blood through the liver. A healthy liver is able to regenerate most of its own cells when they become damaged. With end-stage cirrhosis, the liver can no longer effectively replace damaged cells. A healthy liver is necessary for survival. Cirrhosis is the twelfth leading cause of death by disease, accounting for 27,000 deaths each year. The condition affects men slightly more often than women. Heavy alcohol consumption and chronic hepatitis C have been the most common causes of cirrhosis. Obesity is becoming a common cause of cirrhosis, either as the sole cause or in combination with alcohol, hepatitis C, or both. Usually years of chronic injury are required to cause cirrhosis. The goals of treatment are to slow the progression of scar tissue in the liver and prevent or treat the complications of the disease. Hospitalization may be necessary for cirrhosis with complications. Treatment for cirrhosis also addresses specific complications. For edema and ascites, the doctor will recommend diuretics—medications that remove fluid from the body. Large amounts of ascitic fluid may be removed from the abdomen and checked for bacterial peritonitis. Oral antibiotics may be prescribed to prevent infection. Severe infection with ascites will require intravenous (IV) antibiotics. may prescribe a beta-blocker or nitrate for portal hypertension. Beta-blockers can lower the pressure in the varices and reduce the risk of bleeding. Gastrointestinal bleeding requires an immediate upper endoscopy to look for esophageal varices. The doctor may perform a band-ligation using a special device to compress the varices and stop the bleeding. People who have had varices in the past may need to take medicine to prevent future episodes.

Formulation and Evaluation of Theophylline Controlled Release Matrix Tablets using Xanthan gum

Controlled release matrix tablets of theophylline were prepared with hydrophilic polymer xanthan gum and evaluated. Controlled release matrix tablets of theophylline were prepared by wet granulation technique by varying polymer ratios (1:1 and 1:2) and hardness (5, 6 and 7 kg/cm2). Tablets were prepared by wet granulation technique. The granules are subjected for preformulation studies. Compressed tablets were evaluated for hardness, uniformity of weight, friability, drug content, thickness and diameter. All the formulation showed compliance with pharmacopoeial standards. IR spectroscopy revealed that there was no interaction between the drug and the polymer used in the formulation. In vitro dissolution studies were performed using Disso 2000 (paddle type). Among all formulations F6 showed controlled 73.18 + 1.55 % after 10 hr. The kinetic treatment showed that the drug release followed higuchi model. F-6 formulation was subjected to stability studies at three different temperatures for 6months period. It was found to be stable. From this study it was proved that the release of theophylline from matrix tablets was influenced by both polymer ratio and hardness.

Studies on formulations and evaluation of floating tablets containing anti-ulcer drugs

Floating drug delivery systems are the systems which are retained in the stomach for a longer period of time and thereby improve the bioavailability of drugs. Different approaches for gastroretentive dosage forms include floating, raft, expanding or swelling, bioadhesive or mucoadhesive and high/low-density systemsFamotidine, an anti-ulcer drug, suffers from poor bioavailability (50%), as famotidine is very less soluble in alkaline PH. Famotidine used in combination with antacids promotes local delivery of these drugs to the receptor of the parietal cell wall. Local delivery also increases bioavailability at the stomach wall receptor site and increases the efficacy of drugs to reduce acid secretion. Thus, the present work is aimed to formulate floating tablets of famotidine using an effervescent approach for gastroretentive drug delivery system. Floating tablets were prepared using directly compression technique using polymers like HPMC K4M and HPMCK100M for their gel-forming properties. The HPMC alone polymer unable to controlled on release rate it release drug >90% in 4-6 hrs while in combination with Xanthan gum it release >90% in 8 hrs. The results indicate that gas powered gastroretentive floating Tablets of famotidine containing 40mg HPMCK100M and Xanthan gum provides a better option for controlled release action and improved bioavailability.

Antifungal Activity of Embelia Ribes Plant Extracts

Aim of the present study was to investigate the antifungal activity of the Embelia ribes plant extracts using standard in vitro antifungal susceptibility test methods like NCCLS (The National Committee for clinical laboratory standard M27-A2 Protocol).Antifungal screening of Embelia ribes not studied in detail and not extended to the different spectrum of fungal which are causing human diseases. Total four different types of extracts were prepared using different solvents and TLC characterized. Petroleum ether extract, Solvent ether extract, Methanol extract and water extract. Assays were performed in 96 well plates and detection was carried out with colorimetric plate reader at 530nm. With screening for the antifungal activity using NCCLS method, MIC50 were obtained with the help of the graph pad prism software. NCCLS method revealed that methanol extract and Embelin had lowest MIC50 range of 120mg/L against Candida albican (MTCCno.183) and among four Candida species tested Embelin had reported MIC50 values below 700mg/L. Solvent ether extract, petroleum ether extract, methanol extract and embelin reported to have MIC50 in range of 300-700mg/L against Candida albica (MTCCno.227)and Candida.parapsilosis(MTCCno.1744) Petroleum ether extract shows lowest MIC50 range of 250mg/L against Candida parapsilosis(MTCCno.1744)and 360mg/L against Candida laurintis (MTCC no.2898) while Water extract required higher MIC50 value for all species. Thus the result shows that the percentage growth was increased with the decrease in the concentration of the plant extracts, except for the water extract. The line for the water extract is roughly linear at all concentrations.

Oral Insulin Delivery: Facts, Developments and Challenges

Diabetes mellitus is a group of syndromes characterized by hyperglycemia which could be managed and controlled through medication and Insulin The current advocacy of intensive insulin therapy regimens involving multiple daily subcutaneous injections places a heavy burden of compliance on patients and has prompted interest in developing alternative, less invasive routes of delivery. The oral route is considered to be the most convenient and desired route of drug delivery which will help eliminate the pain caused by injection, psychological barriers associated with multiple daily injections and possible infections. Oral delivery of Insulin as a non-invasive therapy for Diabetes Mellitus is still a challenge to the drug delivery technology, since it is degraded due to the presence of enzymes in the acidic environment of stomach and also its absorption through the gastrointestinal mucosa is questionable. In developing oral protein delivery systems with high bioavailability, various practical approaches might be most helpful like protecting insulin from enzymatic degradation, use of penetration enhancers , chemical modification, Bioadhesive delivery system, use of microspheres and nanoparticales to improve bioavailability of insulin. Despite, various techniques each having its own limitation and advantages, the oral route scores over the others for the ease of comfort with which the therapeutic agents can be administered to the patients work on attempts to deliver insulin orally has definitely gathered momentum and is no longer considered with pessimism to develop the oral insulin drug delivery system.

Hepatoprotective activity of laticiferous plant species (Pergularia daemia and Carissa carandas) from Western Ghats, Tamilnadu, India

The roots of Pergularia daemia and Carissa carandas have used to treat liver disease and jaundice among the herbal practitioners of Western Ghats Tamilnadu, India.The present study is to evaluate the hepatoprotective effects of the ethanol and aqueous extracts of roots of Pergularia daemia and Carissa carandas were against ethanol induced hepatotoxicity in rats. The hepatotoxic of ethanol and the hepatoprotective effects of ethanol and aqueous extracts of roots of P. daemia (PDEE & PDAE) and C. carandas (CCEE & CCAE) were estimated their liver function test, serum lipid profile, levels of lipid peroxidation and the activity of liver antioxidant enzyme glutathione. The PDEE, PDAE, CCEE and CCAE at a dose level of 100 mg/kg and 200 mg/kg produce significant hepatoprotection by decreasing serum transaminase (SGPT & SGOT), alkaline phosphate, bilirubin and lipid peroxidation, while significantly increased the levels of liver glutathione and serum protein. The effects of PDEE, PDAE, CCEE and CCAE were comparable with standard drug silymarin.

Transferosomes: A Novel Approach for Transdermal Drug Delivery

Poor patient compliance is a frequent problem in daily clinical practice. The unfavorable pharmacokinetic of the drug, the inconveniences of the standard from of such drug application and the side effects due to the administration route often are the reasons for this. The high and self-optimizing deformability of typical composite transfersomes membrane, which are adaptable to ambient tress allow the ultra deformable transfersomes to change its membrane composition locally and reversibly, when it is pressed against or attracted into narrow pore. The transfersomes components that sustain strong membrane deformation preferentially accumulate, while the less adaptable molecules are diluted at sites of great stress. This dramatically lowers the energetic cost of membrane deformation and permits the resulting, highly flexible particles, first to enter and then to pass through the pores rapidly and efficiently. This behavior is not limited to one type of pore and has been observed in natural barriers such as in intact skin. Transfersomes possess an infrastructure consisting of hydrophobic and hydrophilic moieties together and as a result can accommodate drug molecules with wide range of solubility. Transfersomes can deform and pass through narrow constriction (from 5 to 10 times less than their own diameter) without measurable loss. This high deformability gives better penetration of intact vesicles. They can act as a carrier for low as well as high molecular weight drugs e.g. analgesic, anesthetic, corticosteroids, sex hormone, anticancer, insulin, gap junction protein, and albumin.

Formulation and evaluation of fast dissolving tablets of Rupatadine fumarate

The demand of fast dissolving tablets has been growing, during the last decade especially for geriatric and pediatric patients because of swallowing difficulties. Rupatadine fumarate is H1 and PAF antagonist used primarily in treatment of allergic rhinitis symptoms, seasonal or perennial. Fast dissolving tablets of Rupatadine fumarate were prepared by direct compression method.The tablets were prepared by using mannitol, microcrystalline cellulose as filler, crospovidone, croscarmillose, SSG as super disintegrants in different concentration (2-5%). Total twelve formations and one control tablet were prepared and evaluated for Hardness, friability, weight variation, content uniformity, wetting time, water absorption ratio, disintegration time and invitro drug release. Optimised formulation F4 was compared with control formulation for disintegration time and % drug release. The stability studies were performed as per ICH guidelines. The Optimized formulation (F4) showed no significant variations for the tablets parameters and it was stable for the specified time period. It was concluded the FDT for Rupatadine fumarate can be formulated for emergency treatment of allergic rhinitis.

Taste abatement of Metoclopramide Hydrochloride using ion exchange resins

The purpose of present research work was mask the bitter taste of Metoclopramide HCl using weak cation ion exchange resins (Indion 234) that contained crosslinked polyacrylic backbone. The drug resin complexes (DRC) were prepared by batch process by taking drug: resin ratios 1:1, 1:2 and 1:3. The optimum drug: resin ratio and the time required for maximum complexation was determined. The drug resinates were evaluated for the drug content, taste, micromeritic properties, drug release and infrared studies. The effect of batch process, complexation time, activation of ion exchange resin, temperature, complexation mode and pH on Metoclopramide HCl loading with Indion-234 were also carried out. IR analysis, assay content and decomplexation studies give evidence of complex formation. The taste evaluation depicted the successful taste masking of Metoclopramide HCl with drug resin complexes

Investigation of anxiolytic effects of Mitragyna parvifolia stem-bark extracts on animal models

The purpose of this investigation was to characterize the putative anxiolytic-like activity of methanolic, ethyl acetate extract and alkaloid rich fraction prepared from the stem-bark of Mitragyna parvifolia (Roxb.) Korth (Rubiaceae) using the elevated plus maze (EPM) and marble burying test (MBT) in mice. The extracts increased the time spent on and the number of entries into the open arms of the EPM in doses of 200 and 400 mg/kg p.o., respectively. This effect was comparable to that of negative control group treated with 0.5 % CMC and positive control the benzodiazepine diazepam (1.0 mg/kg p.o.) was used as a standard. When evaluated by MBT the number of marbles buried by mice was decreased significantly as compared to control group CMC 0.5 %. Fluoxetine (10 mg/kg p.o.) was used as a standard for comparison. These results indicate that all the extract were effective in dose dependent manner and proved statistically significant at higher doses but alkaloid rich fraction was found to be more potent in producing anxiolytic effects by both test. It suggest that the anxiolytic-like activities of this plant are mainly mediated via the GABAergic system. Neither diazepam nor the test extracts produced any overt behavioral change or motor dysfunction in the performed tests.

Infectious Mononucleosis : A Review

Infectious mononucleosis is an infectious, very widespread viral disease caused by the Epstein-Barr virus( EBV), a type of Herpes virus. It is most common among adolescents and young adults and is characterized by fever, sore throat and fatigue, along with several other possible signs and symptoms. Primary infections with EBV in childhood either remain silent or are accompanied merely by mild signs and symptoms in the throat and respiratory tract, whereas the highest rate of infectious disease occurs in older children and young adults, especially college students where the transmission of virus takes place through saliva during unprotected sexual acts. EBV infects the epithelium of the oropharynx and salivary glands. Potential mortal complications include splenic rupture, bacterial superinfections, hepatic failure and the development of viral myocarditis.Meningitis, encephalitis, hemiplegia and transverse myelitis may take place.Diagnostic criterion is the presence of 50% lymphocytes with at least 10% atypical lymphocytes (large, irregular nuclei), while the person also has fever, pharyngitis and adenopathy. Diagnosis is to be confirmed by a serological test. The antiviral drug valacyclovir has recently been shown to lower or eliminate the presence of the EBV in subjects afflicted with acute mononucleosis.

Comparison of Leaf and Root Extract of Achyranthes aspera for Its Analgesic Activity

Throughout the history the man has used several forms of therapy for relief of pain, among them; medicinal herbs have gained popularity because of its wide use and less side effect. Achyranthes aspera, for example is a commonly used folk medicine in India for various purpose. The plant root and leaf extract were prepared by using alcohol and distilled water in proportion (50:50). The extract of Achyranthes aspera was examined for centrally acting analgesic activity by using hot plate method, tail flick method and acetic acid induced writhing method for peripherally acting analgesic activity. The doses administered were 200 mg/kg and 400 mg/kg. The animal that administered a dose of 400mg/kg leaf extract has shown the maximum analgesic activity. The aspirin is taken as standard drug.

Floating Drug Delivery System-A Review

Floating Drug delivery system are designed to prolong the gastric residence time after oral administration, at particular site and controlling the release of drug especially useful for achieving controlled plasma level as well as improving bioavailability. In recent years scientific and technological advancements have been made in the research and development of controlled release oral drug delivery systems by overcoming physiological adversities like short gastric residence times and unpredictable gastric emptying times. Floating drug delivery systems are the systems which are retained in the stomach for a longer period of time and thereby improve the bioavailability of drugs. Floating dosage systems form important technological drug delivery systems with gastric retentive behavior and offer several advantages in drug delivery. Treatment of gastrointestinal disorders such as gastro-esophageal reflux. Improved drug absorption, because of increased GRT and more time spent by the dosage form at its absorption site. Ease of administration and better patient compliance. Minimizing the mucosal irritation due to drugs, by drug releasing slowly at controlled rate.

Solubilized formulation and evaluation of Reloxifene for prevention and treatment of osteoporosis in postmenopausal women

An increasing number of new chemical entities emerging from drug discovery and reaching drug development are poorly or very poorly water soluble. Our study aimed at developing solubilized formulation and evaluation of insoluble drug raloxifene (RLX) with improved bioavailability for the treatment of osteoporosis in postmenopausal women. Preformulation studies were conducted to determine the physical characteristic of drug like bulk density, particle size and solubility. Solid dispersions were prepared by hot melt method by employing 6 different carriers and mixing ratios (1:1, 1:2, and 1:3). And selection of suitable complexing agent/ carriers and ratio was done on the basis of solubility. DSC studies were made to define the physical state of drug in the carrier and possible interaction of RLX- carrier complex. Compatibility of excipients with RLX- carrier complex was tested with regard to their taste, in order to increase the palatability of the RLX formulation. Totally 10 trial bathes of RLX formulation were conducted to select prototype formula, batch S0010 was selected as optimized formulation. The best formulation obtained was investigated by preliminary stability studies at fresh (stored at RT) and stressed (stored at 40ºC & 75% RH for 1 month) conditions and initial RLX formulation were compared with aged (1 month) one. No substantial changes in its stability were observed.

Formulation and evaluation of bi-layered floating tablets of Theophylline

Bi-layered floating tablets of theophylline were developed using wet granulation technique. The current study aims at formulation and evaluation of bi-layered floating tablets of theophylline. The floating tablets of theophylline were formulated using polymers namely hydroxyl propyl methyl cellulose, sodium carboxy methyl cellulose, methyl cellulose and the tablets were evaluated. Two layered tablet formulations were designed with an immediately releasing layer consisting of theophylline with lactose as diluents and sustained release layer with slow releasing swellable matrix consisting of theophylline in hydroxyl propyl methyl cellulose, sodium carboxy methyl cellulose and methyl cellulose alone or in combination. The formulations were tested for drug release, floating time, floating lag time, drug content. Tablets formulated employing a combination of hydroxyl propyl methyl cellulose and methyl cellulose provide slow release of theophylline over a period of 9 hours and were found suitable for maintenance portion of bi-layered floating tablets. Theophylline release from these tablets was diffusion controlled and followed first order kinetics. The tablets exhibited good floating behavior in the stomach for 9 hours.

Carrier Erythrocytes (Red Blood Cells) for Delivery of Biopharmaceuticals

Application of erythrocytes as promising slow drug release or site-targeted delivery systems for a variety of bioactive agents from different fields of therapy has gained a remarkable degree of interest in recent years. The term biopharmaceutical is most commonly used to refer to all therapeutic, prophylactics,, and in vivo diagnostic agents produced using live organisms or their functional components. At least in the US, biopharmaceuticals are often considered to include products manufactured using both ‘new’ technologies (recombinant DNA and monoclonal antibody/hybridoma) and ‘old’ technologies (fermentation, non- recombinant cell culture derived proteins, vaccines, and other products from live organisms including blood/plasma products).Thus, a biopharmaceutical results from bio-processing and can, therefore, be defined as the intersection of pharmaceutical technology and biotechnology. This, in turn, has evoked plenty of research projects with the ultimate goal of using the potential capabilities of these carriers in different clinical situations. Biopharmaceuticals are among the most widely exploited candidates for being delivered to the host body using these cellular carriers. Biopharmaceuticals, therapeutically significant peptides and proteins, nucleic acid-based biologicals, antigens and vaccines, are among the recently focused pharmaceuticals for being delivered using carrier erythrocytes. Here there is, the potential applications of erythrocytes in drug delivery have been reviewed with a particular stress on the studies and laboratory experiences on successful erythrocyte loading and characterization of the different classes of biopharmaceuticals.

Effect of Piracetam on Experimental Anterograde and Retrograde Amnesia

Piracetam is a cyclic derivative of g-aminobutyric acid (GABA) reported to improves learning and memory consolidation, facilitates inter-hemispheric transfer and increases the cerebral resistance to cognitive impairments induced by hypoxia and other noxious stimuli including ageing. Therefore, the present study was designed to investigate the effect of piracetam on scopolamine (3 mg Kg-1, i.p.), cyclohexamide (28 mg Kg-1, i.p.), diazepam (1 mg Kg-1, i.p.), sodium nitrite (75 mg Kg-1, i.p.) and BN52021 (15 mg Kg-1, i.p.) were administred to mice before acquisition or retrieval trial using water maze test. Scopolamine, cyclohexamide and diazepam have produced only anterograde amnesia. Sodium nitrite has produced both anterograde and retrograde amnesia. BN52021 (PAF receptor antagonist) has produced only retrograde amnesia. The present results exhibit that the anterograde amnesia produced by scopolamine, cyclohexamide and sodium nitrite has been prevented by piracetam (200 mg Kg-1, i.p.). On the other hand diazepam induced anterograde amnesia has not been affected by piracetam. However, retrograde amnesia produced by sodium nitrite and BN52021 has been attenuated by piracetam (200 mg Kg-1, i.p.). It is speculated that ameliorative effect of piracetam in experimental amnesia may be due to increase in intracellular calcium, restoration of synthesis of cerebral proteins, improvement in cholinergic mechanism and consequent restoration of brain cell fluidity.

Development, Optimization and In-Vitro Evalution of Glibenclamide Solid Dispersion Using Different Polymer

Drugs administered orally in solid dosage form should dissolve in gastrointestinal fluids before they are absorbed. Drugs with united solubility in aqueous media may exhibit dissolution rate limited absorption profile. Thus the rate of dissolution of the drugs in the gastrointestinal fluids could influence the rate and extent of absorption. In the case of poorly soluble drug the dissolution rate always influences its absorption. These solid dispersions provided sustained absorption of nifedipine in beagle dogs with good availability after oral administration. Stability studies indicated that these dispersions were stable for at least 6 months under accelerated conditions. Similar dispersions of dipyridamole also showed delayed absorption with good bioavailability.

Fast dissolving tablet: A review on revolution of novel drug delivery system and new market opportunities

Oral delivery is currently the gold standard in the pharmaceutical industry where it is regarded as the safest, most convenient and most economical method of drug delivery having the highest patient compliance. The tablet is the most widely utilized oral dose format. A novel tablet concept which offers ease of oral administration and benefits of increased patient compliance is the fast dissolving/disintegrating tablet (FDDT). This tablet format is designed to allow administration of an oral solid dose form in the absence of water or fluid intake. Such tablets readily dissolve or disintegrate in the saliva generally within<60 seconds. The oral drug delivery market was estimated to be worth $35bn in 2006 & forecast to reach$52bn by 2010 with a CAGR of 10%. Of this, the FDDT, taste masked & micro emulsion formulation segments constitute a 22% share with an expected CAGR of 17% to 2010.There is a clear opportunity for new enhanced oral products arising within thismarketsegment. Formulation advances using a conventional tabletting process have led to the development of mechanically robust tablets which readily dissolve/disintegrate within <50 seconds and can be formulated in a range of sizes from 10 -15mm. The tablets produced are stable, and can withstand shipment in conventional tablet containers without loss of integrity.Pre-clinical canine studies with a range of formulations have demonstrated palatability and ease of administration.A number of FDDT products for human and veterinary administration are currently under development and the delivery of water soluble as well as lipophilic drug compounds. Fast- or mouth dissolving tablets have been formulated for pediatric, geriatric, and bedridden patients and for active patients who are busy and traveling and may not have access to water.

Synthesis of some novel trifluoromethylated tetrahydropyrimidines using etidronic acid and evaluation for antimicrobial activity

A simple and convenient, etidronic acid catalyzed, one-pot cyclocondensation reaction of 1, 3-diketone, arylaldehydes and urea to furnish trifluoromethyl tetrahydropyrimidine derivatives with excellent yield is described. The catalytic application of etidronic acid was investigated under various reaction conditions. All the synthesized compounds were evaluated for antimicrobial activity. The results obtained demonstrated that 40% of the synthesized compounds exhibited significant antimicrobial activity against all the tested micro organisms.

Development, In-Vitro Evaluation and Physical Characterization of Medicated Chewing Gum: Chlorohexidine Gluconate

Absorption of drugs through the oral cavity was noted as early as 1847 by Sobrero, the discoverer of nitroglycerin, and systemic studies of oral cavity absorption were first reported by Walton and Lacey in 1935. As a site for drug delivery, the oral cavity offers many advantages over other routes of drug administration. The mucosal lining of the oral cavity are readily accessible. During the chewing process, most of the medications contained within the gum product are released into the saliva and are either absorbed through the buccal mucosa or swallowed and absorbed through the gastrointestinal tract. Delivery systems containing actives for oral administration now include various chewing gum formulations. Chewing gums permit release of the active ingredient over time as the gum product is masticated, or chewed. The action of saliva on the gum further facilitates release of the active, as well as its subsequent absorption by the mucous membranes lining the mouth, throat, larynx and esophagus.