DEVELOPMENT AND VALIDATION OF ULTRAVIOLET SPECTROPHOTOMETRIC METHOD FOR QUANTITATIVE ESTIMATION OF FAMOTIDINE IN BULK AND TABLET DOSAGE FORM

  Objectives: The purpose of the study is to develop a simple, precise, economical, accurate, reproducible, and sensitive method for the estimation of famotidine (FAM) in bulk and its pharmaceutical dosage forms by ultraviolet (UV) absorption spectrophotometry.Methods: The method uses 0.1 N HCl, pH 1.20 as a solvent for the quantitative estimation of FAM in bulk and its tablets dosage form by UV absorption spectrophotometry.Results: FAM exhibited absorbance maxima at 266 nm in 0.1 N HCl, pH 1.20 solvent. The developed method was validated as per the ICH analytical method validation guidelines. Beer's law was obeyed in range of 0-30 μg/ml with r2=0.9998. The limit of detection and limit of quantification values of FAM were found to be 0.152 and 0.461 μg/ml, respectively. The mean percentage recovery for developed method was found to be in the range of 99.35-99.48%, respectively, for the marketed dosage forms. The developed method was also found to be robust and ensures bench-top stability.Conclusion: The developed method was found to be suitable for the routine quantitative analysis of FAM in bulk and pharmaceutical dosage form. It was also concluded that developed UV spectrophotometry method was accurate, precise, linear, reproducible, robust, and sensitive

FORMULATION AND EVALUATION OF FAMOTIDINE MICRO BALLOONS WITH ENHANCED ANTI-ULCER ACTIVITY

Objective: The aim of the present study was to formulate and optimize famotidine loaded micro balloons for enhancing bioavailability, increasing gastric residence time of drug and to achieve sustained release in the stomach.Methods: Microballoons were prepared using emulsion solvent diffusion method using HPMC K4M as the polymer. All the formulated microspheres were subjected to various evaluation parameters such as % drug entrapment, micromeritics properties, % buoyancy and in vitro drug release studies. The formulation was optimized using 32 full factorial design. Optimized formulation was subjective to in vivo floating (X-ray) and in vivo antiulcer studies.Results: The microballoons were smooth and spherical in shape and were porous in nature due to hollow cavity. Sustained/controlled release of drug was observed for more than 12 h. based on the results of % drug entrapment, in vitro drug release and % buoyancy studies, formulation F6 was selected as optimized formulation. The release kinetics of optimized formulation followed Higuchi model and mechanism of release was non-Fickian diffusion. Examination of the X-ray radiographic images taken during the study indicated that the optimized formulation remained buoyant and uniformly distributed in the gastric contents for a long period. In ethanol-induced ulcer model, drug-loaded microballoons treated group showed significant ulcer protection index of 83.26% as compared to the marketed brand of famotidine 76. 09% and untreated control group.Conclusion: Famotidine-loaded floating micro balloons were successfully prepared and prove to be useful for the prolonged gastric residence of the drug, better bioavailability, patient compliance and anti-ulcer activity

DEVELOPMENT AND VALIDATION OF UV SPECTROPHOTOMETRIC METHOD FOR QUANTITATIVE ESTIMATION OF LAFUTIDINE IN BULK AND PHARMACEUTICAL DOSAGE FORM

Objective: The objectives of the present research was to develop a simple, precise, economical, accurate, reproducible and sensitive method for the quantitative estimation of lafutidine in bulk and its pharmaceutical dosage forms by Ultra Violet (UV) absorption spectrophotometry.Methods: The method uses 0.1 N HCl, pH 1.20 as a solvent of choice for the quantitative estimation of lafutidine in bulk and its tablets dosage form by UV absorption spectrophotometry at a wavelength of 290 nm. The method was validated for parameters like linearity, range, precision, Limit of Detection (LOD), Limit of Quantification (LOQ), accuracy, recovery and stability of the analyte.Results: Lafutidine exhibited absorbance maxima at 290 nm in 0.1 N HCl, pH 1.20 solvent. The developed method was validated as per the ICH validation guidelines. Beer's law was obeyed in range of 0-30 µg/ml with r2= 0.9997. The LOD and LOQ values of lafutidine were found to be 0.545 µg/ml and 1.654 µg/ml respectively. The mean % recovery for the developed method was found to be in the range of 99.25 to 99.45 % respectively for the marketed dosage forms. The developed method was also found to be robust.Conclusion: The developed method was found suitable for the routine quantitative analysis of lafutidinein bulk and pharmaceutical dosage form. It was also concluded that developed UV spectrophotometry method was accurate, precise, linear, reproducible, robust and sensitive

Physical stability and bio-efficacy enhancement of Neem kernel aqueous extract by optimized amount of botanical synergist for the control of early stages of mosquitoes

The aim of present study is to enhance the stability of physic-chemical characteristics of neem kernel aqueous extract by botanical stabilizer system. There are variety of bioactive constituents are present in neem which give broadspectrum of insecticidal activity. Neem aqueous extract is commonly used and found very effective in pest control applications without harming the environment. However, due to hydrolytically unstable characteristics of neem active ingredients which results its lesser bioactivity and limits its usage in aqueous form.  To overcome this un-stability issue oil extracted botanical stabilizer (Prosopis juliflora) were used in various ratios. In 70: 30 ratios, neem aqueous extract was found stable without any turbidity, p H change and fungal growth. Active ingredient, Azadirachtin was found stable with very less degradation i.e only 20-30 % degradation. This may possibly be due to inhibition of hydrolytic reactions. Bio-efficacy evaluation data also showed improved and stable mosquito larvae mortality % i.e 75-90% with 8 µg/g LD50 value. The approach used in this study could be very useful in long term stability of neem kernel extract in various geographical conditions without adding toxic solvents or chemical compositions

Utjecaj davanja maslaca obogaćenoga konjugiranom linolnom kiselinom na incidenciju i patohistološke promjene raka mliječne žlijezde štakorica uzrokovanoga 7,12-dimetilbenz[a]anthracenom.

A study was conducted to investigate the influence of Conjugated Linoleic Acid (CLA) feeding on cancer incidence and histopathological changes in DMBA induced mammary gland carcinogenesis rats. Female Wistar rats of 21 days were taken for the study and the animals were randomly divided into three groups of 30 animals each. Group I animals were fed with a soybean based diet, whereas group II and group III animals were fed with a low CLA and high CLA ghee based diet, respectively. Soybean oil, low CLA and high CLA ghee were included at the level of 20 per cent in the animal diet. Feeding with test diets started on the day of weaning. The animals were given 7,12 dimethyl-benz[a]anthracene(DMBA) at 5 mg per animal as a single dose by oral intubation at the age of 55 days and the test diets were continued up to 32 weeks after DMBA administration. At the end of 32 weeks all the animals were sacrificed, tumour data recorded and histopathology performed. The tumour incidence in groups I, II and III was 83.33, 63.33 and 46.07 per cent respectively. Histopathology revealed fibroma, adenoma, fibroadenoma in all the groups whereas in group I showed adenocarcinoma. Therefore, the results of the present study showed CLA not only inhibited benign type tumours but malignant tumours as well.Istraživan je utjecaj davanja maslaca od bivoljega mlijeka obogaćenoga konjugiranom linolnom kiselinom na incidenciju i patohistološke promjene u nastanku raka mliječne žlijezde štakorica uzrokovanoga 7,12-dimetilbenz[a]antracenom. Wistar štakorice u dobi od 21 dana bile su nasumce podijeljene u tri skupine po 30 životinja. Prva skupina bila je hranjena hranom na bazi soje, dok je druga dobivala hranu na bazi bivoljega mlijeka s malom koncentracijom konjugirane linolne kiseline, a treća hranu s dodatkom veće količine konjugirane linolne kiseline. Sojino ulje i linolna kiselina dodavani su u hranu u količini od 20%. Hranidba navedenom hranom započela je na dan zalučenja. Svakoj je životinji peroralno dan 7,12-dimetilbenz[a]antracen (DMBA) u količini od 5 mg u dobi od 55 dana, a testirana hrana davana je do 32 tjedna nakon primjene DMBA. Sve su životinje bile žrvovane nakon 32 tjedna te pretražene na pojavnost i patohistološke značajke tumora. Incidencija tumora u I skupini bila je 83,33%, u II skupini 63,33% i u III skupini 46,07%. Patohistološki je ustanovljen fibrom, adenom i fibroadenom u štakorica svih skupina, dok je u štakorica I skupine ustanovljen i adenokarcinom. Rezultati su pokazali da je konjugirana linolna kiselina imala inhibirajući učinak i na dobroćudni i na zloćudni tumor

Role of Decomposers in Agricultural Waste Management

In this chapter, agricultural waste residue management by bio-organisms is discussed along with different types of decomposition processes. Tons of agricultural wastes are produced every year. These agricultural wastes create major environmental problems without effective means of management methods. There are many technologies being used for the decomposition, which mainly include anaerobic decomposition, compositing, fermentation, etc. All these decomposition processes depend upon the different soil-inhabiting microbes. These microbes are the key components of agri-residue decomposition process. Every step of decomposition requires different microbes. Various sets of catalytical enzymes are involved for the catabolic procedures of organic matter. By successive catabolic reactions, all the organic matters are mineralized into soil essential constituents, which will be the most effective sources of macro- and micronutrients for the soil fertility. Working efficiency of these microbes depends upon different parameters like moisture, temperature, pH, etc. The vitality and efficiency of microbes can be enhanced by using various inert carriers. If the efficiency of these soil microbes enhances by various factors, then the rate of decomposition could be enhanced to handle this ever-increasing problem of agriculture residue in near future

Physical Stability and Bio-Efficacy Enhancement of Neem Kernel Aqueous Extract by Optimized Amount of Botanical Synergist for the Control of Early Stages of Mosquitoes

297-303The aim of present study is to enhance the stability of physico-chemical characteristics of neem kernel aqueous extract by botanical stabilizer system. There are variety of bioactive constituents are present in neem which give broad-spectrum of insecticidal activity. Neem aqueous extract is commonly used and found very effective in pest control applications without harming the environment. However, due to hydrolytically unstable characteristics of neem active ingredients which results its lesser bioactivity and limits its usage in aqueous form. To overcome this un-stability issue oil extracted botanical stabilizer (Prosopis juliflora) (Junglee kikar)) were used in various ratios. In 70-30 (NKP-KP) composition (NKP- Neem kernel powder; KP- Kiker powder), neem aqueous extract was found stable without any turbidity, pH change, and fungal growth. Active ingredient, Azadirachtin was found stable with very less degradation i.e only 20–30% degradation. This may possibly be due to inhibition of hydrolytic reactions. Bio-efficacy evaluation data also showed improved and stable mosquito larvae mortality per cent i.e 75–90% with 8 µg/g LD50 value. The approach used in this study could be very useful in long term stability of neem kernel extract in various geographical conditions without adding toxic solvents or chemical compositions

In Vitro and In Vivo Toxicity Evaluation of Natural Products with Potential Applications as Biopesticides

The use of natural products in agriculture as pesticides has been strongly advocated. However, it is necessary to assess their toxicity to ensure their safe use. In the present study, mammalian cell lines and fish models of the zebrafish (Danio rerio) and medaka (Oryzias latipes) have been used to investigate the toxic effects of ten natural products which have potential applications as biopesticides. The fungal metabolites cavoxin, epi-epoformin, papyracillic acid, seiridin and sphaeropsidone, together with the plant compounds inuloxins A and C and ungeremine, showed no toxic effects in mammalian cells and zebrafish embryos. Conversely, cyclopaldic and α-costic acids, produced by Seiridium cupressi and Dittrichia viscosa, respectively, caused significant mortality in zebrafish and medaka embryos as a result of yolk coagulation. However, both compounds showed little effect in zebrafish or mammalian cell lines in culture, thus highlighting the importance of the fish embryotoxicity test in the assessment of environmental impact. Given the embryotoxicity of α-costic acid and cyclopaldic acid, their use as biopesticides is not recommended. Further ecotoxicological studies are needed to evaluate the potential applications of the other compounds

Dodatak kroma u teladi azijskog vodenog bivola (Bubalus bubalis) pod stresom od hladnoće: učinci na prirast, hranidbenu iskoristivost te staničnu i humoralnu imunost

Various stressors significantly increase urinary excretion of chromium (Cr), suggesting that Cr may be physiologically linked to the responses to control stress. The aim of this study was to determine the physiological responses of buffalo calves to increased Cr supply under low ambient temperature. In a randomized complete block design, twenty-four Murrah buffalo calves were assigned to 4 treatments for a period of 120 days. Treatments included either no supplemental Cr (control), 0.5 mg of supplemental Cr/kg DM, 1.0 mg of supplemental Cr/kg DM, or 1.5 mg of supplemental Cr/kg DM. Buffalo calves were monitored daily for physiological variables, dry matter intake (DMI) and fortnightly for body mass change. Blood samples were collected at fortnightly intervals and analyzed for the biomarkers of immunity and plasma trace mineral concentration. At the end of the 120 day experimental period, a 7 day metabolic trial was conducted. The average temperature-humidity index (THI) and relative humidity (RH) during the study were 58.10 units and 52.0% respectively. Physiological variables, DMI and growth performance did not differ among all treatments. 1.5 mg Cr/kg DM increased B and T-cell proliferation, neutrophil phagocytic activity and ferric reducing antioxidant power (FRAP) value, whereas plasma total immunoglobulin (TIg) and immunoglobulin G (IgG) concentrations were the highest in the 1.0 and 1.5 mg Cr/kg DM group. Nutrient digestibility, nitrogen (N) metabolism and trace mineral bioavailability did not differ between treatments, while the bioavailability of Cr showed a positive correlation with supplemental Cr level. The results suggest that in cold conditions, increased Cr supply can improve immune response without affecting physiological response, growth performance and nutrient utilization in buffalo calves.Različiti stresori značajno povećavaju izlučivanje kroma (Cr) mokraćom što naznačuje da Cr može biti fiziološki vezan s odgovorom za kontrolu stresa. Cilj je ovog rada bio odrediti fiziološke odgovore u bivolje teladi na povećani dodatak Cr u uvjetima niske temperature okoliša. Prema metodi slučajnog odabira skupina, 24 Murrah bivolska teleta bila su raspodijeljena u četiri skupine koje su bile različito tretirane u razdoblju od 120 dana. Životinjama jedne skupine dodavano je 0,5 mg Cr/kg suhe tvari, druge skupine 1,0 mg Cr/kg suhe tvari, a treće skupine 1,5 mg Cr/kg suhe tvari, dok kontrolnoj skupini Cr nije bio dodavan. U teladi su dnevno bile promatrane fiziološke varijable, uzimanje suhe tvari te svaka dva tjedna promjena tjelesne mase. Uzorci krvi bili su uzimani u razmacima od 14 dana i pretraženi na biomarkere imunosti i koncentraciju minerala u tragovima u plazmi. Na kraju pokusnog razdoblja od 120 dana proveden je sedmodnevni metabolički pokus. Prosječni indeks temperature i vlažnosti tijekom istraživanja iznosio je 58,10 jedinica dok je relativna vlažnost bila 52,0 %. Fiziološke varijable, uzimanje suhe tvari i prirast reducirajućeg željeza nisu se razlikovali među skupinama. Količina od 1,5 mg Cr/kg suhe tvari povećala je proliferaciju B- i T-limfocita, fagocitoznu aktivnost neutrofila i vrijednost antioksidacijske sposobnosti, dok su koncentracije ukupnih imunoglobulina plazme i imunoglobulina G (IgG) bile najveće u skupinama koje su dobivale 1,0 odnosno 1,5 mg Cr/kg suhe tvari. Nutritivna probavljivost, metabolizam dušika (N) i biološka raspoloživost minerala u tragovima nisu se razlikovali među skupinama. Biološka raspoloživost Cr bila je u korelaciji s razinom njegova dodatka. Rezultati upućuju na zaključak da povećani dodatak Cr u hladnoći može poboljšati imunosni odgovor bez utjecaja na fiziološki odgovor, prirast i hranidbenu iskoristivost u bivolje teladi

A chemical probe for BAG1 targets androgen receptor-positive prostate cancer through oxidative stress signaling pathway

BAG1 is a family of polypeptides with a conserved C-terminal BAG domain that functions as a nucleotide exchange factor for the molecular chaperone HSP70. BAG1 proteins also control several signaling processes including proteostasis, apoptosis and transcription. The largest isoform, BAG1L, controls the activity of the androgen receptor (AR) and is upregulated in prostate cancer. Here, we show that BAG1L regulates AR dynamics in the nucleus and its ablation attenuates AR target gene expression especially those involved in oxidative stress and metabolism. We show that a small molecule, A4B17 that targets the BAG domain downregulates AR target genes similar to a complete BAG1L knockout and upregulates the expression of oxidative stress-induced genes involved in cell death. Furthermore, A4B17 outperformed the clinically approved antagonist enzalutamide in inhibiting cell proliferation and prostate tumor development in a mouse xenograft model. BAG1 inhibitors therefore offer unique opportunities for antagonizing AR action and prostate cancer growth