ENDOCRINOLOGICAL ROLE OF LEPTIN IN OBESITY AND ASTHMA

Objective: Role of leptin resistance in correlation between obesity and asthma. Methods: High-caloric diet was given for 8 weeks to induce obesity. Ovalbumin followed by aluminum hydroxide was given to induce asthma. The animal was treated with leptin analog (0.4 mg/kg, i.p. for 7 days) and leptin antagonist (3 mg/kg, p.o., for 7 days). Biochemical parameters such as serum leptin, ghrelin, and tumor necrosis factor alpha (TNF-α) and physical parameters such as tidal volume and airflow rate were estimated to confirm the state of asthma and obesity, respectively. Results: It was found that leptin and ghrelin were elevated in obese and obese asthmatic condition, responsible for leptin resistance. Treatment with leptin analog and leptin antagonist significantly increases and decreases serum leptin levels, respectively. There was no significant change in TNF-α and ghrelin level after leptin analog treatment. The result of respiratory parameters improved with leptin analog. From our study, we found beneficial role of leptin analog in obese asthmatic condition. Conclusion: Leptin is an alternative treatment approach to treat obese asthmatic condition

PREPARATION, CHARACTERIZATION, AND OPTIMIZATION OF MICROEMULSION FOR TOPICAL DELIVERY OF ITRACONAZOLE

Microemulsions (ME) have been proved to increase the cutaneous absorption of both lipophilic and hydrophilic medicaments when compared to conventional vehicles (emulsions, pure oils, aqueous solutions). Hence the aim of present investigation is to prepare, characterize and optimize microemulsion of Itraconazole (ITZ). Itraconazole is an anti fungal agent, most widely used in the ringworm infection. It is classified as class III drug as per BCS classification. It indicates lower permeability through skin. Therefore objective of the research is to improve permeability of Itraconazole through skin. Microemulsion was prepared using eucalyptus oil, tween 20 and methanol as oil phase, surfactant and co-surfactant respectively. Pseudo ternary phase diagrams were constructed to find out optimum ratio of oil: Smix (surfactant: Co-Surfactant): water. A 32 full factorial design was applied for the optimization of prepared microemulsion. Microemulsion was evaluated for globule size, zeta potential, in-vitro diffusion study etc. Results of globule size measurements and zeta potential indicated ME7 had high stability then other formulation of microemulsion. For the optimization transdermal flux and %Q6 was selected as dependant variables. Results of optimization study also revealed ME 7 as optimized microemulsion for high permeability to the skin. Further ME7 was compared to marketed Itraconazole preparation (ITASPORE) and evaluated using similarity factor F2. Results of F2 value was not near to 100 indicated there is no similarity in diffusion profiles of ME7 and ITASPORE. Hence, indirectly it suggest there was increased in permeability of drug by preparing microemulsion

PREPARATION AND EVALUATION OF SELF MICROEMULSIFYING DRUG DELIVERY SYSTEM FOR FEXOFENADINE HYDROCHLORIDE

Developinga drug product with desirable bioavailability is a challenge for sparinglywater soluble drugs such as Fexofinadine hydrochloride. Objective: In the present investigation self microemulsifying drugdelivery system (SMEDDS) of Fexofenadine hydrochloride was developed forimproving solubility and dissolution rate of drug. Material Method: Solubility of Fexofenadine hydrochloride wasdetermined in various non-aqueous vehicles such as oils, surfactants, andco-surfactants. Psuedoternary phase diagrams were constructed to identify theself-micro emulsification region. Four formulations of SMEDDS were selected fromthe optimum concentration of oils, surfactant, and co-surfactants from psuedoternary diagrams. Resultsand Discussion: Selected formulations were evaluated for droplet size,in-vitro drug dissolution, drug content and solubility of drug. The optimumformulation was 20% oleic acid, 26.3% ACONON MC8 and 53.3% PEG 400. Self-microemulsification with the combination of oleic acid and ACONON MC8 was foundhigher. Conclusion: The resultsobtained from in vitro dissolutionindicated Fexofenadine hydrochloride in SMEDDS dissolved rapidly and completelyin phosphate buffer pH 6.8 which was used as dissolution medium

Sinteza i farmakološko ispitivanje novih 4-(3-etilfenil)-1-supstituiranih 4H-[1,2,4]triazolo[4,3-a]kinazolin-5-ona kao nove klase H1-antihistaminika

A series of novel 4-(3-ethylphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-ones (4a-j) were synthesized by the cyclization of 3-(3-ethylphenyl)-2-hydrazino-3H-quinazolin-4-one (3) with various one-carbon donors. The starting material, compound 3, was synthesized from 3-ethyl aniline by a new innovative route with improved yield. When tested for their in vivo H1-antihistaminic activity on conscious guinea pigs, all test compounds protected the animals from histamine induced bronchospasm significantly. Compound 4-(3-ethylphenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-one (4b) emerged as the most active compound of the series and it is more potent (74.6 % protection) compared to the reference standard chlorpheniramine maleate (71 % protection). Compound 4b shows negligible sedation (10 %) compared to chlorpheniramine maleate (30 %). Therefore compound 4b can serve as the leading compound for further development of a new class of H1-antihistamines.Ciklizacijom 3-(3-etilfenil)-2-hidrazino-3H-kinazolin-4-ona (3) s različitim donorima jednog C atoma sintetizirana je serija novih 4-(3-etilfenil)-1-supstituiranih 4H-[1,2,4]triazolo[4,3-a]kinazolin-5-ona (4a-j). Početni spoj 3 pripravljen je iz 3-etil anilina na novi, inovativni način, s poboljšanim iskorištenjem. U testovima in vivo na zamorcima, svi testirani spojevi pokazali su značajno zaštitno djelovanje protiv bronhospazma induciranog histaminom. Spoj 4-(3-etilfenil)-1-metil-4H-[1,2,4]triazolo[4,3-a]kinazolin-5-on (4b) najaktivniji je među testiranim spojevima (zaštita 74.6 %) i jači od referentnog standarda klorfeniramin maleata (zaštita 71 %). Spoj 4b pokazuje zanemarivu sedaciju (10 %) u usporedbi s klorfeniramin maleatom (30 %). Stoga spoj 4b može biti vodeći spoj za daljnji razvoj nove klase H1-antihistaminika

RP-HPLC Method Development and Validation of Pazufloxacin in Their Bulk and Formulation

The present work was the development of a simple, efficient, and reproducible reverse-phase high performance liquid chromatographic (RP-HPLC) method for determination of Pazufloxacin (PFX) in bulk and its injection dosage form. The solvent system and wavelength were optimized in order to maximize the sensitivity of the proposed method and detection wavelength was carried out at 249 nm. The separation was achieved on HPLC binary gradient system equipped with HPLC 3000 series UV detector and Agilent Zorbax column C18 (4.6mm×50mm×5µm). The optimized mobile phase composition was methanol: phosphate buffer pH 4 (50:50%v/v). The separation of PFX was carried out on Kromasil C-18 (250 × 4.6 mm×5 ????m) column using phosphate buffer pH 4 and methanol by linear gradient program. Flow rate was 1.0 ml/min with a column temperature of 30?C. The method was validated in terms of accuracy, precision, linearity, LOD & LOQ of sample solution as per ICH guidelines. Linearity was observed in the concentration range of 5-25 ?g/ml & gave mean correlation coefficient 0.998. The developed RP-HPLC method was found to be accurate, precise and was successful applied to a Pazufloxacin bulk powder and its marketed formulation for qualitative estimation of Pazufloxacin

HPTLC Method for the Simultaneous Estimation of Valsartan and Hydrochlorothiazide in Tablet Dosage Form

A simple, precise, accurate and rapid high performance thin layer chromatographic method has been developed and validated for the simultaneous estimation of valsartan and hydrochlorothiazide in combined dosage forms. The stationary phase used was precoated silica gel 60F254. The mobile phase used was a mixture of chloroform: methanol: toluene: glacial acetic acid (6:2:1:0.1 v/v/v/v). The detection of spots were carried out at 260 nm. The method was validated in terms of linearity, accuracy, precision and specificity. The calibration curve was found to be linear between 300 to 800 ng/spot for valsartan and 100 to 600 ng/spot for hydrochlorothiazide. The limit of detection and the limit of quantification for the valsartan were found to be 100 and 300 ng/spot respectively and for hydrochlorothiazide 30 and 100 ng/spot respectively. The proposed method can be successfully used to determine the drug content of marketed formulation

Development and Validation of a HPTLC Method for the Estimation of Sumatriptan in Tablet Dosage Forms

A simple, precise, accurate and rapid high performance thin layer chromatographic method has been developed and validated for the estimation of sumatriptan in tablet dosage forms. The stationary phase used was precoated silica gel 60F254. The mobile phase used was a mixture of methanol:water:glacial acetic acid (4.0:8.0:0.1, v/v/v). The detection of spots was carried out at 230 nm. The method was validated in terms of linearity, accuracy, precision and specificity. The calibration curve was found to be linear between 200 to 800 ng/spot. The limit of detection and the limit of quantification for the sumatriptan were found to be 63.87 and 193.54 ng/spot, respectively. The proposed method can be successfully used to determine the drug content of marketed formulation

EVALUATION OF PHYSICO-CHEMICAL PARAMETERS OF DIFFERENT SHODHIT GUGGUL

Objective: The present study was aimed to identify the physicochemical data of shodhit guggul. Guggul is a gum-resin exudate from the plant Commiphora weightii (Arn.) Bhandari, belonging to Burseraceae family. In Ayurveda, guggul is always purified. This purification is known as Shodhan. Shodhan is a process by which guggul is made non-toxic, effective, suitable and fit for therapeutic purposes.Methods: The seven different shodhan dravya were used to prepare shodhit guggul. They were evaluated by performing physicochemical parameters including five different extractive value; total ash, acid insoluble, water soluble and sulphated ash value; pH, and loss on drying.Results: Analytical results of raw guggul showed total ash, acid insoluble ash, water soluble ash and sulphated ash value to 5.36±0.04%, 0.96±0.03%, 4.51±0.03 % and 8.40±0.04% respectively. These all values of each shodhit guggul were different. The extractive value of raw guggul was comparable with standard value while the extractive value of each shodhit guggul was totally different. The pH value of 1% w/v and 10% w/v aqueous solution of raw guggul was 6.44±0.18 though pH of each shodhit guggul was changed. The loss on drying of raw guggul was found to be 1.88±0.02%w/v, however, this value was different for each shodhit guggul.Conclusion: The present study revealed that the different shodhan process with specific shodhan dravya affects the physicochemical parameters. The analysis and comparison of the data showed the difference in the properties of seven shodhit guggul with respect to raw Guggul

Stability-indicating Simultaneous HPTLC Method for Olanzapine and Fluoxetine in Combined Tablet Dosage Form

A rapid, selective and stability-indicating high performance thin layer chromatographic method was developed and validated for the simultaneous estimation of olanzapine and fluoxetine in combined tablet dosage form. Olanzapine and fluoxetine were chromatographed on silica gel 60 F254 TLC plate using methanol:toluene (4:2 v/v) as the mobile phase and spectrodensitometric scanning-integration was performed at a wavelength of 233 nm using a Camag TLC Scanner III. This system was found to give compact spots for both olanzapine (Rf value of 0.63±0.01) and fluoxetine (Rf value of 0.31±0.01). The polynomial regression data for the calibration plots showed good linear relationship with r2=0.9995 in the concentration range of 100-800 ng/spot for olanzapine and 1000-8000 ng/spot for fluoxetine with r2=0.9991. The method was validated in terms of linearity, accuracy, precision, recovery and specificity. The limit of detection and the limit of quantification for the olanzapine were found to be 30 and 100 ng/spot, respectively and for fluoxetine 300 and 1000 ng/spot, respectively. Olanzapine and fluoxetine were degraded under acidic, basic and oxidation degradation conditions which showed all the peaks of degraded product were well resolved from the active pharmaceutical ingredient. Both drugs were not further degraded after thermal and photochemical degradation. The method was found to be reproducible and selective for the simultaneous estimation of olanzapine and fluoxetine. As the method could effectively separate the drugs from their degradation products, it can be employed as a stability-indicating method