An evaluation of spectral and statistical parameters of ion pair complexation of Zafirlukast using chromogenic dyes in solid dispersion-based formulations.

The purpose of present work was to develop a novel analytical method for orally given leukotriene antagonist Zafirlukast (ZST), present in Meglumine and Eudragit EEPO based solid dispersion formulation. Four simple, extraction-free, fast, and economical methods based on charge transfer complexation among nitrogen of ZST with sulfonyl group comprising chromogenic mediator bromophenol blue (BPB-Method B), bromothymol blue (BTB-Method C) and bromocresol green (BCG-Method D). The first method (A) is based on the analysis using 0.1 M HCl as a solvent at λmax 242 nm while chromogenic methods yield color complex at λmax 415 nm (BPB-Method B), λmax 420 nm (BTB-Method C) and λmax 435 nm (BCG-Method D). The Beer's Law stayed linear in the concentration ranges of 1-10, 10-75, 5-40 and 15-100 µg/ml for methods A, B, C and D, respectively. The spectral and thermodynamic characterization of each method was carried out by the application of Molar Absorptivity, LOD, LOQ, Association Constant and Gibbs free energy (ΔGo). The methods were statistically optimized and evaluated by F-Distribution Value, P-Value, Shapiro-Wilk P-Value, regression analysis, Q-Q plot, prediction interval, residual histogram and plots. Various experimental conditions affecting the complexation and stability of chromogenic complexes are cautiously studied including optimal temperature, chromogenic agent volume, color stability, recovery, precision and accuracy. All the measurements were executed under ICH guidelines. It can be established that proposed would be an appropriate prospective analytical approach for estimation of ZST in pure bulk, solid dispersions and dosage forms.

Development and optimization of metoclopramide containing polymeric patches: impact of permeation enhancers

Abstract The study is aimed to develop a monolithic controlled matrix transdermal patches containing Metoclopramide as a model drug by solvent casting method. Eudragit L100, Polyvinylpyrrolidone K-30, and Methylcellulose were used in different ratios and Polyethylene glycol 400 added as a plasticizer. Resulting patches were evaluated for their physicochemical characters like organoleptic characters, weight variation, folding endurance, thickness, swelling index, flatness, drug content, swelling index, percentage erosion, moisture content, water vapor transmission rate and moisture uptake. Formed patches were also evaluated through Fourier transform spectroscopy (FT-IR), X-ray diffraction (XRD), Differential Scanning calorimetry (DSC) and Scanning Electron Microscopy (SEM). Results of SEM unveiled smooth surface of drug-loaded patches. In-vitro dissolution studies were conducted by using dissolution medium phosphate buffer saline pH 7.4. Effect of natural permeation enhancers was elucidated on two optimized formulations (Z4 and Z9). Different concentrations (5%-10 %) of permeation enhancers i.e. Olive oil, Castor oil and Eucalyptus oil were evaluated on Franz diffusion cell using excised abdominal rat skin. Z4-O2 (Olive oil 10%) had enhanced sustain effect and flux value (310.72) close to the desired flux value. Z4-O2 followed Higuchi release model (R2= 0.9833) with non-fickian diffusion release mechanism (n=0.612)

Combination of eudragit EPO with poloxamers for improved solubility and dissolution of Zafirlukast: An evaluation of solid dispersion formulations.

This study investigated the effect of solid dispersions (SD) on solubility and release of Zafirlukast (ZA) by physical mixture (PM), solvent evaporation (SE) and kneading method (KM) with Eudragit EPO (EPO) as binary component and Poloxamer 188 (P188) and Poloxamer 407 (P407) as ternary components. The binary and ternary systems caused an increase of 322 folds and 356 folds in aqueous solubility of ZA, respectively. Formulations were characterized for solubility, FTIR, PXRD, DSC, SEM and dissolution studies. P407 was found to be an excellent solubility booster in combination with EPO. It was concluded that solubility and dissolution rate of ZA increased significantly when SD of the ZA was prepared by solvent evaporation method (1:7 ratio) using 15% P407 as ternary component.

A mechanistic evaluation of the traditional uses of Nepeta ruderalis in gastrointestinal and airway disorders.

CONTEXT: Nepeta ruderalis Buch.-Ham. (Lamiaceae), locally known as Badranj Boya, is an aromatic herb used traditionally as an antispasmodic, antidiarrhoeal, and anti-asthamatic remedy. OBJECTIVE: Aqueous methanolic extract of N. ruderalis was studied to investigate its traditional uses. MATERIALS AND METHODS: Study was conducted from September 2015 to February 2016. In vitro spasmolytic and broncho-relaxant activity of crude extract of N. ruderalis (whole plant) was evaluated at 0.01-10 mg/mL final bath concentration in isolated rabbit jejunum and tracheal tissues, using PowerLab data acquisition system (Transonic Systems Inc., Ithaca, NY). In vivo antidiarrhoeal activity was evaluated in castor oil-induced diarrhoeal mice at the dose of 300 and 500 mg of crude extract orally. RESULTS: Crude extract of N. ruderalis completely relaxed spontaneously contracting, high K+ (80 mM) and carbachol (1 µM) induced contracted jejunum with an EC50 value of 5.85 (5.45-6.27), 4.0 (3.80-4.23) and 2.86 (2.48-3.29), similar to verapamil. Nr.Cr relaxed high K+ and carbachol induced contractions, at 5 and 10 mg/mL with an EC50 value of 2.37 (2.11-2.67) and 3.26 (2.9-3.67), respectively, and also displaced calcium concentration-response curves toward right at 0.1 and 0.3 mg/mL. Nr.Cr exhibited antidiarrhoeal protection at a dose of 300 and 500 mg/kg, similar to verapamil, whereas no acute toxicity signs were seen up to 5 g/kg in healthy mice. DISCUSSION AND CONCLUSION: Results suggest the presence of spasmolytic and broncho-relaxant effects in the crude extract of N. ruderalis, possibly mediated through calcium channel-blocking activity, providing the pharmacological basis for its traditional uses in gastrointestinal and airway disorders.

DEVELOPMENT OF COMPRESSED COATED POLYPILL WITH MUCOADHESIVE CORE COMPRISING OF ATORVASTATIN/CLOPIDOGREL/ASPIRIN USING COMPRESSION COATING TECHNIQUE.

The study was conducted to formulate and assess a novel polypill comprising of atorvastatin calci- um (ATVC), clopidogrel bisulfate (CLB) and aspirin (ASP) which, after in vivo correlation, can be intended for use in hyperlipidemic chronic heart disease patients. Polypill was made by the compression coating technique (CCT) with multiple active ingredients along with different concentrations of mucoadhesive and sustained release polymers, i.e., Carbopol 934 (CAB), Methocel k15 (MTH) and sodium carboxymethyl cellulose (NaCMC). The effect of different concentration of polymers on physical properties, wash off time, mucoadhe- sion strength, swelling behavior, surface pH and drug release kinetics were investigated. In vitro drug release studies showed that combination of CAB-NaCMC (1 : 1) retarded drug release up to 96.7 ± 1.15%, while com- bination of CAB-MTH and MTH-NaCMC retarded drug release up to 81.9 ± 1.5% and 101.4 ± 1.3%, respec- tively, at the same polymer concentration. Core enteric coated tablet of ATVC (K 11) was compressed over with CLB and ASP granules with the help of CCT and produced the desired results with zero order release rate thus indicating successful formulation of proposed polypill.