Qualitative Portrayal of Esomeprazole Magnesium by Exploring Diverse Analytical and Investigative Approaches

Purpose: The present study was intended to qualitatively analyze and drive meaningful statistics for Esomeprazole magnesium; to establish its inherent properties qualitatively & quantitatively. Methods: Esomeprazole magnesium was analyzed using various traditional & modern analytical and investigative tools viz FTIR, HPLC, UV spectroscopy, X-ray diffraction, zetasizer. Results: The absorption maxima were found at 301 nm with UV Spectrophotometric and HPLC analysis. The particle size of the drug was analyzed through Malvern zetasizer employing water as diluent and found to be 11.818 µm. The quantitative solubility of Esomeprazole magnesium was predicted in various solvents at 25 0C and found that it was most soluble in methanol and was least soluble in distilled water. Solubility was also found to be pH-dependent. Solubility increases with an increase in pH. The order of solubility determined was; Methanol (1.214 mg/ml) > Phosphate buffer pH- 7.4 (0.521 mg/ml) > Simulated Intestinal fluid pH-6.8 (0.475 mg/ml) > Phosphate buffer pH- 6.8 (0.466 mg/ml) > Simulated Gastric fluid pH-1.2 (0.147 mg/ml) > 0.1 N HCl (0.131 mg/ml) > Distilled water (0.017 mg/ml). The predicted log P value was found to be 2.39. Conclusion: Esomeprazole magnesium was qualitatively analyzed using various analytical techniques to establish its inherent properties quantitatively. It is an off-white amorphous powder with a characteristic obnoxious odor and slightly bitter taste. The drug was identified through FTIR, using the classification of characteristic peaks of functional groups in the spectrum and also additionally through analytical methods viz HPLC, UV spectroscopy and found the absorption maxima at 301 nm. The linear regression analyses of a standard plot from UV spectrophotometric analysis demonstrate an unswerving relationship in the concentration range of 5-30μg/ml. The log P value indicates that the drug is significantly lipophilic. Various Micromeritic parameters like the Angle of repose, compressibility index, and Hausner's ratio predict the inherent flow properties of Esomeprazole magnesium as Fair (aid not needed). The present study will be an asset in the development of a modified released quick action formulation (Tablet-in-Tablet), to offer quick and protracted relief in gastritis and allied disorders.

Development and Characterization of Oral Nanosuspension Using Esomeprazole Magnesium Trihydrate

Background: Nanosuspension has arisen as a lucrative, remunerative, as well as a potent approach to improve the solubility and dissolution rate of poorly soluble drug entities. Several challenges are still present in this technology which need more research. Objective: The prime aim of this research work is to develop, optimize and characterize the oral nanosuspension using esomeprazole magnesium trihydrate as a drug candidate. Methods: The drug nanosuspensions were prepared using both approaches; Top-down and Bottom-up as the combinational approach. Poloxamer 188 was used as a stabilizer in this study. All the important formulation variables, like concentration of stabilizers that may influence characteristics of the nanosuspensions, were optimized. Formulation screening was performed using the optimization process, and the optimized nanosuspension was evaluated for its particle size, polydispersity index, zeta potential, shape, in vitro drug release and stability. Results: For optimization of drug nanosuspension, the effect of Poloxamer 188 concentration and esomeprazole concentration was investigated and the optimal values were 0.3% w/v and 4 mg/ml, respectively. The particle size of nanosuspensions was in the range of 185 to 1048 nm with varying the zeta potential values from -11.2 to -27.5 mV. The in vitro dissolution rate of esomeprazole was increased up to 3-folds, approximately (92% in 90 min) as compared with crude esomeprazole drug (31% in 90 min) due to the decrease in particle size. Conclusion: The result indicated that the combination of top-down and bottom-up approach used for preparing the oral nanosuspension is a suitable approach for poorly aqueous soluble drug moieties like esomeprazole magnesium.

Development and Validation of Stability Indicating Method for Simultaneous Estimation of Esomeprazole and Levosulpiride by HPTLC using Experimental Design

The present study examines simultaneous multiple response optimization using desirability function for the development of an HPTLC method to detect esomeprazole magnesium trihydrate and levosulpiride in pharmaceutical dosage form. HPTLC separation was performed on aluminium plates pre-coated with silica gel 60 F254 as the stationary phase using ethyl acetate:methanol:toluene:ammonia (7:1.5:1.5:0.1% v/v/v) as the mobile phase. Full factorial design applied for the optimization of degradation condition. Esomeprazole magnesium trihydrate and levosulpiride were subjected to acid, alkali hydrolysis, oxidation and photodegradation. Experimental full factorial design has been used during forced degradation to determine significant factors responsible for degradation and to optimize degradation conditions reaching maximum degradation. 32 and 23 full factorial design has been used for optimization of chromatographic condition in acid and base degradation study, respectively. Quantification was achieved based on a densitometric analysis of esomeprazole magnesium trihydrate and levosulpiride over the concentration range of 800-4000 ng/band and 1500-7500 ng/band, respectively at 254 nm. The method yielded compact and well-resolved bands at Rf of 0.70 ± 0.02 and 0.32 ± 0.02 for esomeprazole magnesium trihydrate and levosulpiride, respectively. The linear regression analysis for the calibration plots produced r2 = 0.9967 and r2 = 0.9981 for esomeprazole magnesium trihydrate and levosulpiride, respectively. Method is validated as per ICH (Q2)R1 guideline.