scholarly journals Physicochemical and Microbiological Stability of a New Oral Clonidine Solution for Paediatric Use

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Camille Verlhac ◽  
Damien Lannoy ◽  
Florence Bourdon ◽  
Marie Titecat ◽  
Emilie Frealle ◽  
...  
Keyword(s):  
Membrane Filtration ◽  
Degradation Products ◽  
Potassium Citrate ◽  
Oral Solution ◽  
Opiate Withdrawal ◽  
Potassium Sorbate ◽  
Physical Parameters ◽  
Forced Degradation ◽  
Microbiological Stability ◽  
Glass Bottles

AbstractBackgroundAs many drugs are unavailable for paediatric use, hospital pharmacies are often required to develop suitable formulations themselves. Clonidine is commonly used in paediatrics (in severe hypertension, in opiate withdrawal syndrome, in tics and Gilles de la Tourette syndrome or in anaesthetic premedication) but no appropriate formulation has been drawn up. The aims of this work were to develop an oral solution of clonidine dedicated to children and to assess its physicochemical and microbiological stability.MethodsFormulation of an oral solution of clonidine hydrochloride suitable for neonates and paediatrics was developed using the active pharmaceutical ingredient (API), with as few excipients as possible and without any complex excipient vehicle. A stability study was made according to GERPAC-SFPC guidelines. At each point in time (D0, D1, D7, D15, D29, D60 and D90), visual aspect (limpidity), pH and osmolality were established. Clonidine concentration was quantified using a stability-indicating HPLC-UV-DAD method previously developed from a forced degradation study and validated according to SFSTP Pharma. Microbiological stability was also tested according to the European Pharmacopeia monograph with the best adapted method (by comparing membrane filtration and inclusion). Solutions were stored in amber glass bottles with an oral adapter for up to 3 months in two different conditions: 5 °C +/– 3 °C and at 25 °C +/– 2 °C with 60 % residual humidity (climatic chamber).ResultsThe formulated oral solution is composed of API at a concentration of 10 µg/mL and of potassium sorbate (0.3 %), citric acid, potassium citrate (pH 5 buffer) and sodium saccharine (0.025 %). Forced degradation highlighted six degradation products and the method was validated in the acceptance limits of ± 5 %. On D29, the mean percentages of the initial clonidine concentrations (+/–standard deviation) were 92.95+/–1.28 % in the solution stored at 25 °C +/– 2 °C and 97.44+/–1.21 % when stored at 5 °C +/– 3 °C. On D90, means were respectively 81.82+/–0.41 % and 93.66+/–0.71 %. The visual aspect did not change. Physical parameters remained stable during the study: pH varied from 4.94 to 5.09 and osmolality from 82 to 92 mOsm/kg in the two conditions tested here. Membrane filtration appeared to be the more sensitive method. Whatever the storage conditions,<1 micro-organism/mL was identified (only environmental) with no detectedE.coli.ConclusionsThis formulation is stable for at least 3 months at 5 °C +/– 3 °C in amber glass bottles and for one month when stored at room temperature. Microbiological stability was proven in accordance with the European Pharmacopeia.

Synthesis and Characterization of Potential and Degraded Impurities of Regadenoson

2020 ◽  
Vol 16 (8) ◽  
pp. 1130-1139
Author(s):  
Singaram Sathiyanarayanan ◽  
Chidambaram Subramanian Venkatesan ◽  
Senthamaraikannan Kabilan
Keyword(s):  
Mass Spectra ◽  
Degradation Products ◽  
Hplc Method ◽  
Forced Degradation ◽  
Spectroscopic Techniques ◽  
A2a Adenosine Receptor ◽  
Degradation Study ◽  
Related Substances ◽  
Adenosine Receptor Agonist

Background: Regadenoson is an A2A adenosine receptor agonist that is a coronary vasodilator and commonly used as a pharmacologic cardiac stressing agents. Methods: HPLC method was used for the analysis of related substances. The degraded impurities during the process were isolated and characterized by IR, Mass and NMR spectral analysis. Results: Forced degradation study of regadenoson under conditions of hydrolysis (neutral, acidic and alkaline) and oxidations suggested in the ICH Q1A(R2) was accomplished. The drug showed significant degradation under all the above conditions. On the whole, five novel degradation products were found under diverse conditions along with process related impurities which were not reported earlier. Conclusion: All the degradation products were well characterized by using advanced spectroscopic techniques like IR, 1H NMR, 13C NMR and Mass spectra. The identification of these impurities will be productive for the quality control during the production and stability behavior of the regadenoson drug substance.

Development and Validation of a Stability-Indicating Chromatographic Method for the Determination of Indacaterol Maleate with Glycopyrronium Bromide in Mixture

2019 ◽  
Vol 15 (7) ◽  
pp. 694-702
Author(s):  
Sonia Talaat Hassib ◽  
Hanaa Abdelmenem Hashem ◽  
Marwa Ahmed Fouad ◽  
Nehal Essam Eldin Mohamed
Keyword(s):  
Chromatographic Method ◽  
Degradation Products ◽  
Reversed Phase ◽  
Chronic Obstructive ◽  
Forced Degradation ◽  
Uv Detector ◽  
Obstructive Pulmonary Disease ◽  
Mortality And Morbidity ◽  
Glycopyrronium Bromide

Introduction: (COPD) Chronic Obstructive Pulmonary Disease is a partially reversible and treatable lung disease, characterized by progressive limitation of airflow. It is one of the main causes of mortality and morbidity worldwide. Methods: An easy, precise and selective reversed-phase liquid chromatographic method, with stabilityindicating assay was established and validated for the determination of indacaterol maleate and glycopyrronium bromide in the mixture. In addition, a forced degradation study was performed for indacaterol maleate, comprised of hydrolysis by acid and base, degradation by oxidation and heat, and photo-degradation. Separation and forced degradation were done by isocratic elution using a reversed phase phenyl column and (methanol: phosphate buffer) at ratio (65:35, v/v) with 3.5 pH buffer as an eluent at 1 mL min-1 as a flow rate. Quantitation was accomplished using a UV detector at 210 nm. Results: The method showed good separation of glycopyrronium bromide, indacaterol maleate and its degradation products. Accuracy, linearity, and precision were acceptable over 10-160 µg mL-1 and 10- 80 µg mL-1 concentration range for indacaterol maleate and glycopyrronium bromide, respectively. Conclusion: The proposed method does not require any previously done separation steps, making it applicable for the analysis of the drugs under investigation in their pharmaceutically marketed preparations.

scholarly journals Validated Stability Indicating RP-HPLC Method for Simultaneous Estimation of Codeine Phosphate and Chlorpheniramine Maleate from Their Combined Liquid Dosage Form

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Ramakrishna Kommana ◽  
Praveen Basappa
Keyword(s):  
Limit Of Detection ◽  
Degradation Products ◽  
Hplc Method ◽  
Simultaneous Estimation ◽  
Forced Degradation ◽  
Codeine Phosphate ◽  
Chlorpheniramine Maleate ◽  
Combination Drug ◽  
Stability Indicating ◽  
Rp Hplc

The present paper describes the development of quick stability indicating RP-HPLC method for the simultaneous estimation of codeine phosphate and chlorpheniramine maleate in the presence of its degradation products, generated from forced degradation studies. The developed method separates codeine phosphate and chlorpheniramine maleate in impurities/degradation products. Codeine phosphate and chlorpheniramine maleate and their combination drug product were exposed to acid, base, oxidation, dry heat, and photolytic stress conditions, and the stressed samples were analysed by proposed method. The proposed HPLC method utilizes the Shimadzu HPLC system on a Phenomenex C18 column (, 5 μ) using a mixture of 1% o-phosphoric acid in water : acetonitrile : methanol (78 : 10 : 12) mobile phase with pH adjusted to 3.0 in an isocratic elution mode at a flow rate of 1 mL/min, at 23°C with a load of 20 μL. The detection was carried out at 254 nm. The retention time of codeine phosphate and chlorpheniramine maleate was found to be around 3.47 min and 9.45 min, respectively. The method has been validated with respect to linearity, robustness, precision, accuracy, limit of detection (LOD), and limit of quantification (LOQ). The developed validated stability indicating HPLC method was found to be simple, accurate, and reproducible for the determination of instability of these drugs in bulk and commercial products.

Validation of Analytical Methods for Tacrolimus Determination in Poly(ε-caprolactone) Nanocapsules and Identification of Drug Degradation Products

2021 ◽  
Vol 21 (12) ◽  
pp. 5920-5928
Author(s):  
Guilherme A. Camargo ◽  
Amanda M. Lyra ◽  
Fernanda M. Barboza ◽  
Barbara C. Fiorin ◽  
Flávio L. Beltrame ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
High Performance ◽  
Degradation Products ◽  
Multiple Reaction Monitoring ◽  
Forced Degradation ◽  
Alkaline Stress ◽  
Drug Degradation ◽  
Relative Standard ◽  
Polymeric Nanocapsules ◽  
Alkaline Conditions

The aim of this paper was to use chromatographic tools for validating an analytical method for the tacrolimus (TAC) determination in polymeric nanocapsules and for identifying the drug degradation products after alkaline stress. A rapid Ultra-High-Performance Liquid Chromatography coupled with photo-diode array (UHPLC-PDA) method was successfully performed using the following chromatographic conditions: the Shimadzu Shim-pack XR-ODS III C18 column (100 mm×2.00 mm, 2.2 μm), the mobile phase consisting of methanol and acidified ultrapure water (89:11 v/v), the flow rate of 0.55 mL·min−1, and the ultraviolet (UV) detection at 235 nm. This method was validated as per International Council for Harmonisation (ICH) guidelines. In addition, a TAC forced degradation assay was carried out after alkaline stress and its degradation products were investigated using Liquid Chromatography coupled tandem mass spectroscopy (LC-MS/MS). The calibration curve was linear in the range of 100.0–300.0 μg·mL−1 (r >0.9999). Accuracy was confirmed by the TAC recovery of 96.55 to 98.19%. Precision (intraday and interday) were demonstrated by relative standard deviation lower than 0.89% and 3.25%, respectively. Selectivity and robustness were also proved. The method developed it was successfully applied to quantify TAC from polymeric nanocapsules, showing a high loading efficiency rate (>96.47%). The main drug degradation product observed in a multiple reaction monitoring (MRM) experiment was m/z 844, confirming the susceptibility of TAC under alkaline conditions; this finding was first time described.

STABILITY INDICATING UPLC METHOD FOR ESTIMATION OF METFORMIN HYDROCHLORIDE AND NATEGLINIDE SIMULTANEOUSLY IN THE PRESENCE OF STRESS DEGRADATION PRODUCTS

INDIAN DRUGS ◽  
2020 ◽  
Vol 57 (05) ◽  
pp. 56-64
Author(s):  
Rani A Prameela ◽  
S. Madhavi ◽  
Rao B. Tirumaleswara ◽  
Sudheer Reddy CH.
Keyword(s):  
Limit Of Detection ◽  
Degradation Products ◽  
Potassium Dihydrogen Phosphate ◽  
Metformin Hydrochloride ◽  
Forced Degradation ◽  
Dihydrogen Phosphate ◽  
Limit Of Quantification ◽  
Pharmaceutical Dosage Forms ◽  
Column Temperature

A novel Ultra Performance Liquid Chromatography (UPLC) method was developed and validated for the simultaneous determination of antidiabetic drugs metformin hydrochloride and nateglinide. The method was developed using a Waters ACQUITY UPLC SB C18 (100 × 2.1 mm, 1.8 μm) column. The mobile phase consisting of 0.01 % potassium dihydrogen phosphate buffer (pH 5.8): acetonitrile (50: 50 V/V) was used throughout the analysis. The flow rate was 0.3 mL/min, the injection volume was 1.0 μL, column temperature was 30 0C, run time 3 min and detection was carried at 238 nm using a TUV detector. The retention times of metformin hydrochloride and nateglinide were found to be 1.28 1.71 min, respectively. Metformin hydrochloride and nateglinide were found to be linear over the concentration range of 125-750 and 15-90 μg/mL. The limit of detection and the limit of quantification for metformin hydrochloride were found to be 0.22 and 0.68 μg/mL, respectively, and, for nateglinide, 0.02 and 0.6 μg/mL, respectively. Developed method was validated as per ICH guidelines. The specificity of the method was confirmed by forced degradation study. The suggested method is suitable for determination of metformin hydrochloride and nateglinide in bulk and pharmaceutical dosage forms.

A New, Rapid and Simple RP-HPLC Method for Stability Quantification of a Protease Inhibitor in Tablets

2021 ◽  
Author(s):  
Rochele Cassanta Rossi ◽  
Josué Guilherme Lisbôa Moura ◽  
Vanessa Mossmann ◽  
Patrícia Weimer ◽  
Pedro Eduardo Fröehlich
Keyword(s):  
Quality Control ◽  
Protease Inhibitor ◽  
Degradation Products ◽  
Gradient Elution ◽  
Hplc Method ◽  
Array Detector ◽  
Forced Degradation ◽  
Control Analysis ◽  
Quality Control Laboratory ◽  
The Stability

Abstract Fosamprenavir calcium is a protease inhibitor widely used in the treatment and prevention of human immunodeficiency virus and acquired immunodeficiency syndrome. This protease inhibitor serves as a prodrug of amprenavir, offering better oral bioavailability. Although this drug was approved by the FDA in 2003, there are few methods established for quantifying the stability for quality control analysis of fosamprenavir-coated tablets. The purpose of the study was to develop and validate a method for determining the stability of fosamprenavir-coated tablets (Telzir®) that may be applied by any quality control laboratory. Chromatographic separation was performed using a Vertical RP-18 column programmed to run a gradient elution with sodium acetate buffer and acetonitrile. Flow rate was 1.2 mL min−1 for a total run time of 15 min. Ultraviolet detection was set at 264 nm and the use of a photodiode array detector in scan mode allowed selectivity confirmation by peak purity evaluation. The analyte peak was found to be adequately separated from degradation products generated during forced degradation studies. Thus, the proposed method was found to accurately indicate stability and was sufficient for routine quantitative analysis of fosamprenavir in coated tablets without interference from major degradation products and excipients.

LC-MS/MS method for the characterization of the forced degradation products of Entecavir

2014 ◽  
Vol 37 (4) ◽  
pp. 368-375 ◽  
Author(s):  
Thippani Ramesh ◽  
Pothuraju Nageswara Rao ◽  
Ramisetti Nageswara Rao
Keyword(s):  
Degradation Products ◽  
Forced Degradation

scholarly journals Development of a Stability Indicating Method for Simultaneous Analysis of Five Water-Soluble Vitamins by Liquid Chromatography

2018 ◽  
Vol 3 (4) ◽  
pp. 207-218 ◽  
Author(s):  
Mouloud Yessaad ◽  
Lise Bernard ◽  
Daniel Bourdeaux ◽  
Philip Chennell ◽  
Valérie Sautou
Keyword(s):  
Liquid Chromatography ◽  
Degradation Products ◽  
Pharmaceutical Preparations ◽  
Water Soluble ◽  
Alkaline Solutions ◽  
Array Detector ◽  
Forced Degradation ◽  
Metaphosphoric Acid ◽  
Stability Indicating ◽  
Stability Indicating Method

Abstract Background Water-soluble vitamins are often included simultaneously in pharmaceutical formulations as food complements or in parenteral nutrition mixtures. Given their sensitivity to heat, light or pH variations, it is important to study their stability using validated stability indicating methods. We thus aimed to validate a liquid chromatography (LC) stability-indicating method for the simultaneous quantification of 5 water-soluble vitamins. Methods We analyzed four water-soluble B vitamins (nicotinamide, pyridoxine, folic acid, cyanocobalamin) and ascorbic acid using a LC method with diode array detector. They were separated on a C18 stationary phase under gradient elution of solvent A [0.2 % of metaphosphoric acid in water and acetonitrile 98:2] and solvent B (100 % acetonitrile). All vitamins were subjected to forced degradation conditions and we showed that the obtained degradation products didn’t interfere with the vitamins. Results The method allows the separation of the 5 water-soluble vitamins in a 30 minute run without any interference from the breakdown products obtained with acid/alkaline solutions, hydrogen peroxide, temperature and light. It meets all the qualitative and quantitative criteria for validation with an acceptable accuracy and good linearity. Conclusions This stability-indicating method can be used for carrying out stability studies of water-soluble vitamins in pharmaceutical preparations.

scholarly journals STABILITY INDICATING HPLC METHOD FOR DETERMINATION OF VILAZODONE HYDROCHLORIDE

2017 ◽  
Vol 9 (4) ◽  
pp. 123
Author(s):  
Birva A. Athavia ◽  
Zarna R. Dedania ◽  
Ronak R. Dedania ◽  
S. M. Vijayendra Swamy ◽  
Chetana B. Prajapati
Keyword(s):  
Limit Of Detection ◽  
Degradation Products ◽  
Hplc Method ◽  
Alkaline Condition ◽  
Forced Degradation ◽  
Molecular Formula ◽  
Stability Indicating ◽  
Dry Heat ◽  
Limit Of Quantitation

Objective: The aim and objective of this study was to develop and validate Stability Indicating HPLC method for determination of Vilazodone Hydrochloride.Methods: The method was carried out on a Phenomenex, C18 (250x4.6 mm, 5 µm) Column using a mixture of Acetonitrile: Water (50:50v/v), pH adjusted to 3.3 with Glacial Acetic Acid for separation. The flow rate was adjusted at 1 ml/min and Detection was carried out at 240 nm.Results: The retention time of vilazodone hydrochloride was found to be 2.3 min. The calibration curve was found to be linear in the range 25-75µg/ml with a correlation coefficient (R2=0.996). The limit of detection and limit of quantitation were found to be 4.78µg/ml and 14.48µg/ml respectively. The % recovery of vilazodone hydrochloride was found to be in the range of 98.21±0.08 % to 99.07±0.64%. The proposed method was successfully applied for the estimation of vilazodone hydrochloride in marketed tablet formulation.Vilazodone Hydrochloride was subjected to forced degradation under Acidic, Alkaline, Oxidation, Dry Heat and Photolytic degradation conditions. Vilazodone hydrochloride showed 3.12% degradation under acidic condition, 4.78% under alkaline condition, 7.8% under oxidation condition, 3.53% under dry heat condition and 4.9% under photolytic condition.Acid degradation impurity was identified and characterised by LC-MS/MS was found to be 1-(4-Penten-1-yl) piperazine having molecular weight 154.253 (m/z 155.08) and Molecular Formula C9H18N2.Conclusion: A simple, precise, rapid and accurate Stability Indicating HPLC method has been developed and validated for the determination of Vilazodone Hydrochloride in presence of its degradation products as per the ICH Guidelines. 

Sign in / Sign up

Export Citation Format

Share Document