scholarly journals Stability of an ophthalmic formulation of polyhexamethylene biguanide in gamma-sterilized and ethylene oxide sterilized low density polyethylene multidose eyedroppers

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4549 ◽  
Author(s):  
Yassine Bouattour ◽  
Philip Chennell ◽  
Mathieu Wasiak ◽  
Mireille Jouannet ◽  
Valérie Sautou
Keyword(s):  
Ethylene Oxide ◽  
Acanthamoeba Keratitis ◽  
Low Density Polyethylene ◽  
Array Detector ◽  
Eye Drops ◽  
Low Density ◽  
Stability Indicating ◽  
Stability Indicating Method ◽  
Polyhexamethylene Biguanide ◽  
Initial Ph

Background Polyhexamethylene biguanide (PHMB) eye drops are a frequently used medication to treat Acanthamoeba keratitis. In the absence of marketed PHMB eye drops, pharmacy-compounding units are needed to prepare this much needed treatment, but the lack of validated PHMB stability data severely limits their conservation by imposing short expiration dates after preparation. In this study we aim to assess the physicochemical and microbiological stability of a 0.2 mg/mL PHMB eye drop formulation stored in two kinds of polyethylene bottles at two different temperatures. Methods A liquid chromatography coupled with diode array detector stability-indicating method was validated to quantify PHMB, using a cyanopropyl bonded phase (Agilent Zorbax Eclipse XDB-CN column 4.6 × 75 mm with particle size of 3.5 μm) and isocratic elution consisting of acetonitrile/deionized water (3/97 v/v) at a flow rate of 1.3 mL/min. PHMB eye drops stability was assessed for 90 days of storage at 5 and 25 °C in ethylene oxide sterilized low density polyethylene (EOS-LDPE) and gamma sterilized low density polyethylene (GS-LDPE) bottles. The following analyses were performed: visual inspection, PHMB quantification and breakdown products (BPs) screening, osmolality and pH measurements, and sterility assessment. PHMB quantification and BP screening was also performed on the drops emitted from the multidose eyedroppers to simulate in-use condition. Results The analytical method developed meets all the qualitative and quantitative criteria for validation with an acceptable accuracy and good linearity, and is stability indicating. During 90 days of storage, no significant decrease of PHMB concentration was found compared to initial concentration in all stored PHMB eye drops. However, BP were found at day 30 and at day 90 of monitoring in both kind of bottles, stored at 5 and 25 °C, respectively. Although no significant variation of osmolality was found and sterility was maintained during 90 days of monitoring, a significant decrease of pH in GS-LDPE PHMB eye drops was noticed reaching 4 and 4.6 at 25 °C and 5 °C respectively, compared to initial pH of 6.16. Discussion Although no significant decrease in PHMB concentration was found during 90 days of monitoring in all conditions, the appearance of BPs and their unknown toxicities let us believe that 0.2 mg/mL PHMB solution should be conserved for no longer than 60 days in EOS-LDPE bottles at 25 °C.

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.

Development and Validation of a Stability Indicating RP-HPLC Method for Hydrocortisone Acetate Active Ingredient, Propyl Parahydroxybenzoate and Methyl Parahydroxybenzoate Preservatives, Butylhydroxyanisole Antioxidant, and Their Degradation Products in a Rectal Gel Formulation

2015 ◽  
Vol 98 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Magda Ascaso ◽  
Pilar Pérez-Lozano ◽  
Mireia García ◽  
Encarna García-Montoya ◽  
Montse Miñarro ◽  
...  
Keyword(s):  
Active Ingredient ◽  
Active Substance ◽  
Degradation Products ◽  
Gradient Elution ◽  
Hplc Method ◽  
Array Detector ◽  
Hydrocortisone Acetate ◽  
Stability Indicating ◽  
Stability Indicating Method ◽  
The Stability

Abstract A stability indicating method was established through a stress study, wherein different methods of degradation (oxidation, hydrolysis, photolysis, and temperature) were studied simultaneously to determine the active ingredient hydrocortisone acetate, preservatives propyl parahydroxybenzoate, and methyl parahydroxybenzoate, antioxidant butylhydroxyanisole (BHA), and their degradation products in a semisolid dosage gel form. The proposed method was suitably validated using a Zorbax SB-Phenyl column and gradient elution. The mobile phase consisted of a mixture of methanol, acetonitrile, and water in different proportions according to a planned program at a flow rate of 1.5 mL/min. The diode array detector was set at 240 nm for the active substance and two preservatives,and 290 nm for BHA. The validation study was conducted according to International Conference on Harmonization guidelines for specificity, linearity, repeatability, precision, and accuracy. The method was usedfor QC of hydrocortisone acetate gel and for the stability studies with the aim of quantifying the active substance, preservatives, antioxidant, and degradation products. It has proved to be suitable as a fast and reliable method for QC.

Validated stability indicating HPLC method to quantify lamivudine and dolutegravir in tablets

2020 ◽  
Vol 11 (4) ◽  
pp. 5082-5088
Author(s):  
Rama Kumar Kandula ◽  
Raja Sundararajan
Keyword(s):  
Limit Of Detection ◽  
Hplc Method ◽  
Array Detector ◽  
Limit Of Quantification ◽  
Method Performance ◽  
Therapy Regimen ◽  
Stability Indicating ◽  
Stability Indicating Method ◽  
Relative Standard ◽  
The Stability

Dovato tablets (lamivudine and dolutegravir combination) are full therapy regimen for the Type 1 human immunodeficiency virus (HIV-1) infection in adults without history of antiretroviral therapy. The aim of present research focused on development of validated stability indicating method for the quantification of lamivudine and dolutegravir in combined dosage form.The separation was achieved on a Cosmicsil C18 column. The mobile phase consisted of 0.1% orthophosphoric acid (pH 3.5) – acetonitrile (50:50, v/v). Photodiode array detector was used to detect the analytes at 258 nm. The method performance was validated in compliance with the recommendations of the International Conference on Harmonization.The method was validated with selectivity, limit of detection (0.262 μg/ml for lamivudine and 0.238 μg/ml for dolutegravir), linearity (150-450 μg/ml for lamivudine and 25-75 μg/ml for dolutegravir), limit of quantification (0.874 μg/ml for lamivudine and 0.793 μg/ml for dolutegravir), accuracy (percent recovery was nearer to 100%), precision (percent relative standard deviation was less than 2.0%) and robustness (system suitability values are within limits). The stability indicating method was performed by under the various stress conditions. Degradants did not interfere with lamivudine and dolutegravir detection. The developed method can suggest that quantification of lamivudine and dolutegravir in quality control of analytical laboratories.

Quality by Design Approach to Develop Stability Indicating Method to Quantify Related Substances and Degradation Products of Sacubitril by High Performance Liquid Chromatography

2020 ◽  
Vol 58 (9) ◽  
pp. 844-858
Author(s):  
Sivaganesh Bommi ◽  
Subbalakshmi Jayanty ◽  
Satyanarayana Raju Tirumalaraju ◽  
Sivasankar Bandaru
Keyword(s):  
Mobile Phase ◽  
Method Development ◽  
Quality By Design ◽  
Array Detector ◽  
Priority Review ◽  
Forced Degradation ◽  
Stability Indicating ◽  
Stability Indicating Method ◽  
Neprilysin Inhibitor ◽  
Relative Standard

Abstract Sacubitril (SBT) is a neprilysin inhibitor, approved by food and drug administration (FDA) in 2015, under the FDA’s priority review process. In this work, we report the validated stability indicating method of SBT by employing quality by design (QbD) principles related to analytical method development, capable in separation of 11 impurities. Chromatographic separation was performed on an ascentis phenyl hexyl column using 10 mM KH2PO4 as a mobile phase-A and the pH adjusted to 2.1. Methanol: acetonitrile (70:30 v/v) solvent mixture was employed as the mobile phase-B in a gradient mode of elution at a flow rate 0.8 mL/min at 30°C. The column effluents were monitored by a photo diode array detector set at a wavelength of maximum absorption 254 nm noted for all the impurities and furthermore for SBT. This method was remarked to be accurate in the range from 92 to 116%, precise with relative standard deviation 0.9% for SBT (0.8 mg/mL) and 1.0 to 2.1% for its related impurities (0.0005 mg/mL) also linear with correlation coefficient r ≥ 0.9989. The limits of quantification for all impurities were 0.05% with respect to sample concentration 0.8 mg/mL. The developed method revealed a good method operable design range for the experimental chromatographic conditions. Forced degradation of SBT carried under acidic, basic and oxidative stressed conditions manifested that the method is stability indicating.

scholarly journals Development and validation of a stability-indicating analytical method for simultaneous determination of drugs employed in canine leishmaniasis treatment

2020 ◽  
Vol 4 (2) ◽  
pp. 24-30
Author(s):  
Patrícia Espinosa Dos Santos ◽  
Ana Carla Lucca ◽  
Marcos Serrou do Amaral ◽  
Nájla Mohamad Kassab
Keyword(s):  
Simultaneous Determination ◽  
Degradation Products ◽  
Canine Leishmaniasis ◽  
Array Detector ◽  
Liquid Chromatograph ◽  
Drug Degradation ◽  
Stability Indicating ◽  
Stability Indicating Method ◽  
Pharmaceutical Form

We developed and validated a stability-indicating method for the simultaneous determination of allopurinol and ketoconazole in the pharmaceutical form of capsules. A Dionex® liquid chromatograph equipped with a diode array detector (DAD) and InertSustain® C18 column (4.6 x 100 mm x 3 μm) was used and InertSustain® C18 column (4.6 x 100 mm x 3 μm). The chromatographic separation occurred in the isocratic mode with a flow rate of 0.45 mL min-1 and mobile phase composed of acetonitrile: water (52:48 v/v) with pH adjusted to 3.0. The wavelengths used were 250 nm for allopurinol and 225 nm for ketoconazole. The method was validated by evaluating the parameters of linearity, limits of detection and quantification, precision, accuracy, robustness, and selectivity. The method presented linearity. It was precise, with coefficients of variation lower than 2.0%, and accurate, with recovery close to 100.00%. Robustness was indicated by the Plackett-Burman model, and the method was not significantly influenced by any of the variations. The selectivity was proven by the peak purities close to 1000 in both the presence of excipients and drug degradation products. Therefore the proposed method is simple and fast, with separation for both drugs less than four minutes.

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