Stability-Indicating UHPLC Method for the Determination of Desvenlafaxine: Application to Degradation Kinetics

This study was aimed to investigate the degradation behavior and physicochemical stability of desvenlafaxine using reversed-phase ultra-high-performance liquid chromatography (RP-UHPLC) system. The chromatogram was developed on Eclipse XDB-C8 column (150 x 4.6 mm, 5μm). The eluents were monitored through a photo diode array plus (PDA+) detector at 210 nm using an isocratic method with a flow rate of 1.5 ml/min. Mobile phase composition was 30:70 v/v mixture of 0.1 % trifluoroacetic acid (TFA) in water and methanol. Forced degradation studies were performed on drug substance of desvenlafaxine as per International Conference on Harmonization (ICH) prescribed stressed conditions (Q1A(R2) and Q1B) using hydrolytic (acidic, basic, and neutral), oxidative and photolytic methods. The drug substance was found highly labile to acidic (0.5 N hydrochloric acid, 18.65 % degradation in 2 hours at 70°C), basic (1.0 N sodium hydroxide, 11.01 % degradation in 12 hours at 70°C) and oxidative (3 % hydrogen peroxide, 17.05 % degradation in 2 hours at 50°C) stressed conditions, but a great resistance was observed towards dry heat (maximum degradation 0.27 % in 10 days from ambient to higher temperature, 80°C), moist heat (maximum degradation 0.25 % in 2 hours at 80°C and 75 % relative humidity) as well as in photolytic degradation (maximum degradation 0.23 % in 10 days at UV light of 315 - 400 nm). A pseudo-first order kinetic was followed in acidic, basic and peroxide degradation methods which paved a way to calculate the half-life of the drug substance desvenlafaxine under ICH mentioned stressed conditions. The results were also statistically analyzed and the % RSD values were compared with recommended guidelines. Dhaka Univ. J. Pharm. Sci. 20(2): 167-176, 2021 (December)

VALIDATED STABILITY INDICATING SPECTROSCOPIC METHOD FOR ESTIMATION OF DEGRADATION BEHAVIOUR OF VALSARTAN AND HYDROCHLOROTHIAZIDE IN TABLET FORMULATION

A simple, accurate and precise UV spectrometric method has been developed for the simultaneous determination of valsartan and hydrochlorothiazide in tablet dosage form. Spectra of valsartan and hydrochlorothiazide in methanol and water (50:50 V/V) show λ max at 250.0 nm and 271.4 nm, respectively. Valsartan and hydrochlorothiazide are subjected to various stress conditions like acid, alkali, thermal and photolytic degradation. Beer’s law was obeyed in concentration range of 4- 24 µg mL-1 for valsartan and 0.5-3 µg mL-1 for hydrochlorothiazide at their respective wavelengths. The proposed method was successfully applied to tablet dosage form for determination of both drugs. The percentage recovery of valsartan and hydrochlorothiazide were found to be 100.19 % and 99.51 %, respectively. A novel accurate and precise stability indicating spectroscopic method has been developed for estimation of valsartan and hydrochlorothiazide.

Development of a 3D-Printed Dosing Platform to Aid in Zolpidem Withdrawal Therapy

The long-term use of benzodiazepine receptor agonists (BZRAs) is associated with multiple side effects, such as increased sedation, hangover or an elevated risk of dependency and abuse. Unfortunately, the long-term use of BZRAs is reaching worrying intake rates, and therefore, the need for action is high. It was demonstrated already that the overall willingness of patients for deprescription increased when a slow dose reduction scheme with the possibility for dose increase, if needed, is employed. The current study aims to develop a flexible dosing platform of zolpidem hemitartrate (ZHT) to facilitate such withdrawal therapy. As this is the first report on the extrusion and 3D printing of ZHT, its thermal behaviour and sensitivity towards photolytic degradation was characterised. It was shown that ZHT possesses multiple polymorphs and was especially prone to oxidative photolysis. Next, a variety of immediate release polymers (Eudragit EPO, Kollidon VA64, Kollidon 12PF and Soluplus) were blended and extruded with Polyox WSR N10 to investigate their feedability and printability by mechanical and rheological analysis. The addition of PEO was shown to enable printing of these brittle pharmaceutical polymers, although the processing temperature was deemed critical to avoid surface defects on the resulting filaments. An EPO(70)PEO(30) system was selected based on its suitable mechanical properties and low hygroscopicity favoring ZHT stability. The matrix was blended with 1% or 10% API. The effect of certain printing parameters (caplet size, nozzle diameter, % overlap) on dissolution behaviour and caplet weight/dimensions/quality was assessed. A flexible dosing platform capable of delivering <1 mg and up to 10 mg of ZHT was created. Either caplet modification (incorporation of channels) or disintegrant addition (Primojel, Explotab, Ac-Di-Sol, Primellose and Polyplasdone-XL) failed to achieve an immediate release profile. This study provides the first report of a 3D-printed flexible dosing platform containing ZHT to aid in withdrawal therapy.

Stability Indicating RP-HPLC Method For Determination Of Itraconazole In Bulk Drug And In Capsule Dosage Form

Stability Indicating RP HPLC method was developed for estimation of Itraconazole in bulk drug and in capsule dosage form. An isocratic separation was achieved using Phenomenex symmetry C8 (250 ×4.6 mm) 5?m [Part number - 00G-4249-E0] column with a flow rate of 1.0 ml/min and detection wavelength at 254 nm. The mobile phase consisted of 20 mM potassium dihydrogen orthophosphate buffer (pH=5.5): Acetonitrile: Methanol (20:40:40 % v/v). The method was rectilinear from 10-60 ?g/ml and displayed adequate precision (RSD < 2.0%) & accuracy (99.31-101.16%). The proposed method is found to be specific with respect to degradation product formed after Acidic hydrolysis, Oxidation, Thermal and Photolytic degradation. The Itracoazole was found to be stable under alkaline stress condition. Acidic, thermal, photolytic stress conditions showed moderate degradation whereas the oxidative stress condition showed severe degradation. The proposed chromatographic method can be used for estimation of drug during stress testing & formal stability studies.

Soft Modelling of the Photolytic Degradation of Moxifloxacin Combining Surface enhanced Raman Spectroscopy and Multivariate Curve Resolution

The antibiotic moxifloxacin had a recent surge in its use due to its broad spectrum of activity. However, due to the low metabolization inside the organism, it became an environmental concern. Here, the photolytic degradation of moxifloxacin antibiotic in alkaline medium was carried out and monitored through SERS spectroscopy. Multivariate curve resolution method was applied to extract quantitative and kinetic information about the whole process, using correlation constraint to simultaneously quantify the variation of moxifloxacin concentration. The results showed that the photolysis follows an apparent first order kinetics with half-life of 47.5 min. Also, SERS spectrum along with the calculated Raman spectra suggest that cleavage of the diazabicyclonyl substituent is the preferred photodegradation pathway, in agreement with previous reports.

DEVELOPMENT OF A VALIDATED STABILITY-INDICATING METHOD FOR ESTIMATION OF ETHIONAMIDE IN TABLETS BY RP-HPLC AND CHARACTERIZATION OF ITS ISOLATED ALKALI DEGRADATION PRODUCT

A simple, accurate, reproducible and specific stability-indicating RP-HPLC method was developed for estimation of ethionamide in tablets. Ethionamide was exposed to acid, alkali and neutral hydrolysis at elevated temperatures, to thermolytic degradation, peroxide-mediated oxidation at room temperature in dark and to photolytic degradation. The drug was found stable to thermolytic and photolytic conditions and to neutral hydrolysis. However, substantial degradation was obtained in acid and alkali hydrolysis and complete degradation in peroxide-medicated oxidation. Similar degradation behavior was observed when ethionamide tablets were exposed to the mentioned forced degradation conditions. The method showed adequate resolution of drug from its potential degradation products on C18 (250 × 4.6 mm, 5µ) column using mobile phase of methanol: water (50: 50 % V/V) at 1 mL/min. The drug and its potential degradation products were detected at 290 nm. The method was validated as per the ICH Q2(R1) guidelines. The enrichment of the alkali degradation product was performed and isolated by preparative TLC and further confirmed by NMR and IR spectroscopy.

Stability indicating assay method for determination of Febuxostat by RP-HPLC

Objective: A simple, rapid, precise and accurate RP-HPLC stability indicating method was developed and validated for estimation of Febuxostat in bulk drug and marketed tablet formulation. Methods: The chromatographic separation was achieved on Agilent C18 (250 x 4.6mm, 5 µm) using solvent 15 mM ammonium acetate buffer (pH 4.8) and acetonitrile (30:70 v/v) as a mobile phase at flow rate of 1 mL/min and at ambient column temperature analysis were carried out at detection wavelength 315nm. Result: The method was validated for linearity, precision, accuracy, specificity, LOD and LOQ, and robustness. The linearity was studied in the concentration range of 5-25 µg/mL and correlation coefficient was found to be 0.999. The limit of detection and limit of quantitation were found to be 0.37 µg/mL and 1.13 µg/mL. Febuxostat was subjected to stress condition of degradation including acidic, alkaline, oxidation, photolytic and thermal degradation. Febuxostat is more sensitive toward acidic condition than oxidation and less sensitive towards alkaline, thermal and photolytic degradation. Conclusion: The method is simple, reliable, sensitive and precise which could separate the drug and their degraded product formed under various stress conditions, thus it can be employed as stability indicating method for the determination of FBX in bulk and pharmaceutical dosage form.

Potential of Nb2O5 nanofibers in photocatalytic response for organic pollutants remediation

Due to the pollution caused by different organic pollutants, various photocatalytic nanomaterials for environmental remediation have been promoted. In this study, Nb2O5 nanofibers were obtained by electrospinning technique, presenting controlled crystallinity and high specific surface area to improve the photoactivity response. The structural characterization indicated Nb2O5 nanofibres with orthorhombic phase formation, and the photoluminescence measurements showed different energy levels contributing to the electronic transition events. The nanofibers with a bandgap up to 3.6 eV were applied to photocatalysis of dyes [Rhodamine B (RhB) or Methylene Blue (MB)], and Prozac®, listed as an emergent pollutant. In the optimized condition (pH = 9), the RhB and MB photocatalysis was 59% and 93% more efficient than photolysis due to ζ = − 50 ± 5 mV for EtOH_550 sample that increased the interaction with MB (cationic) compared to RhB unprotonated (pKa = 3.7). Therefore, Prozac® (pKa = 10.7) was selected due to protonated form at pH = 9 and showed 68% ±1 adsorption in 30 min for EtOH_550. The Prozac® photocatalytic degradation under UV light irradiation was up to 17% higher than the photolytic degradation. The formation of hydroxyl radicals in the photocatalytic system (EtOH_550) was proven by the Coumarine probe assay, corroborating with the greater amount of α-[2-(Methylamino)ethyl]benzylalcohol (MAEB), a by-product obtained after Prozac® oxidation. Additionally, the material achieved specific catalytic activity for the different organic compounds (RhB, MB, or Prozac®), showing that only using dyes may not be ideal to conclude the great material applicability in environmental remediation studies. Therefore, Nb2O5 nanofibers were efficient for the degradation of three different pollutants under UV light, proving to be a viable alternative for environmental remediation.