Ezzat M. Abdel-Moety

Stability-indicating determination of meropenem in presence of its degradation product

Stability-indicative determination of meropenem (MERM) in the presence of its open-ring degradation product, the metabolite, is investigated. The degradation product has been isolated, via acid-degradation, characterized and confirmed. Selective quantification of MERM, singly in bulk form, pharmaceutical formulations and/or in the presence of its major degradate is demonstrated. The indication of stability has been undertaken under conditions likely to be expected at normal storage. Among the analytical techniques adopted for quantification are spectrophotometry [first-derivative ((1)D), first-derivative of ratio spectra ((1)DD) and bivariate analysis], as well as chromatography [coupled TLC-densitometry and HPLC].

Selective determination of ertapenem in the presence of its degradation product

Stability-indicative determination of ertapenem (ERTM) in the presence of its beta-lactam open-ring degradation product, which is also the metabolite, is investigated. The degradation product has been isolated, via acid-degradation, characterized and elucidated. Selective quantification of ERTM, singly in bulk form, pharmaceutical formulations and/or in the presence of its major degradant is demonstrated. The indication of stability has been undertaken under conditions likely to be expected at normal storage conditions. Among the spectrophotometric methods adopted for quantification are first derivative ((1)D), first derivative of ratio spectra ((1)DD) and bivariate analysis.

First-derivative spectrophotometric and gas-liquid chromatographic determination of caffeine in foods and pharmaceuticals I. Rapid determination of caffeine in coffee, tea and soft drinks

ZusammenfassungEs wird ein einfaches derivativspektrophotometrisches Verfahren zur schnellen Bestimmung von Coffein in Kaffee, Tee und Colagetränken beschrieben, gleichfalls eine gaschromatographische Methode für denselben Zweck. Die Wiederfindung bei beiden Verfahren zeigte gute Ergebnisse mit relativ niedrigen Abweichungen. Die erhaltenen Ergebnisse sind mit denen eines arzneibuchlichen Verfahrens verglichen worden.SummaryA simple and rapid spectrophotometric method is described for the determination of caffeine in coffee, tea and soft drinks. To exclude the irrelevant absorptions, due to the presence of some accompanying naturally occurring ingredients in the analysed multicomponent drinks, the derivative method is found to be superior. Another gas-liquid chromatographic (GLC) procedure for the quantitation of the analeptic agent, in bulk form and in the same drinks, is also investigated. The recovery testing of the proposed methods gives good percentage mean recoveries with relatively low deviations. The results of the methods described are compared with those obtained by direct UV-spectrophotometry as well as by applying an official pharmacopoeial procedure for caffeine.

Double-Track Electrochemical Green Approach for Simultaneous Dissolution Profiling of Naproxen Sodium and Diphenhydramine Hydrochloride

HIGHLIGHTSNovel use of ISEs for simultaneous acquisition of dissolution profiles of binary co‐formulated tablets.ISEs exceptionally provide straight forward way for dissolution testing.No preliminary separation in reference to UV spectrophotometry and HPLC.Promising approach to the ICH and FDA regulatory requirements to perform dissolution tests.Faster, more sensitive, greener with respect to spectroscopic and chromatographic methods. ABSTRACT Acquisition of the dissolution profiles of more than single active ingredient in a multi‐analyte pharmaceutical formulation is a mandatory manufacturing practice that is dominated by utilization of the off‐line separation‐based chromatographic methods. This contribution adopts a new “Double‐Track” approach with the ultimate goal of advancing the in‐line potentiometric sensors to their most effective applicability for simultaneous acquisition of the dissolution profiles of two active ingredients in a binary pharmaceutical formulation. The unique abilities of these sensors for real‐time measurements is the key driver for adoption of “green analytical chemistry” (GAC) principles aiming to expand the application of eco‐friendly analytical methods With the aim of performing a side‐by‐side comparison, this work investigates the degree of adherence of ISEs to the 12 principles of GAC in multicomponent dissolution profiling with respect to the HPLC. For the proof of concept, a binary mixture of naproxen sodium (NAPR) and diphenhydramine hydrochloride (DIPH) marketed as Aleve pm® tablets was selected as a model for which dissolution profiles were attained by two techniques. The first “Double‐Track” in‐line strategy depends on dipping two highly integrated membrane sensors for continuous monitoring of the dissolution of each active pharmaceutical ingredient (API) by tracing the e.m.f change over the time scale. For the determination of NAPR, sensor I was developed using tridodecyl methyl ammonium chloride as an anion exchanger, while sensor II was developed for the determination of DIPH using potassium tetrakis (4‐chlorophenyl) borate as a cation exchanger. The second off‐line strategy utilizes a separation‐based HPLC method via off‐line tracking the increase of peak area by UV detection at 220 nm over time using a mobile phase of acetonitrile: water (90:10) pH 3. The advantages of the newly introduced “Double‐Track” approach regarding GAC principles are highlighted, and the merits of these benign real‐time analyzers (ISEs) that can deliver equivalent analytical results as HPLC while significantly reducing solvent consumption/waste generation are described.

Photodegradation and photostability-indication of mequitazine

The photochemical behavior is investigated for mequitazine (MQ) illustrating possible mechanisms and photodegradation products formed. Accelerated photolysis is done for MQ under justified stress conditions by subjecting aqueous drug solutions to radiation for specified period of time. Synthesis of the main photodegradants, the sulfoxide, is achieved. Selective quantification of MQ, singly in bulk form, pharmaceutical formulations and/or in the presence of its photodegradants is demonstrated. The indication of stability has been undertaken under conditions likely to be expected at normal storage conditions using a simple colorimetric method based on oxidation of the intact phenothiazine drug by potassium iodate in acid medium to form a red colored product adequate for quantitative estimation of the studied drug.

UV-spectrophotometry versus HPLC–PDA for dual-drug dissolution profiling: which technique provides a closer step towards green biowaiver concept? Novel application on the recent FDA-approved mixture Aleve pm

Dissolution testing is a very significant tool that adds in vivo relevance to in vitro analytical data, thus providing a realistic in vitro/in vivo correlation. Dissolution profiling serves as a predictor of biological performance since the rate limiting step in the absorption of any drug is the rate of release from its pharmaceutical formulation. Being a routine procedure in quality control laboratories for initial approval process and scaling-up, the development of more and more eco-friendly methods for dissolution monitoring is considered as a worldwide trendy goal. In the present contribution, a comparison was highlighted between the two analytical techniques of utmost importance in acquisition of dissolution profiles: UV-spectrophotometry and HPLC–PDA focusing on the greenness of each one for further consolidation of the biowaiver concept. Both techniques were applied on the recently FDA-approved combination naproxen sodium (NAPR) and diphenhydramine hydrochloride (DIPH) formulated as Aleve pm® tablets. For the first time, this binary mixture was analyzed by three UV-spectrophotometric methods. NAPR was directly determined by zero-order spectrophotometry at 330xa0nm, where the spectrum of DIPH shows zero contribution. Whereas DIPH was determined by three simple methods exploiting the ratio spectra calculated using the spectrum of 20xa0µg/ml NAPR as a divisor. The first proposed method was ratio difference (RD), the second was ratio subtraction, and the last one was derivative ratio method. Being the simplest method, RD was the spectrophotometric method of choice that was applied in monitoring the dissolution of DIPH from Aleve pm® tablets. Although RD method has been widely described in many publications dealing with pharmaceutical analysis, it is the first article that opens a new horizon for RD method in the way of being a real-life application rather than only a method for determination. The second technique was a previously published HPLC–PDA, in which dissolution was then monitored by calculating the peak area of each component drug over time. Methods’ validation was performed agreeing with the ICH guidelines. The advantages and challenges of each technique are discussed in a side-by-side comparison giving a key to recognize which one can positively influence environmental well-being.Graphical abstract