Quality control of pharmaceuticals with NIR: From lab to process line

This work describes a general framework for assessing the active pharmaceutical ingredient (API) and excipient concentrations simultaneously in pharmaceutical dosage forms based on laboratory-scale measurements. The work explores the comprehensive development of a near infrared (NIR) analytical protocol for the quantification of the API and excipients of a pharmaceutical formulation. The samples were based on a paracetamol (API) formulation with three excipients: microcrystalline cellulose, talc, and magnesium stearate. The developed method was based on laboratory-scale samples as calibration samples and pilot-scale samples (powders and tablets) as model test samples. Both types of samples were produced according to an experimental design. The samples were measured in reflectance mode in a Fourier-transform NIR spectrometer. Additionally, a new method for determining the minimum number of calibration samples was proposed. It was concluded that the use of laboratory-scale samples to construct the calibration set is an effective way to ensure the concentration variability in the development of calibration models for industrial applications. With this method, both API and excipients can be determined in high-throughput applications in the pharmaceutical industry.     

Theoretical physics to analytics

This paper is based on the author’s lecture at the Congress of Russian Analysts in April 2010. Attention is paid to the natural advance in the old trend towards the introduction of the achievements of experimental physics into the practice of analytical chemistry. As a result, many things originally appeared in the closed world of physical laboratories have came to the wide expanse of instrumental analytics. Now the collaboration of physics with analytical chemists is going to the next level, practical needs in the determination of compounds rather than elements as result in the sophistication of the facilities for the processing of experimental data, which in turn calls for the use of not only new experimental methods but also many branches of theoretical physics for solving analytical problems. This problem is considered on several examples demonstrating important applied results.     

Glassy state of pharmaceuticals. IV. Studies on glassy pharmaceuticals by thermomechanical analysis

The glassy state of indomethacin was examined by thermomechanical analysis (TMA). The influences of the method of preparation and the measurement conditions of the sample on the TMA curves were investigated. The TMA curves of glassy indomethacin having hemispherical and plane surfaces were examined. Expansion was observed on the TMA curves in the region of glass transition temperature (Tg), which had been confirmed by differential scanning calorimetry. The TMA curves for the sample with the plane surface showed distinct expansion. It was further found that the glass transition shifted to lower temperatures as the heating rate was decreased and the loading increased. The TMA curves of brucine, griseofulvin and phenobarbital were similar to that of indomethacin. The relaxation process of glassy indomethacin below Tg was followed in terms of the variation of mechanical properties of samples.     

Human exhaled air analytics: biomarkers of diseases

Over the last few years, breath analysis for the routine monitoring of metabolic disorders has attracted a considerable amount of scientific interest, especially since breath sampling is a non-invasive technique, totally painless and agreeable to patients. The investigation of human breath samples with various analytical methods has shown a correlation between the concentration patterns of volatile organic compounds (VOCs) and the occurrence of certain diseases. It has been demonstrated that modern analytical instruments allow the determination of many compounds found in human breath both in normal and anomalous concentrations. The composition of exhaled breath in patients with, for example, lung cancer, inflammatory lung disease, hepatic or renal dysfunction and diabetes contains valuable information. Furthermore, the detection and quantification of oxidative stress, and its monitoring during surgery based on composition of exhaled breath, have made considerable progress. This paper gives an overview of the analytical techniques used for sample collection, preconcentration and analysis of human breath composition. The diagnostic potential of different disease-marking substances in human breath for a selection of diseases and the clinical applications of breath analysis are discussed.     

Spectrophotometric determination of clozapine in pharmaceuticals

New Spectrophotometric methods for the assay of clozapine (CZP) in pure and dosage forms are described. Method A is based on the oxidative coupling reaction of CZP with 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) in the presence of ceric ammonium sulphate to form a coloured species (_max 570 nm). Method B is also based on the oxidative coupling reaction of CZP withP-,N,N-dimethylpheny-lenediamine dihydrochloride (DMPD) in the presence of sodium hypochlorite to form a coloured species (_max 690 nm). Method C is based on the formation of coloured charge-transfer complex between CZP and chloranilic acid (_max 540 nm). Regression analysis of Beer-Lambert plots showed good correlation in the concentration ranges 2–25, 10–120 and 15–300 g/ml for methods A, B and C, respectively. The validity of the proposed methods was tested by analysing pharmaceutical dosage forms containing CZP and the relative standard deviation values were within 1.0%.     

FIA-FT-IR determination of ibuprofen in pharmaceuticals

A method has been developed for the determination of Ibuprofen (2-[4-isobutylphenyl]-propionic acid) in pharmaceuticals by FT-IR, using the carbonyl band which this compound presents at 1710 cm(-1) in carbon tetrachloride solutions. Samples are dissolved in carbon tetrachloride. In this solvent the excipients are not soluble and so the drug can be directly determined without any additional treatment. The use of a simple FIA manifold permits one to carry out this analysis with a low consumption of reagent and the FT-IR provides a continuous monitoring of the spectral base-line which permits an accurate determination of the maximum in the absorbance band. Also, the FIA system permits easy and fast sampling and cleaning of the measurement cell. The method has a dynamic range between 0.5 and 20 mg/ml with a sensitivity of 0.366 +/- 0.004 au . mg(-1) . ml . mm(-1) and a variation coefficient of 0.8% for 5 independent measurements of a real sample containing 200 mg of Ibuprofen per capsule. The developed procedure provides concentration values comparable with those found by UV spectrophotometry in the analysis of real samples but is free from matrix interferences.     

Sample preparation in analysis of pharmaceuticals

Sample preparation is a very important and essential step in environmental analysis. This article presents an overview of extraction methods for environmental samples, focusing especially on pharmaceuticals as there is great concern about them as pollutants.     

Titrimetric determination of chloramphenicol in pharmaceuticals

The simple titrimetric procedure to be described is based on acid hydrolysis of chloramphenicol and quantitative oxidation of the product by potassium dichromate in one step.     

Titrimetric determination of chloramphenicol in pharmaceuticals

The simple titrimetric procedure to be described is based on acid hydrolysis of chloramphenicol and quantitative oxidation of the product by potassium dichromate in one step.     

Bromatometric assay of simvastatin in pharmaceuticals

Titrimetric and spectrophotometric methods are proposed for the determination of simvastatin (SMT) in bulk drug and in tablets. The methods employ bromate-bromide mixture in acid medium as the brominating agent and iron (III) and thiocyanate as auxiliary regents. In titrimetry, SMT is treated with a measured excess of bromate-bromide mixture in HCl medium, and after a definite time, the unreacted bromine is determined iodometrically. In spectrophotometric method, the residual bromine is reduced by iron (II) and the resulting iron (III) is complexed with thiocyanate, and the absorbance is measured at 470 nm. In both methods, the amount of in situ generated bromine corresponds to the SMT content. The experimental conditions are optimized. Titrimetry is applicable over 1–10 mg range and the calculations are based on the molar ratio of 1: 0.666 (SMT: KBrO3). In spectrophotometric method, Beer’s law is obeyed over the concentration range 1–10 µg/mL. The calculated molar absorptivity is 3.02 × 10⁴ L/mol cm and the corresponding sandel sensitivity being 0.0081 µg/cm². The limit of detection (LOD) and limit of quantification (LOQ) are calculated to be 0.10 and 0.31 µg/mL, respectively. The intra-day and inter-day precision calculated from the analysis of pure SMT were less than 2 and 2.7%, respectively. The methods were satisfactorily applied to the determination of SMT in tablets, and no interferences from common tablet excipients were observed. The validity of the methods was further ascertained by parallel assay by an established technique and by recovery studies.     

Pressurized liquid extraction of pharmaceuticals from sewage-sludge

A method for the quantitative determination of ten pharmaceuticals in sewage sludge was developed by using pressurized liquid extraction (PLE) and HPLC-MS with ESI (HPLC-(ESI)MS). The PLE was optimized with regard to solvents and operational parameters, such as temperature, pressure, extraction time, and purge time. The optimum conditions were: 50 mM phosphoric acid/methanol (1:1 v/v) as the extraction solvent, temperature of 100 degrees C, pressure of 100 bar, extraction time 15 min, 2 cycles, flush volume 150% and purge time 300 s. All recoveries for pharmaceuticals were over 68% except for salicylic acid. The repetitivity and reproducibility between days expressed as RSD was lower than 8% for repetitivity and 10% for reproducibility. The LOD of all compounds was lower than 10 microg/kg of dry weight of sewage sludge. The method was applied to determine the pharmaceuticals in sewage sludge from two domestic sewage treatment plants (STPs). The samples were collected every three months between February 2004 and June 2005. Some pharmaceuticals were determined in the samples and naproxen showed the highest value (242 microg/kg of dry weight).     

Rheology of food,cosmetics and pharmaceuticals

The major recent advances in the rheology of food, cosmetics and pharmaceuticals have been developed in the fields of emulsions and gels. Concerning emulsion rheology, this review has been specially focused on the problem of wall slip, processing and modelling of its non-linear viscoelasticity behaviour. Concerning the rheology of gels, the most relevant contributions have been made on the improvement of gel strength by acidification of several protein dispersions.     

Polarographic determination of chlorpheniramine maleate in pharmaceuticals

The electroreduction of chlorpheniramine maleate has been investigated by a.c. and d.c. polarography, coulometry and cyclic voltammetry. Polarograms recorded from 0.2 M sulphuric acid exhibit a single well-defined 2-electron wave. The current is diffusion-controlled and proportional to the concentration in the entire range 0.3–400 μg ml^?1. A simple and rapid method for the determination of chlorpheniramine maleate in tablets is described.     

The thermal and photostability of solid pharmaceuticals

Drugs degrade to different extents on separate exposure to heat, moisture, oxidation and light. Combination of these stresses causes very complex behaviour. Many studies have been reported of the thermal behaviour of drugs in the solid-state, but most of the information available on the photodegradation of drugs refers to reactions in solution, (usually aqueous) and photoreactions in the solid-state are even more complex. In drug formulations, the presence of excipients adds further complications because the excipients may increase, have no effect on, or decrease the inherent stabilities of the drug. The literature has been explored to review the thermal and photostabilities of solid pharmaceuticals. This revised version was published online in August 2006 with corrections to the Cover Date.     

Chromatofocusing of paracetamol-containing pharmaceuticals on reversed-phase sorbents

The chromatofocusing technique has been applied for the formation of ascending linear and quasilinear pH gradients within columns with reversed-phase sorbents Diasorb D-130-C₁₈ and Diasorb-100-CN-mono for the first time. It was found that the optimum composition of mobile phases was 25 mM KH₂PO₄ + 25% CH₃CN (pH 3.0) for the starting solution and 3.15 mM KH₂PO₄ + 25% CH₃CN (pH 6.8–7.0) for the eluent. Separation of components of Maxicold and Efferalgan-C pharmaceuticals has been carried out by the chromatofocusing technique on the Diasorb-100-CN-mono sorbent.     

Impurity profiling of pharmaceuticals by thin-layer chromatography

Although there is a tendency in current pharmacopoeias for favouring HPLC, thin-layer chromatography (TLC) is still a very popular and frequently used analytical method in the pharmaceutical industry. This paper highlights the possibilities of this method in the different areas of pharmaceutical analysis like in-process and intermediate control, illustrated by impurity testing of active ingredients and final products, as well as its application in pharmaceutical research and development, based on some examples reported mainly in the last five years.