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In the pharmaceutical industry, the unexpected appearance of crystalline forms could impact the therapeutic efficacy of an Active Pharmaceutical Ingredient (API). For quality control, a thorough qualitative and quantitative monitoring of pharmaceutical solid forms is essential to ensure the detection and the quantification of crystalline forms, wither different or with the same chemical composition (polymorphs) at a low detection level. The purpose of this paper was to review and highlight the importance of choosing adequate solid-state techniques for detection and quantification APIs that present polymorphism - based on limits of detection (LOD) and quantification (LOQ), pharmacopeias specifications, international guidelines and studies reported in the literature. To this study, the powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Infrared and Raman spectroscopies and solid-state nuclear magnetic resonance (NMR) were the solid-state techniques analyzed. Additionally, the Argentine, Brazilian, British, European, International, Japanese, Mexican and the United States of America pharmacopeias were reviewed. Based on the analysis performed, the advantages and disadvantages of these techniques, as well as the LOD and LOQ values of APIs were reported. In comparison to these solid-state techniques, reference material used for identification analyses should be previously identified with the corresponding polymorph. Without this previous procedure, the patterns, the spectra, and DSC curves of the reference material can only be used to confirm the mixture of solid forms, not being able to specify which polymorphs are contained in the sample. A major advantage of PXRD is the use of the calculated diffraction patterns obtained from the Crystallographic Information Frameworks (CIFs) files which could be used as a reference pattern without any other information, assistance technique, or physical standards. Regarding the quantification aspect, different pharmacopeias suggest various methods such as the PXRD combining with Rietveld method, which can be used to obtain lower LOD values for minority phases in the mixture of different substances without the need for a calibration curve. Raman spectroscopy can detect polymorphs in small particles and solid-state NMR spectroscopy is a powerful technique for quantification not only crystalline but also crystalline-amorphous mixtures. Finally, this review intends to be a useful tool to control, with efficiency and accuracy, the polymorphism of APIs in pharmaceutical compounds.

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Abstract The globalization of the pharmaceutical market has enabled access to a considerable number of new medicinal products. Consequently, the circulation of substandard medicinal products has also increased. To minimize this problem, post-marketing quality sampling and testing programs are performed to monitor and confirm that the medicinal products available in the market meet appropriate quality requirements. In this review, the post-approval sampling and testing procedures of six regulatory authorities were compared with the goal of strengthening these market surveillance systems. Similarities were observed between the procedures adopted by different regulatory authorities. However, the agencies were not always transparent about the results of these monitoring procedures. A probable mismatch between the registration procedures and the quality requirements listed in official compendiums was observed, which resulted in dissonance and contradiction between the specifications approved by the regulatory authorities and those required in the pharmacopeias. Therefore, strengthening harmonization projects related to these activities can help minimize such difficulties.

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This study proposes an analytical procedure for microwave-assisted sample preparation of dietary supplements for athletes using dilute nitric acid solution followed by determination of elemental impurities (As, Cd, Hg and Pb) by inductively coupled plasma mass spectrometry (ICP-MS) according to the United States Pharmacopeia Chapters 2232 and 233. Calibration strategies as internal standardization (IS), multi-isotope calibration (MICal), and one-point standard addition (OP SA) were applied for correction of matrix effects. The optimization of the sample preparation procedure was performed using Doehlert experimental design based on overall desirability results (residual acidity, dissolved organic carbon and recoveries reached for certified reference material of Typical Diet) for each calibration method evaluated. Accuracy was also evaluated by recovery experiments according to the permissible daily exposure specific for each element and samples were spiked with element concentrations of 0.5J and 1.5J in order to check accuracies for As, Cd, Hg and Pb. Recoveries ranged from 82 to 120% using IS, 90 to 125% using MICal, 88 to 120% using OP SA and the repeatability was demonstrated by a precision lower than 10% RSD. Ten samples of dietary sport supplements were analyzed using the three calibration methods evaluated and the concentrations of As, Cd and Pb determined in eight samples were lower than the limits established by the Chapter 2232.

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Introdução: A entrega tópica de medicamentos é essencial na Dermatologia. Devido à dificuldade de permeação do estrato córneo, as técnicas de drug delivery vêm recebendo destaque. O uso de formulações não específicas para este fim nos faz atentar para possíveis efeitos adversos e para a segurança microbiológica destas formulações. Objetivo: Avaliar crescimento bacteriano e fúngico no sérum anidro fluido por meio do teste de esterilidade simples. Materiais e métodos: O teste de esterilidade simples foi realizado em um sérum anidro contendo ativos lipofílicos e hidrofílicos. Este teste foi realizado três meses após a manufatura do produto. Resultados: A formulação estudada foi aprovada no teste de esterilidade simples realizado três meses após a manufatura do produto, mesmo sem uso de conservantes na formulação. A formulação em estudo foi aprovada no teste de esterilidade possivelmente devido ao fato de o veículo sérum ser de origem mineral e anidra, características que não favorecem a proliferação de micro-organismos. Conclusões: Embora somente o veículo contando ativos específicos tenha sido testado, os resultados deste estudo são promissores e demonstram a necessidade de estudos futuros que englobem de forma mais ampla o assunto.

Introduction: Topical delivery of drugs is essential in Dermatology. Due to the difficulty of permeation of the stratum corneum, drug delivery techniques have been highlighted. The use of non-specific formulations for this purpose makes raises the concern of possible adverse events and the microbiological safety of these formulations. Objective: To assess bacterial and fungal growth in anhydrous fluid serum through simple sterility test. Materials and methods: The simple sterility test was performed on an anhydrous serum containing lipophilic and hydrophilic active substances. This test was performed three months after the manufacture of the product. Results: The formulation studied was approved in the simple sterility test conducted three months after the manufacture of the product, even without the use of preservatives in the formulation. Discussion: The assessed formulation was approved in the sterility test possibly due to the fact that the serum vehicle has mineral and anhydrous origin, characteristics that do not favor the proliferation of microorganisms. Conclusions: Although only the vehicle counting specific assets has been tested, the results of this study are promising and demonstrate the need for future studies broadly encompassing this subject.

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Analisam-se as posições de Pedro Arata, Moisés Santiago Bertoni, Carlos Leonhardt e Guillermo Furlong no debate sobre o papel da Companhia de Jesus na introdução e no desenvolvimento das ciências na América platina. Escritas entre 1890 e fins de 1950, as obras desses autores tanto analisam o conhecimento médico, farmacêutico e botânico dos missionários jesuítas nos séculos XVII e XVIII quanto avaliam a contribuição da Companhia para o pensamento científico nos países de colonização ibérica. Suas posições antecipam o debate historiográfico sobre o reacionarismo da ordem jesuíta e as reflexões sobre a contribuição dos saberes indígenas sobre a farmacopeia americana para o conhecimento que os missionários levaram aos continentes em que atuaram.

The positions of Pedro Arata, Moisés Santiago Bertoni, Carlos Leonhardt and Guillermo Furlong in the debate about the role of the Society of Jesus in the introduction and development of science in the La Plata region are investigated. Written between 1890 and the late 1950s, these authors’ works not only analyze the medical, pharmaceutical and botanical knowledge of the Jesuit missionaries in the 1600s and 1700s, but also evaluate their contribution to scientific thinking in the countries colonized by Spain and Portugal. Their positions foretaste the historiographical debate about the reactionary nature of the Jesuit order and reflections about the contribution made by indigenous knowledge of American pharmacopeia to the knowledge the missionaries took to the continents where they were active.

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