Structure, Solubility and Stability of Orbifloxacin Crystal Forms: Hemihydrate versus Anhydrate.

Orbifloxacin (ORBI) is a widely used antimicrobial drug of the fluoroquinolone class. In the official pharmaceutical compendia the existence of polymorphism in this active pharmaceutical ingredient (API) is reported. No crystal structure has been reported for this API and as described in the literature, its solubility is very controversial. Considering that different solid forms of the same API may have different physicochemical properties, these different solubilities may have resulted from analyses inadvertently carried out on different polymorphs. The solubility is the most critical property because it can affect the bioavailability and may compromise the quality of a drug product. The crystalline structure of ORBI determined by SCXRD is reported here for the first time. The structural analysis reveals that the ORBI molecule is zwitterionic and hemihydrated. ORBI hemihydrated form was characterized by the following techniques: TG/DTA, FTIR-ATR, and PXRD. A second crystalline ORBI form is also reported: the ORBI anhydrous form was obtained by heating the hemihydrate. These ORBI solid forms were isomorphous, since no significant change in unit cell and space group symmetry were observed. The solid-state phase transformation between these forms is discussed and the equilibrium solubility data were examined in order to check the impact of the differences observed in their crystalline structures.

Quality evaluation of the Finasteride polymorphic forms I and II in capsules.

Finasteride (FNS) is a specific competitive inhibitor of steroid type-II 5α-reductase and is widely used for the treatment of benign prostatic hyperplasia, prostate cancer, and androgenetic alopecia. FNS has two polymorphic forms identified as Form I and Form II. It is known that polymorphism can cause significant differences in the physicochemical properties of a compound such as melting point, density, morphology, solubility, and color. Thus, proper qualitative and quantitative monitoring of the solid-state forms is crucial to ensure high-quality products. There are no published papers studying the influence of the FNS polymorphs on the physicochemical quality of capsules. Furthermore, the available analytical methods are time-consuming, expensive, use buffer or do not demonstrate stability-indicating capacity. The aim of this work was to validate a rapid high-performance liquid chromatography (HPLC) method to evaluate FNS in capsules and to study the physicochemical properties of polymorphic forms, evaluating their possible influence in the dissolution profile and stability of FNS in capsules. Capsules containing Forms I and II of FNS were prepared and subjected to quality control studies, dissolution profiles and a stability study at 50°C. A significant effect of polymorphism on the FNS solubility and dissolution properties was observed. These results suggest that changes in the effects of FNS can occur if a suitable control study is not performed on the raw material used to produce the capsules.

Polymorphism: an evaluation of the potential risk to the quality of drug products from the Farmácia Popular Rede Própria

Polymorphism in solids is a common phenomenon in drugs, which can lead to compromised quality due to changes in their physicochemical properties, particularly solubility, and, therefore, reduce bioavailability. Herein, a bibliographic survey was performed based on key issues and studies related to polymorphism in active pharmaceutical ingredient (APIs) present in medications from the Farmácia Popular Rede Própria. Polymorphism must be controlled to prevent possible ineffective therapy and/or improper dosage. Few mandatory tests for the identification and control of polymorphism in medications are currently available, which can result in serious public health concerns.

O polimorfismo em sólidos é um fenômeno frequente em fármacos e pode levar a problemas na qualidade dos medicamentos por alterar suas propriedades físico-químicas, em especial a solubilidade e, consequentemente, a biodisponibilidade. Nesse trabalho realizou-se levantamento bibliográfico sobre os principais estudos e problemas relacionados ao polimorfismo em fármacos presentes nos medicamentos disponibilizados pela Farmácia Popular do Brasil. O polimorfismo deve ser controlado a fim de evitar possível ineficácia terapêutica e/ou dosagem inapropriada dos medicamentos. Destacamos que são poucos os ensaios obrigatórios para identificação e controle desse fenômeno em medicamentos, o que pode acarretar grande problema de saúde pública.

Controle de qualidade físico-químico e microbiológico em 2347 amostras manipuladas em 2010 e 2011 / Physicochemical and microbiological quality of 2347 samples of medications compounded in Brazil in 2010 and 2011

O setor magistral promove o acesso da população a medicamentos essenciais e fornece produtos individualizados. Entretanto, a qualidade dos medicamentos manipulados no Brasil é frequentemente questionada, apesar de existirem poucos dados científicos abrangentes sobre a qualidade destes produtos. O objetivo deste trabalho foi fazer um levantamento de análises físico-químicas e microbiológicas realizadas em 2347 amostras de produtos manipulados entre janeiro de 2010 e dezembro de 2011, em 117 diferentes farmácias de 49 municípios brasileiros. Os municípios selecionados foram todos aqueles que possuem farmácias conveniadas ao laboratório que realizou o estudo. Das amostras analisadas, 21,4% apresentaram não conformidades físico-químicas, sendo que vários hormônios e antibióticos foram reprovados. Com relação aos ensaios microbiológicos, 0,96% das bases galênicas e 0,20% dos produtos acabados analisados apresentaram não conformidades, sendo identificados micro-organismos patogênicos nestes produtos. Apesar das exigências cada vez maiores das autoridades sanitárias em relação a produtos manipulados, com base nestes resultados, nós chamamos atenção quanto à qualidade destes produtos.

Compounding pharmacies allow the population access to essential medications and individualized products. Despite the insufficient comprehensive scientific data on this issue, the quality of medications compounded in Brazil is often questioned. the aim of the present study was to evaluate the physicochemical and microbiological quality of 2347 samples of medications compounded between January 2010 and December 2011 at 117 different pharmacies located in 49 Brazilian cities. All cities with pharmacies affiliated to the laboratory that undertook the study were selected. A total of 21.4% of the samples analyzed exhibited physicochemical non-compliance and a number of hormones and antibiotics were rejected in the tests. Regarding microbiological tests, 0.96% of the galenic bases and 0.20% of the finished products analyzed exhibited non-compliance. Moreover, pathogens were identified in these products. Despite the demands of health authorities for higher standards regarding compounded medications, the present findings call the quality of such products into question.