Assay and physicochemical characterization of the antiparasitic albendazole

Abstract

The aim of this study was to characterize three batches of albendazole by pharmacopeial and complementary analytical techniques in order to establish more detailed specifications for the development of pharmaceutical forms. The ABZ01, ABZ02, and ABZ03 batches had melting points of 208 °C, 208 °C, and 209 °C, respectively. X-ray diffraction revealed that all three batches showed crystalline behavior and the absence of polymorphism. Scanning electron microscopy showed that all the samples were crystals of different sizes with a strong tendency to aggregate. The samples were insoluble in water (5.07, 4.27, and 4.52 mg mL -1 , respectively) and very slightly soluble in 0.1 M HCl (55.10, 56.90, and 61.70 mg mL -1 , respectively) and additionally showed purities within the range specified by the Brazilian Pharmacopoeia 5th edition (F. Bras. V; 98% to 102%). The pharmacopeial assay method was not reproducible and some changes were necessary. The method was validated and showed to be selective, specific, linear, robust, precise, and accurate. From this characterization, we concluded that pharmacopeial techniques alone are not able to detect subtle differences in active pharmaceutical ingredients; therefore, the use of other complementary techniques is required to ensure strict quality control in the pharmaceutical industry.Uniterms: Albendazole/characterization. Antiparasitics/quality control.O objetivo do trabalho foi caracterizar três lotes de albendazol com técnicas analíticas farmacopéicas e complementares a fim de estabelecer especificações mais detalhadas para o desenvolvimento de formas farmacêuticas. Os lotes ABZ01, ABZ02 e ABZ03 apresentaram fusão em 208 °C, 208 °C e 209 °C. Foi possível evidenciar, por difração de raios X, que os três lotes apresentaram comportamento cristalino e ausência de polimorfismo. Através da microscopia eletrônica de varredura verificou-se que todas as amostras apresentaram cristais com diferentes tamanhos e forte tendência de agregação. As amostras foram insolúveis em água (5,07; 4,27 e 4,52 µg mL -1 ) e muito pouco solúveis em HCl 0,1M (55,10; 56,90 e 61,70 µg mL -1 ) e, ainda, apresentaram pureza dentro da faixa especificada pela F.Bras.V (98% a 102%). O método farmacopéico de doseamento não foi reprodutível, e algumas mudanças foram necessárias. O método foi validado e demonstrou ser seletivo, específico, linear, robusto, preciso e exato. A partir dessa caracterização, pode-se concluir que apenas técnicas farmacopéicas não são capazes de detectar diferenças sutis entre os ingredientes farmacêuticos ativos, necessitando, portanto, de uso de outras técnicas complementares para garantir um rígido controle de qualidade na indústria farmacêutica.Unitermos: Albendazol/caracterização. Antiparasitários/controle de qualidade.

Role of excipients in the crystallization of Albendazole

“…This modified habit of treated crystals with least AR imparted better flow property compared with pure ABZ and control batch [29]. Flow property of pure drug was poor (Table 2) because of small and irregular shaped particles with a strong tendency to aggregate because of electrostatic charge generated on their surface [20,21]. Control batch crystals were improved in their flow property.…”

“…12A) showed very small particles with strong tendency to aggregate due to electrostatic charges generated on its surface. Also, its irregular shape resulted into poor flow [20,21]. SEM images of control batch (Fig.…”

“…1). Based on powder rheology, it is classified as a powder with poor flow property and compressibility [20][21][22]. Besides, Albendazole has low aqueous solubility (log P is 13.94) and high permeability (BCS Class II), which limits its oral absorption [23][24][25].…”

Determination of the main solid-state form of albendazole in bulk drug, employing Raman spectroscopy coupled to multivariate analysis

“…The Form I of ALB is the most frequently available, whilst Form II can be obtained by concentration of a methanolic solution of ALB, where the drug is sparingly soluble; both forms demonstrated to be physically stable [12,16]. However, the solid state landscape of ALB could become more complicated, since the presence of up to five phases in solid ALB has been recently described based on Rietveld analysis of powder X-ray diffraction data [17].…”

“…There is an undergoing conflict regarding the assignment of ALB to Class II (low solubility and high permeability) [16,19] or Class IV (low solubility and low permeability) [25] in the biopharmaceutics classification system [26], making ALB a unique case of study and turning crucial the solid-state characterization of the drug substance.…”