Indomethacin–Saccharin Cocrystal: Design, Synthesis and Preliminary Pharmaceutical Characterization

Basavoju, Srinivas; Boström, Dan; Velaga, Sitaram P.

doi:10.1007/s11095-007-9394-1

Cited by 350 publications

(332 citation statements)

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“…One of the challenging tasks in the pharmaceutical industry is to design pharmaceutical solid materials with specific physicochemical properties (Besavoju et al, 2008). Solubility is one of the important parameters that have an impact on therapeutic effectiveness since it influences dissolution from dosage forms.…”

Section: Introductionmentioning

confidence: 99%

Characterisation, solubility and intrinsic dissolution behaviour of benzamide: dibenzyl sulfoxide cocrystal

Grossjohann

Eccles

Maguire

et al. 2012

International Journal of Pharmaceutics

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This study examined the 1:1 cocrystal benzamide: dibenzyl sulfoxide, comprising the poorly water soluble dibenzyl sulfoxide (DBSO) and the more soluble benzamide (BA), to establish if this cocrystal shows advantages in terms of solubility and dissolution in comparison to its pure components and to a physical mixture. Solubility studies were performed by measuring DBSO solubility as a function of BA concentration, and a ternary phase diagram was constructed. Dissolution was examined through intrinsic dissolution studies. Solid-state characterisation was carried out by powder X-ray diffraction (PXRD), energy-dispersive X-ray diffraction (EDX), infra-red spectroscopy (ATR-FTIR) and thermal analysis. DBSO solubility was increased by means of complexation with BA. For the cocrystal, the solubility of both components was decreased in comparison to pure components. The cocrystal was identified as metastable and incongruently saturating. Dissolution studies revealed that dissolution of DBSO from the cocrystal was not enhanced in comparison to the pure compound or a physical mix, while BA release was retarded and followed square root of time kinetics. At the disk surface a layer of DBSO was found. The extent of complexation in solution can change the stability of the complex substantially. Incongruent solubility and dissolution behaviour of a cocrystal can result in no enhancement in the dissolution of the less soluble component and retardation of release of the more soluble component

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Section: Introductionmentioning

confidence: 99%

Characterisation, solubility and intrinsic dissolution behaviour of benzamide: dibenzyl sulfoxide cocrystal

Grossjohann

Eccles

Maguire

et al. 2012

International Journal of Pharmaceutics

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“…Cocrystals of glutaric acid and 2-[4-(4-chloro-2-fluorphenoxy)phenyl]pyrimidine-4-carboxamide showed 0.08% moisture at high 95% RH and cocrystals were found stable at different conditions [41] . Indomethacin-saccharin cocrystals showed low water sorption during relative humidity studies and no dissociation or transformation occurred at experimental conditions [45] . Relative humidity stability behaviour of theophylline cocrystals with different coformers (oxalic acid, malonic acid, maleic acid and glutaric acid) was observed at different RH (0, 43, 75 and 98%) for different time intervals (1 d, 3 d, 1 w and 7 w).…”

Section: Stabilitymentioning

confidence: 93%

“…In relative humidity stress, automated water sorption/desorption studies are performed to determine the effect of water on the formulation. Several researchers studied the behaviour of cocrystals under relative humidity stress conditions [41,[45][46][47] . Cocrystals of glutaric acid and 2-[4-(4-chloro-2-fluorphenoxy)phenyl]pyrimidine-4-carboxamide showed 0.08% moisture at high 95% RH and cocrystals were found stable at different conditions [41] .…”

Section: Stabilitymentioning

confidence: 99%

“…Scanning electron microscope is the instrument used to determine the particle size and morphological analysis of cocrystals. A high energy electron beams scan the atoms that provide the information about the sample surface's topography [12,45,46] . Dissolution study is used to determine the amount of drug release with time in dissolution medium and predict the in vivo performance of the formulation.…”

Section: Evaluation Of Cocrystalsmentioning

confidence: 99%

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Pharmaceutical Cocrystals: An Overview

Kumar¹,

Nanda²

2017

pharmaceutical-sciences

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“…9,19 A simples mudança do pH da solução pode ser responsável por manter a estabilidade termodinâmica ou a vantagem da solubilidade do sistema. Como pode ser observado na Figura 4, o comportamento da curva de solubilidade de cocristais formados por coformadores com características variadas difere da curva de solubilidade do fármaco.…”

Section: Figura 1 Número De Artigos Publicados Por Ano Com O Tema Counclassified

Cocristais: uma estratégia promissora na área farmacêutica

et al. 2016

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COCRYSTALS: A PROMISING STRATEGY IN PHARMACEUTICAL SCIENCES. Pharmaceutical cocrystals have emerged as a useful strategy to improve the aqueous solubility of poorly water soluble drugs by aiming to enhance their oral absorption and bioavailability. Aqueous cocrystal solubility can be orders of magnitude higher than that of the constituent drug and this solubility advantage can be fine-tuned based on environmental conditions such as pH and the presence of drug solubilizing agents. This review presents a brief overview of pharmaceutical cocrystals regarding cocrystal design, obtainment methods, with particular focus on cocrystal solubility, and the solubility modulation by solution phase chemistry.Keywords: cocrystals; drug; solubility; transition point; thermodynamic stability. INTRODUÇÃOO setor de fármaco-medicamentos representa uma área estratégica sob o ponto de vista tecnológico/produtivo nacional. Vários são os desafios da produção de medicamentos competitivos e de qualidade no Brasil, como a oferta de insumos, a pesquisa de novas moléculas ativas e a sua inserção no mercado. Neste sentido, a utilização de inovações incrementais surge como alternativa à problemática do setor, destacando-se a manipulação da forma cristalina dos fármacos, síntese de polimorfos, sais, complexos e, mais recentemente, os cocristais. 1 Cocristais são materiais cristalinos homogêneos, compostos por dois ou mais compostos em proporção estequiométrica definida e que são sólidos em condições ambientes (25 ºC/1 atm). 2,3 Ao longo das últimas décadas, os cocristais têm recebido atenção significativa por parte da indústria farmacêutica, e diversos cocristais farmacêuticos têm sido relatados. Cocristais farmacêuticos, por sua vez, são compostos por um ingrediente farmacêutico ativo (IFA) e uma molécula não tóxica ou outro IFA, chamado de coformador. Ligações de hidrogênio entre as moléculas neutras do fármaco e do coformador orientam a formação do cocristal. 2,4 A síntese de cocristais tem sido uma estratégia cada vez mais utilizada para melhorar a solubilidade, a taxa de dissolução in vitro, e consequentemente, a biodisponibilidade de fármacos pouco solúveis, sem a necessidade de mudar a estrutura molecular e/ou a interação farmacológica. [5][6][7] No entanto, a avaliação da solubilidade e estabilidade dos cocristais em solução ainda não está consolidada. Um levantamento realizado no período de 1999 a 2015 (Figura 1) revelou um crescente número de publicações envolvendo a síntese e a caracterização dos cocristais, mas um reduzido número de publicações envolvendo outros aspectos essenciais no desenvolvimento de formulações contendo cocristais, como estudos de solubilidade, química em solução, estabilidade e a influência de excipientes.Considerando que a baixa solubilidade aquosa é um dos principais problemas associados às entidades químicas farmacêuticas, os

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Indomethacin–Saccharin Cocrystal: Design, Synthesis and Preliminary Pharmaceutical Characterization

Cited by 350 publications

References 35 publications

Characterisation, solubility and intrinsic dissolution behaviour of benzamide: dibenzyl sulfoxide cocrystal

Characterisation, solubility and intrinsic dissolution behaviour of benzamide: dibenzyl sulfoxide cocrystal

Pharmaceutical Cocrystals: An Overview

Cocristais: uma estratégia promissora na área farmacêutica

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