Effects of nanosuspension and inclusion complex techniques on the in vitro protease inhibitory activity of naproxen

Abstract

This study investigated the effects of nanosuspension and inclusion complex techniques on in vitro trypsin inhibitory activity of naproxen-a member of the propionic acid derivatives, which are a group of antipyretic, analgesic, and non-steroidal anti-inflammatory drugs. Nanosuspension and inclusion complex techniques were used to increase the solubility and anti-inflammatory efficacy of naproxen. The evaporative precipitation into aqueous solution (EPAS) technique and the kneading methods were used to prepare the nanosuspension and inclusion complex of naproxen, respectively. We also used an in vitro protease inhibitory assay to investigate the anti-inflammatory effect of modified naproxen formulations. Physiochemical properties of modified naproxen formulations were analyzed using UV, IR spectra, and solubility studies. Beta-cyclodextrin inclusion complex of naproxen was found to have a lower percentage of antitryptic activity than a pure nanosuspension of naproxen did. In conclusion, nanosuspension of naproxen has a greater anti-inflammatory effect than the other two tested formulations. This is because the nanosuspension formulation reduces the particle size of naproxen. Based on these results, the antitryptic activity of naproxen nanosuspension was noteworthy; therefore, this formulation can be used for the management of inflammatory disorders.Uniterms: Naproxen/nanosuspension/anti-inflammatory activity. Naproxen/inclusion complex/antiinflammatory activity. Naproxen/solubility. Protease inhibition.O objetivo do presente estudo foi investigar a atividade anti-inflamatória in vitro de nanossuspensões e do complexo de inclusão contendo naproxeno. Esse fármaco é derivado de ácido propiônico, com ação analgésica, antipirética e antiinflamatória. A obtenção dessas formulações teve por finalidade o aumento da solubilidade e da atividade anti-inflamatória do fármaco. Os métodos por precipitação em solução aquosa por evaporação e por empastagem foram modificados para a obtenção da nanossuspensão e do complexo de inclusão, respectivamente. Para a avaliação da atividade anti-inflamatória das formulações utilizou-se ensaio in vitro modificado de inibição de tripsina. As propriedades físico-químicas das formulações propostas foram determinadas utilizando espectroscopia UV e de infravermelho, além de estudos de solubilidade. O complexo de inclusão de naproxeno apresentou menor atividade antitripsina, quando comparado ao composto livre e à nanossuspensão. Em conclusão, entre as formulações avaliadas, a nanossuspensão de naproxeno apresentou maior efeito anti-inflamatório. Esse efeito foi devido à redução da dimensão das partículas de naproxeno para a escala nanométrica. Com base nos resultados obtidos, a atividade da nanossuspensão de naproxeno foi notável. Dessa forma, essa formulação apresenta potencial para o tratamento de distúrbios inflamatórios.Unitermos: Naproxeno/nanossuspensão/atividade anti-inflamatória. Naproxeno/complexo de inclusão/ atividade anti-inflamatória. Naproxeno/solubilidade. Inibição da protease.

Anti-Arthritic and Anti-Inflammatory Potential of Spondias mangifera Extract Fractions: An In Silico, In Vitro and In Vivo Approach

“…Tris-HCl buffer solution was used as a control. The formula that was used for the calculation of % inhibition is mentioned below [ 31 ]. % inhibition = (1 − Ac/At) 100 …”

Formation of nanosuspensions in bottom-up approach: theories and optimization

“…Particle agglomeration is the outcome of attractive forces between the particles in the absence of considerable energy barrier; the latter is proven to be more important [80]. In this regard, high levels of hydrophobicity of particles decrease the wettability of their surface, resulting in aggregation [81]. Accordingly, hydrophobic particles tend to agglomerate to reduce the system free energy, as shown in the case of naproxen particles [82].…”

“…In this system, increase of the surface area, because of nanoformulation, enhances the contacts between particles and outer medium, ultimately resulting in high surface energy. This can cause thermodynamic instability [8] and aggregation of nanoparticles [81].…”

“…Therefore, crystal particles confer better stability to the system [69]. However, this may interfere with the dissolution rate of nanosuspension [1,23,81,104].…”

A comparative study of the novel spectrophotometric methods versus conventional ones for the simultaneous determination of Esomeprazole magnesium trihydrate and Naproxen in their binary mixture

“…It works by inhibiting both the COX-1 and COX-2 enzymes. Literature survey reveals that there are some UV [10][11][12][13][14] and HPLC [15][16][17][18], HPTLC [19], UPLC [17], LC/MS [20,21], Capillary electrophoresis [22] methods for the estimation of Naproxen in pharmaceutical formulations, and in rat serum by HPTLC [23]. The official method for independent determination of Naproxen is by acid-base titration and that for Esomeprazole magnesium is by HPLC [24].…”