In vitro/in vivo performance of different complexes of itraconazole used in the treatment of vaginal candidiasis

Abstract

A large majority of new chemical entities and many existing drug molecules exhibit poor aqueous solubility, which may limit their potential use in developing drug formulations, with optimum bioavailability. One of the approaches to improve the solubility of a poorly water soluble drug and eventually its bioavailability is complexation with agents like humic acid (HA), fulvic acid (FA), β-cyclodextrin (β-CD), 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and caffeine (Caff). The current work emphasized at employing these agents to prepare different complexes and their in vitro/in vivo assessment. All the complexes evaluated for their complexation efficiency and authenticated by molecular modeling; conformational analysis, differential scanning calorimetry (DSC), X-ray diffraction (XRD), nuclear magnetic resonance (NMR) and mass spectroscopy. Furthermore, the complexes were assessed in an in vivo, rat vaginal model for their efficacy in treatment of vaginal candidiasis. Amongst the five tested complexes, fulvic acid-itraconazole complex yielded better solubility as well as in vivo efficacy and therefore may further be explored for developing a commercial formulation for treating vaginal candidiasis. A maioria das novas entidades químicas e muitas moléculas de fármacos existentes apresenta fraca solubilidade em água, o que pode limitar seu uso potencial no desenvolvimento de formulações com biodisponibilidade ideal. Uma das abordagens para melhorar a solubilidade de um fármaco pouco solúvel em água e, eventualmente, a sua biodisponibilidade é a complexação com agentes como o ácido húmico (HA), ácido fúlvico (FA), β-ciclodextrina (β-CD), 2-hidroxipropil-β-ciclodextrina (HP-β-CD) e cafeína (Caff). O presente trabalho baseia-se no uso desses agentes para preparar diferentes complexos e suas avaliações in vitro/in vivo. Todos os complexos foram avaliados quanto à eficiência de complexação por modelação molecular, análise conformacional, calorimetria de varredura diferencial (DSC), difração de raios-X (XRD), ressonância magnética nuclear (RMN) e espectroscopia de massas. Além disso, os complexos foram avaliados in vivo, em ratas, no tocante à sua eficácia no tratamento de candidíase vaginal. Entre os cinco complexos testados, o complexo de ácido fúlvico-itraconazol foi o que apresentou melhor solubilidade, bem como melhor eficácia in vivo e, portanto, pode ser explorado para o desenvolvimento de uma formulação comercial para o tratamento de candidíase vaginal. Uniterms

Co-Loaded Curcumin and Methotrexate Nanocapsules Enhance Cytotoxicity against Non-Small-Cell Lung Cancer Cells

“…At higher drug concentrations, this process was faster since this gradient was the driving force for drug dissolution. Moreover, at higher drug-loading concentration, CUR and/or MTX could be distributed near to the nanocapsules surface providing a more rapid in vitro release [43]. In that sense, NCUR-2, prepared at the higher theoretical drug concentration of 3.0 mg•mL −1 , presented a faster dissolution and reached a complete release in almost 2 days.…”

A Pharmaco-Technical Investigation of Thymoquinone and Peat-Sourced Fulvic Acid Nanoemulgel: A Combination Therapy

“…On the other hand, the absorption bands at 3650–3600 cm −1 (H-bonded OH groups), 2940–2900 cm −1 (aliphatic C–H stretching), 1720–1700 cm −1 (C–O stretching and COOH-OH deformation), and 1099 cm −1 (polysaccharide C–O stretching or silicate impurity Si–O stretching) were particularly noticeable in the pure FA, whereas in the FTIR spectra of the lyophilized NE (KBr), the bands were observed at 3398.72 (-OH), 3289.74 (-OH), 2905.89 (C-H, stretching), 2292 (O=C=O, stretching), 2058.13 (C-H, bending), 1738.90 (C=O, ester), 1648.24 (C=O, stretching), 1424.49 (C-H bending, methyl), 1287.54 (C-H, rocking), 1083.08 (-C-O), 928.76 (C-H wagging, alkene), and 874.76 cm −1 (C=C, bending). Collectively, a slight shift in the peaks was observed in the spectra of the lyophilized NE as compared to the pure drug and fulvic acid, thus indicating its amalgamated/complexed nature [ 41 ]. In the case of the mannitol (cryoprotectant), the peaks were very close to the NE spectra, as it was used in excess to ensure an effective lyophilization of the NE.…”