Psoralen (PSO) and 5-methoxypsoralen (5-MOP) are widely used drugs in oral photochemotherapy against vitiligo and major bioactive components of root bark extract of Brosimum gaudichaudii Trécul (EBGT), previously standardized by LC-MS. However, the exceptionally low water solubility of these psoralens can cause incomplete and variable bioavailability limiting their applications and patient adherence to treatment. Therefore, the purpose of this work was to investigate the effects of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex on the solubility and jejunal permeability of PSO and 5-MOP from EBGT. Characterization of inclusion complexes were evaluated by current methods in nuclear magnetic resonance studies on aqueous solution, Fourier transform infrared spectroscopy, thermal analysis, and scanning electron microscopy in solid state. Ex vivo rat jejunal permeability was also investigated and compared for both pure psoralens and plant extract formulation over a wide HP-β-CD concentration range (2.5 to 70 mM). Phase solubility studies of the PSO- and 5-MOP-HP-β-CD inclusion complex showed 1:1 inclusion complex formation with small stability constants (Kc < 500 M−1). PSO and 5-MOP permeability rate decreased after adding HP-β-CD by 6- and 4-fold for pure standards and EBGT markers, respectively. Nevertheless, the complexation with HP-β-CD significantly improved solubility of PSO (until 10-fold) and 5-MOP (until 31-fold). As a result, the permeability drop could be overcome by solubility augmentation, implying that the HP-β-CD inclusion complexes with PSO, 5-MOP, or EBGT can be a valuable tool for designing and developing novel oral drug product formulation containing these psoralens for the treatment of vitiligo.
Diante da aplicabilidade dos extratos de Brosimum gaudichaudii no tratamento do vitiligo, o objetivo do estudo foi desenvolver um método analítico por cromatografia em camada delgada de alta eficiência (CCDAE) para a quantificação simultânea de psoraleno e bergapteno, presentes no extrato liofilizado de B. gaudichaudii, a fim de se tornar um método alternativo para o controle de qualidade dos extratos produzidos a partir desta espécie. O extrato liofilizado foi produzido a partir do extrato mole das raízes de B. gaudichaudii preparadas com solução hidroalcoólica a 55 % (v/v). A metodologia para análise dos compostos bergapteno e psoraleno, presentes no extrato liofilizado, foi desenvolvida e validada por cromatografia em camada delgada (CCD)/densitometria. A melhor resolução, separação e identificação dos marcadores, ocorreram em cromatoplacas de sílica RP 18 F254 (Merck) e fase móvel composta por acetonitrila: água 60:40. Os fatores de retenção (FR) para o psoraleno e o bergapteno foram 0,41 e 0,35, respectivamente. O método de análise desenvolvido se mostrou linear, preciso e exato. Desta forma, a densitometria por CCD ou CCDAE se mostrou uma técnica alternativa para identificação e separação destas furanocumarinas, sendo importante para o desenvolvimento de novos produtos contendo extratos de B. gaudicaudii para o tratamento do vitiligo.
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