The solubility–permeability interplay and oral drug formulation design: Two heads are better than one

Antiviral effect of phytochemicals from medicinal plants: Applications and drug delivery strategies

“…This solubilitypermeability interplay was shown for formulations based on cyclodextrins [162][163][164], surfactants [165], cosolvents [166], and hydrotropes [167,168]. In amorphous solid dispersions (ASD), on the other hand, the solubility increases (via supersaturation) with unchanged permeability, and thus, ASD may be preferred over other carrier systems, given supersaturation can be achieved and maintained for sufficient time [169].…”

Hydrotropic Solubilization of Lipophilic Drugs for Oral Delivery: The Effects of Urea and Nicotinamide on Carbamazepine Solubility–Permeability Interplay

“…Since the equilibrium aqueous solubility of the drug controls its membrane/aqueous partition coefficient, which in turn controls the drug’s (passive) intestinal permeability, increased equilibrium solubility inherently decreases the drug’s partitioning and the overall permeability, resulting in the solubility–permeability tradeoff obtained with cyclodextrins, surfactants and cosolvents (Miller and Dahan, 2012; Beig et al, 2013b). On the other hand, ASD formulations that allow to achieve and maintain supersaturation which is a non-equilibrium increase of the drugs’ apparent solubility, do not affect neither the drug’s partitioning not its permeability, circumventing the complication of the solubility–permeability tradeoff (Dahan et al, 2016). This analysis highlights that the data presented in this article unequivocally indicate that the mechanism for hydrotropic drug solubilization involves modification of the equilibrium aqueous solubility of the drug.…”

“…Likewise, surfactants (Miller et al, 2011; Hens et al, 2015) and cosolvent-based delivery systems resulted in permeability decrease concomitantly to the solubility increase (Beig et al, 2012; Miller et al, 2012b). On the other hand, no such tradeoff was observed with amorphous solid dispersions (ASD) irrespective of the supersaturation level attained (Miller et al, 2012a; Dahan et al, 2013a, 2016). This fundamental difference between different solubilization methods and ASD formulations represent a significant advantage of the latter, as ASD may increase the drug flux across the intestinal barrier (which is the product of solubility times permeability) more easily than the above mentioned solubilization techniques.…”

Pró-fármacos de rosuvastatina de maior solubilidade em água

“…A análise do SCB utiliza um modelo de transporte in vitro juntamente com dados de permeabilidade humana para estimar a absorção de fármacos in vivo. Este sistema de classificação leva em consideração dois fatores importantes, que afetam diretamente a velocidade e extensão da absorção oral de formas farmacêuticas sólidas de liberação imediata, são elas: solubilidade e permeabilidade gastrintestinal (AMIDON et al,1995(AMIDON et al, , 2014DAHAN et al, 2009DAHAN et al, , 2016 A determinação da dose também é um fator importante no SCB. Fármacos altamente solúveis são definidos como os que tem a maior dose dissolvida em 250 mL em todas as faixas de pH do trato gastrintestinal (pH 1-6.8) (WILLIAMS et al, 2013).…”

“…A introdução de análise combinatória computacional e high throughput screening (HTS) trouxeram diversas vantagens em selecionar as moléculas mais promissoras devido à potência e/ou seletividade, com grandes chances de se tornarem hits. Contudo, dependendo das bibliotecas de moléculas utilizadas, podem dar origem a compostos mais lipofílicos, de alta massa molecular e com baixa solubilidade em água, que pode resultar em compostos líderes com propriedades físico-químicas e biofarmacêuticas inadequadas, limitando seu desenvolvimento (STELLA, NTI-ADDAE, 2007;STEGEMANN et al, 2007;CLAS et al, 2014;ALLER et al, 2015;DAHAN et al, 2016;JORNADA et al, 2016).…”