Hydrophobic ion pairing: Key to highly payloaded self-emulsifying peptide drug delivery systems

Impact of different hydrophobic ion pairs of octreotide on its oral bioavailability in pigs

“…Our results, however, showed that a ratio of 1:3 is more efficient. These data are in agreement with previous studies demonstrating that either an equivalent or slightly higher ratio is most efficient for HIP formation (6). Because of its D-amino acids and due to its cyclic structure, octreotide is stabilized against degradation by intestinal proteases (17).…”

“…Within recent years, hydrophobic ion pairing (HIP) emerged as valuable tool to improve the lipophilic character of peptide drugs in order to protect them towards enzymatic degradation by intestinal peptidases (4) and to improve their membrane permeability (5). Furthermore, due to hydrophobic ion pairing therapeutic peptides can be incorporated in self-emulsifying drug delivery systems (SEDDS) (6). Lipase stable SEDDS provide an even more pronounced protective effect for incorporated HIPs towards intestinal peptidases (7).…”

API ionic liquids: probing the effect of counterion structure on physical form and lipid solubility

“…24 When pairing an API with a counterion of low polarity in order to improve solubility in lipids the complex can be referred to as a lipophilic salt (LS) or hydrophobic ion pair (HIP). [25][26][27][28] This alternate denition also recognises the fact that LSs with melting points above 100 C (and therefore not strictly ionic liquids) may also have benet.…”

Sistemas de entrega de fármacos autoemulsificables: una plataforma de desarrollo alternativa para la industria farmacéutica colombiana

“…Mediante la modificación molecular de los principios activos se puede alterar sus propiedades fisicoquímicas con la finalidad de aumentar su lipofilicidad y ser incorporados en SEDDS para mejorar su biodisponibilidad mediante la estimulación del transporte linfático para su absorción [87]. El uso de contraiones lipofílicos (emparejamiento iónico) [62,146] y la esterificación de los principios activos (profármacos) [147,148] permiten aumentar su solubilidad en la fase oleosa de los SEDDS con el objetivo de promover su absorción sistémica. En particular, el emparejamiento iónico es una alternativa muy atractiva para la administración de péptidos orales debido al extenso metabolismo de primer paso hepático al que son sometidos al ser administrados por la vía oral [149,150].…”