Gastroretentive particles formulated with thiomers: development and in vitro evaluation

Abstract

The objective of this study is to develop and evaluate gastroretentive particulate delivery systems using Riboflavin-5′-monophosphate sodium salt dihydrate (RF5′PNa) as model drug. Poly(acrylic acid)-cysteine and chitosan-4-thiobuthylamidine were evaluated and compared as anionic and cationic polymers for gastroretentive particles.Permeation studies were performed with freshly excised stomach mucosa from rats. Polymers and combination with glutathione were evaluated for permeation enhancing properties. Furthermore, particles were prepared by air jet milling and characterized.Permeation studies showed that the apparent permeability coefficients for RF5′PNa with thiomers and glutathione are 1.511-fold and 2.354-fold higher than control, respectively. It can be seen from the results glutathione in combination with thiomers has a significant influence for increasing permeation. Poly(acrylic acid)-cysteine and chitosan-4-thiobuthylamidine particles demonstrated a mean diameter of 336.5 ± 16.5 and 396.3 ± 17.0 nm and zeta potential of −19.98 ± 1.015 and 27.15 ± 0.500 mV, respectively. The drug loading of Poly(acrylic acid) particles was significantly higher than chitosan particles. The release rate of RF5′PNa from the thiolated particles was slower compared with unmodified particles. Moreover, thiolated particles showed higher mucoadhesive properties compared to unmodified particles.Overall, thiolated particles of both anionic and cationic polymers had improved mucoadhesive and controlled release properties. Therefore, they could be promising for gastroretentive delivery systems.