title: A comprehensive in vitro and in vivo evaluation of thiolated matrix tablets as a gastroretentive delivery system.
abstract: The aim of this study was to investigate the potential of thiolated matrix tablets for gastroretentive delivery systems. Poly(acrylic acid)-cysteine (PAA-Cys) and chitosan-4-thiobuthylamidine (chitosan-TBA) were evaluated as anionic and cationic thiolated polymers and riboflavin was used as a model drug. Tablets were prepared by direct compression and each formulation was characterized in terms of disintegration, swelling, mucoadhesion, and drug release properties. Thereafter, the gastric residence times of tablets were determined with in vivo study in rats. The resulting PAA-Cys and chitosan-TBA conjugates displayed 172.80 ± 30.33 and 371.11 ± 72.74 µmol free thiol groups, respectively. Disintegration studies demonstrated the stability of thiolated tablets up to 24 h, whereas tablets prepared with unmodified PAA and chitosan disintegrated within a time period of 1 h. Mucoadhesion studies showed that mucoadhesion work of PAA-Cys and chitosan-TBA tablets were 1.341- and 2.139-times higher than unmodified ones. The mucoadhesion times of PAA, PAA-Cys, chitosan, and chitosan-TBA tablets were 1.5 ± 0.5, 21 ± 1, 1 ± 0.5, 17 ± 1 h, respectively. These results confirm the theory that thiol groups react with mucin glycoproteins and form covalent bonds to the mucus layer. Release studies indicated that a controlled release was provided with thiolated tablets up to 24 h. These promising in vitro results of thiolated tablets were proved with in vivo studies. The thiolated tablets showed a gastroretention time up to 6 h, whereas unmodified tablets completely disintegrated within 1 h in rat stomach. Consequently, the study suggests that thiolated matrix tablets might be promising formulations for gastroretentive delivery systems.
authors.affiliation: Department of Pharmaceutical Technology, Faculty of Pharmacy, Ege University, Bornova, 35100, Izmir, Turkey. zeynep.ay@ege.edu.tr
authors.forename: Zeynep Ay
authors.initials: ZA
authors.lastname: Senyigit
authors.forename: Anja
authors.initials: A
authors.lastname: Vetter
authors.forename: Tamer
authors.initials: T
authors.lastname: Guneri
authors.forename: Andreas
authors.initials: A
authors.lastname: Bernkop-Schnürch
mesh_terms: D000180:Acrylic Resins / Q000008:administration & dosage / Q000737:chemistry*; D000268:Adhesiveness; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002686:Chitin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D003545:Cysteine / Q000737:chemistry; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D005752:Gastric Mucins / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects*; D006023:Glycoproteins / Q000378:metabolism; D008297:Male; D010599:Pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D012256:Riboflavin / Q000008:administration & dosage / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000008:administration & dosage / Q000737:chemistry*; D013607:Tablets / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry* / Q000191:economics
chemical_list: D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005752:Gastric Mucins; D006023:Glycoproteins; D013438:Sulfhydryl Compounds; D013607:Tablets; C493042:chitosan-4-thiobutylamidine; C047874:gastric mucus glycoproteins; D002686:Chitin; C006903:carbopol 940; D003545:Cysteine; D012256:Riboflavin