Synthesis and in vitro characterization of a preactivated thiolated acrylic acid/acrylamide-methylpropane sulfonic acid copolymer as a mucoadhesive sprayable polymer

• Published in: International journal of pharmaceutics 2020-06, Vol.583, p.119371-119371, Article 119371
• Main Authors: Prüfert, Felix, Hering, Ulrike, Zaichik, Sergey, Le, Nguyet-Minh Nguyen, Bernkop-Schnürch, Andreas
• Format: Article
• Language: English
• Subjects: Acrylamide - administration & dosage; Acrylamide - chemistry; Acrylates - administration & dosage; Acrylates - chemistry; Adhesiveness; Animals; Caco-2 Cells; Cell Survival - drug effects; Cysteine - administration & dosage; Cysteine - chemistry; Humans; Intestinal Mucosa - chemistry; Mucoadhesion; Mucus - chemistry; Nicotinic Acids - administration & dosage; Nicotinic Acids - chemistry; Polymers - administration & dosage; Polymers - chemistry; Preactivated Thiomer; Rheology; Sprayable excipient; Sulfhydryl Compounds - administration & dosage; Sulfhydryl Compounds - chemistry; Sulfonic Acids - administration & dosage; Sulfonic Acids - chemistry; Swine; Thiomer
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2020.119371

[Display omitted] Development of a preactivated thiomer as sprayable excipient for mucoadhesive formulations. CG4500 (acrylic acid/acrylamide-methyl propane sulfonic acid copolymer) was thiolated by conjugation with L-cysteine and preactivated by further modification with 2-mercaptonicotinic acid (MNA) in a two-step synthesis and characterized regarding degree of modification and cytotoxicity on Caco-2 cells. The mucoadhesive properties of this novel thiomer were evaluated via rheological synergism, tensile and mucosal residence time studies. Furthermore, the sprayability of the thiomer was evaluated. The newly synthesized derivatives CG4500-SH and CG4500-S-S-MNA showed mean coupling rates of 651 µmol thiol groups and 264 µmol MNA per gram polymer, respectively. Even for the unmodified polymer a rheological synergism was observed with isolated porcine intestinal mucus, which was 2.81-fold higher in case of the preactivated thiomer. Mucoadhesion studies on freshly excised porcine intestinal mucosa confirmed these results via a 2.43-fold higher total work of adhesion and a 2.31-fold higher mucosal residence time of the preactivated thiomer. In sprayability tests it was shown that solutions of the preactivated thiomer could be sprayed in concentrations up to 12% (m/V). The novel polymer CG4500-S-S-MNA is a promising sprayable excipient for mucoadhesive formulations.