Felix Prüfert1, Ulrike Hering1, Sergey Zaichik1, Nguyet-Minh Nguyen Le2, Andreas Bernkop-Schnürch3. 1. Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. 2. Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria; Department of Industrial Pharmacy, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam. 3. Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. Electronic address: andreas.bernkop@uibk.ac.at.
Abstract
AIM: Development of a preactivated thiomer as sprayable excipient for mucoadhesive formulations. METHODS: 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. RESULTS: 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). CONCLUSION: The novel polymer CG4500-S-S-MNA is a promising sprayable excipient for mucoadhesive formulations.
AIM: Development of a preactivated thiomer as sprayable excipient for mucoadhesive formulations. METHODS: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. RESULTS: 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). CONCLUSION: The novel polymerCG4500-S-S-MNA is a promising sprayable excipient for mucoadhesive formulations.
Authors: Muhammad Zaman; Sadaf Saeed; Rabia Imtiaz Bajwa; Muhammad Shafeeq Ur Rahman; Saeed Ur Rahman; Muhammad Jamshaid; Muhammad F Rasool; Abdul Majeed; Imran Imran; Faleh Alqahtani; Sultan Alshehri; Abdullah F AlAsmari; Nemat Ali; Mohammed Alasmari Journal: Pharmaceutics Date: 2021-05-11 Impact factor: 6.321