Enhanced ophthalmic bioavailability and stability of atropine sulfate via sustained release particles using polystyrene sulfonate resin

• Published in: International journal of pharmaceutics 2024-07, Vol.660, p.124294, Article 124294
• Main Authors: Li, Falan, Ye, Xinyue, Li, Mingwei, Nie, Qin, Wang, Huihui, Zhang, Guoqing, Dong, Liyun, Wang, Caifen, Wu, Li, Liu, Hongfei, Wang, Lifeng, Peng, Can, Zhang, Jiwen
• Format: Article
• Language: English
• Subjects: Administration, Ophthalmic; Animals; Aqueous Humor - metabolism; Atropine - administration & dosage; Atropine - chemistry; Atropine - pharmacokinetics; Atropine sulfate; Bioavailability; Biological Availability; Delayed-Action Preparations - pharmacokinetics; Drug Liberation; Drug Stability; Hypromellose Derivatives - chemistry; Male; Mean residence time; Myopia; Ophthalmic Solutions - administration & dosage; Ophthalmic Solutions - pharmacokinetics; Polysaccharides, Bacterial - chemistry; Polystyrenes - chemistry; Polystyrenes - pharmacokinetics; Rabbits; Sodium polystyrene sulfonate resin; Stability; Sustained-release; Tears - metabolism
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2024.124294

ATS interacts with the SPSR via cation exchange. The ATS@SPSR suspension eye drops had a sustained release property and improved stability of ATS in vitro. As a result, ATS@SPSR suspension eye drops prolonged the ocular mean residence time of ATS in the tear fluid and enhanced the bioavailability of ATS in the tear fluid and aqueous humor of New Zealand rabbits. [Display omitted] Atropine sulfate (ATS) eye drops at low concentrations constitute a limited selection for myopia treatment, with challenges such as low ophthalmic bioavailability and inadequate stability. This study proposes a novel strategy by synthesizing ophthalmic sodium polystyrene sulfonate resin (SPSR) characterized by a spherical shape and uniform size for cationic exchange with ATS. The formulation of ATS@SPSR suspension eye drops incorporates xanthan gum and hydroxypropyl methylcellulose (HPMC) as suspending agents. In vitro studies demonstrated that ATS@SPSR suspension eye drops exhibited sustained release characteristics, and tropic acid, its degradation product, remained undetected for 30 days at 40 °C. The ATS levels in the tear fluids and aqueous humor of New Zealand rabbits indicated a significant increase in mean residence time (MRT) and area under the drug concentration–time curve (AUC0-12h) for ATS@SPSR suspension eye drops compared to conventional ATS eye drops. Moreover, safety assessment confirmed the non-irritating nature of ATS@SPSR suspension eye drops in rabbit eyes. In conclusion, the cation-responsive sustained-release ATS@SPSR suspension eye drops enhanced the bioavailability and stability of ATS, offering a promising avenue for myopia treatment.