OphthalMimic: A new alternative apparatus without animal tissue for the evaluation of topical ophthalmic drug products

• Published in: Methods (San Diego, Calif.) Vol. 228; pp. 1 - 11
• Main Authors: Barbalho, Geisa N., Falcão, Manuel A., Alves Amaral, Venâncio, Contarato, Jonad L.A., Barbalho, Aliucha M., Kaori Diógenes, Gabriela, Mariana Gomes Silva, Melyssa, Carvalho de Barros do Vale Rochelle, Beatriz, Gelfuso, Guilherme M., Cunha-Filho, Marcilio, Gratieri, Tais
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2024
• Subjects: 3D-printed device; Administration, Ophthalmic; Animal Testing Alternatives - methods; Animals; Chitosan - chemistry; Cornea - drug effects; Cornea - metabolism; Drug delivery; Fluconazole - administration & dosage; Gelatin - chemistry; Humans; Ocular delivery; Ophthalmic Solutions - chemistry; Poloxamer - chemistry; Polymeric membrane; Printing, Three-Dimensional; Retention time; Tears - chemistry; Polymeric membrane; Drug delivery; Retention time; Ocular delivery; 3D-printed device
• ISSN: 1046-2023; 1095-9130
• DOI: 10.1016/j.ymeth.2024.05.005

•Novel in vitro methods are necessary to substitute costly, slow, and highly complexin vivomodels to evaluate ophthalmic formulations.•The efficacy of topical ophthalmic drug products depends directly on formulation residence time in the eye, which must be sufficient for the drug to penetrate the cornea to reach the site of action at therapeutic levels.•A new in vitro alternative method that mimics the in vivo dynamic barriers of the eye by using a dynamic tear flow system and a synthetic barrier to simulate the cornea is presented.•The OphtalMimic is a promising tool for comparing the performance of ophthalmic formulations regarding their residence time. The necessity of animal-free performance tests for novel ophthalmic formulation screening is challenging. For this, we developed and validated a new device to simulate the dynamics and physical–chemical barriers of the eye for in vitro performance tests of topic ophthalmic formulations. The OphthalMimic is a 3D-printed device with an artificial lacrimal flow, a cul-de-sac area, a support base, and a simulated cornea comprised of a polymeric membrane containing poly-vinyl alcohol 10 % (w/v), gelatin 2.5 % (w/v), and different proportions of mucin and poloxamer, i.e., 1:1 (M1), 1:2 (M2), and 2:1 (M3) w/v, respectively. The support base is designed to move between 0° and 50° to replicate the movement of an eyelid. We challenged the model by testing the residence performance of poloxamer®407 16 % and poloxamer®407 16 % + chitosan 1 % (PLX16CS10) gels containing fluconazole. The test was conducted with a simulated tear flow of 1.0 mL.min−1 for 5 min. The OphthalMimic successfully distinguished PLX16 and PLX16C10 formulations based on their fluconazole drainage (M1: 65 ± 14 % and 27 ± 10 %; M2: 58 ± 6 % and 38 ± 9 %; M3: 56 ± 5 % and 38 ± 18 %). In conclusion, the OphthalMimic is a promising tool for comparing the animal-free performance of ophthalmic formulations.