Duygu Acar1, Irene Teresa Molina-Martínez2, Miguel Gómez-Ballesteros3, Manuel Guzmán-Navarro4, José Manuel Benítez-Del-Castillo5, Rocío Herrero-Vanrell6. 1. Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain. Electronic address: duyacar@ucm.es. 2. Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC) and the Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Calle Profesor Martín Lagos, s/n, 28040 Madrid, Spain. Electronic address: iremm@farm.ucm.es. 3. Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC) and the Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Calle Profesor Martín Lagos, s/n, 28040 Madrid, Spain. Electronic address: mgballesteros@farm.ucm.es. 4. Biomedical Sciences Department, Pharmacy and Pharmaceutical Technology Unit, Faculty of Pharmacy, University of Alcalá, Ctra. de Madrid-Barcelona (Autovía A2) Km. 33,600, 28805 Alcalá de Henares, Madrid, Spain. Electronic address: manuel.guzman@uah.es. 5. Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC) and the Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Calle Profesor Martín Lagos, s/n, 28040 Madrid, Spain; Ocular Surface and Inflammation Unit, San Carlos Clinical Hospital, Calle Profesor Martín Lagos, s/n, 28040 Madrid, Spain. Electronic address: benitezcastillo@gmail.com. 6. Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Complutense University of Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain; Sanitary Research Institute of the San Carlos Clinical Hospital (IdISSC) and the Ocular Pathology National Net (OFTARED) of the Institute of Health Carlos III, Calle Profesor Martín Lagos, s/n, 28040 Madrid, Spain. Electronic address: rociohv@farm.ucm.es.
Abstract
PURPOSE: Artificial tears are widely used in the treatment of dry eye disease, although current formulations do not closely resemble natural tears. The purpose of this study was the design and characterization of a novel in situ gelling artificial tear formulation, containing both lipid and aqueous components, in order to resemble natural tears and replenish the tear film. METHODS: Liposomes, containing phosphatidylcholine, cholesterol, vitamins A and E, were prepared by the thin-film hydration method. The aqueous phase of the formulation was comprised of gellan gum, hydroxypropyl methylcellulose, levocarnitine, electrolytes (sodium chloride and potassium chloride), trehalose, and borates. The artificial tear was characterized in terms of liposome size, pH, surface tension, and viscosity. In vitro tolerance studies were performed in a human epithelial carcinoma cell line (HeLa) and a murine macrophage cell line (J774). In vivo tolerance was assessed in rabbits. RESULTS: Liposomes presented a unimodal distribution with a mean size of 200.1 ± 4.4 nm. The resulting surface tension was 53.4 ± 1.1 mN/m (at 33 °C) and the pH was 7.6 ± 0.1. The viscosity of the formulation presented a mean value of 4.0 ± 0.1 mPa s within the shear rate interval of 200-1000 s-1 at 33 °C. Cell viability remained higher than 90% in both cell lines. No discomfort or clinical signs were observed in rabbits. CONCLUSIONS: The liposome-based and in situ gelling artificial tear formulation presented good tolerance and suitable properties for topical ophthalmic administration. It may be beneficial in the treatment of dry eye disease.
PURPOSE: Artificial tears are widely used in the treatment of dry eye disease, although current formulations do not closely resemble natural tears. The purpose of this study was the design and characterization of a novel in situ gelling artificial tear formulation, containing both lipid and aqueous components, in order to resemble natural tears and replenish the tear film. METHODS: Liposomes, containing phosphatidylcholine, cholesterol, vitamins A and E, were prepared by the thin-film hydration method. The aqueous phase of the formulation was comprised of gellan gum, hydroxypropyl methylcellulose, levocarnitine, electrolytes (sodium chloride and potassium chloride), trehalose, and borates. The artificial tear was characterized in terms of liposome size, pH, surface tension, and viscosity. In vitro tolerance studies were performed in a humanepithelial carcinoma cell line (HeLa) and a murine macrophage cell line (J774). In vivo tolerance was assessed in rabbits. RESULTS: Liposomes presented a unimodal distribution with a mean size of 200.1 ± 4.4 nm. The resulting surface tension was 53.4 ± 1.1 mN/m (at 33 °C) and the pH was 7.6 ± 0.1. The viscosity of the formulation presented a mean value of 4.0 ± 0.1 mPa s within the shear rate interval of 200-1000 s-1 at 33 °C. Cell viability remained higher than 90% in both cell lines. No discomfort or clinical signs were observed in rabbits. CONCLUSIONS: The liposome-based and in situ gelling artificial tear formulation presented good tolerance and suitable properties for topical ophthalmic administration. It may be beneficial in the treatment of dry eye disease.
Authors: Maria Luisa Moyá; Manuel López-López; José Antonio Lebrón; Francisco José Ostos; David Pérez; Vanesa Camacho; Irene Beck; Vicente Merino-Bohórquez; Manuel Camean; Nuria Madinabeitia; Pilar López-Cornejo Journal: Pharmaceutics Date: 2019-02-06 Impact factor: 6.321
Authors: Barbara Vigani; Silvia Rossi; Giuseppina Sandri; Maria Cristina Bonferoni; Carla M Caramella; Franca Ferrari Journal: Pharmaceutics Date: 2020-09-10 Impact factor: 6.321