J Appl Biomed 14:299-305, 2016 | DOI: 10.1016/j.jab.2016.06.001

Investigation of betahistine dihydrochloride biocompatibility and nasal permeability in vitro

Bissera Pilichevaa,*, Milena Draganova-Filipovab, Plamen Zagorchevc, Margarita Kassarovaa
a Department of Pharmaceutical Sciences, Faculty of Pharmacy, Medical University-Plovdiv, 15A Vasil Aprilov Blvd., Plovdiv, Bulgaria
b Department of Medical Biology, Faculty of Medicine, Medical University-Plovdiv, 15A Vasil Aprilov Blvd., Plovdiv, Bulgaria
c Department of Medical Physics and Biophysics, Faculty of Pharmacy, Medical University-Plovdiv, 15A Vasil Aprilov Blvd., Plovdiv, Bulgaria

Betahistine dihydrochloride, which is widely prescribed for the treatment of symptoms associated with Meniere's syndrome, is generally administered orally in solid or liquid formulations. There is a strong need of profound investigation of alternative routes of administration of betahistine to overcome difficulties related to oral administration. The aim of this study was to evaluate betahistine cytotoxicity and permeability in vitro and to assess the drug's relevance for incorporation in drug delivery systems for nasal administration. RPMI epithelial model was used to evaluate drug permeability in vitro. The cytotoxicity of betahistine was assessed by MTT test. Chitosan microspheres were used as a betahistine delivery system. RPMI 2650 formed a thick, impermeable cell layer on the apical side of the filter inserts and developed enough TEER values to confirm confluence. According to the obtained results, BET showed high permeability coefficients (Papp values in the range 2.3 × 10-5 to 19 × 10-5) and could, therefore, be successfully used in nasal drug delivery formulations. Also, BET exhibited a good safety profile regarding nasal epithelium toxicity. A dose-dependent reduction in cell viability was observed. The microspheres as drug delivery systems affected BET permeation profiles due to the presence of chitosan as an absorption enhancer.

Received: February 25, 2016; Revised: May 26, 2016; Accepted: June 1, 2016; Published: November 1, 2016  Show citation

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Pilicheva B, Draganova-Filipova M, Zagorchev P, Kassarova M. Investigation of betahistine dihydrochloride biocompatibility and nasal permeability in vitro. J Appl Biomed. 2016;14(4):299-305. doi: 10.1016/j.jab.2016.06.001.
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