International Journal of Nanomedicine (Feb 2020)
The Oral Administration of Lidocaine HCl Biodegradable Microspheres: Formulation and Optimization
Abstract
Bushra T ALQuadeib, Eram KD Eltahir, Modhi F Alagili Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11671, Saudi ArabiaCorrespondence: Bushra T ALQuadeibDepartment of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 84428, Riyadh 11671, Saudi ArabiaTel +966 505653169Fax +966 118052932Email [email protected]: Lidocaine (LID) is a local anesthetic that is administered either by injection and/or a topical/transdermal route. However, there is a current need to develop efficacious methods for the oral delivery of LID with optimized bioavailability.Methods: We developed oral LID biodegradable microspheres that were loaded with alginate-chitosan with different mass ratios, and characterized these microspheres in vitro. We also developed, and utilized, a simple and sensitive HPLC-tandem mass spectrometry (LC-MS-MS) method for assaying LID microspheres.Results: The mean particle size (MPS) of the LID microspheres ranged from 340.7 to 528.3 nm. As the concentration of alginate was reduced, there was a significant reduction in MPS. However, there was no significant change in drug entrapment efficiency (DEE), or drug yield, when the alginate concentration was either increased or decreased. DSC measurements demonstrated the successful loading of LID to the new formulations. After a slow initial release, less than 10% of the LID was released in vitro within 4 h at pH 1.2. In order to evaluate nephrotoxicity, we carried out MTT assays of LID in two types of cell line (LLC-PK1 and MDCK). LID significantly suppressed the cell toxicity of both cell lines at the concentrations tested (100, 200, and 400ng/μL).Conclusion: Experiments involving the oral delivery of LID formulations showed a significant reduction in particle size and an improvement in dissolution rate. The formulations of LID developed exhibit significantly less toxicity than LID alone.Keywords: lidocaine, oral delivery, alginate–chitosan microspheres, in vitro characterization, dissolution rate, MTT assay
