Modeling and formulation of lidocaine containing Liposomes

Abstract

MODELING AND FORMULATION OF LIDOCAINE CONTAINING LIPOSOME A. Shalamaev Master thesis/ scientific supervisor prof. dr. V. Briedis; Lithuanian University of Health sciences, Faculty of Pharmacy, department of Clinical pharmacy. Kaunas. The aim: Biopharmaceutical assessment of liposomal lidocaine system and its in-vitro release and encapsulation efficiency. Tasks: Validation ultra-performance liquid chromatography (UPLC) method was used for identification and quantification of Lidocaine. Establishment of liposomes formulation and quality evaluation. In-vitro release tests (IVRT) achieved by using modified diffusion cell. Methods used: Quantitative analysis of Lidocaine hydrochloride composed in formulations, in- vitro release samples and samples obtained after encapsulation efficiency testing was performed by chromatography method developed in department of Clinical pharmacy. Detection of Lidocaine hydrochloride was achieved using ACQUITY UPLC H-Class chromatography system (Waters, USA) equipped with a Photodiode Array (PDA) detector at 230 nm. Calibration graphs were plotted according to the linear regression analysis, which gave a correlation coefficient (R2) of 0.9997. The method was tested and validated for repeatability and reproducibility according to ICH Q2 (R1) guideline “Validation of Analytical Procedures: Text and Methodology” (1) (table 1.) Results: Optimized batches of Lidocaine containing liposome prepared with lipoid S75 of 315 mg/mL with 23.11 mg/mL tested for in-vitro releases of liposomal lidocaine showed 1 hour mean flux were 3005,67 μg/cm2 ± 721,40 while 3 hours flux were 5471,23 μg/cm2 ±1548,8. Encapsulation efficiency median was 30,8% ± 7,38%. stability test for 14 days of liposome with lidocaine showed stable pH around 6 compare to empty liposomes that showed reduction. Size were 74-81 nm over period of 14 days, while liposomal PBS fluctuated 90-110,5 nm, PDI showed PDI stability of 0,253 ± 0,054 after 14 days. Conclusions: 1. Lipid Nanocarrier systems containing lidocaine were formulated and this is confirmed by particles size, PDI, pH data obtained from three experimental batches of optimized formulations. 2.The stability of formulated liposomal systems with lidocaine was tested for 14 6 days and satisfactory stability were confirmed, further stability testing is should be performed in order to confirm long term stability of the optimized formulations. 3. Evaluation of lidocaine release from liposomal systems demonstrated relatively high flux of lidocaine if compared diffusion of lidocaine from solution through semi-permeable membrane