Preparation and Characterisation of Lignocaine Loaded PLGA Microparticles Suitable for Intra- Articular Drug Delivery

Abstract

BACKGROUND: Insufficient pain management following knee replacement surgeries can slow and prevent full recovery of function. Local drug delivery providing a prolonged analgesic effect can potentially address this issue. Injectable microparticles made from biodegradable and biocompatible polymers like poly (lactic-co-glycolic acid) (PLGA) are promising drug delivery systems for this purpose. OBJECTIVE: The objective of this study was to develop lignocaine containing PLGA microparticles suitable for intra-articular administration which could provide a prolonged anaesthetic effect over seven to fourteen days. METHODS: Lignocaine loaded microparticles were prepared by oil in water solvent evaporation technique using capped and uncapped PLGA. An ultraviolet spectroscopic method was developed and validated for the quantification of lignocaine. Various ratios of lignocaine to PLGA were tested to optimize particle formation and the lignocaine content in the formed microparticles. Changes in the process parameters and starting material were examined to check the effect on the microparticles produced. The microparticles were then characterized for size, surface morphology, drug loading, entrapment efficiency, thermal properties, drug release and degradation of polymer. RESULTS: The optimum ratio of lignocaine to polymer ratio was 0.2:1. The thermal analysis indicated a concentration dependant plasticizing effect of lignocaine on PLGA, quantified by observed glass transition temperatures. Modification of production processes, including change in buffer, molecular weight of PVA and method of solvent evaporation gave microparticles with different sizes (4 to 8 µm), yield (60 to 77%), drug loading (2 to 8% w/w) and drug release patterns. In vitro release studies showed typical triphasic drug release profile with batches differing in burst release. Some batches released almost 50% of the drug within 24 hours, while some batches gave a small burst followed by constant drug delivery for up to 40 days. The degradation of polymers was complete in 48 days, with uncapped PLGA showing faster degradation in comparison with capped PLGA. CONCLUSION: Modification of process parameters was achieved to obtain particles with differing properties. The most suitable batch for intra-articular delivery was prepared using uncapped, low molecular weight PLGA. It had 3% w/w drug loading, appropriate particle size (8 µm) and released 90% of the drug by Day 20.