Lidocaine loaded biodegradable nanospheres. II. Modelling of drug release

Abstract

The mechanism of the release of encapsulated lidocaine from spherical nanoparticles based on poly(D,L-lactic acid) polymer carrier (PLA) was studied through mathematical modelling. The drug was incorporated in the PLA matrix with particle sizes from approximately 250 to 820 nm and corresponding loadings varying from about 7 to 32% (w/w). The rate of release correlated with the particle drug loading and was fastest at small particles with a low drug content. It was about four times slower at large particles with a high loading when the process of release took up to 100 h. Two simple models, diffusion and dissolution, were applied for the description of the experimental data of lidocaine release and for the identification of the release mechanisms for the nanoparticles of different drug loading. The modelling results showed that in the case of high drug loadings (about 30% w/w), where the whole drug or a large part of it was in the crystallised form, the crystal dissolution could be the step determining the release rate. On the other hand, the drug release was diffusion-controlled at low loadings (less than 10% w/w) where the solid drug was randomly dispersed in the matrix. The estimated values of the diffusion coefficient of lidocaine in these particles were in the range of 5-7x10(-20) m(2)/s. A significant influence of both crystal dissolution and drug diffusion on the overall rate of release was assumed at PLA nanoparticles with medium lidocaine loadings.