Lidocaine loaded biodegradable nanospheres II. Modelling of drug release

The mechanism of the release of encapsulated lidocaine from spherical nanop articles based on poly(D,L-lactic acid) polymer carrier (PLA) was studied t hrough mathematical modelling. The drug was incorporated in the PLA matrix with particle sizes from approximately 250 to 820 nm and col responding loa dings varying from about 7 to 32% (w/w). The rate of release correlated wit h the particle drug loading and was fastest at small particles with a low d rug 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, di ffusion and dissolution, were applied for the description of the experiment al data of lidocaine release and for the identification of the release mech anisms for the nanoparticles of different drug loading. The modelling resul ts 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 h and, the drug release was diffusion-controlled at low loadings (less than 1 0% w/w) where the solid drug was randomly dispersed in the matrix. The esti mated values of the diffusion coefficient of lidocaine in these particles w ere in the range of 5-7 X 10(-20) m(2)/s. A significant influence of both c rystal dissolution and drug diffusion on the overall rate of release was as sumed at PLA nanoparticles with medium lidocaine loadings. (C) 1999 Publish ed by Elsevier Science B.V. All rights reserved.