Different types of ibuprofen- and lidocaine-loaded, poly(lactic-co-glycolic acid)
(PLGA)-based microparticles and thin, free films of various dimensions were prepared
and physico-chemically characterized in vitro. The obtained experimental results were
analyzed using mathematical theories based on Fick's second law of diffusion. Importantly,
the initial drug loadings were low in all cases (4%, w/w), simplifying the mathematical
treatment and minimizing potential effects of the acidic/basic nature of the two model
drugs on polymer degradation. Interestingly, the type of drug and device geometry
strongly affected the resulting release kinetics and relative importance of the involved
mass transport mechanisms. For instance, the relative release rate was almost unaffected
by the system size in the case of spherical microparticles, but strongly depended
on the thickness of thin, free films, irrespective of the type of drug. Ibuprofen
and lidocaine release was found to be primarily diffusion controlled from the investigated
PLGA-based microparticles for all system sizes, whereas diffusion was only dominant
in the case of the thinnest free films. Interestingly, the type of drug did not significantly
affect the resulting polymer degradation kinetics. However, ibuprofen release was
always much faster than lidocaine release for all system geometries and sizes. This
can probably be attributed to attractive ionic interactions between protonated, positively
charged lidocaine ions and negatively charged, deprotonated carboxylic end groups
of PLGA, hindering drug diffusion. The determined apparent diffusion coefficients
of the drugs clearly point out that the mobility of an active agent in PLGA-based
delivery systems does not only depend on its own physico-chemical properties and the
type of PLGA used, but also to a large extent on the size and shape of the device.
This has to be carefully taken into account when developing/optimizing this type of
advanced drug delivery systems.