*3.4. Riboflavin Release*

Figure 6 shows the release of riboflavin loaded PVA and PLA carriers in pH = 1.2 medium. Carriers without drug delivery orifices were prepared from both biodegradable polymers and dissolution studies were performed. In the case of PLA, which is insoluble in water, no drug release was expected, while in the case of PVA, after a short time a practically linear release of riboflavin was observed. If an orifice for drug release was formed on the support, the drug delivery profile was completely changed, as shown in Figure 6. There were 1, 2, 3, or 4 orifices in the 3D printed carriers. The location and the number of the pores were customized in the CAD design, so the indirect effect of the CAD modifications could have been inspected. The PLA is water-insoluble, so erosion of the body does not affect drug release. This case is clearly controllable by the number of carrier orifices, both the total amount of liberated riboflavin and the rate of drug release.

The results of the model-dependent evaluation of the dissolution profiles are shown in the third table. The correlations during the fits are between 0.9925 and 0.9999, so they are considered adequate. The kinetic evaluation of the dissolution profiles (Table 3) of riboflavin loaded PLA-based carrier system also show that increasing the number of orifices in the carrier accelerated the dissolution and also increased the maximum amount of drug released, i.e., the infinite value of M increased.

**Figure 6.** Drug release profile of riboflavin loaded PLA and PVA carriers printed containing various number of orifices (zero—cross; one—triangle; two—circle; three—square; four—diamond; n = 3; mean ± SD) with fitted Weibull (dotted lines).

In the instance of the PVA carrier, not only do the orifices play an important role in drug release, but also erosion and deformation of the printed object. This is demonstrated by the fact that the dissolution profile of drug loaded PVA-based systems differs from the PLA-based system. Erosion of PVA is slower in time than the dissolution of riboflavin (Biopharmaceutics Classification System I), so here the PVA carrier can slow drug release. In contrast to the drug loaded PLA carrier, the presence of only one orifice in this system meant almost 100% drug release, since, as our previous studies show, the skeleton was completely dissolved in the first hours of dissolution. As the number of orifices increased, as expected, the *τ<sup>d</sup>* value decreased. It is also important to note that the maximum amount of drug released in the case of PLA printlets is obtained in a shorter time, which is also shown by the low tau values according to the Weibull model; however, due to the rigid, water-insoluble wall, drug occlusion occurs. In the case of PVA carriers, the maximum

amount of active ingredient available is higher; there is no such occlusion, but the value of tau is higher compared to PLA, which is probably because the wall material forms a gel not only towards the release medium but also towards the cavity.

**Table 3.** Kinetic parameters of dissolution estimated according to Weibull distribution function (pH = 1.2).

