Differential Scanning Calorimetry

Results and Discussion 66 The impact of the smaller diameter, and therefore more demanding conditions during extrusion are observable in the lower diagram of Figure 35. Dominating were a high intensity peak at 6° and a broadened peak with likewise high intensity at 10° in range of the complex. A differentiation between PEG and MLC was not possible anymore. The increased peak intensity could be attributed to the formation of crystalline regions. The higher shear rate, elevated temperature and pressure, which are caused by the extrusion with a 300 µm nozzle, could be responsible for amplifying crystallization (146).

For comprehensive conclusions the XRPD-data alone would not suffice. But in combination with the subsequent DSC analysis, more precise statements could be generated.

Results and Discussion 67 mixture and the MLC support the formation of the complex, especially in combination with the XRPD data. The broad peak in the MLC thermograms suggests an intermediate state of an amorphous complex with crystalline parts.

Figure 36: DSC-thermograms of the MLC compounds, their physical mixture and the MLC in a temperature range of 0 - 200 °C; Heat rate: 5 K min-1

The thermograms of the PEG-PLGA polymers, the MLC and their extrudates are presented in Figure 37. Due to its higher molecular weight, the TG of PEG-PLGA7P at 37.0 °C lay above the TG of PEG-PLGA6P at 25.6 °C. The TG of the PEG-PLGA6P-MLC extrudate was elevated to approximately 37.3 °C through the addition of the MLC. Also, a reduction and broadening of the glass transition step height was observed for PEG-PLGA6P. A second glass transition at 69 °C indicated a not completely homogeneous composition, even though the absence of the broad minocycline melting point hints towards a compatibility of both components. The subsequent thermal event up to 80 °C could have originated from undissolved magnesium stearate within the polymer matrix.

In the case of the PEG-PLGA7P-MLC extrudate, a novel melting point at 40 °C was observable, which is accompanied by the glass transition of the PEG-PLGA7P. Additionally, three broad melting points occurred in the range of 45 to 80 °C, leaving the impression of an incompatible mixture, in contrast to the XRPD-data.

Combining the results of both analytical procedures, the complex is likely to be mainly present in form of a solid solution inside the PEG-PLGA6P-MLC extrudates. As

0 25 50 75 100 125 150 175 200

MLC Physical Mixture Magnesium stearate

Endo the rmic He atf low [m W]

Temperature T [°C]

Minocycline

Results and Discussion 68 mentioned beforehand, the XRPD-data could suggest a similar situation for PEG-PLGA7P, but the DSC-data confirms the macroscopic noticeable deficits.

Figure 37: DSC-thermograms of different PEG-PLGA-MLC extrudates and their basic compounds in a temperature range from 0 to 100 °C; Heat rate: 5 K min^-1

Figure 38 illustrates the influence of PEG 1500 and the impact of the reduced diameter.

It has to be noted that the thermogram of PEG 1500 has been scaled down. The reason therefore is the high intensity melting peak of PEG 1500 at 50 °C. A depiction with a shared scaling would result in indeterminable peaks, due to their comparably low intensity.

The thermograms revealed a not completely homogeneous state inside the PEG-PLGA6P-MLC extrudates, when paired with PEG. The addition of PEG created novel peaks in the range of 55 °C to 60 °C and around 80 °C. Notably, a content of 5% PEG led to peaks with greater intensity compared to the PEG-PLGA6P-MLC extrudates with 10% PEG. The intensification could imply the presence of more crystalline regions compared to the extrudates with 10% PEG content. Contrary, the findings of the XRPD-data exhibited reversed results (4.7.2). There, hints for a higher crystalline partition within the 10% PEG containing extrudates were recorded. The higher PEG content may have resulted in a more efficient filling of the interstitial space between the PEG-PLGA-polymer chains. This could explain the less prominent thermal events in the thermogram of the 10% PEG extrudates and would also give account of their enduring flexibility in contrast to their 5% PEG counterparts. It is also possible, that the

0 20 40 60 80 100

Extrudate PEG-PLGA_7P Extrudate PEG-PLGA_6P

PEG-PLGA_7P PEG-PLGA_6P

Magnesium stearate MLC

Endothermic Heat Flow [mW]

Temperature T [°C]

Results and Discussion 69 lipophilic complex hinders the implementation of lower concentrations of a hydrophilic plasticizer. Regarding the formation of a higher crystalline share inside the PEG containing extrudates, these systems should be addressed as solid dispersions.

The increased mechanic and thermal stress during the extrusion of the 300 µm extrudates, was also noticeable during the DSC analysis. The recorded peaks at 60 °C and 80 °C were more distinct compared to their 600 µm relatives. So, their thermogram resembles an intermediate of the just discussed 600 µm extrudates with 5% and 10% PEG. In consideration with the broad high intensity peaks of the XRPD-analysis, these 300 µm extrudates equally qualify as solid dispersions.

Figure 38: DSC-thermograms of PEG-PLGA6P-MLC extrudates combined with PEG 1500 and varying diameters (300 and 600 µm)

Thus, if XRPD and DSC analysis are unitedly applied, they can offer an in-depth representation of the situation within solid systems. For the extrudates, different solid states were observable depending on their composition and on the applied extrusion parameters. Hence, these values could serve as quality markers for the further development. Also, valuable data concerning the MLC was gathered, which complements the characterization of the complex in chapter 4.2.