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Tablets & Capsules January 2016 47 polymer extrudates remained un- changed under the processing temper- atures studied. It was also observed that API-poly- mer extrudates processed at or above 160°C released more API than API- polymer extrudates processed at 140°C. This could be attributed to the API's melting point, which plays a role in API-polymer miscibility: When processed at 140°C (below its 147°C melting point), the API stays in crys- talline form, thereby limiting its release (Figure 6). Furthermore, it was observed that HPMCAS substitution level plays an important role in enhancing the solubility of felodipine, which released faster and more com- pletely from the felodipine-HPMCAS L-grade extrudates (Figure 7). This result stems from felodipine's higher lipophilicity (logP of 3.9), which makes it dissolution-rate-limited, and from the higher succinoyl content of the L-grade polymer, which offers higher hydrophilicity and thereby improves the dissolution rate. The PXRD of the felodipine-HPM- CAS extrudates showed that the API is completely amorphous for 6 months under accelerated conditions. DSC of the stability samples at 25°C/60% RH and 40°C/75% RH for 6 months showed no exothermic peaks of recrystallization. These results indicate that the API in the felodipine-HPM- CAS solid dispersion remains in the amorphous state (Figure 8). Also, the Tg of both formulations was lower at 40°C/75% RH than it was for formula- tions held at 25°C/60% RH, which indicates that moisture plays a critical role in the stability of the solid disper- sions. Figure 9 shows that the dissolu- tion profiles of the felodipine-HPM- CAS extrudates (L and M grades) Table 1 Effect of extrusion temperature on pH-solubility behavior Extruder target process temperature Extruder process condition HMPCAS type Zones (C°) Feeder speed Extruder speed Extruder load (%) Melt pressure Specific energy 1 2 3 4 5 6 7 8 Felodipine- HMPCAS LG 40 80 100 140 163 162 161 151 300 330 21 119 0.36 Felodipine- HMPCAS MG 40 80 110 140 165 160 162 150 300 330 25 30 0.23 Felodipine- HMPCAS HG 40 82 100 140 162 162 161 151 300 330 22 0 0.17 Figure 6 Effect of extrusion temperature on felodipine-HPMCAS LG Felodipine-HPMCAS LG @ 180°C Felodipine-HPMCAS LG @ 160°C Felodipine-HPMCAS LG @ 140°C Felodipine only 0 50 100 150 200 250 300 100 90 80 70 60 50 40 30 20 10 0 Felodipine release (%) Time (min) Figure 7 Effect of polymer grade on felodipine solubility enhancement 0 50 100 150 200 250 300 350 100 90 80 70 60 50 40 30 20 10 0 Felodipine release (%) Time (min) Felodipine only Felodipine-HPMCAS LG @ 160°C Felodipine-HPMCAS MG @ 160°C Felodipine-HPMCAS HG @ 160°C