The influence of drug physical state on the dissolution enhancement of solid dispersions prepared via hot-melt extrusion: a case study using olanzapine.
In this study, we examine the relationship between the physical structure and dissolution behavior of olanzapine (OLZ) prepared via hot-melt extrusion in three polymers [polyvinylpyrrolidone (PVP) K30, polyvinylpyrrolidone-co-vinyl acetate (PVPVA) 6:4, and Soluplus® (SLP)]. In particular, we examine whether full amorphicity is necessary to achieve a favorable dissolution profile. Drug–polymer miscibility was estimated using melting point depression and Hansen solubility parameters. Solid dispersions were characterized using differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy. All the polymers were found to be miscible with OLZ in a decreasing order of PVP>PVPVA>SLP. At a lower extrusion temperature (160°C), PVP generated fully amorphous dispersions with OLZ, whereas the formulations with PVPVA and SLP contained 14%-16% crystalline OLZ. Increasing the extrusion temperature to 180°C allowed the preparation of fully amorphous systems with PVPVA and SLP. Despite these differences, the dissolution rates of these preparations were comparable, with PVP showing a lower release rate despite being fully amorphous. These findings suggested that, at least in the particular case of OLZ, the absence of crystalline material may not be critical to the dissolution performance. We suggest alternative key factors determining dissolution, particularly the dissolution behavior of the polymers themselves.
Maria Fátima
MF
Pina
Min
M
Zhao
João F
JF
Pinto
João J
JJ
Sousa
Duncan Q M
DQ
Craig
D014150:Antipsychotic Agents / Q000737:chemistry*; D001569:Benzodiazepines / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D006358:Hot Temperature; D000077152:Olanzapine; D011092:Polyethylene Glycols / Q000737:chemistry*; D011145:Polyvinyls / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D012995:Solubility; D044366:Transition Temperature; D014753:Vinyl Compounds / Q000737:chemistry*; D014961:X-Ray Diffraction
D014150:Antipsychotic Agents; D005079:Excipients; D011145:Polyvinyls; D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D001569:Benzodiazepines; D011092:Polyethylene Glycols; D011205:Povidone; D000077152:Olanzapine