An Insight Into the Impact of Polymers on the Hydrate Conversion of Olanzapine Form I in Aqueous Suspensions.
The potential of polyethyleneglycol (PEG), polyvinylpyrrolidone (PVP), and hydroxypropylcellulose (HPC) to inhibit the hydration of olanzapine (OLZ) in aqueous environments was assessed. OLZ Form I (OLZ) suspended in water (A) or in aqueous polymer solutions (2%, 0.2%, 0.02%, and 0.002%) (PEG 6000 [B], PEG 40,000 [C], HPC LF [D], or PVP K30 [E]). Filtered samples were analyzed by different techniques (X-ray powder diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry,1H-nuclear magnetic resonance spectroscopy). OLZ hydration showed to be faster in water than in PEG solutions, regardless of the polymer molecular weight. OLZ in D and E suspensions remained anhydrous at concentrations of 2%-0.02%. The NMR measurements revealed that all of these polymers were able to establish hydrogen bonds with the OLZ molecule and increased its saturation solubility, but only D and E showed to increase the wettability of the OLZ particles due to binding of these polymers to the surface of hydrate nuclei/first crystals OLZ crystals. This study provided an insight into the mechanisms of OLZ hydrate protection by polymers. It confirmed the advantage of using PVP K30 or HPC LF in wet granulation in concentrations as low as 0.02% to prevent formation of OLZ hydrates, due to the combined effect of H-bond ability and the strong bonding of these polymers to the surface of the crystals.
iMed.ULisboa -Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, P-1649-003 Lisboa, Portugal.
Maria C
MC
Paisana
Pharmazeutisches Institut, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, D-72076 Tübingen, Germany.
Martin A
MA
Wahl
iMed.ULisboa -Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, P-1649-003 Lisboa, Portugal. Electronic address: jfpinto@ff.ul.pt.
João F
JF
Pinto
D000932:Antiemetics / Q000737:chemistry*; D001569:Benzodiazepines / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D003460:Crystallization; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D000077152:Olanzapine; D011092:Polyethylene Glycols / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water / Q000737:chemistry*
D000932:Antiemetics; D005079:Excipients; D014867:Water; D001569:Benzodiazepines; D011092:Polyethylene Glycols; D002482:Cellulose; C008079:hydroxypropylcellulose; D011205:Povidone; D000077152:Olanzapine
FTIR; NMR; amorphous; calorimetry (DSC); granulation; hydration; physical stability; polymorphism; solid state; water in solids