TY - JOUR

T1 - Role of polymeric excipients in the stabilization of olanzapine when exposed to aqueous environments

AU - Paisana, Maria

AU - Wahl, Martin

AU - Pinto, João

A2 - Rades, Thomas

A2 - Grohganz, Holger

A2 - Löbmann, Korbinian

N1 - Funding Information: The Authors acknowledge "Funda??o para a Ci?ncia e a Tecnologia", Lisbon, Portugal for providing the financial support to this work (PTDC/CTM/098688/2008 and SFRH/BD/90118/2012). Publisher Copyright: © 2015 by the authors.

PY - 2015

Y1 - 2015

N2 - Hydrate formation is a phase transition which can occur during manufacturing processes involving water. This work considers the prevention of hydration of anhydrous olanzapine and hydrate conversions in the presence of water and polymers (polyethyleneglycol; hydroxypropylcellulose; polyvinylpyrrolidone) in forming pellets by wet extrusion and spheronisation. Anhydrous olanzapine was added to water with or without those polymers prior to extrusion with microcrystalline cellulose. Assessment of olanzapine conversion was made by XRP-Diffraction; FTIR spectroscopy; calorimetry (DSC) and microscopy (SEM for crystal size and shape). The addition of water converted the anhydrous form into dihydrate B and higher hydrate; whereas polyethyleneglycol promoted a selective hydrate conversion into the higher hydrate olanzapine form. Both polyvinylpyrrolidone and hydroxypropylcellulose prevented the hydrate transformations of the anhydrous drug; the latter even in the presence of hydrate seeds. This may be explained by the higher H-bond ability; higher network association and higher hydrophobicity of hydroxypropylcellulose by comparison with polyethyleneglycol and polyvinylpyrrolidone; which could contribute to its higher affinity to the crystal surfaces of the hydrate nuclei/initial crystals and promoting steric hindrance to the incorporation of other drug molecules into the crystal lattice; thus, preventing the crystal growth. The addition of microcrystalline cellulose needed for the pellets production (final product) did not eliminate the protector effect of both hydroxypropylcellulose and polyvinylpyrrolidone during pellets' processing and dissolution evaluation.

AB - Hydrate formation is a phase transition which can occur during manufacturing processes involving water. This work considers the prevention of hydration of anhydrous olanzapine and hydrate conversions in the presence of water and polymers (polyethyleneglycol; hydroxypropylcellulose; polyvinylpyrrolidone) in forming pellets by wet extrusion and spheronisation. Anhydrous olanzapine was added to water with or without those polymers prior to extrusion with microcrystalline cellulose. Assessment of olanzapine conversion was made by XRP-Diffraction; FTIR spectroscopy; calorimetry (DSC) and microscopy (SEM for crystal size and shape). The addition of water converted the anhydrous form into dihydrate B and higher hydrate; whereas polyethyleneglycol promoted a selective hydrate conversion into the higher hydrate olanzapine form. Both polyvinylpyrrolidone and hydroxypropylcellulose prevented the hydrate transformations of the anhydrous drug; the latter even in the presence of hydrate seeds. This may be explained by the higher H-bond ability; higher network association and higher hydrophobicity of hydroxypropylcellulose by comparison with polyethyleneglycol and polyvinylpyrrolidone; which could contribute to its higher affinity to the crystal surfaces of the hydrate nuclei/initial crystals and promoting steric hindrance to the incorporation of other drug molecules into the crystal lattice; thus, preventing the crystal growth. The addition of microcrystalline cellulose needed for the pellets production (final product) did not eliminate the protector effect of both hydroxypropylcellulose and polyvinylpyrrolidone during pellets' processing and dissolution evaluation.

KW - Anhydrous

KW - Extrusion

KW - Hydrate

KW - Hydroxypropylcellulose

KW - Olanzapine

KW - Pellet

KW - Polyethyleneglycol

KW - Polymorphism

KW - Polyvinylpyrrolidone

KW - Spheronisation

U2 - 10.3390/molecules201219832

DO - 10.3390/molecules201219832

M3 - Journal article

C2 - 26703534

AN - SCOPUS:84954356936

VL - 20

SP - 22634

EP - 223282

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 12

M1 - 200649

ER -