TY - JOUR

T1 - The evaluation of physical properties of injection molded systems based on poly(ethylene oxide) (PEO)

AU - Pajander, Jari

AU - Rensonnet, Alexia

AU - Hietala, Sami

AU - Rantanen, Jukka

AU - Baldursdottir, Stefania

N1 - Copyright © 2016 Elsevier B.V. All rights reserved.

PY - 2017/2/25

Y1 - 2017/2/25

N2 - The effect of product design parameters on the formation and properties of an injection molded solid dosage form consisting of poly(ethylene oxide)s (PEO) and two different active pharmaceutical ingredients (APIs) was studied. The product design parameters explored were melting temperature and the duration of melting, API loading degree and the molecular weight (Mw) of PEO. The solid form composition of the model APIs, theophylline and carbamazepine, was of specific interest, and its possible impact on the in vitro drug release behavior. Mw of PEO had the greatest impact on the release rate of both APIs. High Mw resulted in slower API release rate. Process temperature had two-fold effect with PEO 300,000g/mol. Firstly, higher process temperature transformed the crystalline part of the polymer into metastable folded form (more folded crystalline regions) and less into the more stable extended form (more extended crystalline regions), which lead to enhanced theophylline release rate. Secondly, the higher process temperature seemed to induce carbamazepine polymorphic transformation from p-monoclinic form III (carbamazepine (M)) into trigonal form II (carbamazepine (T)). The results indicated that the actual content of carbamazepine (T) affected drug release behavior more than the magnitude of transformation.

AB - The effect of product design parameters on the formation and properties of an injection molded solid dosage form consisting of poly(ethylene oxide)s (PEO) and two different active pharmaceutical ingredients (APIs) was studied. The product design parameters explored were melting temperature and the duration of melting, API loading degree and the molecular weight (Mw) of PEO. The solid form composition of the model APIs, theophylline and carbamazepine, was of specific interest, and its possible impact on the in vitro drug release behavior. Mw of PEO had the greatest impact on the release rate of both APIs. High Mw resulted in slower API release rate. Process temperature had two-fold effect with PEO 300,000g/mol. Firstly, higher process temperature transformed the crystalline part of the polymer into metastable folded form (more folded crystalline regions) and less into the more stable extended form (more extended crystalline regions), which lead to enhanced theophylline release rate. Secondly, the higher process temperature seemed to induce carbamazepine polymorphic transformation from p-monoclinic form III (carbamazepine (M)) into trigonal form II (carbamazepine (T)). The results indicated that the actual content of carbamazepine (T) affected drug release behavior more than the magnitude of transformation.

KW - Calorimetry, Differential Scanning

KW - Carbamazepine

KW - Chromatography, Gel

KW - Drug Compounding

KW - Drug Liberation

KW - Polyethylene Glycols

KW - Powder Diffraction

KW - Spectroscopy, Fourier Transform Infrared

KW - Theophylline

KW - X-Ray Diffraction

KW - Journal Article

U2 - 10.1016/j.ijpharm.2016.12.050

DO - 10.1016/j.ijpharm.2016.12.050

M3 - Journal article

C2 - 28025074

VL - 518

SP - 203

EP - 212

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1-2

ER -