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The impact of the injection mold temperature upon polymer crystallization and resulting drug release from immediate and sustained release tablets.
Int J Pharm. 2018 Apr 25; 541(1-2):108-116.IJ

Abstract

It was the aim of this study to elucidate the impact of the injection mold temperature upon the polymer crystallinity, its microstructure and the resulting drug release from immediate and sustained release tablets containing semi-crystalline polymers. The immediate release formulation contained 20% (w/w) ketoprofen (KETO) in poly (ethylene oxide) (PEO) and the sustained release formulation contained 20-40% (w/w) metoprolol tartrate (MPT) in polycaprolactone (PCL). Physical mixtures of drug-polymer were characterized via isothermal crystallization experiments using DSC and rheological measurements to elucidate the impact of the drug solid-state upon the crystallization kinetics. Tablets were prepared using various thermal histories (extrusion barrel temperature and injection mold temperatures). Polymer crystallinity and microstructure in the tablets was characterized via DSC and polarized optical microscopy. The polymer microstructure was altered by the various applied thermal histories. The differences in PEO crystallinity induced by the various mold temperatures did not affect the KETO dissolution from the tablets. On the other hand, MPT (20-40% w/w) dissolution from the PCL matrix when extruded at 80 °C and injection molded at 25 and 35 °C was significantly different due to the changes in the polymer microstructure. More perfect polymer crystals are obtained with higher mold temperatures, decreasing the drug diffusion rate through the PCL matrix. The results presented in this study imply that the injection mold temperature should be carefully controlled for sustained release formulations containing hydrophobic semi-crystalline polymers.

Authors+Show Affiliations

Laboratory of Pharmaceutical Process Analytical Technology, Ottergemsesteenweg 460, 9000 Ghent, Belgium. Electronic address: jeroen.vanrenterghem@ugent.be.Laboratory of Pharmaceutical Process Analytical Technology, Ottergemsesteenweg 460, 9000 Ghent, Belgium.Laboratory of Pharmaceutical Technology, Ottergemsesteenweg 460, 9000 Ghent, Belgium.Inflammation Research Center, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, 9052 Ghent, Belgium; Department of Plant Systems Biology, VIB, Ghent, Belgium; Department of Plant Biotechnology and Bioinformatics, Ghent University, 9052 Gent, Belgium.Laboratory of Pharmaceutical Technology, Ottergemsesteenweg 460, 9000 Ghent, Belgium.Laboratory of Pharmaceutical Process Analytical Technology, Ottergemsesteenweg 460, 9000 Ghent, Belgium.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29409747

Citation

Van Renterghem, Jeroen, et al. "The Impact of the Injection Mold Temperature Upon Polymer Crystallization and Resulting Drug Release From Immediate and Sustained Release Tablets." International Journal of Pharmaceutics, vol. 541, no. 1-2, 2018, pp. 108-116.
Van Renterghem J, Dhondt H, Verstraete G, et al. The impact of the injection mold temperature upon polymer crystallization and resulting drug release from immediate and sustained release tablets. Int J Pharm. 2018;541(1-2):108-116.
Van Renterghem, J., Dhondt, H., Verstraete, G., De Bruyne, M., Vervaet, C., & De Beer, T. (2018). The impact of the injection mold temperature upon polymer crystallization and resulting drug release from immediate and sustained release tablets. International Journal of Pharmaceutics, 541(1-2), 108-116. https://doi.org/10.1016/j.ijpharm.2018.01.053
Van Renterghem J, et al. The Impact of the Injection Mold Temperature Upon Polymer Crystallization and Resulting Drug Release From Immediate and Sustained Release Tablets. Int J Pharm. 2018 Apr 25;541(1-2):108-116. PubMed PMID: 29409747.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The impact of the injection mold temperature upon polymer crystallization and resulting drug release from immediate and sustained release tablets. AU - Van Renterghem,Jeroen, AU - Dhondt,Heleen, AU - Verstraete,Glenn, AU - De Bruyne,Michiel, AU - Vervaet,Chris, AU - De Beer,Thomas, Y1 - 2018/02/01/ PY - 2017/11/20/received PY - 2018/01/25/revised PY - 2018/01/30/accepted PY - 2018/2/8/pubmed PY - 2018/9/8/medline PY - 2018/2/8/entrez KW - Crystallization KW - Injection molding KW - Rheology KW - Semi-crystalline polymers KW - Solid dispersion SP - 108 EP - 116 JF - International journal of pharmaceutics JO - Int J Pharm VL - 541 IS - 1-2 N2 - It was the aim of this study to elucidate the impact of the injection mold temperature upon the polymer crystallinity, its microstructure and the resulting drug release from immediate and sustained release tablets containing semi-crystalline polymers. The immediate release formulation contained 20% (w/w) ketoprofen (KETO) in poly (ethylene oxide) (PEO) and the sustained release formulation contained 20-40% (w/w) metoprolol tartrate (MPT) in polycaprolactone (PCL). Physical mixtures of drug-polymer were characterized via isothermal crystallization experiments using DSC and rheological measurements to elucidate the impact of the drug solid-state upon the crystallization kinetics. Tablets were prepared using various thermal histories (extrusion barrel temperature and injection mold temperatures). Polymer crystallinity and microstructure in the tablets was characterized via DSC and polarized optical microscopy. The polymer microstructure was altered by the various applied thermal histories. The differences in PEO crystallinity induced by the various mold temperatures did not affect the KETO dissolution from the tablets. On the other hand, MPT (20-40% w/w) dissolution from the PCL matrix when extruded at 80 °C and injection molded at 25 and 35 °C was significantly different due to the changes in the polymer microstructure. More perfect polymer crystals are obtained with higher mold temperatures, decreasing the drug diffusion rate through the PCL matrix. The results presented in this study imply that the injection mold temperature should be carefully controlled for sustained release formulations containing hydrophobic semi-crystalline polymers. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/29409747/The_impact_of_the_injection_mold_temperature_upon_polymer_crystallization_and_resulting_drug_release_from_immediate_and_sustained_release_tablets_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(18)30073-5 DB - PRIME DP - Unbound Medicine ER -