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Dissolution enhancement of carbamazepine using twin-screw melt granulation.
Eur J Pharm Biopharm. 2020 Mar; 148:77-87.EJ

Abstract

The current study explored the twin-screw melt granulation (TSMG) as a potential technology for the water solubility enhancement of biopharmaceutical classification system (BCS) class II drugs. As a model drug, carbamazepine (CBZ) was formulated with three different polymers as melt granules produced in a co-rotating twin-screw granulator. Polyethylene glycol 6000 (PEG 6000) and Kolliphor® (poloxamer) P407 were used as binding materials at two different granulation temperatures (Tmax: 70 °C; 100 °C). Additionally, Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) was chosen as binder of higher melting/ granulation temperature (Tmax: 140 °C). Temperature dependent polymorphic transition of CBZ during melt granulation was observed and identified using XRPD- (X-ray powder diffraction) and FTIR- (Fourier transform infrared spectroscopy) analysis. The effects of polymer type, polymer content (10, 15, 20% (w/w)) and granulation temperature on polymorphic transition, their impact on wettability (contact angle via drop shape-analysis), and the resulting dissolution performance at non-sink conditions in phosphate buffer (pH 6.8), were studied. This study showed that TSMG led to a crystalline system facilitating supersaturation when brought in solution, even when high drug loads (up to 90% (w/w)) were used. In general, for all granules produced, the supersaturation level and its duration varied with the extent of polymorphic transition and binder concentration. The results of this study indicated the importance of temperature control and polymer selection for tailoring desired dissolution profiles.

Authors+Show Affiliations

Department of Pharmaceutics, University of Bonn, Germany.Department of Pharmaceutics, University of Bonn, Germany. Electronic address: karl.wagner@uni-bonn.de.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31954840

Citation

Steffens, Kristina E., and Karl G. Wagner. "Dissolution Enhancement of Carbamazepine Using Twin-screw Melt Granulation." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 148, 2020, pp. 77-87.
Steffens KE, Wagner KG. Dissolution enhancement of carbamazepine using twin-screw melt granulation. Eur J Pharm Biopharm. 2020;148:77-87.
Steffens, K. E., & Wagner, K. G. (2020). Dissolution enhancement of carbamazepine using twin-screw melt granulation. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 148, 77-87. https://doi.org/10.1016/j.ejpb.2020.01.006
Steffens KE, Wagner KG. Dissolution Enhancement of Carbamazepine Using Twin-screw Melt Granulation. Eur J Pharm Biopharm. 2020;148:77-87. PubMed PMID: 31954840.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dissolution enhancement of carbamazepine using twin-screw melt granulation. AU - Steffens,Kristina E, AU - Wagner,Karl G, Y1 - 2020/01/16/ PY - 2019/10/28/received PY - 2020/01/07/revised PY - 2020/01/13/accepted PY - 2020/1/20/pubmed PY - 2020/11/21/medline PY - 2020/1/20/entrez KW - Carbamazepine KW - Crystalline state KW - Dissolution enhancement KW - Extruder KW - Melt granulation KW - Polymer content KW - Polymorphic transition KW - Twin-screw granulator SP - 77 EP - 87 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 148 N2 - The current study explored the twin-screw melt granulation (TSMG) as a potential technology for the water solubility enhancement of biopharmaceutical classification system (BCS) class II drugs. As a model drug, carbamazepine (CBZ) was formulated with three different polymers as melt granules produced in a co-rotating twin-screw granulator. Polyethylene glycol 6000 (PEG 6000) and Kolliphor® (poloxamer) P407 were used as binding materials at two different granulation temperatures (Tmax: 70 °C; 100 °C). Additionally, Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) was chosen as binder of higher melting/ granulation temperature (Tmax: 140 °C). Temperature dependent polymorphic transition of CBZ during melt granulation was observed and identified using XRPD- (X-ray powder diffraction) and FTIR- (Fourier transform infrared spectroscopy) analysis. The effects of polymer type, polymer content (10, 15, 20% (w/w)) and granulation temperature on polymorphic transition, their impact on wettability (contact angle via drop shape-analysis), and the resulting dissolution performance at non-sink conditions in phosphate buffer (pH 6.8), were studied. This study showed that TSMG led to a crystalline system facilitating supersaturation when brought in solution, even when high drug loads (up to 90% (w/w)) were used. In general, for all granules produced, the supersaturation level and its duration varied with the extent of polymorphic transition and binder concentration. The results of this study indicated the importance of temperature control and polymer selection for tailoring desired dissolution profiles. SN - 1873-3441 UR - https://www.unboundmedicine.com/medline/citation/31954840/Dissolution_enhancement_of_carbamazepine_using_twin_screw_melt_granulation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(20)30016-3 DB - PRIME DP - Unbound Medicine ER -