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Simplified formulations with high drug loads for continuous twin-screw granulation.
Int J Pharm. 2015 Dec 30; 496(1):12-23.IJ

Abstract

As different batches of the same excipients will be intermixed during continuous processes, the traceability of batches is complicated. Simplified formulations may help to reduce problems related to batch intermixing and traceability. Twin-screw granulation with subsequent tableting was used to produce granules and tablets, containing drug, disintegrant and binder (binary and ternary mixtures), only. Drug loads up to 90% were achieved and five different disintegrants were screened for keeping their disintegration suitability after wetting. Granule size distributions were consistently mono-modal and narrow. Granule strength reached higher values, using ternary mixtures. Tablets containing croscarmellose-Na as disintegrant displayed tensile strengths up to 3.1MPa and disintegration times from 400 to 466s, resulting in the most robust disintegrant. Dissolution was overall complete and above 96% within 30 min. Na-starch glycolate offers tensile strengths up to 2.8MPa at disintegration times from 25s to 1031s, providing the broadest application window, as it corresponds in some parts to different definitions of orodispersible tablets. Tablets containing micronized crospovidone are not suitable for immediate release, but showed possibilities to produce highly drug loaded, prolonged release tablets. Tablets and granules from simplified formulations offer great opportunities to improve continuous processes, present performances comparable to more complicated formulations and are able to correspond to requirements of the authorities.

Authors+Show Affiliations

Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Universitaetsstr. 1, 40225 Duesseldorf, Germany. Electronic address: Robin.Meier@hhu.de.Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Universitaetsstr. 1, 40225 Duesseldorf, Germany; Faculty of Bio- and Chemical Engineering, Technical University Dortmund, Emil-Figge-Str. 68, 44227 Dortmund, Germany. Electronic address: Markus.Thommes@bci.tu-dortmund.de.Novartis AG, 4002 Basel, Switzerland. Electronic address: Norbert.Rasenack@novartis.com.Novartis AG, 4002 Basel, Switzerland. Electronic address: Markus.Krumme@novartis.com.Novartis AG, 4002 Basel, Switzerland. Electronic address: Klaus-Peter.Moll@novartis.com.Institute of Pharmaceutics and Biopharmaceutics, Heinrich-Heine-University, Universitaetsstr. 1, 40225 Duesseldorf, Germany. Electronic address: Kleinebudde@hhu.de.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26024821

Citation

Meier, R, et al. "Simplified Formulations With High Drug Loads for Continuous Twin-screw Granulation." International Journal of Pharmaceutics, vol. 496, no. 1, 2015, pp. 12-23.
Meier R, Thommes M, Rasenack N, et al. Simplified formulations with high drug loads for continuous twin-screw granulation. Int J Pharm. 2015;496(1):12-23.
Meier, R., Thommes, M., Rasenack, N., Krumme, M., Moll, K. P., & Kleinebudde, P. (2015). Simplified formulations with high drug loads for continuous twin-screw granulation. International Journal of Pharmaceutics, 496(1), 12-23. https://doi.org/10.1016/j.ijpharm.2015.05.060
Meier R, et al. Simplified Formulations With High Drug Loads for Continuous Twin-screw Granulation. Int J Pharm. 2015 Dec 30;496(1):12-23. PubMed PMID: 26024821.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Simplified formulations with high drug loads for continuous twin-screw granulation. AU - Meier,R, AU - Thommes,M, AU - Rasenack,N, AU - Krumme,M, AU - Moll,K-P, AU - Kleinebudde,P, Y1 - 2015/05/27/ PY - 2015/02/24/received PY - 2015/05/19/revised PY - 2015/05/23/accepted PY - 2015/5/31/entrez PY - 2015/5/31/pubmed PY - 2016/9/16/medline KW - Continuous processes KW - Drug load KW - Granule and tablet quality KW - Simplified formulations KW - Twin-screw granulation SP - 12 EP - 23 JF - International journal of pharmaceutics JO - Int J Pharm VL - 496 IS - 1 N2 - As different batches of the same excipients will be intermixed during continuous processes, the traceability of batches is complicated. Simplified formulations may help to reduce problems related to batch intermixing and traceability. Twin-screw granulation with subsequent tableting was used to produce granules and tablets, containing drug, disintegrant and binder (binary and ternary mixtures), only. Drug loads up to 90% were achieved and five different disintegrants were screened for keeping their disintegration suitability after wetting. Granule size distributions were consistently mono-modal and narrow. Granule strength reached higher values, using ternary mixtures. Tablets containing croscarmellose-Na as disintegrant displayed tensile strengths up to 3.1MPa and disintegration times from 400 to 466s, resulting in the most robust disintegrant. Dissolution was overall complete and above 96% within 30 min. Na-starch glycolate offers tensile strengths up to 2.8MPa at disintegration times from 25s to 1031s, providing the broadest application window, as it corresponds in some parts to different definitions of orodispersible tablets. Tablets containing micronized crospovidone are not suitable for immediate release, but showed possibilities to produce highly drug loaded, prolonged release tablets. Tablets and granules from simplified formulations offer great opportunities to improve continuous processes, present performances comparable to more complicated formulations and are able to correspond to requirements of the authorities. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/26024821/Simplified_formulations_with_high_drug_loads_for_continuous_twin_screw_granulation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-5173(15)00488-3 DB - PRIME DP - Unbound Medicine ER -