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Binder-free twin-screw melt granulation: An effective approach to manufacture high-dose API formulations.
Int J Pharm. 2021 Sep 05; 606:120886.IJ

Abstract

This study investigates the use of twin-screw binder-free melt granulation (BFMG) in the development of high-dose solid dose formulations for low melting point thermally stable drugs. Both ibuprofen and guaifenesin are examined. By granulating pure API powder, it is shown that BFMG can successfully be used to produce granules that contain 100% API. A design of experiments (DoE) response surface methodology was used to establish the design space for the end-product. The effects of the most relevant process variables (barrel operating temperature, powder feed rate, screw speed and screw configuration) on granule properties (outlet temperature, size distribution, morphology, flowability, compressibility, porosity) and tablet attributes (tensile strength and in-vitro dissolution) were thoroughly studied. Barrel temperature (alone or in interactions with the other variables) represented the most significant variable for both drugs since it governs the formation of granules by partial melting and subsequent agglomeration of the fed powder. Interestingly, the shear action originated by screw speed and screw configuration resulted in various significant responses depending on the drug substance, indicating that it can also be affected by the nature of the processed molecule. Flow properties were improved (i.e., lower Hausner ratio) for both drugs after formation of granules. Tabletability was also tested by preparing 600 mg tablets for all samples. Surprisingly, the resulting granules were highly compactible, requiring only 1% lubricant to form strong tablets containing 96% API and 3% disintegrant. The results also showed that tablets become harder as the granule size increased, especially for guaifenesin. As expected, in-vitro dissolution results indicated that tablets and capsules showed slightly slower dissolution rates than the granules.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Cotabarren I
C-SOPS, Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, 98 Brett Road, Piscataway, NJ 08854, USA; Departamento de Ingeniería Química (DIQ) - Universidad Nacional del Sur (UNS) and Planta Piloto de Ingeniería Química (PLAPIQUI, UNS-CONICET) Bahía Blanca, Buenos Aires, Argentina.
Omar TA
C-SOPS, Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, 98 Brett Road, Piscataway, NJ 08854, USA; College of Pharmacy, University of Mosul, Mosul 41002, Iraq.
Muzzio FJ
C-SOPS, Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, 98 Brett Road, Piscataway, NJ 08854, USA. Electronic address: fjmuzzio@yahoo.com.

MeSH

Drug CompoundingExcipientsParticle SizePowdersTabletsTechnology, Pharmaceutical

Pub Type(s)

Journal Article

Language

eng

PubMed ID

34298107

Citation

Cotabarren, Ivana, et al. "Binder-free Twin-screw Melt Granulation: an Effective Approach to Manufacture High-dose API Formulations." International Journal of Pharmaceutics, vol. 606, 2021, p. 120886.
Cotabarren I, Omar TA, Muzzio FJ. Binder-free twin-screw melt granulation: An effective approach to manufacture high-dose API formulations. Int J Pharm. 2021;606:120886.
Cotabarren, I., Omar, T. A., & Muzzio, F. J. (2021). Binder-free twin-screw melt granulation: An effective approach to manufacture high-dose API formulations. International Journal of Pharmaceutics, 606, 120886. https://doi.org/10.1016/j.ijpharm.2021.120886
Cotabarren I, Omar TA, Muzzio FJ. Binder-free Twin-screw Melt Granulation: an Effective Approach to Manufacture High-dose API Formulations. Int J Pharm. 2021 Sep 5;606:120886. PubMed PMID: 34298107.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Binder-free twin-screw melt granulation: An effective approach to manufacture high-dose API formulations. AU - Cotabarren,Ivana, AU - Omar,Thamer A, AU - Muzzio,Fernando J, Y1 - 2021/07/21/ PY - 2021/04/09/received PY - 2021/06/28/revised PY - 2021/07/11/accepted PY - 2021/7/24/pubmed PY - 2021/9/8/medline PY - 2021/7/23/entrez KW - Binder free granulation KW - High-dose formulations KW - Melt granulation KW - Solid dosage forms KW - Twin screw granulator SP - 120886 EP - 120886 JF - International journal of pharmaceutics JO - Int J Pharm VL - 606 N2 - This study investigates the use of twin-screw binder-free melt granulation (BFMG) in the development of high-dose solid dose formulations for low melting point thermally stable drugs. Both ibuprofen and guaifenesin are examined. By granulating pure API powder, it is shown that BFMG can successfully be used to produce granules that contain 100% API. A design of experiments (DoE) response surface methodology was used to establish the design space for the end-product. The effects of the most relevant process variables (barrel operating temperature, powder feed rate, screw speed and screw configuration) on granule properties (outlet temperature, size distribution, morphology, flowability, compressibility, porosity) and tablet attributes (tensile strength and in-vitro dissolution) were thoroughly studied. Barrel temperature (alone or in interactions with the other variables) represented the most significant variable for both drugs since it governs the formation of granules by partial melting and subsequent agglomeration of the fed powder. Interestingly, the shear action originated by screw speed and screw configuration resulted in various significant responses depending on the drug substance, indicating that it can also be affected by the nature of the processed molecule. Flow properties were improved (i.e., lower Hausner ratio) for both drugs after formation of granules. Tabletability was also tested by preparing 600 mg tablets for all samples. Surprisingly, the resulting granules were highly compactible, requiring only 1% lubricant to form strong tablets containing 96% API and 3% disintegrant. The results also showed that tablets become harder as the granule size increased, especially for guaifenesin. As expected, in-vitro dissolution results indicated that tablets and capsules showed slightly slower dissolution rates than the granules. SN - 1873-3476 UR - https://www.unboundmedicine.com/medline/citation/34298107/Binder_free_twin_screw_melt_granulation:_An_effective_approach_to_manufacture_high_dose_API_formulations_ DB - PRIME DP - Unbound Medicine ER -