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A quality-by-design study for an immediate-release tablet platform: examining the relative impact of active pharmaceutical ingredient properties, processing methods, and excipient variability on drug product quality attributes.
J Pharm Sci. 2014 Feb; 103(2):527-38.JP

Abstract

The impact of filler-lubricant particle size ratio variation (3.4-41.6) on the attributes of an immediate-release tablet was compared with the impacts of the manufacturing method used (direct compression or dry granulation) and drug loading (1%, 5%, and 25%), particle size (D[4,3]: 8-114 μm), and drug type (theophylline or ibuprofen). All batches were successfully manufactured, except for direct compression of 25% drug loading of 8 μm (D[4,3]) drug, which exhibited very poor flow properties. All manufactured tablets possessed adequate quality attributes: tablet weight uniformity <4% RSD, tablet potency: 94%-105%, content uniformity <6% RSD, acceptance value ≤ 15, solid fraction: 0.82-0.86, tensile strength >1 MPa, friability ≤ 0.2% weight loss, and disintegration time < 4 min. The filler-lubricant particle size ratio exhibited the greatest impact on blend and granulation particle size and granulation flow, whereas drug property variation dominated blend flow, ribbon solid fraction, and tablet quality attributes. Although statistically significant effects were observed, the results of this study suggest that the manufacturability and performance of this immediate-release tablet formulation is robust to a broad range of variation in drug properties, both within-grade and extra-grade excipient particle size variations, and the choice of manufacturing method.

Authors+Show Affiliations

Pfizer Worldwide Research and Development, Groton, Connecticut, 06340.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24375069

Citation

Kushner, Joseph, et al. "A Quality-by-design Study for an Immediate-release Tablet Platform: Examining the Relative Impact of Active Pharmaceutical Ingredient Properties, Processing Methods, and Excipient Variability On Drug Product Quality Attributes." Journal of Pharmaceutical Sciences, vol. 103, no. 2, 2014, pp. 527-38.
Kushner J, Langdon BA, Hicks I, et al. A quality-by-design study for an immediate-release tablet platform: examining the relative impact of active pharmaceutical ingredient properties, processing methods, and excipient variability on drug product quality attributes. J Pharm Sci. 2014;103(2):527-38.
Kushner, J., Langdon, B. A., Hicks, I., Song, D., Li, F., Kathiria, L., Kane, A., Ranade, G., & Agarwal, K. (2014). A quality-by-design study for an immediate-release tablet platform: examining the relative impact of active pharmaceutical ingredient properties, processing methods, and excipient variability on drug product quality attributes. Journal of Pharmaceutical Sciences, 103(2), 527-38. https://doi.org/10.1002/jps.23810
Kushner J, et al. A Quality-by-design Study for an Immediate-release Tablet Platform: Examining the Relative Impact of Active Pharmaceutical Ingredient Properties, Processing Methods, and Excipient Variability On Drug Product Quality Attributes. J Pharm Sci. 2014;103(2):527-38. PubMed PMID: 24375069.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A quality-by-design study for an immediate-release tablet platform: examining the relative impact of active pharmaceutical ingredient properties, processing methods, and excipient variability on drug product quality attributes. AU - Kushner,Joseph, AU - Langdon,Beth A, AU - Hicks,Ian, AU - Song,Daniel, AU - Li,Fasheng, AU - Kathiria,Lalji, AU - Kane,Anil, AU - Ranade,Gautam, AU - Agarwal,Kam, Y1 - 2013/12/20/ PY - 2013/05/31/received PY - 2013/10/22/revised PY - 2013/10/29/accepted PY - 2013/12/31/entrez PY - 2014/1/1/pubmed PY - 2014/11/6/medline KW - content uniformity KW - excipients KW - factorial design KW - formulation KW - hardness KW - oral drug delivery KW - quality by design (QBD) KW - solid dosage form KW - tableting SP - 527 EP - 38 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 103 IS - 2 N2 - The impact of filler-lubricant particle size ratio variation (3.4-41.6) on the attributes of an immediate-release tablet was compared with the impacts of the manufacturing method used (direct compression or dry granulation) and drug loading (1%, 5%, and 25%), particle size (D[4,3]: 8-114 μm), and drug type (theophylline or ibuprofen). All batches were successfully manufactured, except for direct compression of 25% drug loading of 8 μm (D[4,3]) drug, which exhibited very poor flow properties. All manufactured tablets possessed adequate quality attributes: tablet weight uniformity <4% RSD, tablet potency: 94%-105%, content uniformity <6% RSD, acceptance value ≤ 15, solid fraction: 0.82-0.86, tensile strength >1 MPa, friability ≤ 0.2% weight loss, and disintegration time < 4 min. The filler-lubricant particle size ratio exhibited the greatest impact on blend and granulation particle size and granulation flow, whereas drug property variation dominated blend flow, ribbon solid fraction, and tablet quality attributes. Although statistically significant effects were observed, the results of this study suggest that the manufacturability and performance of this immediate-release tablet formulation is robust to a broad range of variation in drug properties, both within-grade and extra-grade excipient particle size variations, and the choice of manufacturing method. SN - 1520-6017 UR - https://www.unboundmedicine.com/medline/citation/24375069/A_quality_by_design_study_for_an_immediate_release_tablet_platform:_examining_the_relative_impact_of_active_pharmaceutical_ingredient_properties_processing_methods_and_excipient_variability_on_drug_product_quality_attributes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(15)30707-3 DB - PRIME DP - Unbound Medicine ER -