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Assessment of Intragranular and Extragranular Fracture in the Development of Tablet Tensile Strength.
Mitra, Biplob; Hilden, Jon; Litster, James.
Affiliation
  • Mitra B; Drug Product Development, Celgene Corporation, Summit, New Jersey 07901; Small Molecule Design and Development, Eli Lilly and Co., Indianapolis, Indiana 46285; Department of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana 47907. Electronic address: bmitra@celgene.com.
  • Hilden J; Small Molecule Design and Development, Eli Lilly and Co., Indianapolis, Indiana 46285; School of Materials Engineering, Purdue University, West Lafayette, Indiana 47907.
  • Litster J; Department of Chemical and Biological Engineering, University of Sheffield, Sheffield, UK; School of Chemical Engineering, Purdue University, West Lafayette, Indiana 47907.
J Pharm Sci ; 107(10): 2581-2591, 2018 10.
Article in En | MEDLINE | ID: mdl-29803616
ABSTRACT
When a tablet is compacted from deformable granules and then broken, the fracture plane may cleave granules in 2 (intragranular fracture) or separate neighboring granules (extragranular fracture). In this study, a novel method was developed to quantify the extent of intragranular versus extragranular fracture by compacting tablets from multicolored ideal granules and evaluating fracture surfaces. The proportions of intragranular and extragranular fracture were quantified and modeled in light of a new metric; the deformation potential, Δ, reflecting the solid fraction increase as an initial granule bed is compressed into a final tablet. Results show that a measurable tablet strength is achieved at Δ > 0.18, but intragranular fracture is not observed until Δ > 0.21. At very large Δ, tablets experience almost exclusively intragranular fracture, yet the tablet tensile strength is considerably lower than that of a tablet compacted from raw powders versus precompacted granules. Thus, secondary compaction of granules appears to weaken the granule matrix, leading to reduced tablet tensile strength even in the presence of strong extragranular bonding.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Powders / Tablets Language: En Journal: J Pharm Sci Year: 2018 Document type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Powders / Tablets Language: En Journal: J Pharm Sci Year: 2018 Document type: Article