Analysis of the origins of content non-uniformity in high-shear wet granulation

Sarang Oka, David Smrčka, Anjali Kataria, Heather Emady, Fernando Muzzio, František Štěpánek, Rohit Ramachandran

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

In this study, the origins of granule content non-uniformity in the high-shear wet granulation of a model two-component pharmaceutical blend were investigated. Using acetaminophen as the active pharmaceutical ingredient (API) and microcrystalline cellulose as the excipient, the distribution of the API across the granule size classes was measured for a range of conditions that differed in the duration of the initial dry mixing stage, the overall composition of the blend and the wet massing time. The coarse granule fractions were found to be systematically sub-potent, while the fines were enriched in the API. The extent of content non-uniformity was found to be dependent on two factors – powder segregation during dry mixing and redistribution of the API between the granule size fractions during the wet massing phase. The latter was demonstrated in an experiment where the excipient was pre-granulated, the API was added later and wet massed. The content non-uniformity in this case was comparable to that obtained when both components were present in the granulator from the beginning. With increasing wet massing time, the extent of content non-uniformity decreased, indicating that longer wet massing times might be a solution for systems with a natural tendency for component segregation.

Original languageEnglish (US)
Pages (from-to)578-585
Number of pages8
JournalInternational Journal of Pharmaceutics
Volume528
Issue number1-2
DOIs
StatePublished - Aug 7 2017

Fingerprint

Pharmaceutical Preparations
Excipients
Acetaminophen
Powders
microcrystalline cellulose

Keywords

  • Content uniformity
  • Granulation
  • Powder mixing
  • Segregation
  • Wet massing

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Analysis of the origins of content non-uniformity in high-shear wet granulation. / Oka, Sarang; Smrčka, David; Kataria, Anjali; Emady, Heather; Muzzio, Fernando; Štěpánek, František; Ramachandran, Rohit.

In: International Journal of Pharmaceutics, Vol. 528, No. 1-2, 07.08.2017, p. 578-585.

Research output: Contribution to journalArticle

Oka, S, Smrčka, D, Kataria, A, Emady, H, Muzzio, F, Štěpánek, F & Ramachandran, R 2017, 'Analysis of the origins of content non-uniformity in high-shear wet granulation', International Journal of Pharmaceutics, vol. 528, no. 1-2, pp. 578-585. https://doi.org/10.1016/j.ijpharm.2017.06.034
Oka, Sarang ; Smrčka, David ; Kataria, Anjali ; Emady, Heather ; Muzzio, Fernando ; Štěpánek, František ; Ramachandran, Rohit. / Analysis of the origins of content non-uniformity in high-shear wet granulation. In: International Journal of Pharmaceutics. 2017 ; Vol. 528, No. 1-2. pp. 578-585.
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