Impact of Magnesium Stearate Presence and Variability on Drug Apparent Solubility Based on Drug Physicochemical Properties

P. Zarmpi, T. Flanagan, E. Meehan, J. Mann, Nikoletta Fotaki

Research output: Contribution to journalArticlepeer-review

17 Citations (SciVal)


Excipients are major components of oral solid dosage forms, and changes in their critical material attributes (excipient variability) and/or amount (excipient variation) in pharmaceutical formulations may present a challenge for product performance. Understanding the biopharmaceutical factors affecting excipient performance is recommended for the successful implementation of excipient variability on Quality by Design (QbD) approaches. The current study investigated the impact of magnesium stearate (MgSt) variability on the apparent solubility of drugs with a wide range of physicochemical properties (drug ionization, drug lipophilicity, drug aqueous solubility). Compendial and biorelevant media were used to assess the role of gastrointestinal (GI) conditions on the excipient effects on drug apparent solubility. The lipophilic nature of MgSt decreased the apparent solubility of most compounds. The reduction in drug apparent solubility was more pronounced for highly soluble and/or highly ionized drugs and in presence of more highly crystalline or smaller particle size MgSt. The use of multivariate data analysis revealed the critical physicochemical and biopharmaceutical factors and the complex nature of excipient variability on the reduction in drug apparent solubility. The construction of a roadmap combining drug, excipient and medium characteristics allowed the identification of the cases where the presence of excipient or excipient variability may present risks for oral drug performance.

Original languageEnglish
Article number75
JournalAAPS Journal
Issue number4
Publication statusPublished - 21 May 2020


  • drug solubility
  • excipient variability
  • magnesium stearate
  • multivariate data analysis
  • physicochemical properties

ASJC Scopus subject areas

  • Pharmaceutical Science


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