Ionization states in the microenvironment of solid dosage forms: Effect of formulation variables and processing

Ramprakash Govindarajan, Andrey Zinchuk, Bruno Hancock, Evgenyi Shalaev, Raj Suryanarayanan

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Purpose. Evaluation of the effect of formulation composition and processing variables on the microenvironment in solid dosage forms, based on ionization of indicator probes. Materials and Methods. Sulfonephthalein indicators were intimately mixed with individual excipients, binary excipient mixtures or multi-component blends by the solvent deposition method. Diffuse reflectance visible spectroscopy of these solids provided a measure of indicator ionization extent. Indicator solution studies yielded equations relating solution pH to the ratio of the absorbance signals of the ionized to that of the unionized form, for each indicator. These equations and the spectral data of the indicator-treated solids were used to calculate an acidity function, 'pH eq' for the solids. The ionization of incorporated probes was also monitored during various stages of simulated pharmaceutical processing viz. wet and dry mixing. Results. The pHeq provided a measure of the physicochemical environment experienced by the probe in the solid. The surface nature of formulation components and their surface area available for interaction influenced the overall properties of the final blend. The extent of probe ionization varied at different stages of a simulated wet mixing-drying process. The pH of the excipient suspension was not a good predictor of the probe ionization in the final dried solid. Indicator ionization is expected to be influenced by the microenvironmental acidity, polarity and ionic strength. Individual excipient properties contributed to the overall microenvironment in powder mixtures even when dry mixed at low water contents. Conclusions. The environment experienced by a drug in the final solid dosage form will be influenced by the nature of the excipients, the extent of their surfaces available for interaction, surface modification during processing and the amount and nature of solvent used.

Original languageEnglish (US)
Pages (from-to)2454-2468
Number of pages15
JournalPharmaceutical research
Volume23
Issue number10
DOIs
StatePublished - Oct 2006

Bibliographical note

Funding Information:
The authors wish to thank Pfizer Global R&D for financial support and the anonymous reviewers for their insightful comments which helped to improve the manuscript.

Keywords

  • Diffuse reflectance spectroscopy
  • Excipients
  • Microenvironmental acidity
  • Processing
  • Solid dosage forms
  • Sulfonephthalein indicators
  • Surface acidity

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