Journal article
Ionization states in the microenvironment of solid dosage forms : Effect of formulation variables and processing
Pharmaceutical research, Vol.23(10), pp.2454-2468
2006
DOI: 10.1007/s11095-006-9085-3
PMID: 16933092
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 pH(eq) 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.
Details
- Title: Subtitle
- Ionization states in the microenvironment of solid dosage forms : Effect of formulation variables and processing
- Creators
- Ramprakash GOVINDARAJAN - Department of Pharmaceutics, University of Minnesota, 308 Harvard St. SE, Minneapolis, MN 55455, United StatesAndrey ZINCHUK - University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030, United StatesBruno HANCOCK - Pfizer Global R&D, Groton, CT 06340, United StatesEvgenyi SHALAEV - Pfizer Global R&D, Groton, CT 06340, United StatesRaj SURYANARAYANAN - Department of Pharmaceutics, University of Minnesota, 308 Harvard St. SE, Minneapolis, MN 55455, United States
- Resource Type
- Journal article
- Publication Details
- Pharmaceutical research, Vol.23(10), pp.2454-2468
- Publisher
- Springer; New York, NY
- DOI
- 10.1007/s11095-006-9085-3
- PMID
- 16933092
- ISSN
- 0724-8741
- eISSN
- 1573-904X
- Language
- English
- Date published
- 2006
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics
- Record Identifier
- 9984065317602771
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