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Correlation of in vitro dissolution rate and apparent solubility in buffered media using a miniaturized rotating disk
A M Persson1, C Pettersson, A Sokolowski
1Division of Analytical Pharmaceutical Chemistry, Uppsala University, BMC, SE-751 23 Uppsala, Sweden.
Drug Discoveries & Therapeutics
|April 13, 2012
Summary
This study explored the relationship between drug dissolution rate and solubility across Biopharmaceutics Classification System (BCS) classes. A triethanolammonium acetate buffer showed the best correlation, suggesting its utility in early drug screening.
Area of Science:
- Pharmaceutical Sciences
- Drug Discovery and Development
- Physical Chemistry
Background:
- Understanding the relationship between drug dissolution rate (G) and apparent solubility (S) is crucial for predicting in vivo drug performance.
- The Biopharmaceutics Classification System (BCS) categorizes drugs based on solubility and permeability, guiding formulation strategies.
- Investigating the impact of buffer composition and inorganic salts on this correlation is essential for robust in vitro-in vivo correlations.
Purpose of the Study:
- To investigate the correlation between logarithmic values of in vitro dissolution rate (logG) and apparent solubility (logS) for diverse drug substances.
- To evaluate the influence of various inorganic salts (NaCl, NaNO3, Na2HPO4, Na2SO4) and buffer systems on the logG-logS correlation.
- To assess the suitability of a triethanolammonium acetate buffer for predicting drug solubility based on dissolution rates.
Main Methods:
- Utilized seven drug substances representing all BCS classes in four phosphate buffers at pH 7.0 ± 0.1.
- Employed miniaturized rotating disk equipment for rapid dissolution rate determination (approx. 5 mg substance).
- Determined apparent solubility using conventional shake-flask methodology with 1.5 mL volumes, quantified via RP-HPLC-DAD.
Main Results:
- Inorganic anions, particularly phosphate and nitrate, affected drug solubility more than dissolution rates, decreasing solubility for amine drugs compared to chloride.
- The triethanolammonium acetate buffer yielded the best correlation between logG and logS (R² = 0.991).
- The observed correlation suggests dissolution rate can be a reliable indicator of drug solubility in specific aqueous buffer media.
Conclusions:
- The choice of buffer system significantly impacts the correlation between drug dissolution rate and solubility.
- Triethanolammonium acetate buffer demonstrates high predictive power for drug solubility screening based on dissolution data.
- This finding supports the use of dissolution rate measurements in specific buffer systems for early-stage drug development and screening.
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