Methods of formulating and designing liquid drug suspensions containing ion exchange resin particles
Inventors
McMahen, Russell • Tengler, Mark • Sloane, Michael • Lockhart, Daniel
Assignees
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Publication Number
US-9057675-B2
Publication Date
2015-06-16
Expiration Date
Abstract
The invention relates to the formulation and quality control of liquid drug suspensions. In particular, the invention relates to methods of formulating liquid suspensions comprising drug-containing resin particles. The invention also relates to methods of confirming the acceptability of drug-containing resin particles for use in formulating liquid drug suspensions. The invention further relates to methods of formulating liquid suspensions in which drug-containing resin particles, the liquid suspension, or both are modified to achieve a desired in vitro dissolution profile. The invention also relates to a novel dissolution method and methods of predicting in vivo bioequivalence based on in vitro dissolution methods.
Core Innovation
A test method is provided that obtains drug-resin complex particles and combines the particles with a plurality of excipients in a liquid carrier to form a liquid test drug suspension. The method performs an in vitro dissolution assay to generate a test in vitro dissolution profile and compares the test profile to a control in vitro dissolution profile generated for a control drug suspension to determine whether the profiles match, prior to either suspension becoming stable to time-dependent changes to its release profile.
The test drug suspension and the control drug suspension are substantially similar in physicochemical characteristics to a finally formulated suspension that is stable to time-dependent changes to its release profile. The control in vitro dissolution profile correlates to a target in vivo profile of a controlled release liquid suspension drug product, providing the basis for the in vitro comparison.
An additional method is provided for determining the acceptability of drug-resin complex particles for use in a controlled release liquid suspension drug suspension product. A sample of the drug-resin complex particles is formed into a liquid test drug suspension with excipients and a liquid carrier, an in vitro dissolution assay is performed, and the resulting test in vitro dissolution profile is compared to a control in vitro dissolution profile to accept or reject a quantity of drug-resin complex particles.
Claims Coverage
Two independent claims are identified. The inventive coverage centers on matching test and control in vitro dissolution profiles prior to stabilization, with substantially similar physicochemical characteristics to a finally formulated stable suspension and a control profile that correlates to a target in vivo profile.
Matching test and control dissolution profiles prior to stabilization
Drug-resin complex particles are combined with a plurality of excipients in a liquid carrier to form a liquid test drug suspension, and an in vitro dissolution assay generates a test in vitro dissolution profile that is compared to a control in vitro dissolution profile before either suspension becomes stable to time-dependent changes to its release profile.
Substantially similar physicochemical characteristics to a finally formulated stable suspension
The test drug suspension and the control drug suspension are substantially similar in physicochemical characteristics to a finally formulated suspension that is stable to time-dependent changes to its release profile.
Control in vitro dissolution profile correlates to a target in vivo profile
The control in vitro dissolution profile correlates to a target in vivo profile of a controlled release liquid suspension drug product.
Accepting or rejecting drug-resin complex particles based on dissolution profile match
A sample of drug-resin complex particles is formed into a liquid test drug suspension, the test in vitro dissolution profile is compared to a control in vitro dissolution profile, and a quantity of drug-resin complex particles is accepted or rejected based on the comparison.
The independent claims cover in vitro dissolution-profile matching for liquid suspensions formed from drug-resin complex particles, including prior to time-dependent stabilization, with similarity to a finally formulated stable suspension and correlation of the control profile to a target in vivo profile.
Stated Advantages
Enables determining acceptability of drug-resin complex particles by accepting or rejecting based on whether the test in vitro dissolution profile matches the control in vitro dissolution profile.
Aligns in vitro dissolution assessment with a target in vivo controlled release profile via correlation of the control in vitro dissolution profile to the target in vivo profile.
Documented Applications
Use in determining acceptability of drug-resin complex particles for use in a controlled release liquid suspension drug suspension product.
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