Compositions comprising methylphenidate complexed with ion-exchange resin particles
Inventors
Tengler, Mark • McMahen, Russell
Assignees
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Publication Number
US-9072680-B2
Publication Date
2015-07-07
Expiration Date
Abstract
Pharmaceutical compositions of methylphenidate complexed with ion-exchange resin particles to form drug-resin particles are provided. The compositions have a first plurality of drug-resin particles that are uncoated and a second plurality of drug-resin particles that are coated with a delayed release coating. Preferably, the second plurality of drug-resin particles are coated with a triggered-release coating triggered by a pH change and a diffusion barrier coating.
Core Innovation
The invention provides a pharmaceutical composition comprising an ADHD effective agent complexed with ion-exchange resin particles to form drug-resin particles. The ADHD effective agent is methylphenidate, and the composition includes a first plurality of drug-resin particles configured to provide immediate release of methylphenidate and a second plurality of drug-resin particles coated with a triggered-release coating that is triggered by a pH change together with a diffusion barrier coating.
The drug-resin particles are characterized in the description by use of methylphenidate polistirex and comparisons to a reference composition identified as METADATE CD. Human pharmacokinetic evaluation is performed using log-transformed pharmacokinetic parameters including Cmax and multiple AUC windows, as well as derived metrics for d-methylphenidate, l-methylphenidate, and total methylphenidate (d+l).
The description further supports controlled-release behavior through dissolution experiments and food-effect and ethanol-effect studies on extended-release oral disintegrating tablet formulations. Fed versus fasted pharmacokinetic conclusions are reported to meet acceptance ranges for d+l exposures based on defined bioequivalence criteria, and additional evaluations are reported for amphetamine extended-release oral disintegrating tablet products.
Claims Coverage
The partial content indicates coverage of one independent claim. The independent claim includes two main structural inventive elements: an immediate-release and a pH-change triggered-release fraction formed from methylphenidate complexed with ion-exchange resin particles, and an in-human mean plasma concentration profile criterion for d-methylphenidate based on specified AUC/AUC-Tmax parameters being substantially similar to a reference FIG. 20A profile.
Methylphenidate ion-exchange drug-resin particles with immediate and triggered fractions
A pharmaceutical composition comprising an ADHD effective agent complexed with ion-exchange resin particles to form drug-resin particles, where the ADHD effective agent is methylphenidate; the composition comprises a first plurality of drug-resin particles providing immediate release and a second plurality of drug-resin particles coated with a triggered-release coating triggered by a pH change and a diffusion barrier coating.
In-human d-methylphenidate plasma profile substantially similar by AUC/AUC-Tmax parameters
Administration of the composition to a human produces a mean plasma concentration profile for d-methylphenidate having one or more parameters selected from AUC0-3, AUC0-5, AUC0-Tmax, AUC5-12, AUC5-24, AUC(Tmax-24), AUC(Tmax-12), AUC5-t, AUC(Tmax-t), AUC0-24, and AUC0-∞ that is substantially similar to those parameters of at least one in vivo serum profile of compositions comprising methylphenidate-containing drug-resin particles shown in FIG. 20A.
Across the independent claim, coverage centers on methylphenidate complexed with ion-exchange resin particles to form drug-resin particles including an immediate-release fraction and a pH-change triggered-release fraction with a diffusion barrier coating, together with a requirement that human mean d-methylphenidate exposure parameters be substantially similar to the FIG. 20A in vivo serum profile.
Stated Advantages
Documented Applications
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