Lacosamide Multiparticulate Composition for Once-Daily Extended Release
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Solution Overview
Problem
There is a clinical need for an extended release preparation of lacosamide for once daily oral administration to reduce adverse reactions and improve patient compliance, as high daily doses of immediate release preparations lead to high incidence of side effects, which correlate with maximum steady-state plasma concentration and area under the plasma concentration-time curve.
Innovation Solution
A pharmaceutical composition comprising an extended release portion with a drug-loaded core and a pH-independent extended release layer, and an immediate release portion, allowing for controlled release of lacosamide over an extended period, reducing peak-trough fluctuation and side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If high daily dose of immediate release preparation is administered, then therapeutic efficacy is improved, but incidence of adverse reactions increases
Solution Approach 1:
The pharmaceutical composition is divided into two distinct portions: an extended release portion (70-95% of total lacosamide) and an immediate release portion (5-30% of total lacosamide). This segmentation allows the drug to be released in different patterns over time, providing both immediate therapeutic effect and sustained maintenance, thereby achieving effective dose delivery while reducing peak concentration-related side effects
Solution Approach 2:
The invention changes the release rate parameter of lacosamide by using different release mechanisms. The extended release portion uses a pH-independent extended release agent (such as ethyl cellulose or Eudragit RS/RL) to provide slow, controlled release over 12-24 hours, while the immediate release portion provides rapid absorption. This parameter change in release kinetics reduces Cmax,ss while maintaining AUCss, thereby reducing adverse reactions without compromising therapeutic efficacy
2Speed
If immediate release preparation is used, then rapid therapeutic effect is achieved, but frequency of administration must be increased
Solution Approach 1:
The invention merges two release mechanisms into a single dosage form: immediate release particles (providing rapid onset) and extended release particles (providing sustained release). The immediate release portion ensures quick therapeutic effect similar to conventional IR preparations, while the extended release portion maintains stable plasma concentrations over 24 hours, allowing once-daily administration and reducing the burden of frequent dosing
3Loss of time
If extended release preparation is used, then frequency of administration is reduced, but release control complexity increases
Solution Approach 1:
The invention uses pH-independent extended release agents (such as ethyl cellulose, cellulose acetate, or Eudragit RS/RL) that provide consistent release rates across different gastrointestinal pH conditions. This parameter selection simplifies the release control mechanism by eliminating the need for pH-dependent coating systems or complex multi-layer structures, while still achieving extended release over 12-24 hours for once-daily dosing
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The composition achieves reduced peak-trough fluctuation and side effects while maintaining therapeutic efficacy, with AUCss and Cmax,ss comparable to immediate release preparations, facilitating once daily oral administration.
Implementation Method 1
an extended release layer coating the drug-loaded core, comprising a pH independent extended release agent
Implementation Method 2
the drug-loaded core does not comprise the extended release agent
Data Source
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AI summary
The present invention relates to a pharmaceutical composition of lacosamide and a pharmaceutical preparation thereof. The pharmaceutical composition comprises extended release multiparticulates, wherein each of the extended release multiparticulates comprises: (a) a drug-loaded core, comprising lacosamide or a pharmaceutically acceptable salt thereof; and (b) an extended release layer coating the drug-loaded core. The present invention also provides an extended release preparation of lacosamide for once daily oral administration.