Lurasidone Solid Dispersion Amorphous Formulation
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Solution Overview
Problem
Lurasidone, an atypical antipsychotic, has low water solubility and high pH sensitivity, leading to poor bioavailability and food effects, requiring administration with specific dietary restrictions, which limits patient compliance.
Innovation Solution
A solid dispersion of lurasidone with carriers like polyvinyl acetate phthalate, polyvinyl alcohol, and mesoporous silica, combined with surfactants like glycerol esters, is developed to enhance solubility and bioavailability, reducing food effects by maintaining lurasidone in an amorphous form and improving its dissolution rate.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If lurasidone is administered as an immediate release tablet, then the medication can be dissolved in the stomach, but lurasidone precipitates in the intestine due to pH change, reducing bioavailability
Solution Approach 1:
The patent transforms lurasidone from crystalline form to amorphous form through solid dispersion technology, fundamentally changing its physical state and dissolution characteristics. This parameter change enables the drug to maintain solubility across different pH environments in the gastrointestinal tract, preventing precipitation in the intestine and improving overall bioavailability
Solution Approach 2:
The patent creates a composite material system by dispersing lurasidone within a polymer matrix (such as HPMC, PVP, or Eudragit). This composite structure allows the drug to be released and dissolved gradually, maintaining solubility control through the polymer's interaction with the drug molecule and the gastrointestinal environment
2Reliability
If lurasidone is administered with food to improve solubility, then bioavailability increases, but patient compliance decreases due to dietary restrictions requiring more than 350 calories intake
Solution Approach 1:
The solid dispersion formulation makes the drug formulation itself provide the solubility enhancement that previously required external factors (food intake). The amorphous state and polymer matrix inherently maintain drug solubility across pH changes, allowing the medication to work effectively regardless of dietary conditions, thus eliminating the need for patients to follow specific eating guidelines
3Stability of the object's composition
If lurasidone is maintained in crystalline form, then the formulation is stable, but solubility in neutral environment is poor
Solution Approach 1:
The patent applies parameter change by transforming lurasidone from crystalline to amorphous form. The amorphous state eliminates the rigid crystal lattice structure that limits solubility, allowing the drug molecules to be more readily solvated. The polymer matrix stabilizes this amorphous state, preventing recrystallization while maintaining enhanced solubility properties
Solution Approach 2:
The patent utilizes phase transition from crystalline to amorphous state through processes like spray drying, freeze drying, or melt extrusion. This phase transition fundamentally alters the drug's physical properties, creating a metastable amorphous form with higher free energy and thus higher solubility, while the polymer matrix acts as a stabilizer to maintain this phase
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 solid dispersion significantly increases lurasidone's solubility and bioavailability, reducing food effects and improving patient compliance by achieving higher maximum plasma concentration and area under curve, even under fasting conditions.
Implementation Method 1
maintaining lurasidone in an amorphous form and improving its dissolution rate
Implementation Method 2
A solid dispersion of lurasidone with carriers like polyvinyl acetate phthalate, polyvinyl alcohol, and mesoporous silica
Data Source
AI summary
In some embodiments of the present disclosure, a solid dispersion is provided, comprising: lurasidone or its pharmaceutically acceptable salt and a carrier. The material of the carrier comprises polyvinyl acetate phthalate (PVAP), polyvinyl alcohol (PVA), cellulose acetate phthalate (CAP), mesoporous silica, hydroxypropyl methycellulose (HPMC), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, acrylic resin, hydroxypropyl cellulose (HPC), povidone, copovidone, ethyl cellulose, polyoxyethylene glycol, hypromellose acetate succinate (HPMCAS), hypromellose phthalate (HPMCP), or a combination thereof.