Lurasidone Solid Dispersion for Reduced Food-Dependent Bioavailability
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Solution Overview
Problem
Current lurasidone hydrochloride tablets exhibit low bioavailability and are significantly affected by food intake, requiring administration with a minimum of 350 calories to maintain efficacy, which poses challenges for patients with eating disorders or refusal to eat.
Innovation Solution
A lurasidone solid dispersion is formulated using lurasidone in a free base form combined with hydroxypropyl methylcellulose succinate acetate (HPMCAS) as a carrier and a plasticizer, prepared via a melting method to enhance solubility and bioavailability under fasting conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If lurasidone hydrochloride tablets are administered without sufficient food intake, then the administration requirements are relaxed, but the bioavailability decreases significantly (Cmax and AUC decrease 3-fold and 2-fold respectively when calories < 350)
Solution Approach 1:
The patent converts lurasidone from hydrochloride salt form to free base form and formulates it as a solid dispersion. This parameter change in chemical form and physical state fundamentally alters the drug's dissolution characteristics, enabling consistent absorption regardless of food intake conditions
Solution Approach 2:
The patent creates a composite solid dispersion system combining lurasidone free base with specific carriers and excipients. This composite material approach enhances solubility and dissolution rate, making the drug performance independent of gastrointestinal surfactant variations caused by food intake
2Reliability
If lurasidone hydrochloride tablets are formulated with high solubility in acidic media, then the drug stability is improved, but the dissolution in neutral intestinal media decreases rapidly
Solution Approach 1:
The patent changes the pH sensitivity parameter by converting from hydrochloride salt to free base form and creating a solid dispersion. This eliminates the strong pH-dependence of dissolution, enabling consistent dissolution performance across both acidic gastric and neutral intestinal environments
Solution Approach 2:
The solid dispersion acts as an intermediary system that mediates between the drug's inherent pH-dependent solubility characteristics and the varying pH environments of the gastrointestinal tract. The dispersion matrix provides a controlled release mechanism that bypasses the pH solubility issue
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 lurasidone solid dispersion significantly increases dissolution and bioavailability in neutral media, reducing the food effect and ensuring consistent medication efficacy regardless of food intake.
Implementation Method 1
The method of preparing the lurasidone solid dispersion comprises melting a mixture of lurasidone, a pharmaceutical carrier and a plasticizer to obtain the lurasidone solid dispersion
Data Source
AI summary
A lurasidone solid dispersion and a preparation method thereof. The solid dispersion includes a mixture of lurasidone, a pharmaceutical carrier and a plasticizer, in which the lurasidone is in a free base form. The lurasidone solid dispersion obtained by the preparation method has characteristics of high dissolution rate (over 30%) in partial neutral medium (such as pH 6.0), significantly increased bioavailability, and significantly reduced food effect, which overcomes the excessive medication limitation in the prior art, avoids the reduction or even inefficiency of the curative effect caused by improper medication of patients, ensures the normal exertion of the medication effect, thereby increases the flexibility and compliance of patients to take medicine.