Mitapivat Mini-Tablets for Pediatric Swallowability
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Solution Overview
Problem
Current treatments for pyruvate kinase deficiency (PKD) lack an approved medicine that addresses the underlying cause, and existing formulations of mitapivat, an allosteric activator of pyruvate kinase R, are not suitable for pediatric and elderly patients or those with difficulty swallowing, as they come in traditional tablet forms that are hard to swallow and have aversive sensory attributes.
Innovation Solution
Development of mini-tablets containing mitapivat hemisulfate sesquihydrate in various strengths, combined with inactive ingredients like microcrystalline cellulose, mannitol, and croscarmellose sodium, and a film coat, designed to be administered with food vehicles such as chocolate pudding, strawberry jam, or peanut butter to mask bitter taste, suitable for pediatric and difficult-swallowing patients.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If traditional tablet formulations of mitapivat are used, then the drug can be manufactured and administered, but pediatric and elderly patients or those with difficulty swallowing cannot easily take the medication
Solution Approach 1:
The traditional tablet formulation is divided into smaller mini-tablets containing 0.1 mg to 5 mg of mitapivat each. This segmentation allows patients who have difficulty swallowing large tablets to take multiple smaller units, significantly improving ease of administration while maintaining the required dosage flexibility.
2Ease of operation
If mitapivat is administered in traditional tablet form, then the medication can be delivered, but the bitter taste and aversive sensory attributes reduce patient compliance
Solution Approach 1:
Food vehicles such as chocolate pudding, strawberry jam, peanut butter, strawberry yogurt, and apple sauce are introduced as intermediaries between the mini-tablets and the patient's taste receptors. These food vehicles mask the bitter taste and aversive sensory attributes of mitapivat, making the medication acceptable to pediatric and elderly patients while ensuring proper ingestion.
3Quantity of substance
If smaller doses of mitapivat are provided for pediatric patients, then appropriate dosing can be achieved, but traditional tablet formulations are not suitable for these small doses
Solution Approach 1:
The medication is segmented into mini-tablets with dosage strengths of 0.1 mg to 5 mg each, enabling precise dosing for pediatric patients. This segmentation allows clinicians to prescribe appropriate small doses while maintaining administration feasibility, as patients can take one or multiple mini-tablets depending on the required dosage.
Solution Approach 2:
The dosage strength parameter of the formulation is changed from traditional tablet sizes to mini-tablet sizes with varying strengths (0.1 mg to 5 mg). This parameter change enables flexible dosing for pediatric patients while maintaining ease of administration through the small size and compatibility with food vehicles.
Data Source
AI summary
Disclosed is a pharmaceutical mini-tablet comprising mitapivat or a pharmaceutically acceptable salt thereof, and in a particular embodiment comprising a mitapivat sulfate salt, and one or more inactive ingredients selected from a filler, disintegrant, lubricant, binder, and diluent.