Enteric Melatonin Pellets for Sustained Intestinal Release
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Solution Overview
Problem
Existing melatonin compositions do not provide a convenient and effective sustained release dosage form that is easy to swallow and effectively delivers melatonin to the gastrointestinal tract for prolonged therapeutic effects.
Innovation Solution
A melatonin composition comprising individual pellets with a solid core, an active coating containing melatonin and a hydrophilic binder, and an enteric coating that dissolves at a higher pH than the acidic carrier material, allowing sustained release in the intestines, combined with an optional subcoat and separation coating to control pH and release kinetics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If melatonin is administered in an oral tablet dosage form, then it is easy to swallow, but it does not provide sustained release in the intestines
Solution Approach 1:
The dosage form is segmented into multiple functional coatings on individual pellets: an active coating containing melatonin, an enteric coating that dissolves at intestinal pH, and optionally a separation coating and subcoat. This segmentation allows each layer to perform a specific function, achieving sustained release in the intestines while maintaining ease of swallowing as a complete pellet structure.
Solution Approach 2:
The patent applies nested doll by placing multiple coatings in concentric layers around the pellet core: the active coating is nested within the enteric coating, and the separation coating is nested within the subcoat which is nested within the enteric coating. This nested structure enables controlled drug release while maintaining a compact, swallowable form.
2Reliability
If an enteric coating is added to achieve sustained release, then melatonin is protected from stomach acid, but the device complexity increases
Solution Approach 1:
The enteric coating provides local quality by creating a pH-dependent barrier specifically at the stomach-intestinal interface. The coating remains intact in the acidic stomach environment (pH 1-3) and only dissolves in the higher pH intestinal environment (pH 6-7.4), providing protection exactly where needed without requiring complex active control mechanisms.
Solution Approach 2:
The patent utilizes parameter changes, specifically pH changes, to control the dissolution behavior of the enteric coating. The coating material is selected to have a dissolution pH higher than the acidic pH of the carrier material, allowing it to remain stable in the stomach and dissolve only in the intestines where pH is higher, thereby achieving reliable protection with a relatively simple single-layer or multi-layer coating structure.
3Duration of action of moving object
If multiple coating layers are added to control release kinetics, then sustained release is achieved, but the manufacturing process becomes more complex
Solution Approach 1:
The patent applies preliminary action by pre-forming the pellets with their multi-layer coating structure before final dosage form assembly. The enteric coating is applied to the active coating in advance, and the separation coating and subcoat are prepared with predetermined pH properties. This preliminary preparation allows for controlled sustained release while simplifying the final manufacturing step of combining pellets with the carrier material.
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 provides a therapeutically effective sustained release of melatonin in the intestines for several hours, aiding sleep maintenance, while being easy to swallow and avoiding immediate release in the stomach.
Implementation Method 1
An enteric coating is over the active coating. A dissolution pH of the enteric coating is higher than the acidic pH of the aqueous carrier material.
Implementation Method 2
The active coating includes melatonin and a hydrophilic binder. The melatonin may be a powder having a median melatonin particle size of 5 μm to 40 μm lodged in the hydrophilic binder.
Implementation Method 3
The subcoat may include a hydrogel-forming polymer and an acid, the acid imparting a pH of 0.1 to 4.4 to the hydrogel-forming polymer. The separation coating may separate the acid from the melatonin.
Data Source
AI summary
A composition comprises a therapeutically effective oral pharmaceutical dosage form. The dosage form includes an aqueous carrier material having an acidic pH and a plurality of individual pellets having a first dose of melatonin therein. The individual pellets comprises (i) a solid core; (ii) an active coating over the solid core, the active coating including melatonin and a hydrophilic binder; and (iii) an enteric coating over the active coating. A dissolution pH of the enteric coating is higher than the acidic pH of the aqueous carrier material.