Expandable Multi-Excipient Dosage Form for Prolonged Gastric Retention
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Solution Overview
Problem
Traditional oral-delivery dosage forms, such as tablets and capsules, fail to optimally deliver drugs that are soluble at low pH but insoluble at higher pH, limiting bioavailability and prolonged drug release due to short residence time in the upper gastrointestinal tract.
Innovation Solution
Development of a three-dimensional structural framework for pharmaceutical dosage forms comprising a drug, a physiological fluid-absorptive excipient, and a strength-enhancing excipient, which expands in the stomach to form a semi-solid mass that retains the drug for prolonged release.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If traditional solid dosage forms (tablets and capsules) are used, then the dosage form is easy to manufacture and ingest, but the residence time in the upper gastrointestinal tract is short, limiting drug absorption and bioavailability
Solution Approach 1:
The dosage form utilizes pH-dependent solubility parameter changes of the excipient to control its physical state and size. At low pH in the stomach, the excipient is soluble and the dosage form remains small for easy ingestion and gastric retention. At higher pH in the intestine, the excipient becomes insoluble, causing the dosage form to expand and prevent passage through the pylorus, thereby extending residence time in the upper GI tract.
Solution Approach 2:
The dosage form is designed to dynamically change its physical properties (size, solubility, expansion state) in response to environmental pH changes. This dynamic behavior allows it to transition from a small ingestible form in the stomach to an expanded retained form in the intestine, optimizing both ease of ingestion and duration of action.
2Duration of action of moving object
If the dosage form expands rapidly in the stomach, then gastroretention is achieved, but the drug release time is too short (80% released in about two hours)
Solution Approach 1:
The dosage form separates the expansion function and drug release function into distinct components. The excipient provides the expansion mechanism for gastroretention, while the drug is embedded in a matrix that controls its release rate. This segmentation allows the dosage form to expand rapidly for gastric retention while simultaneously releasing drug at a controlled, prolonged rate through diffusion and erosion mechanisms.
Solution Approach 2:
The dosage form employs a composite structure combining the excipient (for expansion and gastroretention) with the drug and additional matrix materials (such as polymers or waxes). This composite material system enables independent optimization of expansion kinetics and drug release kinetics, achieving both rapid gastroretention and prolonged drug release.
3Duration of action of moving object
If floating dosage forms are used to extend residence time, then prolonged gastric retention is achieved, but the patient must maintain upright posture and the stomach must be filled with food and drink
Solution Approach 1:
The dosage form achieves gastric retention through self-generated mechanisms rather than relying on external conditions. The pH-dependent expansion of the excipient creates automatic gastric retention without requiring the patient to maintain specific postures or consume food/drink. The dosage form autonomously responds to the gastric environment to achieve prolonged residence time, eliminating the impractical requirements of floating dosage forms.
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 expanded dosage form maintains its size and releases the drug over an extended period, enhancing bioavailability and convenience by prolonging drug release time in the stomach.
Implementation Method 1
the elements comprise at least a drug, at least a physiological fluid-absorptive excipient, and at least a strength-enhancing excipient. Upon ingestion, the three-dimensional structural framework expands in at least one dimension
Implementation Method 2
one or more fluid-absorptive polymeric constituents
Implementation Method 3
one or more strength-enhancing polymeric constituents; wherein upon exposure to physiological fluid, said one or more strength-enhancing excipients form a fluid-permeable, semi-solid network mechanically supporting the fiber
Implementation Method 4
release drug over prolonged time
Data Source
AI summary
Many drug therapies could be greatly improved by dosage forms that reside in the stomach for prolonged time and release the drug slowly. In this specification, therefore, an expandable, multi-excipient dosage form for prolonged release is disclosed. The dosage form generally comprises a three-dimensional structural framework of solid elements. The elements comprise at least a drug, at least a physiological fluid-absorptive excipient, and at least a strength-enhancing excipient. Upon ingestion, the three-dimensional structural framework expands in at least one dimension and forms an expanded semi-solid mass that can be retained in the stomach and release drug over prolonged time.