Rapidly Disintegrating DPP-IV Tablet via Melt Granulation
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Solution Overview
Problem
Current rapidly disintegrating tablet compositions of DPP-IV inhibitors face challenges in achieving both rapid disintegration and adequate mechanical strength while maintaining low mineral content, particularly sodium and potassium levels within safe limits for diabetic patients with cardiovascular comorbidities.
Innovation Solution
The development of a rapidly disintegrating tablet composition using an acid-base couple with a co-rotating twin screw processor, where an acid and a base react to form carbon dioxide, reducing mineral content and enhancing disintegration time, and incorporating a DPP-IV inhibitor, with specific ratios of citric acid and carbonate salts, and additional excipients to achieve the desired properties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If conventional granulation methods (wet granulation, dry granulation, spray drying, flash heating) are used to achieve high porosity for rapid disintegration, then disintegration speed is improved, but mechanical strength and tablet stability deteriorate
Solution Approach 1:
The patent changes the physical and chemical parameters of the granulation process by using a melt granulation approach where the binder is melted and then cooled to form granules. This parameter change allows achieving both high porosity (for rapid disintegration) and adequate mechanical strength through controlled melting and solidification of the binder material.
Solution Approach 2:
The patent employs composite granule structures formed by combining API particles with binder material in a melt granulation process. The composite nature of these granules, with embedded API particles in a binder matrix, provides both the porosity needed for rapid disintegration and the mechanical strength required for tablet stability during handling and transportation.
2Speed
If low-density alkali earth metal salts and water soluble carbohydrates are used as excipients to achieve rapid disintegration, then disintegration speed is improved, but manufacturing complexity increases due to pre-compaction requirements
Solution Approach 1:
The patent extracts or removes the need for pre-compaction steps by using melt granulation to produce granules with inherent compressibility and binding properties. This eliminates the complex multi-step process required when using low-density excipients, simplifying the manufacturing process while maintaining rapid disintegration characteristics.
Solution Approach 2:
The melt granulated granules are self-sufficient in providing both binding and disintegration properties without requiring additional pre-processing steps. The granules themselves possess the necessary characteristics for direct tablet compression, making the process self-contained and eliminating the need for separate pre-compaction operations.
3Speed
If effervescent compositions with high potassium content are used to achieve rapid disintegration, then disintegration speed is improved, but mineral content safety deteriorates for diabetic patients with cardiovascular disease
Solution Approach 1:
The patent removes or extracts the harmful high potassium content from the formulation by using alternative excipients with low mineral content. The melt granulation process uses binders that do not contribute excessive minerals, thereby eliminating the safety concern for diabetic patients with cardiovascular disease while preserving rapid disintegration properties.
Solution Approach 2:
The patent employs excipients that are metabolically inert or rapidly excreted, providing the disintegration function temporarily without leaving harmful mineral residues in the body. These excipients serve their purpose of enabling rapid disintegration and then are eliminated from the system, preventing accumulation of harmful minerals in patients.
Data Source
AI summary
A rapidly disintegrating tablet comprising a therapeutically effective amount of a DPP- IV inhibitor and an acid-base couple having mineral content below the daily intake limits is disclosed. The rapidly disintegrating tablet has a sodium content less than 10 mg and a potassium content less than 15 mg. A process for preparation of the rapidly disintegrating tablet comprising the DPP-IV inhibitor is also disclosed.