Disintegrant-Free Apremilast Composition for Stable Direct Compression
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Solution Overview
Problem
Current pharmaceutical compositions of apremilast for treating psoriatic arthritis and psoriasis face challenges due to the hygroscopic nature of disintegrants, high concentration requirements, and poor compression properties, leading to processing and manufacturing difficulties.
Innovation Solution
A disintegrant-free stable pharmaceutical composition of apremilast is developed, comprising pharmaceutically acceptable salts and excipients, prepared through a process involving sifting, blending, adding lubricants, and direct compression, which results in a stable and bioequivalent immediate release dosage form.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If disintegrant is used in tablet formulation, then tablet disintegration is improved, but hygroscopic nature leads to softening of tablets and requires protection from atmospheric moisture
Solution Approach 1:
The patent removes the disintegrant component from the tablet formulation entirely, using direct compression of apremilast with excipients like microcrystalline cellulose and lactose monohydrate. This extraction of the harmful disintegrant eliminates the hygroscopic issue while maintaining tablet integrity through the compressibility and binding properties of the remaining excipients.
Solution Approach 2:
The patent changes the formulation parameters by eliminating disintegrants and adjusting the ratio of excipients, particularly using microcrystalline cellulose (26.25-30%) and lactose monohydrate (60-65%) in specific proportions that enable direct compression without disintegrants, thereby avoiding hygroscopic problems while maintaining adequate disintegration through alternative mechanisms.
2Ease of manufacture
If high concentration of disintegrant is used for direct compression, then tablet disintegration is improved, but manufacturing complexity and cost increase
Solution Approach 1:
The patent extracts the disintegrant from the formulation entirely, demonstrating that direct compression can be successfully implemented without any disintegrant. The excipients microcrystalline cellulose and lactose monohydrate provide adequate disintegration function at normal concentrations, eliminating the need for high disintegrant concentrations and associated manufacturing complexities.
3Stability of the object's composition
If disintegrant is used in tablet formulation, then tablet disintegration is improved, but compression properties deteriorate
Solution Approach 1:
The patent removes disintegrants from the formulation and relies on the inherent compression properties of microcrystalline cellulose and lactose monohydrate. These excipients provide excellent compressibility and tablet strength without the need for disintegrants, achieving both good compression properties and adequate disintegration through the porosity and structure of the compressed tablet.
Data Source
AI summary
The present invention relates to a disintegrant free pharmaceutical composition comprising apremilast or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients. Particularly the present invention relates to disintegrant free immediate release dosage form comprising apremilast or pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients. It further relates to process of preparing such composition and its use in psoriatic arthritis and psoriasis.