Lactose-Free Naltrexone Dispersible Tablets for Crohn's Disease
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Solution Overview
Problem
Lactose intolerance in Crohn's disease patients leads to adverse symptoms like diarrhea, bloating, and abdominal pain, and the use of lactose with naltrexone can exacerbate these issues, while existing pharmaceutical compositions often include stabilizers and chelating agents that may not be suitable for all patients.
Innovation Solution
A lactose-free, stable pharmaceutical composition of naltrexone or its pharmaceutically acceptable salt, devoid of stabilizers and chelating agents, with a therapeutically effective dose of less than 10 mg, specifically designed for the treatment of Crohn's disease, including pediatric patients, and formulated into dispersible tablets with optimal disintegration time, content uniformity, and dissolution rate.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If lactose is used as an excipient in naltrexone formulation, then the formulation can be manufactured with conventional excipients, but it causes adverse symptoms like diarrhea, bloating, and abdominal pain in Crohn's disease patients
Solution Approach 1:
The patent removes lactose from the formulation entirely, extracting the harmful excipient that causes adverse symptoms in Crohn's disease patients. The formulation achieves manufacturability without lactose by using alternative excipients like microcrystalline cellulose and pregelatinized starch.
Solution Approach 2:
The patent changes the excipient parameters by substituting lactose with lactose-free alternatives. This parameter change maintains the formulation's manufacturability while eliminating the harmful effects on Crohn's disease patients who are often lactose intolerant.
2Stability of the object's composition
If stabilizers and chelating agents are added to naltrexone formulation, then the stability of naltrexone is improved, but the formulation complexity increases and may not be suitable for all patients
Solution Approach 1:
The patent removes stabilizers and chelating agents from the formulation, extracting these additives to achieve a simpler, cleaner formulation. The stability is maintained through careful selection of compatible excipients and optimized manufacturing parameters rather than relying on additional stabilizing agents.
Solution Approach 2:
The patent employs a simple, straightforward formulation without complex stabilizing systems. The formulation relies on basic, well-characterized excipients that are inherently compatible with naltrexone, avoiding the need for sophisticated long-term stabilization mechanisms.
3Reliability
If high dose naltrexone (50 mg) is used for treatment, then the therapeutic effect for alcohol and opioid dependence is achieved, but it is not suitable for treating Crohn's disease where low dose is required
Solution Approach 1:
The patent changes the dose parameter to accommodate different therapeutic indications. By formulating with lactose-free excipients and ensuring high content uniformity, the formulation enables precise dosing at low levels (1.75-4.5 mg for Crohn's disease) while maintaining the capability for higher doses (50 mg for alcohol and opioid dependence).
Solution Approach 2:
The patent creates a universal formulation that can serve multiple therapeutic purposes. The same lactose-free naltrexone formulation is suitable for both low-dose treatment of Crohn's disease and high-dose treatment of alcohol and opioid dependence, eliminating the need for separate formulations for different indications.
4Speed
If dispersible tablet form is used, then the dissolution rate and bioavailability are improved, but the manufacturing precision requirements increase
Solution Approach 1:
The patent optimizes the physical parameters of the dispersible tablet formulation, including particle size distribution, porosity, and compression force. These parameter changes enable rapid disintegration and dissolution while maintaining manufacturability through conventional tabletting equipment and processes.
Solution Approach 2:
The patent uses a composite excipient system combining microcrystalline cellulose, pregelatinized starch, and other functional excipients. This composite material structure provides both the mechanical integrity needed for tablet formation and the rapid disintegration properties required for fast dissolution and high bioavailability.
Data Source
AI summary
A lactose free, stable pharmaceutical composition having naltrexone or its pharmaceutically acceptable salt thereof. Also disclosed is a process for the preparation of the composition and its use in a method for the treatment of Crohn's disease.