Bisphosphonate Formulation Stability via Maltodextrin Sorbitol Granulation
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Solution Overview
Problem
Current bisphosphonate formulations face issues with low bioavailability, stability under storage conditions, and purity due to complex formation with equipment metal parts during wet granulation, particularly when using granulation solutions containing cellulose derivatives and binders like polyvinylpyrrolidone and starch.
Innovation Solution
The use of a wet granulation method with a granulation solution comprising maltodextrin and sorbitol in a ratio of 0.5 to 5 by weight, which enhances stability and purity, and optionally includes additional pharmaceutically acceptable excipients like polyvinylpyrrolidone and starch, with the option for double granulation and the inclusion of an effervescent couple for improved bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If wet granulation method is used with conventional granulation solutions (cellulose derivatives, polyvinylpyrrolidone, starch), then formulations can be produced, but active substances form complexes with metal parts of equipment causing impurity
Solution Approach 1:
The patent introduces a specific granulation solution composition (maltodextrin and sorbitol in 0.5:5 to 5:0.5 weight ratio) as an intermediary substance that mediates between the wet granulation process and the active substance. This granulation solution prevents direct contact between the active substance and metal equipment surfaces, eliminating complex formation while maintaining the benefits of wet granulation production method.
2Ease of manufacture
If conventional granulation solutions are used, then formulations can be manufactured, but stability under storage conditions (temperature and moisture) is compromised
Solution Approach 1:
The patent changes the chemical composition parameters of the granulation solution from conventional binders (cellulose derivatives, polyvinylpyrrolidone, starch) to a specific maltodextrin-sorbitol mixture. This parameter change in the granulation solution composition provides both manufacturability and enhanced stability under storage conditions including temperature and moisture exposure.
3Quantity of substance
If oral administration of bisphosphonates is given on an empty stomach for maximum absorption, then bioavailability increases, but patient compliance decreases due to gastrointestinal irritation
Solution Approach 1:
The patent changes the physical and chemical parameters of the formulation by using maltodextrin and sorbitol in the granulation process, creating an effervescent formulation with improved dissolution characteristics. This allows the drug to be administered with food or water without significant reduction in absorption, thereby maintaining high bioavailability while improving patient compliance and reducing gastrointestinal irritation.
Data Source
AI summary
The present invention relates to stable, highly bioavailable formulations comprising risedronate or alendronate and/or any pharmaceutically acceptable derivative of them so as to be used in prophylaxis and treatment of bone loss and related diseases; and production methods of said formulations.