Doxycycline Metal Complex Solid Dosage Form
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Solution Overview
Problem
Current methods fail to produce a stable and effective solid dosage form of doxycycline metal complex for pharmaceutical use due to instability in alkaline pH environments and residual solvents, and existing forms like doxycycline hyclate can cause esophageal ulceration, while there is a lack of a convenient solid alternative to liquid suspensions.
Innovation Solution
A process involving an aqueous solution of doxycycline or its salt, admixing a metal salt and a base to form a suspension, followed by drying to create a solid dosage form, which can include pharmaceutically acceptable excipients, allowing for the production of a stable doxycycline metal complex in the form of tablets or capsules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If doxycycline hyclate is used as a solid dosage form, then it provides a convenient solid alternative to liquid suspensions, but it causes esophageal ulceration
Solution Approach 1:
The patent changes the chemical form of doxycycline from hyclate to metal complex (calcium, magnesium, zinc, or aluminum salts), which fundamentally alters the drug's properties. This parameter change maintains solid dosage form convenience while eliminating esophageal ulceration by reducing solubility in the esophageal environment.
Solution Approach 2:
The patent creates a composite material by combining doxycycline with metal salts to form a metal complex. This composite structure provides both the therapeutic activity of doxycycline and the beneficial properties of the metal complex, including reduced esophageal irritation while maintaining solid dosage form advantages.
2Stability of the object's composition
If calcium salts of doxycycline are used, then they provide a stable complex, but they are unstable in alkaline pH environment
Solution Approach 1:
The patent changes the metal salt from calcium (which is alkaline-sensitive) to magnesium, zinc, or aluminum salts. These alternative metal salts form complexes with doxycycline that are more stable across a wider pH range, particularly resistant to degradation in alkaline environments while maintaining complex stability.
3Productivity
If organic solvents are used in the isolation process, then they enable extraction of doxycycline, but they leave residual solvents that make the dosage form unsuitable for human administration
Solution Approach 1:
The patent replaces organic solvent-based extraction mechanisms with an aqueous-based process. By using water-soluble excipients and aqueous processing methods, the patent achieves effective extraction and formulation of doxycycline metal complex without introducing harmful organic residual solvents, making the final dosage form safe for human administration.
4Object-affected harmful factors
If doxycycline metal complex is made as a solid dosage form, then it avoids esophageal ulceration, but it is extremely difficult to manufacture
Solution Approach 1:
The patent introduces water-soluble excipients as intermediaries to facilitate the formation of doxycycline metal complex in solid dosage form. These excipients act as mediators that enable proper complexation, filtration, and formulation processes, transforming the difficult manufacturing process into a feasible aqueous-based formulation approach.
Solution Approach 2:
The patent changes the formulation parameters by using aqueous-based excipients instead of organic solvents. This parameter change enables the use of standard pharmaceutical manufacturing processes for solid dosage forms, improving manufacturability while maintaining the esophageal protection benefits of the solid form.
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
This method enables the creation of a stable, effective solid dosage form of doxycycline metal complex that is absorbed safely, avoiding esophageal ulceration and providing a convenient alternative to liquid suspensions, with the ability to deliver doxycycline and a mineral source, such as calcium, effectively treating bacterial infections.
Implementation Method 1
admixing a base to increase the pH of the aqueous solution, thereby forming a suspension of doxycycline metal
Implementation Method 2
drying the suspension, thereby forming a dry granulation of doxycycline metal complex
Data Source
AI summary
The present invention is a solid dosage form of a doxycycline metal complex. The present invention also includes a process for making a doxycycline metal complex in a solid dosage form. The process comprises the steps of (i) providing an aqueous solution of doxycycline or a physiologically acceptable salt thereof; (ii) admixing a metal salt with the aqueous solution; (iii) admixing a base to increase the pH of the aqueous solution, thereby forming a suspension of doxycycline metal; and (iv) drying the suspension, thereby forming a dry granulation of doxycycline metal complex.