Example: Amlodipine - REVIEW
- Heiner Oberkampf
- Elisa Kendall
- Li Ming Gooi
Disclaimer
This example is for illustration purposes only. The data provided may not be up-to-date, and in some cases, 'dummy' data has been included. The product information included here shall not be used for any other purpose than for educational purposes regarding the IDMP-O implementation.
Introduction
Amlodipine belongs to a class of medications known as calcium channel blockers and is oftentimes used for the treatment of high blood pressure. It is used here as a specific example to demonstrate a case where a pharmaceutical product has an active ingredient which does not form the Basis of Strength Substance (BOSS). Instead it is the active moiety within the active ingredient (also refered to as a reference substance) that forms the BOSS. For more information on BOSS, please refer Pattern: Representing Reference Substances, Reference Strength, and the Basis of Strength, including in Different Jurisdictions - APPROVED for further information.
Table 1 Short recap of definitions that are relevant for the understanding of this page
| Word/ phrase | Explanation |
|---|---|
| Basis of Strength Substance (BOSS) | The active ingredient in a drug product that is measured to provide the product strength. |
| Reference Strength | The quantity or range of quantities of the reference substance present per unitary volume (or mass). |
| Reference Substance | A substance or part of a substance (moiety) that is closely related to another substance (e.g. salt, base), that is the active ingredient of a pharmaceutical product. "Reference substance" is used in expressions of strength when an ingredient in a pharmaceutical product is not the final effector of a pharmacological response. Instead the ingredient can give rise or consists of the reference substance that induces the pharmacological response in an organism. |
| Strength | The quantity or range of quantities of the substance/specified substance present per unitary volume (or mass). It should be noted that the strength here refers to a nominal value instead of an actual measurement. |
Figure 1 Summary depicting the relationships between the pharmaceutical product and its active ingredient and active moiety and their respective strengths using Norvasc as an example.
Table 2 Details of strength expressions for different Amlodipine products. ACTIR is the ingredient code for an active ingredient where another reference substance is the basis of strength. ACTIM is the ingredient code for an active ingredient where the active moiety is the basis of strength. Details on Amlodipine EMC are given as an additional examples, but only Norvasc is fully explained and illustrated in this page.
| Product name | Active ingredient | Substance role | Molecular formula by moiety | Molecular weight of substance (Dalton) | Strength per unit (presentation) | Reference substance | Substance role | Molecular formula by moiety | Molecular weight of substance (Dalton) | Reference strength (presentation) |
|---|---|---|---|---|---|---|---|---|---|---|
Norvasc Amlober | Amlodipine besylate | ACTIR | C2OH25ClN2O5.C6H6O35 | 567.051 | 6.94 mg/ tablet | Amlodipine | ACTIM | C2OH25ClN2O5 | 408.88 | 5.0 mg/ tablet |
| Amlodipine EMC | Amlodipine mesylate monohydrate | ACTIR | C2OH25ClN2O5.CH4O3S.H2O | 523.000 | 6.41 mg/ tablet | Amlodipine | ACTIM | C2OH25ClN2O5 | 408.88 | 5.0 mg/ tablet |
Related Competency Questions:
UC1 CQ02 What is the active moiety of <substance y>?
UC1 CQ03 What are the products that contain substances with common active moiety <active moiety x>?
UC1 CQ03.1 What is the basis of strength for <substance x> in <product y>?
Model Pattern Instantiation
The first competency question, what is the active moiety of <substance y>, is exemplified in Figure 2. The figure shows two substances, amlodipine besylate and amlodipine mesylate monohydrate, each of which contains amlodipine as their active moiety.
Figure 2. Diagram showing the active moiety pattern, including various properties that can be used for question answering.
In order to demonstrate the second competency question, "what products have a given active moiety in common", we need to incorporate the concept of a pharmaceutical product as well as its composition, and connect the elements in the composition to its active moiety(ies). Figure 3 extends the patterns shown in Figure 2 to cover the additional concepts for a single product (Norvasc) and its active ingredient (amlodipine besylate).
Figure 3. Diagram showing the relationships between a product, its composition, and the active moiety of one of the substances it is composed of.
Taking that a step further, we can show the strength of the active ingredient as well as its reference strength to answer the third competency question, as shown below in Figure 4.
Figure 4: Diagram modeling the basis of strength for Norvasc, which has the active ingredient amlodipine besylate, which has the active moiety amlodipine.
Figure 1 was modified from https://www.tcichemicals.com/DE/de/p/A2353