Ingredient Design Strategy

Within the SIRIAM Platform, ingredients are not selected individually or in isolation.

Each ingredient is incorporated only after its role has been defined within the overall formulation architecture.

The position of an ingredient is therefore determined by design rather than by availability, popularity or tradition.

This strategy promotes consistency, reproducibility and long-term platform integrity.

The formulation process follows a hierarchical approach.

An ingredient is never the starting point of development.

Instead, every ingredient must support an already established:

Clinical Purpose

Application Field

Functional Matrix

Regional Signature Matrix

Only after these elements have been defined is ingredient selection initiated.

Within the SIRIAM Platform, every ingredient belongs to one primary design category.

Category I

Vehicle Components

Ingredients responsible for the pharmaceutical carrier system.

Examples include components that establish the physical vehicle.

Category II

Structural Components

Ingredients that contribute primarily to the structural integrity of the formulation.

Their principal role is pharmaceutical rather than regional.

Category III

Functional Components

Ingredients selected because they support the intended function of the formulation within the Release or Integration phase.

Category IV

Regional Signature Components

Ingredients that distinguish one anatomical formulation from another.

These components provide regional identity while remaining compatible with the common platform architecture.

Category V

Technical Components

Ingredients incorporated primarily for pharmaceutical quality.

Examples include components related to:

manufacturing robustness.

• preservation;
• pH adjustment;
• formulation stability;

Before a new ingredient is incorporated, the following questions are addressed.

Step 1

Does the ingredient support the Clinical Purpose?

Step 2

Does it correspond to the intended Application Field?

Step 3

Is the ingredient required within the Functional Matrix?

Step 4

Does it contribute to the Regional Signature Matrix?

Step 5

Is it pharmaceutically compatible with the existing Structural Matrix?

Step 6

Can it be reproducibly incorporated into the standardized platform vehicle?

Only after successful evaluation of all six steps may an ingredient proceed to pharmaceutical review.

Potential ingredients are evaluated according to multiple complementary criteria.

These include:

Anatomical relevance

Compatibility with the intended neurodermal Application Field.

Functional relevance

Contribution to the intended Release or Integration strategy.

Platform compatibility

Compatibility with existing Structural Matrix components.

Pharmaceutical compatibility

Compatibility with:

stability.

Manufacturing feasibility

Availability of pharmaceutical-grade raw materials.

Reproducible magistral preparation.

Development potential

Suitability for future optimization within the SIRIAM Platform.

• vehicle;
• preservation system;
• preparation method;
• packaging;

Each ingredient progresses through a standardized development pathway.

Scientific or Traditional Rationale

↓

Concept Evaluation

↓

Architectural Classification

↓

Prototype Formulation

↓

Professional Review

↓

Pilot Batch

↓

Clinical Evaluation

↓

Pharmaceutical Validation

↓

Master Formula

Progression to the next stage occurs only after multidisciplinary evaluation.

Whenever possible, ingredients already established within the platform are preferred over introducing new substances.

This strategy promotes:

easier quality control.

The introduction of a new ingredient should therefore be justified by a clear added value within the established platform architecture.

• formulation consistency;
• manufacturing simplicity;
• reduced variability;

Ingredient concentrations may evolve throughout the development process.

Optimization may result from:

multidisciplinary discussion.

Optimization of concentration does not necessarily alter the functional identity of the formulation.

• pharmaceutical review;
• preparation experience;
• stability evaluation;
• packaging performance;
• clinical observations;

If an ingredient becomes unavailable or unsuitable, replacement follows the same design pathway as the original selection.

The replacement ingredient should preserve:

pharmaceutical compatibility.

Replacement is therefore based on preservation of formulation architecture rather than direct substitution.

• the Clinical Purpose;
• the Functional Matrix;
• the Regional Signature Matrix;

An ingredient may be removed from the platform if:

multidisciplinary review recommends removal.

Retirement of an ingredient shall be documented in the Development Record.

• pharmaceutical disadvantages outweigh benefits;
• reproducibility cannot be ensured;
• compatibility issues arise;
• superior alternatives become available;

Every ingredient introduced into the SIRIAM Platform should be documented with:

version history.

This documentation ensures transparency and traceability throughout the evolution of the platform.

• category within the Ingredient Design Strategy;
• rationale for inclusion;
• intended role;
• pharmaceutical considerations;
• development history;

The Ingredient Design Strategy is intended as a living framework.

As pharmaceutical science, formulation technology and clinical experience evolve, the strategy may be refined while preserving the core design principles of the SIRIAM Platform.

Professional Review Notes (Anouck Van Aerschot)

Review 15.1 – Classificatie

☐ Bevestigen dat elk ingrediënt correct is ingedeeld als Vehicle-, Structural-, Functional-, Regional Signature- of Technical Component.

☐ Eventuele herclassificatie documenteren.

Review 15.2 – Farmaceutische compatibiliteit

☐ Beoordelen of nieuwe ingrediënten verenigbaar zijn met de huidige voertuigbasis, bewaarsysteem en bereidingsmethode.

☐ Mogelijke interacties of stabiliteitsproblemen registreren.

Review 15.3 – Concentratie-optimalisatie

☐ Concentraties aanpassen op basis van oplosbaarheid, viscositeit, homogeniteit en reproduceerbaarheid.

☐ Wijzigingen vastleggen in de Development Record.

Review 15.4 – Platformharmonisatie

☐ Nagaan of nieuwe ingrediënten werkelijk een meerwaarde bieden ten opzichte van bestaande platformcomponenten.

☐ Onnodige variatie vermijden.

Review 15.5 – Master Formula

☐ Na validatie bevestigen dat de definitieve ingrediëntenlijst voldoet aan de Platform Standards en reproduceerbaar magistral kan worden bereid.

✦ Editor's R&D Note (werkversie)

De Ingredient Design Strategy is een ontwerpinstrument en geen therapeutische rangschikking van ingrediënten. Een ingrediënt wordt niet geselecteerd op basis van vermeende werkzaamheid alleen, maar op basis van zijn plaats binnen de volledige SIRIAM-architectuur. Daardoor blijft het platform coherent, zelfs wanneer formuleringen in de toekomst worden geoptimaliseerd of aangepast.