Pre-formulation of Solid Dosage Forms

Part 1 and 2

Principles of Dosage Form Design

The design of any dosage form is the conversion of a new chemical entity (NCE) (the drug) into a deliverable medicine.

What is preformulation?

The first step in the rational development of dosage forms of a drug into a medicine.

What is solubility?

The maximum amount of a drug that can dissolve in a solvent (like water or stomach fluid) at a given temperature and pH.Once this maximum amount is reached, no more will dissolve — even if you wait longer.

What is dissolution rate?

The speed at which the drug dissolves.

It describes how fast the solid turns into dissolved molecules.

Why is dissolution rate a variable?

Because how fast a drug dissolves can change depending on things like:

• Particle size (smaller = faster)

• Tablet formulation

• Stirring/agitation in the gut

• Surface area exposed

• If the drug is coated

• Whether the tablet is compressed tightly or loosely

• Whether excipients (like disintegrants) are present

So dissolution rate can be manipulated and is not fixed.

Why does solubility and dissolution rate matter in pharmacy?

• Low solubility → poor absorption (low bioavailability)

• Slow dissolution rate → delayed or incomplete absorption

Noyes Whitney Equation for Dissolution Rate

What is BCS?

Biopharmaceutical Classification System

What is BCS only applicable for?

Oral dosage forms

What do we do using the information of BCS?

We can only modify the solubility of the compound, we can’t do much with permeability

Common strategies to address low drug solubility:

What are high risk compounds?

Poorly soluble compounds. They may require one of the non-equilibrium methods or semi solid formulations to enhance dissolution rate and bioavailability via the GI tract

High risk compounds: Methods to make them more soluble:

• Amorphous

• Meta-stable polymorphs

• Solid dispersion

• Lipid based formulations (e.g. soft liquid gelatine capsules)

If a drug has an ionisable group, what will happen?

The solubility will change as a function of pH