Interfacial Properties of Pharmaceutical Suspensions

Pharmaceutical suspensions are crucial liquid dosage forms, classifying as coarse dispersions in which an insoluble solid drug is uniformly spread throughout a liquid medium. Achieving and maintaining this uniformity is a core challenge in drug formulation, largely governed by the interfacial properties of the suspended particles.

This article explores the fundamental science behind suspension stability, the forces that dictate particle behavior, and the desirable features of a high-quality pharmaceutical suspension.

What is a Pharmaceutical Suspension?

A suspension is a biphasic system composed of:

Internal Phase (Dispersed Phase): The therapeutically active ingredient (insoluble solid particles). These particles typically range in size from 0.5 to 5 microns ( $\mu$ m).
External Phase (Suspending Medium/Vehicle): The liquid, which is generally aqueous, but can sometimes be an organic or oily liquid for non-oral use (e.g., parental suspensions).

The uniform dispersion is maintained with the aid of a suspending agent or a combination of agents.

The Science of Stability: Interfacial Properties

When a solid drug is reduced to fine particles (a process called comminution) and dispersed in a liquid, the system becomes thermodynamically unstable.

The work, ∆W, or surface free energy, ∆G, required to create this system is given by the equation:

\Delta G = \gamma_{SL} \cdot \Delta A

Where:

$\Delta G$ is the change in surface free energy (making the system unstable).
$\gamma_{SL}$ is the interfacial tension between the solid particles and the liquid.
$\Delta A$ is the total surface area created by the small particles.

Because the large surface area of small particles (∆ $\Delta A$ ) is associated with a high surface free energy (∆ $\Delta G$ ), the particles are highly energetic and naturally tend to regroup to decrease the total surface area and move toward a more stable state (∆ $\Delta G = 0$ ).

This equilibrium can be approached by two primary means:

Reduction of Interfacial Tension (γ $\gamma_{SL}$ ): This is done by adding a surfactant (a type of suspending agent). While surfactants reduce this tension, they cannot ordinarily make it zero.
Decrease of Interfacial Area ( $\Delta A$ ): This occurs when particles come together to form larger masses, a process known as flocculation or aggregation.

Flocculation vs. Aggregation (Caking)

The way particles decrease their surface area determines the quality and stability of the suspension:

Feature	Flocculation (Loose Aggregation)	Aggregation / Caking (Tight Clumping)
Particle Structure	Floccules: Loose, open-network structures held by weak van der Waals forces.	Aggregates: Close-packed arrangement; may adhere by stronger forces (e.g., crystal growth/fusing).
Separation Distance	Particles reside in the secondary energy minimum (1000–2000 Å separation).	Particles overcome the energy barrier and come into close contact (primary minimum).
Redispersibility	Easily redispersed with gentle agitation.	Forms a hard cake at the bottom, which is difficult to redisperse.
Appearance	Unpleasant in appearance (sediment forms quickly).	Looks elegant initially (settles slowly).

The Role of Electrical Double Layer (DLVO Theory)

The stability of particles (whether they flocculate or aggregate) is determined by the balance between attractive (London–van der Waals) forces and repulsive forces arising from the electric double layer surrounding each particle.

Deflocculated System: Repulsion energy is high, creating a large potential barrier that prevents particles from getting too close. They settle slowly but form a dense sediment that leads to caking.
Flocculated System (Desired): The potential barrier is controlled to be just large enough to prevent particles from entering the primary minimum (close contact), but small enough to allow them to reside in the secondary minimum, forming the desired loosely packed flocs.

✨ Desirable Features of an Ideal Suspension

For therapeutic efficacy and patient acceptance, a pharmaceutical suspension should have the following features:

It must remain homogeneous between doses (or at least for the period between shaking).
Any sediment produced must be readily redispersed upon gentle shaking.
The particle size must remain constant throughout the shelf life (no crystal growth).
The viscosity should allow the suspension to be easily poured from the container.

📋 Classification of Pharmaceutical Suspensions

Suspensions are categorized based on their administration route and the concentration of the solid phase:

Classification Basis	Type of Suspension	Examples
General Class	Oral Suspension	Paracetamol Suspension
	Externally Applied Suspension	Calamine Lotion
	Parenteral Suspension	Insulin Zinc Suspension
Proportion of Solids	Dilute Suspension (2–10% w/v solid)	Cortisone Acetate
	Concentrated Suspension (>50% w/v solid)	Zinc Oxide Suspension
Particle Size	Coarse Suspension (>1 $\mu$ m)	Most standard oral suspensions
	Colloidal Suspension (<1 $\mu$ m)	Specific colloidal preparations
	Nanosuspension (10 ng)	Advanced drug delivery systems