Pharmaceutical Suspensions

(The formulation of Oral Suspensions)

PART 2: STABILIZATION & ROLE OF EXCIPIENTS

DRABE NICKSON.,(M.P.S)
 Lecture objectives
• To discuss the physical stability issues of pharmaceutical suspensions

• To discuss the formulation techniques employed to stabilize suspensions

• To discuss the roles of excipients employed in oral suspensions

 Physical stability problems
The main stability problems encountered in formulation of suspensions
include;-

1. Sedimentation

2. Thermodynamic instability (poor wetting)

 1. Sedimentation
• Particles in a suspension will sediment under action of gravity and settle at the
bottom

• Larger particles reaching the bottom initially and smaller particles filling the voids

• The weight of the supernatant fluid supplies sufficient compressional force

• If repulsion at the primary maximum is overcome, agglomeration results, causing

caking (irreversible)
 Sedimentation cont’d…
(Ostwald ripening!)
• Occasionally some dissolution occurs especially form smaller particles
followed by crystallization out of solution

• The growing crystals cross-link/bridge adjacently settled particles

• Further hardening/reinforcing the ‘caked mass’ at the bottom

• This undesired phenomenon is called Ostwald ripening

 The Advantage of a Flocculated state
Flocculation is the loose aggregation of suspended particles to form
larger ones called flocs or floccules

• These larger and more irregular floccules exhibit poor close packing upon settling

• This arrangement disfavours caking, thus redispersion of sedimented particles is

easier for flocculated systems

• Although flocs sediment at a faster rate, their redistribution on shaking is much

easier
 QUESTION FOR YOU!

1. What is the main pharmaceutical advantage of a flocculated state

in a suspension?
2. By what technique can a formulation scientist achieve controlled
flocculation? Explain how the technique works.
 Decreasing sedimentation rate
...by a look at Stokes Law
a) Increasing viscosity (η) of the vehicle

• This decreases the sedimentation velocity of the particles by increasing the

viscous drag operating on the particles.

• Can be achieved by including viscosity enhancing (suspending) agents;-

Natural gums; Acacia, Tragacanth, Xanthan gum

Others; Carboxymethylcellulose (CMC), Carbomer, methylcellulose etc.

You can choose from these, if you wish
 Decreasing sedimentation rate
...by a look at Stokes Law
b) Particle-size reduction
• Sedimentation rate is inversely proportional to the radius of the suspended particles

• Milling and sifting are the unit processes carried out to achieve the desired particle
size and size distribution

• A low sedimentation rate allows enough time for measurement of equal doses after
the suspension has been shaken
 Thermodynamic instability
• On account of their interfacial tension with the solvent, insoluble medicaments are
classified as;-
a) Diffusible (dispersible) solids
• Have relatively low interfacial tension at their interface with the solvent (vehicle)

• They are easily wettable by the solvent and easy to redisperse on settling

• Examples include; magnesium trisilicate, light magnesium carbonate, bismuth

carbonate and light kaolin

• Ingredients familiar in antacid suspensions

 Thermodynamic instability…..
b) Indiffusible solids
• These present significant interfacial tension thus have poor wettability

• Interfacial energy is amplified by the increased surface area

….due to particle size reduction

• High tendency of aggregation to form porous clumps or just remain spread on the surface

• Examples; aspirin, phenobarbital, and for external use calamine, hydrocortisone, Sulphur
and zinc oxide.
• Most insoluble medicaments are indiffusible
 Enhancing wettability

• Solid-liquid interaction can be improved by reduction of interfacial tension, .

• This lowers interfacial free energy ΔG thus preventing spontaneous aggregation of

suspended particles

• Wetting agents are ingredients that either reduce the solid-liquid interfacial
tension or are cosolvents with a lower surface tension themselves
 Wetting agents
• Hydrophilic colloids; ; acacia and tragacanth gums

• Intermediate HLB surfactants;-

Internal preparations: polysorbates (tweens), sorbitan esters (spans)

External preparations: Sodium lauryl sulphate, quillaia tincture

• Cosolvents; such as ethanol, glycerol and the glycols

 Other Excipients
• Vehicle; commonest is purified water
• Cosolvents; to dissolve other excipients
• Preservatives;
• Sweetening agents
• Antioxidants
• Added electrolytes; for controlled flocculation

See Pharmaceutical solutions for examples

 Methods of Preparation
Read about;-
1. Direct incorporation
2. Precipitation method

WE MAY ILLUSTRATE THEM IN A LAB SESSION

 Readings

1. Aulton’s Pharmaceutics: The Design and Manufacture of Medicines.

Fifth Edition. chapter 26
 Advanced Readings
1. Remington: Essentials of Pharmaceutics, chapter 21 & chapter 24

2. Alexander T Florence & David Attwood: Physicochemical

Principles of Pharmacy; In Manufacture, Formulation and Clinical
Use, sixth Edition. chapter 6
 Good luck
PER MEDICATUM SERVIUM