Liquid Dosage Forms: Pharmaceutical Suspensions

Excipients used in pharmaceutical suspensions

The possible types of excipients used in the formulation of pharmaceutical suspensions include:

1. Solvents/ Vehicles: Solvents (or vehicles) are major components used as a base in which drugs and other excipients are dissolved or dispersed. The most commonly used vehicle for the formulation of pharmaceutical suspensions is purified water. In a few instances, viscous nonaqueous solvents, such as propylene glycol and polyethylene glycols, are used as vehicles to impart stability to suspended drug particles. The choice of solvent used depends on the nature and physicochemical properties of the active pharmaceutical ingredient (API) and the intended use of the formulation.

2. Buffering agents: Buffering agents or pH modifiers are agents that are added to suspensions to control potential changes in the pH of formulations. Citrates and phosphates are commonly used buffers in pharmaceutical suspensions. Citrate buffers are used to stabilize suspensions in the pH range of 3 – 5, while phosphate buffers are used in the pH range of 7 – 8.

3. Preservatives: Preservatives are often added in aqueous suspensions to protect them from microbial contamination. Common preservatives used in pharmaceutical suspensions are parabens, alcohol, glycerin, propylene glycol, and sorbates.

4. Antioxidants: Antioxidants are required in certain pharmaceutical suspensions to enhance the chemical stability of the therapeutic agent, where this may be compromised by oxidation. Examples include thiourea, butyl hydroxy toluene (BHT), tocopherols, ascorbic acid, sodium bisulphate, etc.

5. Wetting agents/ surfactants: Wetting agents are used to improve the flow of the liquid vehicle across the particle surface, which in turn improves the homogeneity of distribution of the drug particles throughout the formulation. Examples include polysorbates, sorbitan esters etc.

6. Antifoaming agents: These are excipients that prevent foam formation during the manufacture of suspensions or when reconstituting powder for suspension. Examples include simethicone, organic phosphates, alcohols, paraffin oils, stearates and glycols

7. Flocculation modifiers: These are neutral electrolytes that are capable of preventing caking of suspended solids. Examples of flocculating agents used in pharmaceutical suspension (usually at concentrations 0.01 – 1.00 %) include sodium or potassium chloride, aluminum chloride, calcium salts, citrates, etc.

8. Suspending agents/ Viscosity-modifiers: These are hydrophilic colloids, such as cellulose derivatives, acacia, and xanthan gum that are added to a suspension to increase viscosity inhibit agglomeration, and decrease sedimentation.

9. Flavoring agents: Flavours e.g., peppermint, lemon oils, butterscotch, ‘tutti-frutti’ flavour etc., are added to pharmaceutical suspensions for taste-masking purposes.

10. Sweeteners: Sweeteners are often added to suspensions to reduce any unpleasant taste of the partially dissolved drug and to improve palatability in general. Examples include sorbitol, corn syrup, sucrose, saccharin, acesulfame, and aspartame.

11. Colorants: These are added to provide a more aesthetic appearance to the final product. The choice of colorant is usually tied to the choice of flavour, and their choices are also linked to the patient population, such as age group and geographic region, and the therapeutic need. For example, a red colorant is usually used with strawberry flavour for pediatric formulations.

12. Humectants: Humectants are added to retard the evaporation of aqueous vehicle from dosage forms during storage and use. Examples include glycerol, propyleneglycol etc.

13. Chelating agents: Chelating agents are added to pharmaceutical suspensions to protect drug substance(s) from catalysts that accelerate oxidative reaction.

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Stability and evaluation of pharmaceutical suspensions

Because suspensions are thermodynamically unstable system, physical stability of suspensions becomes as important as the chemical and biological stability. The major stability factors in pharmaceutical suspension include attributes such as particle size distribution, content uniformity, viscosity, drainability, resuspendability, dissolution rate, pH, and zeta potential.

For a formulator to achieve simultaneous stability for the drug product, it is generally best to start by optimizing the variable with the most restrictive constraint first.

Manufacture of pharmaceutical suspensions

Suspensions are typically manufactured using a high-energy mill to disperse the insoluble powder ingredients in the suspension vehicle. A high energy mill is required to ensure thorough mixing because the vehicle is usually viscous. In addition, the high-energy process can lead to the desired reduction or narrowing of the particle size distribution. A high-shear hand mixer is frequently used in laboratory-scale for suspension manufacture. A colloid mill is usually used for the manufacture of pilot and production scale manufacture of suspensions on a commercial scale.

The powder properties of incoming raw materials are critical and closely controlled to assure the quality attributes of powder blend. These include particle size, shape, charge, size distribution, residual moisture content, flowability, compatibility, and any aggregation tendency. Each ingredient is screened to ensure it is homogeneous and free of agglomerates, followed by mixing with other ingredients in an order that ensures uniform mixing.

The preparation of a suspension involves the mixing of water-soluble components with water to form an aqueous solution. The solid ingredients are then added to this solution under high shear-mixing process in a sequential manner to form a suspension. The suspension is dispensed into bottles using automated liquid dispensing machines.

Powder for suspensions (PFSs), are manufactured as dry powders. These formulations are designed to be rapidly redispersible by gentle mixing in the presence of water. The manufacturing process for PFSs involves mixing the bulk powders of the formulation components followed by dispensing into commercial containers using an automated bottle or sachet-filling machine. Mixing of low quantity ingredients, such as colorants, can be challenging. Usually, such ingredients are premixed and/or adsorbed on the surface of another higher quantity ingredient before being mixed with the rest of the material. In addition, ingredients that may be liquid at room temperature, such as liquid flavours, are adsorbed onto another material before mixing with the bulk of the ingredients. Ingredients can also be co-screened or co-milled to ensure their thorough mixing.

References

• Aulton, M. and Taylor, K. (2013). Aulton’s Pharmaceutics: The Design and Manufacture of Medicines, (4th ed.). Edinburgh: Churchill Livingstone.
• Chaudhari, S. and Patil, P. (2012). Pharmaceutical Excipients: A review. International Journal of Advances in Pharmacy, Biology and Chemistry, 1(1): 21-34.
• Dash, A., Singh, S. and Tolman, J. (2014). Pharmaceutics: Basic Principles and Application to Pharmacy Practice. USA: Elsevier Inc.
• Durgin, J., and Hanan, Z. (2009). Durgin and Hanan’s Pharmacy Practice for Technicians, (4th ). Canada
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• Kulshreshtha A., Singh O. and Wall M. (2010). Pharmaceutical Suspensions: From Formulation Development to Manufacturing. London, New York, Dordrecht Heidelberg: Springer.
• Kumar P., Bhowmik D., Srivastava S., Paswan S. and Dutta A. (2012). Taste Masked Suspension. The Pharma Innovation, 1(2), 1-7.
• Mahato, R and Narang, A. (2018). Pharmaceutical Dosage Forms and Drug Delivery (3rd ed.). New York: Taylor & Francis Group, LLC
• Ofoefule S. I (2002) ed. A Textbook of Pharmaceutical Technology and Industrial Pharmacy for Undergraduate and Postgraduate Students of Pharmacy and Manufacturing Pharmaceutical Industries. Nigeria, Lagos: Samakin (Nig) Enterprises.
• Sachan, A., Singh, D., Kumar, Y. and Kumar, M. (2017). A Review On Excipients Used In Oral Liquid Dosage Forms. International Journal of Pharmacy & Technology, 9(1): 5709-5719.
• Schramm L. L. (2005). Emulsions, Foams, and Suspensions: Fundamentals and Applications. Weinheim: WILEY-VCH Verlag GmbH & Co. KGaA.

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