Pharmaceutical Excipients in Oral Suspensions

Coarse Dispersion, Suspension

• Coarse dispersion is a type of suspension.

Excipients in Oral Suspensions

• There is similarity in excipients used for suspensions and solutions for oral administration.
• The main difference involves excipients used to stabilize suspensions.
• Many excipients used for stabilizing suspensions are similar to those used for solutions.

Vehicles

• Purified water is the most common vehicle.
• Buffers (e.g., citric acid/sodium citrate) are used to control pH.

Excipients for Physical Stability

• Pharmaceutical suspensions are stabilized through controlled flocculation and particle/floccule sedimentation.
• Electrolytes are added for stabilization.
• Surface-active agents affect wetting and flocculation.

Hydrophilic Polymers

• Hydrophilic polymers enhance physical stability and affect flow properties of oral suspensions.
• Polymers adsorb onto drug particles, creating an adsorbed layer.
• Increased polymer concentration increases layer thickness.
• Stearic repulsion prevents particle contact, enhancing stability.

Concentration of Polymer

• Polymer concentration affects the density of the adsorbed polymer layer.
• Optimal concentration enhances repulsion without preventing particle interaction (flocculation).
• Flocculation typically occurs at a distance approximately twice the adsorbed polymer layer thickness.

Type of Polymer

• Polymer type (chemistry) influences stabilization properties through:
  • Adsorption on drug particle surface (affecting layer thickness and integrity).
  • Interactions between polymer chain groups leading to stearic stabilization.

Preservatives

• Oral suspensions are non-sterile.
• Restrictions exist on the number and type of microorganisms.
• Highly pathogenic microorganisms (e.g., Escherichia coli) must be absent.
• Less pathogenic bacteria/fungi growth must be inhibited.
• Specifications for microorganisms in oral products are outlined in pharmacopoeias.

Example Preservatives

• Parabens (esters of parahydroxybenzoic acid) are often used in combination (e.g., methyl/propyl).
• Organic acids (e.g., benzoic acid).

Preservative Selection Considerations

• Preservatives must exist in solution to exert antimicrobial effect.
• Interactions between preservatives and formulation components (e.g., hydrophilic polymers) can decrease the free preservative concentration.
• Preservatives must not adversely affect the suspension's chemical or physical stability.

Sweetening Agents/Flavors

• Sweetening agents (e.g., sucrose, glucose) and flavors are used for taste masking as in solutions.

Antioxidants

• Antioxidants are necessary to enhance the chemical stability of therapeutic agents.
• Selected antioxidants have higher oxidative potential than the drug or inhibit free radical-induced decomposition.
• Examples include sodium sulfite, sodium metabisulfite, sodium formaldehyde sulfoxylate, and ascorbic acid.

Manufacture-Direct Incorporation

• Soluble components are dissolved, then the solid drug is dispersed into the vehicle.
• Mixing rate is critical.
• High speed mixing may lead to higher viscosity, while low speed is appropriate for flocculated systems.

Manufacture - Particle Size Reduction

• Particle size of drug can be reduced using a ball mill.
• Particle size optimization is done before incorporation into the vehicle.

Manufacture - Precipitation Methods

• Three precipitation methods:
  • Organic solvent precipitation: Dissolving water-insoluble drugs in a water-miscible organic solvent, then adding it to water.
  • Precipitation by pH: Changing the pH of the medium.
  • Double Decomposition: Simple chemical reactions generating an insoluble product.

Additional Notes

• Specific examples of formulations discussed include Estradiol Suspension, Insulin Suspension, White Lotion (NF XIII).

This quiz focuses on the various excipients used in oral suspensions, including the differences between those used for suspensions and solutions. It covers topics like vehicles, stability mechanisms, and the role of hydrophilic polymers. Test your knowledge and understand the importance of each component in formulating effective pharmaceutical suspensions.