Pharmaceutical Suspensions Overview

Suspensions

• Finely divided insoluble solid particles dispersed in a fluid (dispersion medium)
• Particle size classifications dictate different types of solutions (true solution, colloidal solution, suspension)
• True solutions have particles < 10⁻⁷ cm
• Colloidal solutions have particles between 10⁻⁷ cm and 10⁻⁵ cm
• Suspensions have particles > 10⁻⁵ cm

Physical Properties of Well-Formulated Suspensions

• Remains homogeneous after shaking and removal of the dose
• Resuspension occurs easily with mild shaking
• No hard cake formation during shelf life, and easily redisperses
• Maintains stability and elegance during shelf life

Parenteral Suspensions

• Free from microbial contamination and must maintain sterility
• Easily drawn into a syringe and injectable

Pharmaceutical Applications of Suspensions

• Used when solid drug swallowing is difficult
• Used when drug solubility in an aqueous medium is poor (e.g., hydrocortisone, neomycin)
• This approach is particularly beneficial in pharmaceutical formulations where certain active ingredients are prone to hydrolysis or other chemical degradation when exposed to water. By creating an insoluble derivative, these drugs can be effectively delivered in a form that preserves their potency, stability, and therapeutic efficacy, while also facilitating their administration in a convenient suspension form.

Stability

• The product exhibits stability for 7 days when stored at room temperature, which typically ranges from 20°C to 25°C (68°F to 77°F). This duration allows for flexibility in handling and transportation before any deterioration occurs.
• When refrigerated, with a temperature set between 2°C and 8°C (36°F and 46°F), it maintains stability for up to 14 days, ensuring its efficacy and quality over a longer period, particularly useful for storage and usage in laboratory settings.

Additional Applications of Suspensions

• Used for vaccines to build up antibodies
• Utilized as X-ray contrast media, enhancing the visibility of internal structures during imaging procedures. (e.g., Barium sulphate)
• Used in aerosols

Formulation of Suspensions - Overview

• Particle Size Control: Finely dividing the drug decreases sedimentation rate, reduces gritty texture of large particles and potential eye irritation from large particles
• Wetting Agents: Wetting agents, also known as surfactants, play a crucial role in various applications by facilitating the interaction between water and insoluble solids. While some solids can be readily wetted and dispersed in water, others may resist wetting due to their hydrophobic properties. The degree of hydrophobicity can significantly vary among different materials. To achieve effective wetting, it is essential to decrease interfacial tension, thus enhancing the spreading and penetration of the liquid over the solid surfaces.
• Flocculation/Deflocculation:
  • Deflocculated: Particles exist as discrete units, slow sedimentation, sediment compaction. Pleasant appearance, slow settling and A cloudy supernatant indicates the presence of suspended particles. This turbidity often arises when solid particles are not completely settled at the bottom of a container, thus remaining in the liquid phase after centrifugation or sedimentation.
  • Flocculated: Particles form loose aggregates, rapid sedimentation, easily redispersable sediment, no hard sediment cake. Unsightly, rapid sedimentation, clear supernatant
• Degree of Flocculation: Correct degree is crucial, under-flocculation is undesirable, over-flocculation is irreversible and can lead to inelegant appearance, high viscosity, and difficulties with redispersion.
• Rheology of Suspensions: High apparent viscosity at low shear rates for slow settling and good suspension, decreasing viscosity at high shear rates for easy pouring
• Viscosity Modifiers:
• polysaccharides (Acacia gum, tragacanth, alginates),
• water-soluble cellulose (methylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose),
• hydrated silicates (bentonite), colloidal silicone dioxide
• Other Formulation Additives: Buffers which maintain chemical stability, density modifiers which ensure sedimentation consistency, flavours, colorants, perfumes, humectants (glycerol, propylene glycol), preservatives, and sweetening agents

Manufacture of Suspensions

• Small scale*: This process combines a powdered drug, a suspending agent for uniform dispersion, and a liquid vehicle. A mortar and pestle ensure thorough mixing for consistent formulations and accurate dosing.*
• Large scale: Concentrated dispersion of suspending agent is prepared first, then slowly added to the vehicle while mixing. Appropriate mixing equipment like impeller blenders or turbine mixers

Stability Testing of Suspensions

• Physical Stability: This concept is critical in understanding the behavior of colloidal systems and dispersions. It can be quantitatively assessed through various parameters including the sedimentation rate, which indicates how quickly particles settle under gravity. Additionally, final volume or height of sediment provides insights into the concentration and stability of the dispersion over time. The ease of redispersion, evaluated through the V/Vo ratio compared over a specified timeline, assesses the ability of the sediment to return to a dispersed state after settling.
• Centrifugation: Useful for accelerating sedimentation rate, and provides relative stability information, but can potentially destroy flocculate structure.
• Rheological Assessment: Used to measure viscosity at various shear rates and provide insights into the structural changes that occur during storage; useful for routine quality control measures
• Temperature Cycling: Helps assess the stability against temperature fluctuations through cycling between high and low temperatures. Useful for assessing crystal growth, by measuring particle size for example.