Industrial Pharmacy: Suspensions PDF

# Industrial Pharmacy: Suspensions ## Suspensions - **Definition:** Preparations containing finely divided drug particles distributed throughout water in which the drug exhibits a minimum solubility. - **Ready-to-use form:** Drug is already suspended in a liquid. - **Reconstitution powders...

# Industrial Pharmacy: Suspensions ## Suspensions - **Definition:** Preparations containing finely divided drug particles distributed throughout water in which the drug exhibits a minimum solubility. - **Ready-to-use form:** Drug is already suspended in a liquid. - **Reconstitution powders:** Dry powders need to be suspended in a liquid at the time of dispensing. - **Uses:** Oral, topical, or parenteral (injection). ## Reasons for Suspension Preparation - **Chemical stability:** Some drugs are unstable in solution but stable when suspended. Examples include *oxytetracycline HCl*. - **Palatability:** Undesirable taste of certain drugs in solution form is avoided. Example: *erythromycin estolate*. - **Ease of swallowing:** Liquid forms are preferred over solid forms. ## Desirable Features of Suspensions 1. **Sedimentation:** Should settle slowly and remain homogenous for at least the time between shaking and removing the required dose. 2. **Redispersion:** Sediment should be readily redispersed upon gentle shaking. 3. **Particle size:** Should remain constant throughout long periods and not show crystal growth. 4. **Viscosity:** Should not be too high and should be poured easily from its container. ## The Sedimentation Rate - **Stokes' law equation:** ```latex \frac{dx}{dt} = \frac{d^2 (p_1 - p_2)g}{18\eta} ``` Where: - *dx/dt* is the sedimentation rate - *d* is the diameter of particles - *p₁* is the density of particles - *p₂* is the density of the medium - *g* is the gravity constant - *η* is the viscosity of the medium - **Factors affecting sedimentation rate:** - **Particle size:** Smaller particles settle slower. - **Density of the dispersed phase:** Higher density leads to faster settling. - **Density of the medium:** Particles less dense than the medium tend to float, which is undesirable. - **Viscosity:** Increasing viscosity slows sedimentation but can make the suspension too thick and difficult to redisperse. ## Examples of Sedimentation Rates | Condition | Rate of Settling (cm/s) | |---|---| | 2.5 µm powder in water | 1.02 x 10⁻⁴ | | 0.25 µm powder in water | 1.02 x 10⁻⁶ | | 2.5 µm powder in glycerin | 4.25 x 10⁻⁸ | | 0.25 µm powder in glycerin | 4.25 x 10⁻¹⁰ | ## Particle Size Reduction - **Ideal particle size:** 1-50 µm - **Methods:** - **Dry milling:** For most suspensions. - **Micropulverization:** For finer particles (10-50 µm). - **Jet milling (micronization):** For extremely small particles (under 10 µm). - **Spray drying:** Creates dry powder with very small particle size. ## Crystal Growth - **Cause:** Solubility of the drug increases with temperature, and crystals can form when the suspension cools. ## Flocculated and Deflocculated Suspensions **Deflocculated suspensions:** - Dispersed particles remain separate. - Settling is slow, but the supernatant remains cloudy. - Caking is a serious problem as liquid can become trapped within the sediment, making it difficult to redisperse. **Flocculated suspensions:** - Particles form aggregates (floccules). - Settling is faster, but the floccules form a loose sediment that is easily redispersed. - Sedimentation volume is large. ## Flocculating Agents - **Function:** Promote particle aggregation, increasing the viscosity and slowing sedimentation. - **Types:** - **Electrolytes:** Alter the zeta potential of particles, causing flocculation. - **Surfactants:** Neutralize the charge on particles, causing flocculation. - **Hydrophilic polymers:** Form a gel-like network that traps particles. ## Suspending Agents - **Function:** Increase the viscosity of the medium, slowing sedimentation and improving stability. - **Examples:** - Carboxymethylcellulose - Xanthan gum ## Wetting Agents - **Function:** Help to wet the dispersed phase, making it more penetrable by water. - **Examples:** - Alcohol - Glycerin ## Evaluation of Suspension Stability **Sedimentation volume:** - The ratio of the ultimate height of the sediment (`H₁`) to the initial height (`H₀`). - A higher sedimentation volume indicates better suspendibility. **Particle size changes:** - **Freeze-thaw cycling:** Used to stress suspensions and assess their stability over time. ## Summary - **Ideal suspension:** Partially flocculated to promote redispersion and minimize sedimentation. - **Key considerations:** Particle size, sedimentation rate, and viscosity. - **Flocculating agents:** Control particle aggregation and viscosity. - **Suspending agents:** Increase viscosity to slow sedimentation. - **Wetting agents:** Enhance the wetting of the dispersed phase.