Lec9, Suspensions PDF

Pharmaceutics 1 9 Lecture Lecture 9 Summary of Lecture 9: Suspensions 1. Factors Affecting Sedimentation Volume Particle Size: Smaller particles settle slower, enhancing sedimentation volume and suspension stability. Particle Density: Higher density increases sedimentation,...

Pharmaceutics 1 9 Lecture Lecture 9 Summary of Lecture 9: Suspensions 1. Factors Affecting Sedimentation Volume Particle Size: Smaller particles settle slower, enhancing sedimentation volume and suspension stability. Particle Density: Higher density increases sedimentation, while densities closer to the dispersion medium improve stability. Viscosity: A higher viscosity medium slows sedimentation and enhances stability, often achieved with suspending agents. Flocculation: Controlled flocculation prevents caking and ensures easy re-dispersion, enhancing sedimentation volume. Summary of Lecture 9: Suspensions 1. Factors Affecting Sedimentation Volume Zeta Potential: Moderate zeta potential promotes controlled flocculation, reducing repulsion. Electrolytes and Ionic Strength: These influence zeta potential and flocculation behavior. Temperature: High temperatures can lower viscosity and stability. Dispersion Medium: Composition and additives like wetting agents impact interaction and stability. Additives and Stabilizers: Surfactants and polymers enhance wettability, prevent aggregation, and improve sedimentation volume. 2. Degree of Flocculation (β): Relates the sediment volume of flocculated systems to deflocculated systems, providing a critical parameter for assessing suspension stability. 3. Powder Wettability: Hydrophobic Powders: Float due to air layers; examples include sulfur and charcoal. Hydrophilic Powders: Easily wetted by water; examples include zinc oxide. Wetting Agents: Surfactants, glycerin, and hygroscopic substances improve wetting by reducing interfacial tension and contact angle. 4. Formulation of Suspensions Controlled Flocculation: Prevents compact sediment formation using electrolytes to reduce zeta potential and create loose particle structures. Structured Vehicles: Use polymers (e.g., methylcellulose) to reduce sedimentation rate, showing pseudoplastic flow and thixotropy properties. 5. Prevention of Caking Achieved by balancing density, using thickeners, and ensuring controlled flocculation. Crystallization should be avoided for long-term stability. 6. Advantages of Suspensions Increased bioavailability for insoluble drugs (e.g., paracetamol). Masking unpleasant drug tastes (e.g., chloramphenicol). Enhanced chemical stability (e.g., procaine penicillin G). Controlled drug release (e.g., depot therapy). Suitable for pediatric and geriatric use compared to tablets or capsules. 7. Examples of Marketed Suspensions Oral Suspensions: Antacids, antibacterials (e.g., ciprofloxacin), analgesics (e.g., ibuprofen). Parenteral Suspensions: Procaine penicillin G, insulin zinc suspension. External Use: Calamine lotion. Vaccines: Cholera vaccine. Diagnostic Agents: Barium sulfate for X-rays. Factors Affecting Sedimentation Volume 1- Particle Size: Smaller particles settle slower due to reduced sedimentation velocity, enhancing the sedimentation volume (F). Uniform particle size distribution promotes suspension stability. 2- Particle Density: Higher particle density increases the sedimentation rate due to greater gravitational force, reducing sedimentation volume. Using particles with densities closer to the dispersion medium helps improve stability  3- Viscosity of the Dispersion Medium: A higher viscosity medium reduces sedimentation by opposing the settling of particles, leading to better suspension stability and a higher sedimentation volume. Viscosity can be increased using suspending agents such as gums or polymers. 4- Flocculation: Controlled flocculation prevents particle aggregation into hard sediments (caking) and ensures easy re-dispersion. Properly flocculated systems form a loose, high- volume sediment that enhances F. 5- Zeta Potential: Particles with high zeta potential repel each other and remain deflocculated, reducing sedimentation volume. Reducing zeta potential to a moderate level promotes controlled flocculation. 6- Electrolytes and Ionic Strength: Electrolytes can influence zeta potential and flocculation behavior, altering sedimentation volume. Proper adjustment of ionic strength can promote controlled flocculation. 7- Temperature: Higher temperatures can lower the viscosity of the medium, increasing sedimentation. Temperature fluctuations may affect the physical stability of suspensions. 8- Nature of the Dispersion Medium: The composition of the dispersion medium (aqueous or non-aqueous) affects the interaction between particles and the medium. Additives such as wetting agents can modify the interaction, improving suspension stability. 9- Additives and Stabilizers: Polymers, surfactants, and wetting agents can enhance particle wettability, reduce aggregation, and improve dispersion. Suspending agents increase viscosity and improve sedimentation volume.  The Degree of Flocculation ( β ) The volume of sedimentation (F) is a useful parameter, however, the Degree of Flocculation ( β ) It the second and more important sedimentation parameter since it relates the volume of flocculated sediment to that in a deflocculated system. β= F/Fα 1 4  Flocculated versus Deflocculated Suspensions 1 5  Powder Wettability The initial dispersion of an insoluble powder is an important step in the manufacturing process Although it may have a high density, the powder floats on the surface of the liquid owing to an adsorbed layer of air The wettability of a powder is determined by the contact angle. Powders which are not easily wetted and accordingly show a large contact angle, such as, sulfur, charcoal, and magnesium stearate are called hydrophobic. Powders which are readily wetted by water are called hydrophilic ,e.g., zinc oxide, talc, and magnesium carbonate. 1 6 The wetting of powders can be improved by one or more of the following methods: Surfactants are useful in reducing the interfacial tension between solid particles and a vehicle in the preparation of a suspension. As a result of the lowered interfacial tension, the contact angle is lowered, air is displaced from the surface of the particles, and wetting and deflocculating are promoted. 5 2 Glycerin and similar hygroscopic substances are also valuable in levigating the insoluble material. Glycerin flows into the voids between the particles to displace the air and during the mixing glycerin coats and separates the particles so that water can penetrate and wet the individual particles. 3 The dispersion of particles of colloidal gums by alcohol, glycerin and propylene glycol, allowing water to penetrate the interstices, is a well- known practice in pharmacy. 18 The dispersion of particles of colloidal gums using alcohol, glycerin, and propylene glycol is a standard pharmaceutical technique. These agents function as wetting or dispersing agents by reducing the surface tension between the colloidal gum particles, which allows water to penetrate the interstitial spaces effectively. This process facilitates the hydration and dispersion of the colloidal gum in aqueous systems, improving its solubility and ease of incorporation into pharmaceutical formulations. Mechanism: Alcohol: Acts as a solvent and reduces the cohesive forces between gum particles, promoting better dispersion. Glycerin: Provides a hygroscopic environment, attracting water molecules to assist in the penetration of the gum matrix. Propylene Glycol: Works similarly to glycerin, acting as a co- solvent to improve dispersion and hydration.  Formulation of Suspensions If the suitable particle size, a suspending and wetting agents are tried to formulate the suspension and yet it tends to be deflocculated, then, one of two methods is employed to prepare flocculated suspension, namely: i)the application of the principles of controlled flocculation to produce flocs which, although they settle rapidly, are easily resuspended with minimum agitation and ii)the use of structured vehicles to maintain deflocculated particles in suspension 20  1. Controlled Flocculation Flocculation must be controlled to prevent formation of compact sediment, difficult to redisperse. Flocculating agents used for This purpose are:- Electrolytes: Act as flocculating agents by reducing the electrical barrier between the particles, as evidenced by a decrease in the zeta potential and the formation of a bridge between adjacent particles so to link them together in a loosely arranged structure 21  The flocculating power increases with the valence of the ions. Therefore, calcium ions are more powerful than sodium or potassium ions. However, trivalent ions are less commonly used because of their toxicity If we dispersed particles of bismuth subnitrate (Bi6O4(HO)4(NO3)6·H2O) in water, particles will possess a large positive charge, or zeta potential. Because of the strong forces of repulsion between adjacent particles, the system is deflocculated 22  The addition of monobasic potassium phosphate (KH2PO4) to the suspended bismuth subnitrate particles causes the positive zeta potential to decrease due to the adsorption of the negatively charged phosphate anion. At a certain positive zeta potential, maximum flocculation occurs. This coincides with the maximum sedimentation volume, F. 23  2. Use of Structured Vehicles Pseudoplastic flow, Plastic flow & Thixotropy Structured vehicles are generally aqueous solutions of natural and synthetic polymers, such as methylcellulose, sodium carboxy- methylcellulose, acacia, tragacanth, etc. These pollymers exhibit Pseudoplastic flow (decreased viscosity as the shearing stress is increased) They are viscosity-imparting agents andbasically reduce the rate of sedimentation The suspension itself may exhibit plastic flow (have yield value) if it contains large amount of flocculated solids 24  55 thixotropy Thixotropy: slow recovery, on standing of a material, of a consistency lost through shearing. It applies for both plastic and pseudplastic flow 12  Prevention of Caking In summary, It is possible to influence settling in various ways to avoid caking (the formation of hard, nonredispersible sediments): 1. By balancing the densities of the disperse phase and the liquid medium to minimum density deference. 2. By the use of thickeners: thickeners are employed to increase the viscosity. Common thickeners include: celluloses, alginates, polyethylene glycol. 14 3. By controlled flocculation as previously explained 4. If a suspension is to remain stable over long periods of storage, crystallization should not occur. Smaller particles are more soluble than large ones. As a result, larger particles grow at the expense of smaller ones. The retardation of crystal growth requires low solubility and a narrow particle size distribution. 15  Why Suspensions? 1. To increase bioavailability of insoluble drugs, e.g., paracetamol suspension, compared to solid dosage forms. 2. To mask bitter taste of drug ,e.g. chloramphenicol palmitate 3. To increase drug chemical stability, e.g., procaine penicillin G 4. To achieve controlled/sustained drug release, e.g., depot therapy in intramuscular and subcutaneous injections 5. Oral Suspensions are more convent for pediatric and geriatric use compared to tablets and capsules 16  Examples of Marketed Suspensions Antacid oral suspension ,eg, Aluminum Hydroxide/Magnesium Hydroxide mixture Antibacterial oral suspension ,e.g., ciprofloxacin suspension Antidiarrheal oral suspensions ,e.g, bismuth subsalicylates suspension Parenteral suspensions ,e.g., Procaine penicillin G and Insulin Zinc Suspension Ophthalmic suspensions ,e.g., betoptic S (betaxolol hydrochloride ophthalmic suspension) used to treat glaucoma Suspension for external use ,e.g., Calamine lotion. X-ray contrast agent ,e.g., Barium sulfate for examination of alimentary tract 17