Suspension 2024 - Lec 1 PDF

Dispersed System Dispersed phase or Internal phase or Discontinuous phase in Dispersion medium or External Phase or Continuous Phase Dispersed systems consist of dispersed phase (particulate mat...

Dispersed System Dispersed phase or Internal phase or Discontinuous phase in Dispersion medium or External Phase or Continuous Phase Dispersed systems consist of dispersed phase (particulate matter), distributed throughout a continuous or dispersion medium. Dispersed systems are classified into 3 categories according to the mean particle diameter of the dispersed phase. Class Size Characteristics of System Examples Oxygen 1- Particles invisible in electron molecules, Less microscope. Molecular ions and than 1.0 2- Particles pass through ultra-filter Dispersion glucose nm and semi-permeable membrane. molecules 3- Particles undergo rapid diffusion in water  Class Size Characteristics of System Examples 1- Particles are not resolved by Colloidal silver ordinary microscopes, detected solution, under electon microscope. Colloidal 1.0 nm Dispersion of 2- Particles pass through filter Dispersion to 0.5 um natural and paper but do not pass semi- synthetic permeable membrane. polymers 3- Particles diffuse very slowly. 1- Particles visible under optical Grains of sand, microscope most Greater Coarse 2- Particles do not pass through pharmaceutical than 0.5 Dispersion normal filter paper or dialyze emulsions and um through semi-permeable membrane suspensions, 3- Particles do not diffuse. red blood cells  SUSPENSIONS Definition: They are preparations containing finely divided drug particles distributed uniformly throughout a vehicle in which the drug exhibits a minimum degree of solubility. A Pharmaceutical suspension is a coarse dispersion. The external phase (suspending medium) is generally aqueous in some cases, may be an organic or oily liquid for non oral use.  Classification 1- Based on general classes (use). Oral suspension Externally applied suspension Parenteral suspension 2- Based on % of solid particles Dilute suspension (2 to10% w/v solid) Concentrated suspension (50% w/v solid) 3- Based on electrokinetic nature of solid particles: Flocculated suspension Deflocculated suspension 4- Based on size of solid particles Colloidal suspension (< 1 micron) Coarse suspension (>1 micron) Nanosuspension (10 nm)  Oral Ocular Otic Routes of Administration Rectal Parenteral Topical  Advantages of Suspensions 1- Certain drugs are chemically unstable in solution but stable when suspended. e.g. Procaine penicillin G 2- Suspension can mask the unpleasant/bitter taste of some drugs. e.g., chloramphenicol (soluble, very bitter) → chloramphenicol palmitate (insoluble ester, palatable). 3- Suspension increases the surface area of the drug to be effective in the GIT e.g., antacids and drugs for treatment of toxicity. 4- Suspensions for topical application e.g., calamine lotion. 5- Duration and onset of action can be controlled and extended. e.g. Protamine Zinc-Insulin suspension. 6- Drug in suspension exhibits higher rate of bioavailability than other dosage forms. bioavailability is in following order, Solution > Suspension > Capsule > Compressed Tablet > Coated tablet 6- Vaccines (for induction of immunity) are often formulated as suspension. 7- Some X- ray contrast media are also formulated as suspensions. e.g., Barium sulfate suspension for either oral or rectal administration.  Disadvantages of Suspensions 1- Physical stability, sedimentation and compaction can causes problems. 2- It is bulky → sufficient care must be taken during handling and transport. 3- It is difficult to formulate. 4- Uniform and accurate dose can not be achieved unless suspension are packed in unit dosage form.  Features desired in a pharmaceutical suspension 1- Suspension should settle slowly and should be readily redispersed upon gentle shaking. 2- Suspension must remain sufficiently homogenous for at least the period between shaking the container and removing the required dose. 3- The viscosity of suspension must not be so high → to facilitate the removal of the product from the container. 4- Suspension for topical used should be smooth, elegant product, free from a gritty texture. 5- It should be physically, chemically and microbiologically stable. 6- Parenteral/ophthalmic suspension should be sterile. Sedimentation rate of the particles of a suspension: Stokes' law is applicable when the particles: 1- A uniform spherical particles in a very dilute suspension. 2- Settling without turbulence and collision with other particles of the dispersed phase, and 3- Settling without chemical or physical attraction or affinity for the dispersion medium.  d2 (ρi - ρe) g Stokes' law V = ------------------- 18 ŋ Where: V is the settling rate, d is the diameter of the particles, ρi is the density of the particle, ρe is the density of the medium, g is acceleration due to the gravity and ŋ is the viscosity of the medium From the equations: The larger the particle size, the greater the sedimentation rate. The greater the density of the particles, the greater the sedimentation rate. The greater the viscosity of the dispersion medium particles, the slower the sedimentation rate. but greater increase in viscosity gives rise to problems like pouring, syringibility and redispersibility of suspension.  Physical features of the Dispersed Phase: 1- Size of the particles Powder → Particle size reduction → Incorporation into the dispersion medium. A. Micro pulverization Methods for particle B. Micronization size reduction C. Spray drying A. Micro pulverization: Using micro pulverizers to obtain particles of about 10 to 50 μm. It is rapid, convenient, and inexpensive method. Used for oral and topical suspension. B. Micronization: Using jet milling (using ultrasonic waves) to obtain particles under 10 μm. Used for parenteral or ophthalmic suspensions. C. Spray drying: Using a spray dryer, a solution of a drug is sprayed and rapidly dried by a current of hot dry air. 2. Degree of flocculation Excessive reduction in particle size → large surface area → large surface free energy → unstable particles → agglomeration of particles to be stable. According to the following equation: ∆F = d. ∆A Where: ∆F surface free energy, ∆A increase in total surface area and d interfacial tension between solid & liquid. Reduction in the surface free energy in the systems may be accomplished either by: 1- ↓ d by addition of surfactant. 2- ↓ surface area (caking or aggregation). Flocks or floccules = loose aggregation of the particles held together by weak particle to particle attractive forces. N.B: Attraction forces → arise from Vander Waal forces. Repulsion forces → arise from electric double layer surrounding each particle. 1- When the repulsion forces > attraction forces → the suspension is deflocculated. 2- When the repulsion forces < attraction forces → the suspension is flocculated. In deflocculated suspension → when sedimentation is complete, the particles form a close packed arrangement with small particles filling the voids between larger ones. The particles in the lower layers of the sediment are pressed by the weight of ones above → the energy barrier is thus overcomed → particles come into close contact forming a hard cake.  Difference between Flocculated and deflocculated suspension Flocculated suspension Deflocculated suspension Particles form flocks and form a Particles as separate entities. network like structure. Rate of sedimentation is high. Rate of sedimentation is slow. Sediment is rapidly formed. Sediment is slowly formed. Sediment is loosely packed and Sediment is very closely packed not form a hard cake. forming hard cake Sediment is easy to redisperse. Sediment is difficult to redisperse. Suspension is not pleasing in Suspension is pleasing in appearance. appearance. The flocs stick to the sides of The flocs do not stick to the sides the bottle. of the bottle.