Coarse Dispersions PhD HalinaFalfushynska
Definition • A Pharmaceutical suspension is a coarse dispersion in which internal phase is dispersed uniformly throughout the external phase. • The internal phase consisting of insoluble solidparticles. • The external phase (suspending medium) is generallyaqueous in some instance, may be an organic or oily liquid for non oral use.
Suspensions • Dispersions containing coarse particles, usually 10 to 50 um in size, are referred to as coarse dispersion. • Dispersions containing particles of smaller size are termed fine dispersions (0.5 to 10 um)
Suspensions Classification • Based On General Classes Oral suspension Externally applied suspension Parenteral suspension • Based On Proportion Of Solid Particles Dilute suspension (2 to10%w/v solid) Concentrated suspension (50%w/v solid) • Based On Electrokinetic Nature Of Solid ParticlesFlocculated suspension Deflocculated suspension • Based On Size Of Solid ParticlesColloidal suspension (< 1 micron) Coarse suspension (>1 micron) Nano suspension (10 ng)
312 PHT • Advantages and Disadvantages due to viscosity of medium Advantages • High viscosity inhibits the crystal growth. • High viscosity prevents the transformation of metastable crystal to stable crystal. • High viscosity enhances the physical stability. Disadvantages • High viscosity hinders the re-dispersibility of the sediments • High viscosity retards the absorption of the drug. • High viscosity creates problems in handling of the material during manufacturing.
Physical Features of the Dispersed Phase of a Suspension Good pharmaceutical suspensions, the particle diameter is between 1 to 50. Particle size reduction is generally accomplished by dry-milling prior to the incorporation of the dispersed phase into the dispersion medium. One of the methods of producing fine drug powders of about 10 to 50 um size is micropulverization. For still finer particles, under 10 um, the process of fluid energy grinding, sometimes referred to as jet-milling or micronizing.
Dispersion Medium • The amount of the suspending agent must not be such to render the suspension too viscous to agitate (to distribute the suspensoid) or to pour. The study of the flow characteristics is termed rheology
Rheological properties • Viscosity - is a measure of the resistance of a fluid which is being deformed by either tensile stress • Flexibility- the ability to recover the form of matter (volume) after deformation. Flexibility causes the alignment marks of finger pressure on the surface of plastiline. • Plasticity - the opposite of the elastic properties of the substance taken and permanent deformation after removing the load. Due to the plasticity of plastiline retain fashioned. • Elasticity - the property of matter experience significant deformation without destroying the structure.
Standard laboratory viscometers for liquids Ostwald viscometers measure the viscosity of a fluid with a known density. Falling Piston Viscometer
Degree of flocculation (β) Sedimentation volume is a ratio of the final or ultimate volume of sediment (Vu) to the original volume of sediment (VO) before settling.
Sustained-Release Suspension • In liquid preparations (suspensions) of the coated particles, the drug remains adsorbed onto resin, but slowly released by the ion-exchange process when taken into gastrointestinal tract. The use of a combination of ion-exchange resins complex and particle coating is called Pennkinetic system. • Examples: • Hydrocodonepolistirex =TussionexPennkinetic Extended-Release Suspension
Characteristics of Oral Suspension • Particles should be small uniform sizes that do not settle rapidly • The particles that do settle to the bottom of the container should not pack in to a hard cake and should be re-dispersed completely and evenly with a minimum amount of agitation
Characteristic of Suspensions • Should not be too viscous to pour freely from the mouth of the bottle • Should have an agreeable odor, color and taste and must not decomposed or support mold growth during storage • Must have therapeutic efficacy
Characteristic of Suspensions • Suspensions for injections must contain particles size such that they can pass freely through the syringe needle called “syringeability”.
Characteristic of Suspensions • Ophthalmic suspension should be formulated such that the particles do not exceed 10 microns. Below this size, the patient experiences no pain when instilled into the eyes.
Dispersion Medium • Suspending agents are added to the dispersion medium to lend its structure to assist in the suspension of the dispersed phase • Examples: Carboxymethylcelulose Methylcellulose Microcrystalline cellulose Polyvinyl pyrolidone, Xanthan gum Bentonite
Example of Preparation Aluminum Hydroxide Compressed Gel 326.8 g Sorbitol Solution 282.0 mL Syrup 93.0 mL Glycerin 25.0 m Methylparaben 0.9 g Propylparaben 0.3 g Flavor q.s Purified water, to make 1000.0 mL USE: ANTACID
EMULSIONS • The word emulsion, came from emulgio, “meaning to milk out”. • Is a dispersion in which the dispersed phase is composed of small globules of a liquid distributed throughout a vehicle in which it is immiscible.
Emulsion terminology • The dispersed phase is referred to as the Internal phase • The dispersion medium as the External or Continuous phase • Emulsions having an oleaginous internal phase and aqueous external phase are referred to as oil-in-water (o/w) emulsions • Emulsions having an aqueous internal phase and an oleaginous external phase are termed water-in- oil (w/o)emulsions.
Theories of Emulsification 1. Surface Tension Theory 2. Oriented-Wedge Theory 3. Plastic or Internal Film Theory 4. Viscosity Theory
Oriented-wedge Theory • Assumes monomolecular layers of emulsifying agent curved around a droplet of the internal phase of the emulsion. • It is based on the presumption that certain emulsifying agents orient themselves about and within a liquid in a manner reflective of their solubility in that particular liquid. • An emulsifying agent having a greater hydrophilic character than hydrophobic character will promote an O/w emulsion and a W/O emulsion results through use of more hydrophobic than hydrophilic emulsifiers.
Plastic or Interfacial-Film Theory • Places the emulsifying agent at the interface between the oil and water, surrounding the droplets of the internal phase as a thin layer of film adsorbed on the surface of the drops. • The film prevents the contact and the coalescence of the dispersed phase, the tougher and more pliable the film, the greater the stability of the emulsion.
Viscosity Theory • States that the viscosity of an emulsion aids emulsification by the mechanical hindrance to coalescence of the globules although it is not the cause of emulsification.
Qualities Required for Emulsifiers • Must be compatible with other ingredients in the formula • Must not interfere with the stability and efficacy of the therapeutic agent • Must be stable to microorganisms • Must be non-toxic • Must possess little or no odor, taste or color • Must promote emulsification and maintain stability of the emulsion for intended shelf-life
The HLB or Hydrophilic- Lipophile Balance • Each emulsifying agents has a hydrophilic portion (water-loving) and a lipophilic portion (oil-loving) with one or other being more or less predominant and influencing • A method indicative of the substances polarity devised and lead to the assigning of an HLB value for each agent. The usual range is between 1 to 20. • Materials that are highly polar or hydrophilic have assigned higher numbers than materials that are less polar and were lipophilic.
Methods of Preparation 1. Continental or Dry gum method 2. English or wet gum method 3. Bottle or Forbes bottle method 4. Auxiliary method 5. In SITU soap method 6. Microemulsions
Continental or Dry gum method ( G + O + W ) • The method is also referred to as the “4:2:1” method because for every 4 parts (volumes) of oil, 2 parts of water and 1 part of gum are added in preparing the initial or primary emulsion. • For instance, if 40 mL of oil are to be emulsified, 20 mL of water and 10 g of gum would be employed, with additional water or other formulation ingredients being added afterward to the primary emulsion
Bottle or Forbes Bottle Method (G+O+W) • For the extemporaneous preparation of emulsions from volatile oils or oleaginous substances of low viscosities, the bottle method is used. (2:2:1)
Auxiliary Methods An emulsion by either the wet gum or dry gum methods can generally be increased in quality by passing it through a hand homogenizer. In this apparatus, the pumping action of the handle forces the emulsion through a very small orifices which reduces the globules of the internal phase to about 5 um and sometime less
In SITU Soap Method • Two types of soap developed by this method are Calcium soaps and Soft soaps. • Calcium soaps water - in - oil emulsions which contain certain vegetable oil (e.g. Oleic acid) in combination with lime water ( Syn: Calcium Hydroxide Solution USP) and prepared by mixing equal volumes of the oil and lime water
Microemulsions • Thermodynamically stable, optically transparent, isotropic mixtures of a biphasic oil-water system stabilized with surfactants. • The diameter of droplets in a microemulsion may be in the range of 100 A (10 microns) to 1000 A whereas in a microemulsion the droplets may be 5000 angstroms in diameter. • Both O/W and W/O microemulsions may be formed spontaneously by agitating the oil and water phases with carefully selected surfactant.