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Disperse systems Disperse systems are liquid preparations containing undissolved or immiscible drug distributed throughout a vehicle. In these preparations, the substance distributed is referred to as the dispersed phase, and the vehicle is termed the dispersing phase or dispersion medium. Together...

Disperse systems Disperse systems are liquid preparations containing undissolved or immiscible drug distributed throughout a vehicle. In these preparations, the substance distributed is referred to as the dispersed phase, and the vehicle is termed the dispersing phase or dispersion medium. Together, they produce a dispersed system.  Disperse systems The particles of the dispersed phase are usually *solid materials that are insoluble in the dispersion medium (suspensions) *In the case of emulsions, the dispersed phase is a liquid that is neither soluble nor miscible with the liquid of the dispersing phase. Emulsification results in the dispersion of liquid drug as fi ne droplets throughout the dispersing phase.  Disperse systems system Particle size True solution Less than 1nm Colloidal dispersions 1nm – 500nm = 0.5μm Fine dispersion 500nm= 0.5μm – 10μm Coarse dispersions 10 – 50μm  Disperse systems Complete and uniform redistribution of the dispersed phase is essential to the accurate administration of uniform doses. For a properly prepared dispersion, this should be accomplished by moderate agitation of the container. Suspensions Definition  A pharmaceutical suspension is a coarse dispersion in which insoluble solid particles, are dispersed in a liquid medium, usually aqueous.  Suspensions may be defined as preparations containing finely divided drug particles (the suspensoid) distributed somewhat uniformly throughout a vehicle in which the drug exhibits a minimum degree of solubility.  (for)/ suspension  Some suspensions are available in ready-to-use form, that is, already distributed through a liquid vehicle with or without stabilizers and other additives.  Prepared suspensions not requiring reconstitution at the time of dispensing are simply designated as “Suspension.”  Other preparations are available as dry powders intended for suspension in liquid vehicles. Generally, this type of product is a powder mixture containing the drug and suitable suspending and dispersing agents to be diluted and agitated with a specified quantity of vehicle, most often purified water.  Drugs that are unstable if maintained for extended periods in the presence of an aqueous vehicle (e.g., many antibiotic drugs) are most frequently supplied as dry powder mixtures for reconstitution at the time of dispensing. This type of preparation is designated in the USP by a title of the form “for Suspension” or “ to be reconstituted ”  Advantage (REASONS FOR SUSPENSIONS)  An aqueous suspension is a useful formulation system for administering an insoluble or poorly soluble drug. The large surface area of dispersed drug ensures a high availability for dissolution and hence absorption.  Certain drugs are chemically unstable in solution but stable when suspended. In this instance, the suspension ensures chemical stability while permitting liquid therapy  The disadvantage of a disagreeable taste of certain drugs in solution form is overcome when the drug is administered as un- dissolved particles of an oral suspension. In fact, chemical forms of certain poor-tasting drugs have been specifically developed for their insolubility in a desired vehicle for the sole purpose of preparing a palatable liquid dosage form. For example, erythromycin estolate is a less water-soluble ester form of erythromycin and is used to prepare a palatable liquid dosage form of erythromycin, the result being Erythromycin Estolate Oral Suspension, USP  Features desired in a pharmaceutical In addition to 1. Therapeutic efficacy, 2. chemical stability of the components of the formulation, 3. permanency of the preparation, and 4. esthetic appeal of the preparation These are desirable qualities in all pharmaceutical preparations  Specifications  An acceptable suspension possesses certain desirable qualities, among which are the following: 1. The suspended material should not settle too rapidly; the particles that do settle to the bottom of the container must not form a hard mass but should be readily dispersed into a uniform mixture when the container is shaken; 2. The particle size of the suspensoid should remain fairly constant throughout long periods of undisturbed standing. 3. The suspension must not be too viscous to pour freely from the bottle or to flow through a syringe needle. (The suspension should pour readily and evenly from its container) Ideal suspensions  The physical stability of a pharmaceutical suspension may be defined as the condition in which the particles do not aggregate and in which they remain uniformly distributed throughout the dispersion.  As this ideal situation is seldom realized it is appropriate to add that if the particles do settle they should be easily re-suspended by a moderate amount of agitation.  SEDIMENTATION RATE OF THE PARTICLES OF A SUSPENSION  The various factors involved in the rate of settling of the particles of a suspension are embodied in the equation of Stoke’ s law,  dx/dt is the rate of settling,  d is the diameter of the particles,  ρi is the density of the particle,  ρe is the density of the medium,  g is the gravitational constant, and  η is the viscosity of the medium  Stoke's equation was derived for an ideal situation in which uniform, perfectly spherical particles in a very dilute suspension settle without producing turbulence, without colliding with other particles of the suspensoid, and without chemical or physical attraction or affinity for the dispersion medium.  Factors affecting the rate of sedimentation  From the equation it is apparent that the velocity of fall of a suspended particle is greater for larger particles than it is for smaller particles, all other factors remaining constant.  Reducing the particle size of the dispersed phase produces a slower rate of descent of the particles.(in a range of 1-50μm)  Also, the greater the density of the particles, the greater the rate of descent, provided the density of the vehicle is not altered. Because aqueous vehicles are used in pharmaceutical oral suspensions, the density of the particles is generally greater than that of the vehicle, a desirable feature.  The rate of sedimentation may be appreciably reduced by increasing the viscosity of the dispersion medium, and within limits of practicality this may be done. However, a product having too high a viscosity is not generally desirable, because it pours with difficulty and it is equally difficult to redisperse the suspensoid. Therefore, if the viscosity of a suspension is increased, it is done so only to a modest extent to avoid these difficulties  The most important single consideration is the size of the particles.  particle size reduction is accomplished by dry milling prior to incorporation of the dispersed phase into the dispersion medium.  Micropulverization is one of the most rapid, convenient, and inexpensive methods of producing fine drug powders of about 10 to 50 μm size. Micropulverizers are high-speed attrition or impact mills that are efficient in reducing powders to the size acceptable for most oral and topical suspensions.  fluid energy grinding, sometimes referred to as jet milling or micronizing, is quite effective, for finer particles, under 10 μm. This method may be employed when the particles are intended for parenteral or ophthalmic suspensions. Particles  spray drying, for extremely small dimensions of particles may be used. A spray dryer is a cone-shaped apparatus into which a solution of a drug is sprayed and rapidly dried by a current of warm, dry air circulating in the cone. The resulting dry powder is collected.  It is not possible for a pharmacist to achieve the same degree of particle- size reduction with such comminuting equipment as the mortar and pestle.  However, many micronized drugs are commercially available to the pharmacist in bulk, such as progesterone.  The reduction in the particle size of a suspensoid is beneficial to the stability of the suspension because the rate of sedimentation of the solid particles is reduced as the particles are decreased in size.  The reduction in particle size produces slow, more uniform rates of settling. However, one should avoid reducing the particle size too much, because fine particles have a tendency to form a compact cake upon settling to the bottom of the container. The result may be that the cake resists breakup with shaking and forms rigid aggregates of particles that are larger and less suspendable than the original suspensoid.  The particle shape of the suspensoid can also affect caking and product stability. It has been shown that symmetrical barrel- shaped particles of calcium carbonate produced more stable suspensions than did asymmetrical needle-shaped particles of the same agent. The needle-shaped particles formed a tenacious sediment cake on standing that could not be redistributed, whereas the barrel-shaped particles did not cake upon standing.  To avoid formation of a cake, it is necessary to prevent agglomeration of the particles into larger crystals or into masses.  One common method of preventing rigid cohesion of small particles of a suspension is intentional formation of a less rigid or loose aggregation of the particles held together by comparatively weak particle-to-particle bonds. Such an aggregation of particles is termed a floc or a floccule, with flocculated particles forming a type of lattice that resists complete settling (although flocs settle more rapidly than fine, individual particles) and thus are less prone to compaction than unflocculated particles. The flocs settle to form a higher sediment volume than unflocculated particles, the loose structure of which permits the aggregates to break up easily and distribute readily with a small amount of agitation.  Flocculation  Particles that tend to flocculate i.e. to group together in a form of light fluffy clumps, settle more rapidly than do individual particles, but they form loosely packed sediments that do not cake and therefore are redispersed easily.  While the small individual particles that settle may pack into a dense sediment which may set into a rigid cake or clay that is difficult to redisperse.  The very rapid settling of large particles hinders accurate measurement of dosage. Deflocculated Flocculated Particles exist in suspension as separate entities Particles form loose aggregates Rate of sedimentation is slow, since each particle Rate of sedimentation is high , particles settles separately and the particle size is minimal settle as flocs (collection of particles) Sediment formed slowly Sediment formed rapidly Sediment pack into a cake difficult to redispose Sediment is loosely packed The sediment eventually becomes very closely The sediment is loosely packed packed, owing to weight of upper layers of Particles do not bond tightly to each sedimenting material. other the sediment is easy to re- disperse Repulsive forces between particles are overcome and a hard cake is formed which is difficult to redispose The suspension has a pleasing appearance since Suspension is unsightly due to rapid the suspended materials remains suspended for a sedimentation relatively long time Clear supernatant , can be minimized if The supernatant remains cloudy even settling is the volume of the sediment is made apparent large  There are several methods of preparing flocculated suspensions, the choice depending on the type of drug and the type of product desired.  For instance, in the preparation of an oral suspension of a drug, clays such as diluted bentonite magma are commonly employed as the flocculating agent. The structure of the bentonite magma and of other clays used for this purpose also assists the suspension by helping to support the floc once formed.  In a parenteral suspension, frequently a floc of the dispersed phase can be produced by an alteration in the pH of the preparation (generally to the region of minimum drug solubility).  Electrolytes can also act as flocculating agents, apparently by reducing the electrical barrier between the particles of the suspensoid and forming a bridge so as to link them together.  The carefully determined concentration of nonionic and ionic surface-active agents (surfactants) can also induce flocculation of particles in suspension and increase the sedimentation  Suspending agents  Are viscosity increasing agents used to reduce sedimentation rate of particles in a vehicle in which they are not soluble. Examples of those are Carboxymethylcellulose (CMC), methylcellulose, microcrystalline cellulose, xanthan gum, polyvinylpyrrolidone, , and bentonite employed to thicken the dispersion medium and help suspend the suspensoid.  When polymeric substances and hydrophilic colloids are used as suspending agents, appropriate tests must be performed to show that the agent does not interfere with availability of the drug. These materials can  bind certain medicinal agents, rendering them unavailable or only slowly available for therapeutic function.  Also, 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. Difference between suspensions and colloids  The major difference between a pharmaceutical suspension and a colloidal dispersion is one of size of the dispersed particles, with the relatively large particles of a suspension liable to sedimentation owing to gravitational forces.  Apart from this, suspensions show most of the properties of colloidal systems. Thank you