Phardose Presentation

8/10/2019 Phardose Presentation

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DISPERSE SYSTEMS

13 DE ALVA, MYCAELA A.14 DECENA, MARK PAULO D.15 ENRIQUEZ, FLOEN MICHAEL S.16 GALVEZ, KRISTINE BERNADETTE S.


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Disperse Systems

Main types of liquid preparations containing undissolved orimmiscible drug distributed in a vehicle

Dispersed phase is the substance distributed

Dispersing phase or medium vehicle

Disperse system together.

The particles are usually solid materials that are insoluble to the liquidmedium

In emulsions dispersed phase is a liquid neither soluble orimmiscible with the liquid of the dispersing phase,

Emulsification results in the dispersion of the liquid drug as finedroplets throughout the dispersing phase


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Disperse Systems

Aerosols the dispersed phase may be small air bubbles throughouta solution or emulsion

Dispersions also consist of droplets of liquid in air

The particles may vary in size from particles visible to colloidaldimensions of 1.0nm and 0.5m.

Coarse dispersions - dispersions that have coarse particles have 10-50m

Includes suspensions and emulsions

Fine dispersions particles that are smaller in size 0.5-10mMagmas and Gels

Colloidal dispersions particles are in colloidal range


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Disperse Systems

particles of Coarse dispersion have the tendency to separate fromthe vehicle and settle below the container than do the particles infine dispersion

Solids settle to the bottom because of their higher density than ofthe medium.

Emulsions contain oils which has generally have less density thanwater, therefore they tend to rise up in the preparation.

Complete and uniform redistribution of the dispersed phase isessential for accurate administration of uniform doses and usuallyaccomplished by moderate agitation.


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SUSPENSIONS


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SUSPENSIONS

are defined as preparations containing finely divided drug particlesdistributed somewhat uniformly throughout in the vehicle in whichthe drug exhibits a minimum degree of solubility.

Ready to Use they are already distributed through a liquid vehicle

Other Preparations dry powders intended for suspension in liquidvehicles.

If drugs are unstable in the presence of aqueous vehicle, it is usually prepared inpowdered form

for oral suspension

oral suspension


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Reasons for Suspension

A. some are unstable in solution but stable in suspension

B. ease of swallowing and flexibility in administration of doses.

C. the disagreeable taste.

Poor tasting drugs are developed to be insoluble in their vehicle

for preparing a palatable liquid dosage form

Ex. Erythromycin Estolate Oral Suspension, USPThe use of insoluble form in suspension reduces taste-masking problems

Oral Suspensions are aqueous preparations with the vehicle flavoredand sweetened to suit the preference of the patient.


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Features Desired in aPharmaceutical Suspension

(therapeutic efficacy, stability of the components and permanencyof the suspension, esthetic) overall desirable qualities.

Specifics to the suspension

Should settle slowly and re-dispersed upon shaking

Particle size of the suspensiod should remain constant in long periods ofstanding

It should pour easily and evenly

Main features depend on the nature of dispersed phase, dispersionmedium and pharmaceutical adjuncts


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Sedimentation Rate of Particles

Stokes law.

Many variables:

Doesnt apply precisely to the usual suspension because:

suspensoid is irregularly shaped and various diameters.

They do collide and cause turbulence

May have affinity in dispersion mediumBasic concepts are applicable to possible adjustments to decrease therate of sedimentation.

Velocity of fall is greater in: larger particles, greater density of particlethan medium (because if less dense than vehicle, it will float)


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Sedimentation Rate of Particles

Rate of sedimentation is reduced: increasing the viscosity of thedispersion medium, but not too high, as it will be difficult toredisperse the suspensoid.

It is only used to a modest extent to avoid the difficulties.

The viscosity characteristics of the suspension is not only measured

by the vehicle used, but also the proportion of the solid particles.Brookfield Viscometer measures the viscosity by the force required torotate a spindle in the fluid being tested.

The physical stability of the suspension appears to be more adjustedby alteration in the dispersed phase rather than changes in itsdispersion medium.


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Brookfield Viscometer anotherpicture in phone


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Physical Features of the DispersedPhase of a Suspension

Spray Drying produces particles of extremely small dimensionsIs a cone shaped apparatus into which a solution of a drug is sprayedand rapidly dried by a current of warm, dry air circulating the cone.

It is impossible for a pharmacist to achieve a same degree ofparticle size reduction using comminuting equipment.

However, micronized drugs are available commercially in bulk,

Eg. Progesterone


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Physical Features of the DispersedPhase of a Suspension

According to Stokes Equation,Smaller particle size is beneficial to the stability of the suspension.

Because the rate of sedimentation is reduced thus providing slow and uniformrate of settling.

Not to small for it may form a compact cake upon settling.It resists breakup with shaking.

Forms larger aggregates that are larger and less suspendable.

Particle Shape also affects caking and stabilitySymmetrical barrel shape are more stable suspensions than needle shapedparticles

Symmetrical Barrel Shape doesnt cake upon standing

(note: needle form tenaciuous sediment cake on standing and cannot beredistributed.

Ex. Calcium Carbonate.


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Method on Avoiding the formationof the Cake

Formation of less rigid or loose aggregation it is held together byweak particle-particle bonds.

Floc or Floccule particles that resists complete settling.

But settle more rapidly than fine, individual particles.

they are less prone to compaction than unflocculated particles

Flocs forms higher sediment volume than unflocculated.

The loose structure permits aggregates to distribute readily with small amountof agitation


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Method of Preparing FlocculatedSuspension

It depends on the type of drug and product desired.Clays are used as flocculating agent in Oral Suspensions

Diluted Bentonite Magma used as flocculating agent.

Its structure supports the floc once it is formed

When clays are unsuitable agents, like for parenteral suspension,Flocs are produced by alteration in the pH of the suspension.

Electrolytes also acts as flocculating agents,Reducing the electrical barrier between the particles by forming a bridge soas link them together.

Concentration between the nonionic and ionic surface acting agentsinduce flocculation and increase sedimentation volume.


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Dispersion Medium

Sometimes, with highly flocculated suspensions, particles settle toorapidly to be consistent with what might be termed apharmaceutically elegant preparation.

Rapid Settling

hinders the accurate measurement of dosage

Produces unsightly a supernatant layer (for esthetics)

Thus suspending agents are added to lend its structure:

CMC, methylcellulose, microcrystalline cellulose, polyvinylpyrolidone, xanthan gum and bentonite

They thicken the suspension medium and help suspend the suspensiod.


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Dispersion Medium

Polymeric Substances and Hydrophilic ColloidsMust have appropriate tests to show that they do not interfere with thedrugs availability.

They bind medicinal agents causing them to be unavailable or slowlyavailable for therapeutic function.

The amount of suspending agent must not be too much to renderthe suspension too viscous to agitate or pour.

Rheology the study of flow characteristics


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Dispersion Medium

Factors that affects the support of the suspensiod to the medium:Density of the suspensiod, whether its flocculated

Amount of material requiring support.

Solid content of the Oral suspension may vary according to:

Dose of drug to be administeredAbility of the medium to support the concentration of the drug whilemaintaining the desirable features of viscosity and flow.

Adult oral suspension = 5mL or 1 teaspoonful

Pediatric Oral Suspension =dose calibrated drops or teaspoon.


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Preparation of Suspensions

Once the powder is wetted, the dispersion medium is added to theportions of powder and is blended thoroughly before addition ofadditional vehicle.

A portion of the vehicle is used to wash the mixing equipment freeof the suspension and bring the suspension to its final volume.

Product is then subjected to the colloid mill to ensure uniformity.

Preservatives are also added against bacterial and mold growth.Example formula for Oral Suspension

Aluminum Hydroxide - antacid


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Sustained Release Suspensions

Sustained release suspensions only have limited success because ofmaintaining the sustained release particles in the liquid disperse systemsis quite difficult.

Product research and technology uses the same ways of preparingtablets and capsules.

Ex. Coated Beads, Drug impregnated wax matrix, microencapsulation andion exchange resin complex.

Pennkinnetic System uses the combination of ion exchange resin complex andparticle coating

The system complexes ionic drugs with ion exchange resins resulting in a drug -resincomplex particles and later coated with ethylcellulose.

Liquid Formulations of the coated particles, the drug remains absorbed onto the resin butslowly released by ion exchange process in the GIT.

Ex. Hydrocodone Polisterex (Tussionex Pennkinetic Extended Release Suspensions,Medeva)


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Extemporaneous Compounding ofPrescriptions

Solid dosage form of the drug and incorporate it in the liquidproduct

Difficulty is the lack of ready information on stability of liquid vehicle

Ex. Leucovorin calcium is stable in milk or antacid and unstable in acidicsolutions

It is known that liquid form has higher decomposition rate than solidforms.Overcoming the difficulty

Contact the manufacturer

Literature and package insert

International Journal of Pharmaceutical Compounding


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Formation of Extemporaneous SuspensionTablets/ capsules are crushed in a mortar and pestle

Vehicle is slowly added to create a paste (Ora Family of preparations)

Slowly diluted to desired volume


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The extent of the formulation depends on the patientNeonate no preservatives, colorings, alcoholAdministered through a tube through mouth and directly in stomach

Alcohol alter liver function, gastric irritation, neurologic depressionAromatic Elixirs are not used as vehicles because it contain alcohol

Same for patients taking depressants for CNS and make the patient ill .

Preservatives -adverse effects on infants

Benzyl Alcohol cause gasping syndrome and deterioration of multiple organs anddeath

Propylene Glycol seizures as stupor in some infants

Formulations for infants should be simple and compounded to supply morethan a few days of medication

To maximize stability, air-tight, light resistant container and placed onrefrigerator. Shake well and watch for color changes


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Packaging and Storage ofSuspensions

Suspensions should be placed in wide mouth bottles , to have anadequate airspace above the liquid for shaking and pouring.

Tight containers protected from freezing, excessive heat and light.

Shake well to ensure uniform distribution for proper dosage.


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Examples of Oral Suspensions


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Antacid Oral Suspensions

Counter the effect of hyperacidity and employed by persons such aspeptic ulcers who must reduce acidity in stomach

Widely employed as OTC for acid indigestion, heartburn and sourstomach.

To counter GERD.

Antacid preparations composed of water-soluble materials that act

within the GIT to counteract acids and soothe irritated linings of the GIT.Sodium Bicarbonate

Water-insoluble salts of aluminum, calcium and magnesium

Aluminum hydroxide, aluminum phosphate, dihydroxyaluminumaminoacetate, calcium carbonate, calcium phosphate, magaldrate,magnesium carbonate, magnesium oxide and magnesium hydroxide


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Sodium Bicarbonate, calcium carbonate, and magnesiumhydroxide neutralizes acid effectively and magnesium trisilicate andaluminum hydroxide are less effective and slow.

Each agent has own side effects

Sodium Bicarbonate sodium overload and systemic alkalosis

Magnesium Preparations lead to diarrhea

Calcium Carbonate hypercalcemia and stimulate stomach for acidsecretion or acid rebound

Aluminum Hydroxide constipation and phosphate depletion withmuscle weakness, bone resorption and hypercalciuria


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Heartburn and gastric distress single dose of sodium bicarbonate andmagnesium hydroxide preparationAcute peptic ulcer and duodenal ulcer -sodium bicarbonate producesmore sodium and magnesium hydroxide induces diarrheaThus, combination of magnesium hydroxide and aluminum hydroxidebecause Aluminum hydroxide has constipating effects and counter theeffects of the magnesium hydroxide which is diarrhea.GERD prefer liquid than tablet because it doesnt require time todisintegrateIt is important for an antacid to act fast because gastric emptyingdoesnt allow it much time in the stomach. FDA requires antacid tablets to disintegrate within 10 minutes in acidconditons.Snacks prolong the stay and action of antacid in stomach.


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Antibacterial Oral Suspensions

Antibiotic substances :Mycin derivatives, tetracycline, sulfonamides and anti-infective agentsor combinations of these

Many are unstable in solution in length of time

Therefore, manufacturers made their products in insoluble froms of thedrug in aqueous suspensions or dry powder for reconstitution for astability standpoint

They are also packed with calibrated droppers for infants to assistdelivery

Dispersing phase is aqueous , colored, sweetened, and flavored

Palmitate form of chloramphenicol is selected for the suspensiondosage form for it is water-insoluble and is flavorless that eliminates thenecessity to mask the bitter taste of chloramphenicol


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Rectal Suspensions

Barium Sulfate for suspensionUsed orally or rectally for diagnostic visualization of the GIT

Mesalamine Suspension

Treatment of Crohn disease and distal ulcerative colitis,proctosigmoiditis, proctitis.

No longer available but is still compounded by pharmacists

Colocort

Hydrocortisone rectal suspension indicated as adjunctive therapy intreatment of ulcerative colitis and packaged in single dose enemadesired for self administration


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Dry Powder for Oral Suspension

Consists of dry powder mixtures or granules that are intended to besuspended in distilled water or some other vehicle prior to oraladministration.for Oral Suspension to distinguish them from prepared suspension Mostly antibiotics

Contain the antibiotic drug, colorants, flavorants, sweeteners, stabilizingagents, suspending agents and preserving agents

In reconstitution, pharmacist loosens the powder by tapping it in hardsurface, and then adds designated amount of water and shakes slurryunit of all of the dry powder has been suspendedManufactures provide slightly oversized container for easy shaking ofcontentsPharmacists should not eyeball the amount of water to be added tofill up the bottle.


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Erythromycin ethylsuccinate + acetyl sulfisoxazole - tx for acutemiddle ear infection caused by strains of Haemophilus Infuenzae

Probenecid + ampicillin = tx for uncomplicated infections caused byNeisseria gonorrhoeae .

Cholestyramine hyperlipidemia


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Barium sulfate Used orally or rectally for diagnostic visualization of the GITIt is practically insoluble in water and safe in large doses because intestines doesntabsorb it.

Pharmacist must be careful with other forms of barium, such as its sulfide, and sulfitebecause they are soluble and poisonous.

Barium Sulfate is a fine, non-gritty odorless, tasteless, white powder.

When used orally dx for hypo pharynx, esophagus stomach, small intestine andcolon.

It renders the GIT to be opaque in x-rays to reveal abnormalities.

When used rectally, it allows visualization of features of the rectum and colon

Commercially, for diagnostic use, is available as bulk powder with suspending agentsto be reconstituted to an oral suspension or enema.

Enema contains units that are ready-to-use and disposable bags are also available.


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