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Extemporaneous dispensing of

SUSPENSIONS

1/29/2010

By

To

Madam Humaira Gul

COLLEGE OF PHARMACYG.C. UNIVERSITY FAISALABAD

Pharm.D 5th (E)

Suspensions

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 solid particles having a specific range of size which is maintained uniformly throughout the suspending vehicle with aid of single or combination of suspending agent. The external phase (suspending medium) is generallyaqueous in some instance, may be an organic or oily liquid for non oral use.

Classification

Based On General Classes

1. Oral suspension 2. Externally applied suspension 3. Parenteral suspension

Based On Proportion Of Solid Particles

1. Dilute suspension (2 to10%w/v solid) 2. Concentrated suspension (50%w/v solid)

Based On Size Of Solid Particles

1. Colloidal suspension (< 1 micron) 2. Coarse suspension (>1 micron) 3. Nano suspension (10 ng)

Based On Electrokinetic Nature Of Solid Particles

1. Flocculated suspension 2. Deflocculated suspension

Flocculated Suspensions

In flocculated suspension, formed flocs (loose aggregates) will cause increase in sedimentation rate due to increase in size of sedimenting particles. Hence, flocculated suspensions sediment more rapidly.

Here, the sedimentation depends not only on the size of the flocs but also on the porosity of flocs. In flocculated suspension the loose structure of the rapidly sedimenting flocs tends to preserve in the sediment, which contains an appreciable amount of entrapped liquid. The volume of final sediment is thus relatively large and is easily redispersed by agitation.

Sedimentation behavior of flocculated and deflocculated suspensions

Deflocculated suspensions

In deflocculated suspension, individual particles are settling, so rate of sedimentation is slow which prevents entrapping of liquid medium which makes it difficult to re-disperse by agitation. This phenomenon also called ‘cracking’ or ‘claying’.

In deflocculated suspension larger particles settle fast and smaller remain in supernatant liquid so supernatant appears cloudy whereby in flocculated suspension, even the smallest particles are involved in flocs, so the supernatant does not appear cloudy.

Advantages and Disadvantages

Advantages

1. Suspension can improve chemical stability of certain drug e.g. Procaine penicillin G 2. Drug in suspension exhibits higher rate of bioavailability than other dosage forms.

bioavailability is in following order, Solution > Suspension > Capsule > Compressed Tablet > Coated tablet

3. Duration and onset of action can be controlled e.g. Protamine Zinc-Insulin suspension

4. Suspension can mask the unpleasant/ bitter taste of drug e.g. Chloramphenicol

Disadvantages

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 cannot be achieved unless suspension are packed in

unit dosage form

Applications

1. Suspension is usually applicable for drug which is insoluble or poorly soluble e.g.Prednisolone suspension

2. To prevent degradation of drug or to improve stability of drug e.g. Oxytetracycline suspension

3. To mask the taste of bitter of unpleasant drug e.g. Chloramphenicol palmitate suspension

4. Suspension of drug can be formulated for topical application e.g. Calamine lotion 5. Suspension can be formulated for parentral application in order to control rate of

drug absorption. 6. Vaccines as a immunizing agent are often formulated as suspension e.g. Cholera

vaccine 7. X-ray contrast agent are also formulated as suspension e.g. Barium sulphate for

examination of alimentary tract.

Extemporananeous Dispensing

Features Desired In Pharmaceutical Suspensions

The suspended particles should not settle rapidly and sediment produced, must be easily re-suspended by the use of moderate amount of shaking.

It should be easy to pour yet not watery and no grittiness. It should have pleasing odour, colour and palatability. Good syringeability. It should be physically, chemically and microbiologically stable. Parenteral/Ophthalmic suspension should be sterilizable.

Preparation

A perfect suspension is one, which provides content uniformity. The formulator must encounter important problems regarding particle size distribution, specific surface area, inhibition of crystal growth and changes in the polymorphic form. The formulator must ensure that these and other properties should not change after long term storage and do not adversely affect the performance of suspension. Choice of pH, particle size, viscosity, flocculation, taste, color and odor are some of the most important factors that must be controlled at the time of formulation.

Formulation Components

The various components, which are used in suspension formulation, are as follows.

Components FunctionAPI Active drug substances Wetting agents They are added to disperse solids in continuous liquid phase. Flocculating agents They are added to floc the drug particles Thickeners They are added to increase the viscosity of suspension. Buffers and pH adjusting agents

They are added to stabilize the suspension to a desired pH range.

Osmotic agents They are added to adjust osmotic pressure comparable to biological fluid.

Coloring agents They are added to impart desired color to suspension and improve elegance.

Preservatives They are added to prevent microbial growth. External They are added to construct structure of the final

liquid vehicle suspension. Procedure:

1. Calculate the amount of drug, vehicle and other formulation components required to prepare desired suspension.

2. Transfer the contents into a clean mortar.3. Triturate the granules to a fine powder.4. Add one-third (1/3) of the specified amount of vehicle and triturate the powder until

a uniform suspension is achieved.5. Transfer the suspension to an amber glass or amber polyethyleneterephthalate

(PET) bottle. A funnel may be used to eliminate any spillage.6. Add another one-third (1/3) of the vehicle to the mortar, rinse the pestle and mortar

by a triturating motion and transfer the vehicle into the bottle.7. Repeat the rinsing (Step 5) with the remainder of the vehicle.8. Close the bottle using a child-resistant cap.9. Shake well to completely dissolve the active drug and to ensure homogeneous

distribution of the dissolved drug in the resulting suspension. 10. Put an auxiliary label on the bottle indicating “Shake Gently Before Use”. [This

compounded suspension should be gently shaken prior to administration to minimize the tendency for air entrapment.]

11. Instruct the parent or guardian that any remaining material following completion of therapy must be discarded by either affixing an auxiliary label to the bottle or adding a statement to the pharmacy label instructions.

12. Place an appropriate expiration date label according to storage condition.

Packaging

Ideal Requirements Of Packaging Material

It should be inert. It should effectively preserve the product from light, air, and other contamination

through shelf life. It should be cheap. It should effectively deliver the product without any difficulty.

Materials Used For Packaging Generally glass and various grades of plastics are used in packaging of suspension.

Closure and LinersWith an exception of ampoules all containers required elastomeric closure.

Factors affecting in selecting closure:

Compatibility with product. Effect of processing should not affect the integrity of the closure. Seal integrity. It should be stable throughout the shelf life. Lot to lot variability has to be considered.

Factors affecting in selecting liner:

Chemical resistance. Appearance Gas and vapor transmission. Removal torque. Heat resistance. Shelf life. Economical factors.

FDA Regulations For Packaging

When FDA evaluates drug, the pharmacist must be firmly convinced that package for aspecific drug will preserve the drug’s efficacy as well as its purity, identity, strength, and quality for the entire shelf life.

The FDA does not approve the container as such, but only the material used incontainer. A list of substance “Generally recognized as safe” (GRAS) have been published by FDA. Under the opinion of qualified experts they are safe in normal conditions. The material does not fall in this category (GRAS) must be evaluated by manufacturer and data has to be submitted to FDA.

The specific FDA regulation for the drug states that “container, closure, and other components of the packaging must not be reactive, additive or absorptive to the extent that identity, strength, quality, or purity of the drug will be affected”.

Storage Requirements (Labeling)

Shake well before use Do not freeze Protect from direct light (For light sensitive drugs).

References

1. Cooper & Gun, Sixth edition, “Dispersed system” Tutorial Pharmacy, Page No. 75-78.2. Ansel C., Allen L.V., Popovich N.G. Eighth edition “Disperse systems” Pharmaceutical

Dosage Forms & Drug Delivery Systems, Lippincott Williams and Wilkins, Philadelphia 2005, Page No. Page No. 387-389, 398.

3. Remington, Twentieth edition, “Pharmaceutical Necessities” The Science and Practice of Pharmacy, Lippincott Williams and Wilkins, Philadelphia 2000, Page No:1017-1021.

4. Remington, Twentieth edition, “Colloidal Dispersions” The Science and Practice of Pharmacy, Lippincott Williams and Wilkins, Philadelphia 2000, Page No. 298-307.

5. http://www.tamiflu.com/hcp/dosing/extprep.aspx 6. http://www.pharmainfo.net/free-books/pharmaceutical-

suspensionsa-review