Topic 9- Suppositories

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Suppositories and

Pessaries

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Introduction

• Suppositories: Solid medicatedpreparations designed for insertion intorectum where they melt, dissolve ordisperse and exert a local , or asystemic eect.

• Pessaries: Solid medicated

preparations designed for insertion intovagina where they melt or dissolve andexert a local or a systemic eect.

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Suppository bases

• In suppositories and pessaries, the drug is

incorporated into an inert vehicle. The vehicle isknown as the base. Such bases should have somedesirable criteria as:

elt at, or !ust below body temperature or dissolvein body "uids.

Solidify #uickly after melting.

$e easily moulded and removed from the mould.

$e chemically stable even when molten.

%elease the active ingredient readily. $e easy to handle.

$e bland, i.e. non&toxic and non&irritant.

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Suppository bases

1- The fatty bases:

i. Theobroma oil 'cocoa butter(.

ii.Synthetic fats

2- Water-soluble and water-miscible bases:

i. )lycerol&gelatin basesii.acrogols

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Theobroma oil

• Theobroma oil has a melting point range of *+&*- and soreadily melts in the body.

• Advantaes: It li#ue/es easily on heating but also sets rapidly when

cooled. It is also bland, therefore no irritation occurs.

• !isadvantaes:• 0olymorphism: Stable 1 form vs. unstable 2 and 3 forms• Shrinks only slightly on cooling and therefore tends to stick

to the mould thus needs a lubricant.• Storage in hot climates.• %eduction of melting point by the addition of soluble drugs. Note: for the previous two points, melting point can be raised by the

addition of beeswax (up to 10%)

• 0rone to oxidation.• $atch to batch variation.


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Synthetic fats

• These are prepared by hydrogenating suitable vegetable oils. They have many of the advantages of theobroma oil but fewer

disadvantages.

!isadvantaes:

• The viscosity of the melted fats is lower than that of

theobroma oil. 4s a result there is a greater risk of drugparticles sedimentation during preparation leading to a lack ofuniform drug distribution which can give locali5ed irritancy. This problem is partly compensated for in that these bases setvery #uickly.

•

These bases become brittle if cooled too rapidly, so should notbe refrigerated during preparation.

• There is a series of grades of synthetic fatty bases, each withdierent hardness and melting point ranges resulting in avariety of drug absorption and release pro/les.

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"lycerol-elatin bases

• These bases are a mixture of glycerol and water stiened

with gelatin. The commonest is )lycerol Suppositories $ase$0, which has 678 w9w gelatin, and +8 w9w glycerol. In hotclimates the gelatin content can be increased to 6;8 w9w.

• )elatin is a puri/ed protein produced by the hydrolysis of thecollagenous tissue, such as skins and bones, of animals.

• Two types of gelatin are used for pharmaceutical purposes, Type 4, which is prepared by acid hydrolysis and is cationic,and Type $, which is prepared by alkaline hydrolysis and isanionic.

• Type 4 is compatible with substances such as boric acid andlactic acid while Type $ is compatible with substances like

5inc oxide.• The

particularly when it is used in the preparation of suppositoriesor pessaries.

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"lycerol-elatin bases

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Disadvantages:

•Glycerol-gelatin bases cause rectal irritation.

•As they issol!e in the "ucous secretions o# the rectu"$ os"osisoccurs %roucing a la&ati!e e##ect.

•'hey are also hygrosco%ic an there#ore re(uire care#ul storage.

•Because o# the )ater content$ "icrobial conta"ination is "ore

li*ely than )ith the #atty bases. Preser!ati!es "ay be ae to the

%rouct$ but can lea to %roble"s o# inco"%atibilities.

•'hey are "uch "ore i##icult to %re%are an hanle than other

bases.

•'he solution ti"e e%ens on the content an (uality o# the gelatin

an also the age o# the su%%ository.

'his ty%e o# base is co""only use #or %essaries rather than

su%%ositories.


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#acrools

• These polyethylene glycols can be blended together toproduce suppository bases with varying melting points,

dissolution rates and physical characteristics.• =rug release depends on the base dissolving rather than

melting 'the melting point is often around >+-(.

• ?igher proportions of high molecular weight polymersproduce preparations which release drug slowly and are also

brittle.

Advantaes:

6. They have no physiological eect.

@. 4re not prone to microbial contamination.

*. ?ave a high water&absorbing capacity.

7. 4s they dissolve, a viscous solution is produced which meansthere is less likelihood of leakage from the body.

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!isadvantaes:

• They are hygroscopic which means they must becarefully stored and this could lead to irritation ofthe rectal mucosa.

• They become brittle if cooled too #uickly and also

may become brittle on storage.• Incompatibility with several drugs and packaging

materials, e.g. ben5ocaine, penicillin and plastic,may limit their use.

•

In addition crystal growth occurs with some drugscausing irritation to the rectal mucosa and, if thecrystals are large, prolonged dissolution times.

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#acrools


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Preparation of suppositories

• Suppository mould 'metal or plastic(

• oulds are made in four si5es: 6, @, 7 and ; g.

• Suppositories containing an active ingredientwhich is insoluble in the base.

•

Suppositories containing an active ingredientwhich is soluble in the base, li#uid or semisolid.

• Suppositories using a glycerol&gelatin base.

!efer bac" to the textboo" for full details (#in$eld,th edition, &hapter ')

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#ould calibration

• The capacity of a suppository mould is nominal and

each mould will have minor variations. Therefore theweight of material contained in dierent moulds maybe dierent and will also depend on the base beingused.

•

It is therefore essential that each mould be cailbratedfor each dierent base.

• The capacity of the mould is con/rmed by /lling themould with the chosen base.

• The total weight of the perfect suppositories is taken

and a mean weight calculated. This value is thecalibration value of the mould for that particular base.

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!isplacement value

• 4 suppository mould is /lled by volume, but the

suppository is formulated by weight.• The volume of a suppository from a particular mould is

uniform but its weight can vary when a drug is presentdue to dierence in densities between the drug and

base.• The displacement value of a drug is the number of

parts by weight of drug which displaces 'occupies thesame volume of( 6 part by weight of the base.

• =isplacement values refer to values for theobroma oil.

These values can also be used for other fatty bases.

• Aith glycerol&gelatin suppository base approximately6.@g occupies the same volume as 6g of theobromaoil.

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To calculate the displacement value of a drug:

Aeight of six unmedicated suppositories B g.

Aeight of six suppositories containing 7+8 drug B ;.;g.

Aeight of base is then B +8 B +96++ x ;.; B >.@; g.Aeight of drug in suppositories B 7+8 B 7+96++ x ;.; B

*.>@.

Aeight of base displaced by drug B & >.@; B +.@ g.

If +.@ g of base is displaced by *.>@ g of drug, then6g of base will be displaced by *.>@9+.@gB 7.;; g.

Therefore displacement value of drug B 7.C 'rounded toone decimal place(.

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!isplacement value


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$% Prepare si& suppositories each containin 2'( m

bismuth suballate.

•Duantities are calculated for an excess of two suppositories. Therefore calculate for eight suppositories.•=E of bismuth subgallate B @.•4 l g mould will be used with mould calibration B +.C7.

To calculate the amount of base re#uired, a simple e#uation isused:

Amount of base = (N x y) – (N x D/ DV)

FB; y B +.C7 = B @>+ mg B +.@> g =E B @.

4mount of base re#uiredB '; x +.C7( G'';x+.@>(9@.( B .>@&+.76 B .C C B .; g

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!isplacement value


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)alculations for more than one dru:

alculate the #uantities re#uired to make 6> suppositorieseach containing 6>+ mg hamamelis dry extract and >+ mg of5inc oxide. 4 @g mould, with mould calibration of @.+7, will beused. alculate for 6 suppositories '@ excess(.

=E of hamamelis dry extract B 6 .>, =E of 5inc oxide B 7..

Aeight of hamamelis dry extract B 6 x +.6> B @.>> g.

Aeight of 5inc oxide B 6 x +.> B C.>@ g.

Aeight of base B 6 x @.+7& '@.>>96.> H C.>@97.( B *7.;&'6. H @.+*( B *+.C> g.

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!isplacement value


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• )alculation of *uantities when the activeinredient is stated as a percentae

In this case, a displacement value is not re#uired.

$% Prepare eiht suppositories containin 1+,inc o&ide. )alculate for l suppositories /2e&cess%. #ould calibration 0 1

Aeight of base re#uired to /ll mould B 6+ x 6 B 6+g.inc oxide is 6;8 of total B 6.;g

Aeight of base re#uiredB l+ &6.; B ;.@ g.

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!isplacement value


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)ontainers for suppositories

• Jach suppository should be wrapped in

greaseproof paper.

• )lass or plastic screw&topped !ars are possiblythe best choice of container forextemporaneously prepared suppositories and

pessaries.• ardboard cartons may be used but these oer

little protection from moisture or heat. They aretherefore not suitable for hygroscopic materials.

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Shelf life

0rovided they are well packaged andthe storage temperature is low,

suppositories and pessaries arerelatively stable preparations. Knlessother information is available, an

expiry date of 6 month is appropriate.

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abellin for suppositories

• ?ow to use the product.•

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Topic 9- Suppositories