11. Suppositories and 11. Suppositories and InsertsInserts

ContentsContents1.1. SuppositoriesSuppositories2.2. Some factors of drug absorption Some factors of drug absorption

from rectal suppositoriesfrom rectal suppositories3.3. Suppository basesSuppository bases4.4. Preparation of suppositoriesPreparation of suppositories5.5. Rectal suppositoriesRectal suppositories6.6. Vaginal suppositoriesVaginal suppositories7.7. Packaging and storagePackaging and storage8.8. Vaginal insertsVaginal inserts

1. Suppositories1. Suppositories

Suppositories are solid dosage forms Suppositories are solid dosage forms intended for insertion into body orifiintended for insertion into body orifices where they melt, soften, or dissolces where they melt, soften, or dissolve and exert local or systemic effects.ve and exert local or systemic effects.

Suppositories are commonly used reSuppositories are commonly used rectally and vaginally and accasionally ctally and vaginally and accasionally urethrally. They have various shapes urethrally. They have various shapes and weights.and weights.

The shape and size of a The shape and size of a suppository must be such that it suppository must be such that it can be easily inserted into the can be easily inserted into the intended orifice without causing intended orifice without causing undue distension, undue distension,

and once inserted, it must be and once inserted, it must be retained for the appropriate retained for the appropriate period.period.

11 ） ） Local actionLocal action Rectal suppositories intended for locaRectal suppositories intended for loca

lized action are most frequently used lized action are most frequently used to relieve to relieve constipationconstipation or or the pain, irrthe pain, irritation, itching, and inflammationitation, itching, and inflammation ass associated with hemorrhoids or other anociated with hemorrhoids or other anorectal conditions.orectal conditions.

A popular laxative, glycerin suppositoA popular laxative, glycerin suppositories promote laxation by the local irriries promote laxation by the local irritation of the mucous membranes.tation of the mucous membranes.

Vaginal suppositories or inserts intended fVaginal suppositories or inserts intended for localized effects are employed mainly aor localized effects are employed mainly as s contraceptivescontraceptives, , antisepticsantiseptics in feminine h in feminine hygiene, and as ygiene, and as specific agentsspecific agents to combat as to combat as invading pathogen.invading pathogen.

Most commonly, the drugs used are Most commonly, the drugs used are nonoxnonoxynol-9ynol-9 （（ 9-9- 壬苯醇醚）壬苯醇醚） for contraception, afor contraception, and nd trichomonacidestrichomonacides （杀滴虫剂）（杀滴虫剂） to combato combat vaginitis caused by t vaginitis caused by Trichomonas vaginaliTrichomonas vaginalis, Candida (Monilia) albicanss, Candida (Monilia) albicans, and other m, and other microorganisms.icroorganisms.

2) 2) Systemic actionSystemic action For systemic effects, the mucous For systemic effects, the mucous

membranes of the rectum and membranes of the rectum and vagina permit the absorption of vagina permit the absorption of many soluble drugs.many soluble drugs.

Although the rectum is used Although the rectum is used frequently as the site for the frequently as the site for the systemic absorption of drugs, the systemic absorption of drugs, the vagina is not as frequently used vagina is not as frequently used for this purpose.for this purpose.

Among the advantages over oral therapy Among the advantages over oral therapy of the rectal route of administration for of the rectal route of administration for achieving systemic effects are these:achieving systemic effects are these:

a) Drugs destroyed or inactivated by the a) Drugs destroyed or inactivated by the pH or enzymatic activity of the stomach pH or enzymatic activity of the stomach or intestines need not be exposed to this or intestines need not be exposed to this destructive environments;destructive environments;

b) Drugs irritating to the stomach may be b) Drugs irritating to the stomach may be giving without causing such irritationgiving without causing such irritation

c) Drugs destroyed by portal circulation c) Drugs destroyed by portal circulation may bypass the liver after rectal may bypass the liver after rectal absorptionabsorption

d) The route is convenient for administratiod) The route is convenient for administration of drugs to adult or pediatric patients whn of drugs to adult or pediatric patients who may be unable or unwilling to swallow o may be unable or unwilling to swallow medicationmedication

e) It is an effective route in the treatment of e) It is an effective route in the treatment of patients with vomiting episodes.patients with vomiting episodes.

Examples of drugs administered rectExamples of drugs administered rectally in the form of suppositories for tally in the form of suppositories for their systemic effects includeheir systemic effects include

a)a) prochlorperazine prochlorperazine （丙氯拉嗪）（丙氯拉嗪） and cand chlorpromazinehlorpromazine （氯丙嗪）（氯丙嗪）

b)b) oxymorphone HCl oxymorphone HCl （盐酸羟吗啡酮）（盐酸羟吗啡酮）c)c) ergotamine tartrateergotamine tartrate （麦角胺酒石酸（麦角胺酒石酸

盐）盐）d)d) indomethacinindomethacine)e) ondansetron ondansetron

2. Some factors of drug 2. Some factors of drug absorption from rectal absorption from rectal

suppositoriessuppositories

1) Physiologic factors1) Physiologic factors Colonic contentColonic content- when deemed desirable, an evacuant ewhen deemed desirable, an evacuant e

nema may be administered and allowenema may be administered and allowed to act before the administration of a d to act before the administration of a suppository of a drug to be absorbed.suppository of a drug to be absorbed.

- Diarrhea, colonic obstruction, and tissDiarrhea, colonic obstruction, and tissue dehydrationue dehydration

Circulation routeCirculation route- The lower hemorrhoidal veins surroThe lower hemorrhoidal veins surro

unding the colon receive the absorbeunding the colon receive the absorbed drug and initiate its circulation thrd drug and initiate its circulation throughout the body, bypass the liver.oughout the body, bypass the liver.

- Lymphatic circulation also assists in Lymphatic circulation also assists in the absorption of rectally administerthe absorption of rectally administered drugs.ed drugs.

pH and lack of bufferingpH and lack of buffering- Because rectal fluids are essentially neBecause rectal fluids are essentially ne

utral in pH and have no effective buffer utral in pH and have no effective buffer capacity, the form in which the drug is capacity, the form in which the drug is administered will not generally be cheadministered will not generally be chemically changed by the rectal environmmically changed by the rectal environment.ent.

- The suppository base employed has a mThe suppository base employed has a marked influence on the release of active arked influence on the release of active constituents incorporated into it.constituents incorporated into it.

2) Physicochemical factors of the drug 2) Physicochemical factors of the drug and suppository baseand suppository base

Lipid-water solubilityLipid-water solubility- A lipophilic drug that is distributed iA lipophilic drug that is distributed i

n a fatty suppository base in low conn a fatty suppository base in low concentration has less of a tendency to ecentration has less of a tendency to escape to the surrounding aqueous fluscape to the surrounding aqueous fluids than would a hydrophilic substanids than would a hydrophilic substance present in a fatty base to an extent ce present in a fatty base to an extent approaching its saturation.approaching its saturation.

- Water soluble bases, for example, PEWater soluble bases, for example, PEG, which dissolve in the anorectal fluG, which dissolve in the anorectal fluids, release for absorption both wateids, release for absorption both water-soluble and oil-soluble drugs.r-soluble and oil-soluble drugs.

- Naturally, the more drug a base contNaturally, the more drug a base contains, the more drug will be available ains, the more drug will be available for potential absorption.for potential absorption.

Particle sizeParticle size- For drugs present in a suppository in thFor drugs present in a suppository in th

e undissolved state, the size of the drug e undissolved state, the size of the drug particle will influence its rate of dissolparticle will influence its rate of dissolution and its availability for absorption.ution and its availability for absorption.

- The smaller the particle size, the more The smaller the particle size, the more readily the dissolution of the particle areadily the dissolution of the particle and the greater the chance for rapid absnd the greater the chance for rapid absorption.orption.

Nature of the baseNature of the base- The possiblity of chemical and/or phThe possiblity of chemical and/or ph

ysical interactions between the mediysical interactions between the medicinal agent and the suppository base, cinal agent and the suppository base, which could affect the stability and/owhich could affect the stability and/or bioavailability of the drug.r bioavailability of the drug.

- If the base is irritating to the mucous If the base is irritating to the mucous membranes of the rectum, it may inimembranes of the rectum, it may initiate a colonic response and prompt tiate a colonic response and prompt a bowel movement, negating the proa bowel movement, negating the prospect of complete drug release and aspect of complete drug release and absorption.bsorption.

3. Suppository bases3. Suppository bases

One of the first requisites for a One of the first requisites for a suppository base is that suppository base is that

it remains solid at room it remains solid at room temperature temperature

but softens, melts or dissolves but softens, melts or dissolves readily at body temperature readily at body temperature

so that the drug it contains may so that the drug it contains may be made fully available soon after be made fully available soon after insertion.insertion.

Classification of suppository basesClassification of suppository bases1) Fatty or oleaginous base1) Fatty or oleaginous base Cocoa butterCocoa butter- is defined as the fat obtained from this defined as the fat obtained from th

e roasted seed of Theobroma cacao.e roasted seed of Theobroma cacao.- At room temperature it is a yellowish,At room temperature it is a yellowish,

white solid having a faint, agreeable white solid having a faint, agreeable chocolate-like odor.chocolate-like odor.

- Chemically, it is a triglyceride primaChemically, it is a triglyceride primarily of oleopalmitostearinrily of oleopalmitostearin （油酸棕榈（油酸棕榈酸硬脂酸三甘油酯）酸硬脂酸三甘油酯） and oleodistearinand oleodistearin（油酸二硬脂酸三甘油酯）（油酸二硬脂酸三甘油酯） ..

- Cocoa butter melts between 30Cocoa butter melts between 30C to 3C to 366C, it is an ideal suppository base.C, it is an ideal suppository base.

- Cocoa butter exhibits marked polymCocoa butter exhibits marked polymorphism.orphism.

Hydrogenated fatty acids of vegetablHydrogenated fatty acids of vegetable oils e oils (palm kernal oil and cottonsee(palm kernal oil and cottonseed oil)d oil)

Fat-based compounds containing coFat-based compounds containing compounds of glycerin with the higher mpounds of glycerin with the higher molecular weight fatty acids, such as molecular weight fatty acids, such as palmitic and stearic acids palmitic and stearic acids (glyceryl (glyceryl monostearate and glyceryl monopalmonostearate and glyceryl monopalmitate)mitate)

2) Water-soluble and water-miscible 2) Water-soluble and water-miscible basesbases

Glycerinated gelatinGlycerinated gelatin- Glycerinated gelatin suppositories Glycerinated gelatin suppositories

may be prepared by dissolving may be prepared by dissolving granular gelatin (20%) in glycerin granular gelatin (20%) in glycerin (70%) and adding a solution or (70%) and adding a solution or suspension of the medication (10%).suspension of the medication (10%).

- Glycerinated gelatin base is most Glycerinated gelatin base is most frequently used in the preparation of frequently used in the preparation of vaginal suppositories, where the vaginal suppositories, where the prolonged localized action of the prolonged localized action of the medicinal agent is usually desired.medicinal agent is usually desired.

- Glycerinated gelatin-based Glycerinated gelatin-based suppositories have a tendency to suppositories have a tendency to absorb moisture due to the absorb moisture due to the hygroscopic nature of glycerin.hygroscopic nature of glycerin.

- The suppository may have a The suppository may have a dehydrating effect and be irritating dehydrating effect and be irritating to the tissues upon insertionto the tissues upon insertion

- Urethral suppositories may be Urethral suppositories may be prepared from a glycerinated gelatin prepared from a glycerinated gelatin base (60% gelatin, 20% glycerin and base (60% gelatin, 20% glycerin and 20% medicated aqueous portion)20% medicated aqueous portion)

Polyethylene glycolsPolyethylene glycols- PEGs are polymers of ethylene oxide and watPEGs are polymers of ethylene oxide and wat

er, prepared to various chain lengths, molecer, prepared to various chain lengths, molecular weights, and physical states.ular weights, and physical states.

- They are available in a number of molecular They are available in a number of molecular weight ranges.weight ranges.

- Various combinations of these PEGs may be cVarious combinations of these PEGs may be combined by fusion, using two or more of the ombined by fusion, using two or more of the various types to achieve a suppository base ovarious types to achieve a suppository base of the desired consistency and characteristics.f the desired consistency and characteristics.

- PEG suppositories do not melt at body tempePEG suppositories do not melt at body temperature but rather dissolve slowly in the bodrature but rather dissolve slowly in the body’s fluids.y’s fluids.

3) Miscellaneous bases3) Miscellaneous bases- mixtures of oleaginous and water-soluble mixtures of oleaginous and water-soluble

or water-miscible materials,or water-miscible materials,- These materials may be chemical or physiThese materials may be chemical or physi

cal mixtures,cal mixtures,- some are preformed emulsions, generally some are preformed emulsions, generally

of the water/oil type,of the water/oil type,- or they may be capable of dispersing in aqor they may be capable of dispersing in aq

ueous fluids. ueous fluids. - E.g. polyoxyl 40 stearate E.g. polyoxyl 40 stearate （聚氧乙烯（聚氧乙烯 4040 硬脂硬脂

酸酯）酸酯）

Polyoxyl 40 stearate is a mixture of thPolyoxyl 40 stearate is a mixture of the monostearate and distearate esters e monostearate and distearate esters of mixed polyoxyethylene diols and tof mixed polyoxyethylene diols and the free glycols. he free glycols.

The average polymer length being eqThe average polymer length being equivalent to about 40 oxyethylene units.uivalent to about 40 oxyethylene units.

The substance is a waxy, white to lighThe substance is a waxy, white to light tan solid that is water-soluble. Its mt tan solid that is water-soluble. Its melting point is generally between 39elting point is generally between 39C C and 45and 45C.C.

4. Preparation of 4. Preparation of suppositoriessuppositories

11 ）） Preparation by moldingPreparation by moldingThe steps in molding includeThe steps in molding include melting the base,melting the base, incorporating any required medicamenincorporating any required medicamen

ts,ts, pouring the melt into molds,pouring the melt into molds, allowing the melt to cool and congeal inallowing the melt to cool and congeal in

to suppositories,to suppositories, removing the formed suppositories froremoving the formed suppositories fro

m the mold.m the mold.

Suppository moldsSuppository molds Commercially available molds can Commercially available molds can

produce individual or large produce individual or large numbers of suppositories of numbers of suppositories of various shapes and sizes.various shapes and sizes.

Molds in common use today are Molds in common use today are made from stainless steel, made from stainless steel, aluminum, brass, or plastic.aluminum, brass, or plastic.

Individual plastic molds may be Individual plastic molds may be obtained to form a single obtained to form a single suppository.suppository.

Lubrication of the moldLubrication of the mold Depending on the formulation, suppoDepending on the formulation, suppo

sitory molds may require lubrication sitory molds may require lubrication before the melt is poured to facilatate before the melt is poured to facilatate clean and easy removal of the molded clean and easy removal of the molded suppositories.suppositories.

Lubrication is seldom necessary when Lubrication is seldom necessary when the suppository base is cocoa butter othe suppository base is cocoa butter or polyethylene glycol.r polyethylene glycol.

Lubrication is usually necessary when Lubrication is usually necessary when glycerinated gelatin suppositories are glycerinated gelatin suppositories are prepared.prepared.

Calibration of the moldCalibration of the mold

Each individual mold is capable of Each individual mold is capable of holding a specific volume of holding a specific volume of material in each of its openings.material in each of its openings.

The pharmacist should calibrate The pharmacist should calibrate each suppository mold for the each suppository mold for the usual base so as to prepare usual base so as to prepare medicated suppositories each medicated suppositories each having the proper quantity of having the proper quantity of medicaments.medicaments.

- Prepare molded suppositories from Prepare molded suppositories from base material alonebase material alone

- After removal from the mold, the After removal from the mold, the suppositories are weighted, and the suppositories are weighted, and the total weight and the average weight total weight and the average weight of each suppository are recorded.of each suppository are recorded.

- To determine the volume of the To determine the volume of the mold, the suppositories are then mold, the suppositories are then carefully melted in a calibrated carefully melted in a calibrated beaker, and the volume of the melt beaker, and the volume of the melt is determined for the total number is determined for the total number as well as the average of one as well as the average of one suppository.suppository.

Volume of base=Total volume of the mVolume of base=Total volume of the mold-the volume of the drug substancesold-the volume of the drug substances

If 12 ml of cocoa butter are required to fiIf 12 ml of cocoa butter are required to fill a suppository mold and if the medicamll a suppository mold and if the medicaments in the formula have a collective voluents in the formula have a collective volume of 2.8 ml, how many gram of cocoa bme of 2.8 ml, how many gram of cocoa butter required? (the density of cocoa buttutter required? (the density of cocoa butter is 0.86 g/mL)er is 0.86 g/mL)

Determination of the amount of Determination of the amount of base requiredbase required

a)a) Weigh the active ingredient for the Weigh the active ingredient for the preparation of a single suppository;preparation of a single suppository;

b)b) Dissolve it or mix it with a portion Dissolve it or mix it with a portion of melted base insufficient to fill of melted base insufficient to fill one cavity of the mold, and add the one cavity of the mold, and add the mixture to a cavity;mixture to a cavity;

c)c) Add additional melted base to the Add additional melted base to the cavity to fill it completelycavity to fill it completely

d)d) Allow the suppository to congeal Allow the suppository to congeal and hardenand harden

e)e) Remove the suppository from the Remove the suppository from the mold and weigh itmold and weigh it

Preparing and pouring the meltPreparing and pouring the melt Using the least possible heat, the Using the least possible heat, the

weighed suppository base weighed suppository base material is melted, generally over material is melted, generally over a water bath, since no great deal a water bath, since no great deal of heat is usually required.of heat is usually required.

Medicinal substances are usually Medicinal substances are usually incorporated into a portion of the incorporated into a portion of the melted base by mixing on a glass melted base by mixing on a glass or porcelain tile with a spatula.or porcelain tile with a spatula.

After incorporation, this material After incorporation, this material is stirred into the remaining is stirred into the remaining base, which has been allowed to base, which has been allowed to cool almost to its congealing cool almost to its congealing point.point.

The melt is poured carefully and The melt is poured carefully and continuously into each cavity of continuously into each cavity of the mold, which has been the mold, which has been previously equilibrated to room previously equilibrated to room temperature.temperature.

When the suppositories are hard, When the suppositories are hard, the mold is removed from the the mold is removed from the refrigerator and allowed to come refrigerator and allowed to come to room temperature.to room temperature.

Then the sections of the mold are Then the sections of the mold are separated, and the suppositories separated, and the suppositories are dislodges.are dislodges.

The solid materials remain suspended if the pThe solid materials remain suspended if the pouring is performed just above the conjealing ouring is performed just above the conjealing point and not when the base is too fluid.point and not when the base is too fluid.

A small quantity of silica gel can be incorporaA small quantity of silica gel can be incorporated into formula to aid in keeping the active dted into formula to aid in keeping the active drug suspended.rug suspended.

In filling each suppository cavity, the pouring In filling each suppository cavity, the pouring must be continuous to prevent layering, whicmust be continuous to prevent layering, which may lead to a product easily broken on hanh may lead to a product easily broken on handling.dling.

To ensure a completely filled mold upon congTo ensure a completely filled mold upon congealing, the melt is poured excessively over eaealing, the melt is poured excessively over each opening, actually using above the level of tch opening, actually using above the level of the mold.he mold.

Density calculations for Density calculations for suppositoriessuppositories

Determination of the dosage Determination of the dosage replacement factor methodreplacement factor method

f={100(E-G)/GX}+1f={100(E-G)/GX}+1

where where EE=the weight of the pure =the weight of the pure base suppositoriesbase suppositories

GG=the weight of suppositories =the weight of suppositories with with X%X% of the active ingredient of the active ingredient

Example 1Example 1Prepare a suppository containing 100 Prepare a suppository containing 100 mg of phenobarbital (f=0.81) using cmg of phenobarbital (f=0.81) using cocoa butter as the base. The weight oocoa butter as the base. The weight of the pure cocoa butter suppository if the pure cocoa butter suppository is 2.0 g. What will be the total weight s 2.0 g. What will be the total weight of each suppository?of each suppository?

Determination of density factor methodDetermination of density factor method1)1) Determine the average blank weight, A, pDetermine the average blank weight, A, p

er mold using the suppository base of inter mold using the suppository base of interesterest

2)2) Weigh the quantity of suppository base nWeigh the quantity of suppository base necessay for 10 suppositories.ecessay for 10 suppositories.

3)3) Weigh 1.0 g of medicationWeigh 1.0 g of medication4)4) Melt the suppository base and incorporatMelt the suppository base and incorporat

e the medication, mix, pour into molds, ce the medication, mix, pour into molds, cool, trim, and remove from the moldsool, trim, and remove from the molds

5)5) Weigh the 10 suppositories and determinWeigh the 10 suppositories and determine the average weight (C).e the average weight (C).

66 ）） determine the density factor as followsdetermine the density factor as followsDensity factor = B/(A-C+B)Density factor = B/(A-C+B)

where where A=average weight of blankA=average weight of blankB=weight of medication per suppositoryB=weight of medication per suppositoryC=average weight of medicated suppositC=average weight of medicated suppositoryory

7) Take the weight of the medication requi7) Take the weight of the medication required for each suppository and divide by thred for each suppository and divide by the density factor of the medication to find e density factor of the medication to find the replacement value of the suppository the replacement value of the suppository basebase

8) Subtract this quantity from the 8) Subtract this quantity from the blank suppository weightblank suppository weight

9) Multiply by the number of 9) Multiply by the number of suppositories required to obtain suppositories required to obtain the quantity of suppository base the quantity of suppository base required for the prescription.required for the prescription.

10) Multiply the weight of drug per 10) Multiply the weight of drug per suppository by the number of suppository by the number of suppositories required to obtain suppositories required to obtain the quantity of active drug the quantity of active drug required for the prescription.required for the prescription.

药物的重量与同体积基质重量的比值称为药物的重量与同体积基质重量的比值称为该药物对基质的置换价该药物对基质的置换价

DV=W/G-(M-W)DV=W/G-(M-W)式中， 式中， G-G- 纯基质平均栓重；纯基质平均栓重； M-M- 含药栓含药栓的平均重量；的平均重量； W-W- 每个栓剂的平均含药重量每个栓剂的平均含药重量

用测定的置换价可以方便地计算出制备这用测定的置换价可以方便地计算出制备这种含药栓需要基质的重量种含药栓需要基质的重量 x:x:

x={G-(y/DV)}.nx={G-(y/DV)}.ny-y- 处方中药物的剂量； 处方中药物的剂量； n-n- 拟制备栓剂的拟制备栓剂的枚数枚数

Example 2Example 2

Prepare 12 acetaminophen 300 Prepare 12 acetaminophen 300 mg suppositories using cocoa mg suppositories using cocoa butter, where the average weight butter, where the average weight of the cocoa butter blank is 2 g of the cocoa butter blank is 2 g and the average weight of the and the average weight of the medicated suppository is 1.8 g.medicated suppository is 1.8 g.

Determination of occupied volume Determination of occupied volume methodmethod

1)1) Determine the average weight per mold Determine the average weight per mold (blank) using the suppository base of (blank) using the suppository base of interestinterest

2)2) Weigh the quantity of suppository base Weigh the quantity of suppository base necessary for 10 suppositoriesnecessary for 10 suppositories

3)3) Divide the density of the active drug by Divide the density of the active drug by the density of the suppository base to the density of the suppository base to obtain a ratioobtain a ratio

4)4) Divide the total weight of active drug Divide the total weight of active drug required for the total number of required for the total number of suppositories by the ratio obtained in suppositories by the ratio obtained in step 3 (this will give the amount of step 3 (this will give the amount of suppository base displaced by the active suppository base displaced by the active drug).drug).

5)5) Substract the amount obtained in stSubstract the amount obtained in step 4 from the total weight of the preep 4 from the total weight of the prescription to obtain the weight of suscription to obtain the weight of suppository base requiredppository base required

6)6) Multiply the weight of active drug pMultiply the weight of active drug per suppository times the number of er suppository times the number of suppositories to be prepared to obtsuppositories to be prepared to obtain the quantity of active drug requiain the quantity of active drug requiredred

Example 3Example 3

Prepare 10 suppositories, each Prepare 10 suppositories, each containing 200 mg of a drug with containing 200 mg of a drug with a density of 3.0. The suppository a density of 3.0. The suppository base has a density of 0.9 and a base has a density of 0.9 and a prepared blank weighs 2.0 g. prepared blank weighs 2.0 g. Using the “determination of Using the “determination of occupied volume method,” occupied volume method,” prepare the required prepare the required suppositories.suppositories.

2) Preparation by compression2) Preparation by compression Suppositories may be prepared by forSuppositories may be prepared by for

cing the mixed mass of the base and tcing the mixed mass of the base and the medicaments into special molds ushe medicaments into special molds using suppository-making machines.ing suppository-making machines.

In preparation of compression into thIn preparation of compression into the molds, the base and the other formue molds, the base and the other formulative ingredients are combined by thlative ingredients are combined by thorough mixing, the friction of the proorough mixing, the friction of the process softening the base into a pastelikcess softening the base into a pastelike consistency.e consistency.

Compression is especially suited for Compression is especially suited for making suppositories that contain making suppositories that contain heat-labile medicinal substances or a heat-labile medicinal substances or a great deal of substances that are great deal of substances that are insoluble in the base.insoluble in the base.

In contrast to the molding method, In contrast to the molding method, compression permits no likelihood of compression permits no likelihood of insoluble matter settling during insoluble matter settling during manufacture.manufacture.

The disadvantage to compression is The disadvantage to compression is that the special suppository machine that the special suppository machine is required and there is some is required and there is some limitation as to shapes of limitation as to shapes of suppositories that can be made.suppositories that can be made.

5. Rectal suppositories5. Rectal suppositories

The rectal route of The rectal route of administration is especially administration is especially useful in instances in which the useful in instances in which the patient is unwilling or unable to patient is unwilling or unable to take medication by mouth.take medication by mouth.

Local anesthetic suppositories Relieve pruritus anihemorrhoids

Hemorrhoidalsuppositories

astringentsprotectivesanestheticslubricants

Cathartic suppositories

bisacodylglycerin

A formula of glycerin suppositories is as followA formula of glycerin suppositories is as follows:s:

Glycerin 91gGlycerin 91g Sodium Stearate 9 gSodium Stearate 9 g Purified Water 5 gPurified Water 5 g Glycerin, a hygroscopic material, contributeGlycerin, a hygroscopic material, contribute

s to the laxative effect of the suppository by ds to the laxative effect of the suppository by drawing water from the intestine and also frorawing water from the intestine and also from its irritant action on the mucous lining.m its irritant action on the mucous lining.

The sodium stearate, a soap, is the solidifyinThe sodium stearate, a soap, is the solidifying agent in the suppository and may also contg agent in the suppository and may also contribute to the laxative action.ribute to the laxative action.

Information for proper use of Information for proper use of suppositoriessuppositories

If suppositories must be stored in the If suppositories must be stored in the refrigerator, they should be allowed to refrigerator, they should be allowed to warm to room temperature before warm to room temperature before insertion.insertion.

The patient should be advised to rub The patient should be advised to rub cocoa butter suppositories gently with cocoa butter suppositories gently with the fingers to melt the surface to the fingers to melt the surface to provide lubrication for insertion.provide lubrication for insertion.

Glycerinated gelatin or polyethylene Glycerinated gelatin or polyethylene glycol suppositories should be glycol suppositories should be moistened with water to enhance moistened with water to enhance lubrication.lubrication.

6. Vaginal suppositories6. Vaginal suppositories

Vaginal suppository are employed Vaginal suppository are employed principally principally

to combat infections occurring in to combat infections occurring in the female genitourinary areathe female genitourinary area

to restore the vaginal mucosa to to restore the vaginal mucosa to its normal stateits normal state

and for contraception.and for contraception.

Among the anti-infective agents found in cAmong the anti-infective agents found in commercial vaginal preparations areommercial vaginal preparations are

NystatinNystatin ClotrimazoleClotrimazole Butoconazole nitrateButoconazole nitrate TerconazoleTerconazole MiconazoleMiconazole Triple sulfasTriple sulfas SulfanilamideSulfanilamide Povidone-iodinePovidone-iodine Clindamycin phosphateClindamycin phosphate Metronidazole and oxytetracyclineMetronidazole and oxytetracycline

Nanoxynol-9, a spermicide, is emploNanoxynol-9, a spermicide, is employed for vaginal contraceptionyed for vaginal contraception

Estrogenic substances as dienestrol aEstrogenic substances as dienestrol are found in vaginal prepareations to re found in vaginal prepareations to restore the vaginal mucosa to its norrestore the vaginal mucosa to its normal state.mal state.

PEGSurfactants

Preservative agent

pH4.5

Rx

Progesterone, micronized powder q.s.PEG 400 60%PEG 8000 40%

The amount of progesterone prescribed pThe amount of progesterone prescribed per suppository ranges from 25 to 600 mg.er suppository ranges from 25 to 600 mg.

The suppositories are used in treating luteThe suppositories are used in treating luteal phase defect, premenstrual syndrome, lal phase defect, premenstrual syndrome, luteal phase spotting, and in the preparatiuteal phase spotting, and in the preparation of the endometrium for implantation.on of the endometrium for implantation.

7. Packaging and storage7. Packaging and storage

Glycerin suppositories and glycerinated Glycerin suppositories and glycerinated gelatin suppositories are packaged in gelatin suppositories are packaged in tightly closed glass containers to tightly closed glass containers to prevent a moisture change in the prevent a moisture change in the content of the suppositories.content of the suppositories.

Suppositories prepared from a cocoa Suppositories prepared from a cocoa butter base are usually individually butter base are usually individually wrapped or otherwise separated in wrapped or otherwise separated in compartmentalized boxes to prevent compartmentalized boxes to prevent contact and adhesion.contact and adhesion.

Suppositories containing light-Suppositories containing light-sensitive drugs are individually sensitive drugs are individually wrapped in an opaque material wrapped in an opaque material such as metallic foil.such as metallic foil.

Suppositories are also commonly Suppositories are also commonly packaged in slide boxes or in packaged in slide boxes or in plastic boxes.plastic boxes.

It is necessary to maintain It is necessary to maintain suppositories in a cool place.suppositories in a cool place.

Suppositories having cocoa butter Suppositories having cocoa butter as the base must be stored below as the base must be stored below 3030C, and preferably in a C, and preferably in a refrigerator (2refrigerator (288C).C).

Glycerinated gelatin suppositories Glycerinated gelatin suppositories are best stored at temperatures are best stored at temperatures below 8below 8C and can routinely be C and can routinely be stored at controlled room stored at controlled room temperature (20temperature (202525C).C).

Suppositories made from a base of Suppositories made from a base of polyethylene glycol may be stored at polyethylene glycol may be stored at usual room temperature.usual room temperature.

8. Vaginal inserts8. Vaginal inserts

Vaginal tablets, frequently referred tVaginal tablets, frequently referred to as vaginal inserts, are usually ovoid o as vaginal inserts, are usually ovoid in shape and are accompanied in thein shape and are accompanied in their packaging with a plastic inserter.ir packaging with a plastic inserter.

Vaginal tablets contain the same typeVaginal tablets contain the same types of antiinfective and hormonal substs of antiinfective and hormonal substances as the vaginal suppositories.ances as the vaginal suppositories.

They are prepared by tablet compresThey are prepared by tablet compression, and are commonly formulated tsion, and are commonly formulated to contain o contain

lactose as the base or fillerlactose as the base or filler starch as the disintegrating agentstarch as the disintegrating agent polyvinylpyrrolidone as a dispersing polyvinylpyrrolidone as a dispersing

agentagent magnesium stearate as a tablet lubrimagnesium stearate as a tablet lubri

cant.cant.

Questions Questions

1. What factors may affect drug 1. What factors may affect drug absorption from rectal absorption from rectal suppositories?suppositories?

2. How many bases are there in 2. How many bases are there in preparing suppositories? preparing suppositories?

3. How to prepare rectal 3. How to prepare rectal suppositories by molding ?suppositories by molding ?

4. How to calculate the quantity of 4. How to calculate the quantity of base?base?