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CONTENT MODULE 3.

June 29, 2024

MODULE 2. SOFT AND ASEPTIC DOSAGE FORMS. PHARMACEUTICAL INCOMPATIBILITIES.

CONTENT MODULE 3. SOFT MEDICAL FORMS. SUPPOSITORIES.

LESSON 18. SUPPOSITORY METHOD OF HAND ROLLING.

Suppositories – dosed medical forms, solid at room temperature and melted or dissolve at the temperature of body.

Depending on a place of introduction suppositories differentiated:

· rectal (suppositoria rectalia), intended for introduction to the rectum;

· vaginal (suppositoria vaginalia), intended for introduction in vagina;

· sticks (bacilli), intended for introduction to motions of fistula, urethra, channel of neck of uterus, acoustic duct and others like that

For the method of preparation suppositories divided into:

· Rolling (hand-pumping0

· pouring.

For the localization procedure:

· local action;

· resorbtion action.

By type of suppositories basis:

· suppositories in hydrophobic bases

· suppositories in hydrophilic bases

Requirements to suppositories:

· Time of melting (for suppositories on hydrophobic bases) – 15 minutes

· Time of dissolution (for suppositories on hydrophilic bases) – 60 minutes

· Length of rectal suppositories must be from 2,5 to 4 centimeters

· A maximal diameter of rectal suppositories is 1,5 centimeters

· Mass of rectal suppositories is from 1,0 to a 4,0 g (middle 3,0)

· Mass of vaginal suppositories must be from 1.5 to a 6,0 gram (middle 4,0)

· Sticks must have a form of cylinder with a sharp end and diameter not more than 1 centimeters.

· Length of sticks must not exceed 10 centimeters, but mass must be from 0,5 to a 1,0 gram.

· Rejections in-bulk suppositories must not exceed ± 5 %. Medicinal matters which are contained in them are guilty to be exactly dosed. Suppositories must have correct and accordingly identical form, homogeneous mass, sufficient hardness (mechanical durability) and fuse at the temperature of body.

· Suppositional mass must be homogeneous, without inclusions, marbling, and sequins.

Disadvantages of suppositories:

· not hygienic of administration

· duration of preparing.

Requirements to the suppositories bases :

· sufficient hardness at a room temperature and ability to fuse (whether to dissolve) at a temperature not higher than 37 °C, that sharply to pass ability from the solid state to the liquid, passing the stage of softening influence – ointment stage; sufficient viscidity, absence of smell, providing of maximal contact between medicinal matters and mucus shell;

· chemical and pharmacological indifference, absence of irritating actions, firmness to the action of external factors (light, heat, moisture, oxygen of air, micro organisms);

· ability easily to acquire the proper form, mixed with the largest possible number of drugs, do not interact with them and be stable during storage;

· easily to free ability medicinal matters, instrumental in the display of them pharmacological action, which depends both on properties of bases and from the method of introduction of medicinal matters in basis;

· presence of the proper reological indexes and optimum structurally mechanical properties.

PRESCRIPTION OF SUPPOSITORIES

Suppositories prescribe in recipes by two methods:

· distributive

· separate.

GENERAL RULES OF PREPARATION SUPPOSITORIES

The main technological task in the preparation of suppositories is that most drugs dispersed evenly not only in suppository mass, but in every suppository, ball or stick, giving them the necessary geometry.

If mass of suppository in a recipe is not marked, prepare 3,0 grams suppository. In child’s practice mass of suppository is necessarily specified in a recipe is must be from 0,5 to 1,5 gram.

If mass of vaginal suppositories is not marked, 4,0 grams suppository. The size of sticks is guilty to be marked in a recipe.

For preparation of suppositories in the conditions of pharmacy utilize the method of deflation, and at presence of facilities of small mechanization are methods of outpouring and pressing.

Medical substances, soluble in basis, in an amount less than 5% dissolve in the liquid (the same to the type of base),

if them more than 5% – dissolve in part of molten base.

Rp.: Furazolidoni 0,004

Olei Cacao 1,0

M., f. supp.

D. t. d. № 15.

S. 1 suppository into the rectum 10-15 days.

highest single dose Furazolidoni

highest daily dose Furazolidoni

Technology

In a mortar placed 0,06 Furazolidoni and dispersed in the solid form the first, and then with 1 drop of sunflower oil (according to the rule Deryagin). Add 15,0 finely grated shavings of cocoa butter, carefully grind for received a homogeneous plastic mass. If necessary, add anhydrous lanolin.

The ready suppository mass weighed, mass write down on the back of the recipe, transferred into a glass pill machine, form a touchstone, with cutter divide at the level of parts and drain plugs for the same shape, length and diameter.

These suppositories wrapped in a capsule, put in a cardboard box, paste the recipe number and fill the front of WPC.

WCP (Front side)

Date № recipe

Furazolidoni 0,06

Olei Helianthi gtt. I

Olei Cacao 15,0

Lanolini anhydrici q.s.

Massae suppositoriorum 15,06 1,0 N. 15

prepared

checked

Suppositories with substances which entered by the type of solution

· If substances which are soluble in base less than 5% – ground from a few drops of vegetable oil

· if more than 5%, with part of the melted cocoa butter (butter is desirable not to melt if it is normal plasticity)

Rp.: Anaesthesini 0.2

Olei Cacao 2.0

М., f. supp.

D. t. d. N. 10.

S. 1 suppository into the rectum

highest single dose Anaesthesini 0,5

highest daily dose Anaesthesini 1,5

Technology.

In a mortar placed 2,0 anestezin, first grind down in dry form and then add a few tricks 20,0 finely grated shavings of cocoa butter, carefully dent to obtain a homogeneous plastic mass. If necessary, add anhydrous lanolin.

The ready suppositories mass weighed, amount write down on the back of the recipe, transferred into a glass pill machine, form a touchstone, with cutter divide at the level of parts and drain plugs for the same shape, length and diameter.

These suppositories wrapped in a capsule, put in a cardboard box, paste the recipe number and fill the front of the WCP.

WCP (Front side)

Date № recipe

Anaesthesini 2,0

Olei Cacao 20,0

Lanolini anhydrici q.s.

Massae suppositoriorum 22,0 2,2 N. 10

prepared

checked

Suppositories with substances which entered by the type of emulsion

· If substances which are soluble in water less than 5%- dissolved in a few drops of water and add shaving cocoa butter,

· if more than 5%, enter by the suspension type with a part of the melted cocoa butter by rule of Deryagin ½ the mass of solids.

Rp.: Novocaini 0,1

Olei Cacao q.s.

M. f. supp.

D. t. d. N. 6.

S. To enter in a rectum on a 1 suppository (at pains).

Technology.

In a mortar dissolve 0,6 novocaine in a few drops of water. Then for a few receptions add 17,4 shaving of butter cacao, carefully kneading to the receipt of homogeneous plastic mass. If necessary add a lanolin waterless. Weighed ready suppository mass, write down on the reverse side of recipe, put on glass of pill machine, form an oilstone, by means of cutter divide at the level of part and the identical pump out suppositories after a form, long and by a diameter. The got suppositories wrap up in capsules , fold in a binary code, glue № on recipe and fill the right side of WCP.

WCP (Front side)

Date № recipe

Aquae purificatae q.s.

Novocaini 0,6

Olei Cacao 17,4

Lanolini anhydrici q.s

Massae suppositoriorum 18,0

3,0 N. 6

prepared

checked

SUPPOSITORY It is solid dosage form meant to be inserted into Body cavity like rectum , urethra, vagina, where they melt or soften to release the drugs and produce their local or systemic effect. It is comes under semi solid preparation because it is prepared by melting all ingredients (bases and other additives along with active ingredient). All types of suppositories are melt at normal body temperature after introducing in body cavity and produce their effect.

ADVANTANGE OF SUPPOSITORY:

ADVANTANGE OF SUPPOSITORY

– It is the alternated dosage form for drugs which have less bioavailability when it is taken orally.

– Drugs having bad odour and taste can be used in suppository form.

– It is suitable for unconscious patients which caot taken drugs orally. It is suitable for drugs which produce irritating effect in GIT.

– It is suitable for infants and old people who find difficulty in swallowing of drugs. It is suitable for the drugs which are destroyed by portal circulation.

DISADVANTAGE OF SUPPOSITORY:

DISADVANTAGE OF SUPPOSITORY

– The manufacturing process is more difficult as compare other formulation.

– The drugs which cause irritation to mucous membrane caot be administrated by this form.

– The most important problem is storage condition because it stored at low temp.(10-20 0c ).

– Other than the bases get liquefied.

– Leakage problem is also most critical problem along with suppository after introducing in body cavity at elevated temperature.

TYPES OF SUPPOSITORY:

TYPES OF SUPPOSITORY RECTAL SUPPOSITORY- It is inserted in the rectal . The weight of suppository used in children is about 1g and in adult about 2g. The shape of suppository used in rectal is torpedo shape. The length is about 3 cm.

(B) URETHRAL SUPPOSITORY:

(B) URETHRAL SUPPOSITORY The weight of this type suppository is about 2g and 60-75 mm long in Females. Those intended for males weigh 4 gm each and are 100-150 mm long. It is available in pencil shape.

(C) VAGINAL SUPPOSITORY:

(C) VAGINAL SUPPOSITORY It is in oviform shape. It is about 3-5g in weight. It is contains the drugs which are used in treatment of the infections of female genitourinary tract and meant for contraception. It is contains the combination of polyethylene glycol of different molecular weights as suppository bases.

(D) NASAL SUPPOSITORY:

(D) NASAL SUPPOSITORY These suppository are meant for introduction into nasal cavity. It is about 1g in weight. The glycero- gelatin is used as suppository bases. (E) EAR CONE It is also known as AURINARIES. These are meant for introduction into the ear. It is cylindrical in shape. It is about 1g in weight.

VARIOUS SHAPES OF SUPPOSITORY :

VARIOUS SHAPES OF SUPPOSITORY

FORMULATION OF SUPPOSITORIES:

FORMULATION OF SUPPOSITORIES (A) SUPPOSITORIES BASES- IDEAL PROPERTIES OF SUPPOSITRIES BASES- The following properties should be required for bases— Bases should be exist in solid form at room temperature. It should not irritate and produced inflamed sensation in body cavity. It should be stable during storage condition , No change in colour, shape , odour. It should retain hardness and shape during manufacturing and handling.

IDEAL PROPERTIES OF SUPPOSITRY BASES:

IDEAL PROPERTIES OF SUPPOSITRY BASES It should not reacts with drugs and additives. It should have good emulsifying and wetting property. It should have acid value less than 0.2 or zero. It should have iodine value less than 7. It should have sponificatioo. range between200-245.

(1) HYDROPHILIC BASES:

(1) HYDROPHILIC BASES WATER DISPERSIBLE BASES- These are the mixture of non ionic surfactants which are chemically related to polyethylene glycol. These are used alone or in combination with other type of bases. Cellulose derivatives like methylcellulose, sod.carboxymethyl cellulose are also comes under this class.

Advantages:

Advantages

– They are suitable for both water soluble and oil soluble drugs.

– They do not support the growth of microbes in the preparation.

– They can be stored at elevated temperature.

Disadvantages–

– This types of bases are interact with few drugs and alter the bioavailability of these drugs.

EXAMPLES:

EXAMPLES Polyoxyethylene sorbitan fatty acid ester(TWEENS) Polyoxyethelene stearates(MYRIS) Sorbitan fatty acid esters(SPANS) Combination of Tween 61(60%) and Tween 60(40%) Combination of Tween 61 (85%) and glyceryl monostearate (15%)

(B) WATER SOLUBLE BASES:

(B) WATER SOLUBLE BASES GLYCERO-GELATIN- This occurs as a gels It is a mixture of gelatin, glycerol, and water. According to BP the composition of the bases – GELATIN- 14% w/w GLYCEROL– 70% w/w WATER– QS For gets a stiff mass , the quantity of gelatin should be increased to 32.5% and reduced the glycerol to 40%.

PREPARATION OF GLYCERO-GELATINE BASES:

PREPARATION OF GLYCERO-GELATINE BASES GLYCEROL WATER GELATINE GLYCERO-GELATINE BASES

ADVANTAGES:

ADVANTAGES

– Suppository prepared by glycero-gelatin bases are strong and translucent unlike cocoa butter suppositories.

– This base is disperse slowly in the body cavity fluids and provides prolonged release and action of drugs.

DISADVANTAGES-

– It absorbs moisture and promotes microbial growth , so this reason preservatives are used .

DISADVANTAGES:

DISADVANTAGES

– The bases are show incompatibility with protiens prescipitants due to the gelatin It causes dehydration and irritation of rectal mucosa It exerts undesirable laxative action.

– It requires special storage condition at about 10-15 0c. Handling and manufacturing of these type of suppository are difficult.

(2) POLY ETHYLENE GLYCOL(POLYGLYCOL):

(2) POLY ETHYLENE GLYCOL (POLYGLYCOL) It is also called as PASTONALS (GERMANY). CARBOWAXES(U.S) They are long chain polymers of ethylene oxide. They occur in liquid and solids. Liquids have mol.weight about 200-600. Solid have mol.weight about more than 1000. They are also called as macrogols. They are the mixture of two or more grades of macrogols used as suppository bases.

EXAMPLES:

EXAMPLES PEG 4000- 33 parts PEG 6000- 47 parts PURIFIED WATER- 20 parts FOR HARD SUPPOSITORY PEG 1000- 75 parts PEG 4000- 25 parts FOR SOFT SUPPOSITORY PEG 1000- 96 parts PEG 4000- 4 parts

ADVANTAGES :

ADVANTAGES

– This base is thermostable.

– It does not get degraded or hydrolysed.

– It does not support microbial growth.

– It dose not move out from body cavity after introducing.

– It has good water absorbing capacity.

– It is chemically stable.

DISADVANTAGES:

DISADVANTAGES

– It is susceptible to rancidification,so it should be stored in dry place away from light.

– It melt easily in warm weather,so it should stored in cool place in warm season. Large quantities of water caot be incorporated into the bases.

– So emulsifier such as tween 61 (6-10%) are useful to increase the absorption of water.

– The physical characteristics of the bases are change from batch to batch.

– Some times leakage may be occur after introducing in body cavity.

(2) LIPOPHILIC BASES:

(2) LIPOPHILIC BASES (a) COCOA BUTTER It is natural triglyceride. Among all fatty acid about 40% are unsaturated fatty acid . It can exist in more than one crystalline form or exhibits polymorphism. At room temperature ,it is yellowish-white with a paints,chocolate like odour. It consists of a mixture of ester of oleic acid,palmatic acid,stearic acid and other fatty acid with glycerol.

ADVANTAGES:

ADVANTAGES

– It is liquified readily on warming and sets rapidly on cooling.

– It has emollient effect which is useful to relieve inflammation.

– It shows good release of water soluble drugs.

– It does not cause irritation in mucous membrane.

DISADVANTAGES:

DISADVANTAGES

– It is susceptible to rancidification ,so it should be stored in dry place away from light.

– It gives soft suppository when formulated along with chloral hydrate , phenol, volatile oil, which have lower melting point.

– The physical property of the base is vary from batch to batch.

– It required extra lubricant during poring in holder. Some times leakage may be occur.

(B) ANTI OXIDANTS:

(B) ANTI OXIDANTS

It is protect the drugs and bases from getting degraded due to oxidation. These are commonly used in all types of suppositories.

EXAMPLES- Ethyl or propyl gallate Ascorbic acid Butylated hydroxy anisole (BHA) Butylated hydroxy toluene (BHT) Hydroquinone Tocopherol

(C) EMULSIFYING AGENTS:

EXAMPLES Poly sorbates (TWEEN 61) Wool alcohol Wool fats

(D) HARDENING AGENTS:

(D) HARDENING AGENTS These are involved in those formulation where the melting point of the bases is decrease by the drugs. These are the agents which are used to bring the melting point to normal.

EXAMPLES Beeswax Macrogols at high molecular weight.

(E) PRESERVATIVES :

(E) PRESERVATIVES These are the agents which are used in prevent the growth of microbial in suppository which contains water soluble bases.

EXAMPLES Chorocresol Methyl paraben Propyl paraben

(F) THICKENING AGENTS:

(F) THICKENING AGENTS These are the agents which are used to increases the viscosity of molten bases and prevent sedimentation of suspended in solid bases. EXAMPLES Aluminium monostearate Colloidal silica Magnisium stearate Steary alcohol

(G) PLASTICIZERS:

(G) PLASTICIZERS These are the agent which are used to improved flexibility of suppositories. It is also used to make the less brittles to suppositories.

EXAMPLES Castor oils Glycerine Glycol Tween 80 Tween 85

METHODS OF PREPARATION OF SUPPOSITORIES:

METHODS OF PREPARATION OF SUPPOSITORIES MOLDS USED IN PREPARATION OF SUPPOSITORIES-

Molds used in preparation of suppositories are the metals devised with different shape. It is consists of two or more parts which are joined with a screw. In side the molds the cavities are made up of aluminium , brass, stainless steel , plastics. Molds have different capacities like 1,2,4,8gm.

PLASTICS MOLDS:

PLASTICS MOLDS

CALIBRATION OF THE MOLDSCC:

CALIBRATION OF THE MOLDS CC The first step is to prepare molded suppositories from base material alone. The suppository’s combined and average weight is recorded. To determine the volume of the mold, the suppositories are melted in a calibrated beaker, and the volume of the melt is determined.

LUBRICANTS USED IN MOLDS:

LUBRICANTS USED IN MOLDS Cocoa butter and glycero-gelatine bases are required lubrication of molds. This is prevent sticking of bases to the wall of molds cavity. It is also useful in easy removal of suppositories from the molds. The lubricants are form a film between the wall of mold cavity and base of suppositories so it prevent adhering of bases to the molds. The nature of lubricants should be different from nature of bases.

EXAMPLES:

EXAMPLES (1) FOR COCOA BUTTER BASES ALCOHOL(90%)- 50ml GLYCEROL – 10ml SOFT SOAP – 10 gm (2) LIQUID PARAFFIN (3) ARACHIS OILS

MANUFACTURING OF SUPPOSITORIES:

MANUFACTURING OF SUPPOSITORIES

Hand molding Automatics Machine Molding Compression Molding Heat Molding HAND MOLDING-

Hand molding is useful when we are preparing a small number of suppositories.

It is suitable for thermo labile drugs.

It is more economical methods.

It is more time consuming and not uniformity process.

STEPS INVOLVED IN HAND MOLDING:

STEPS INVOLVED IN HAND MOLDING

The drugs and other additives are made into a fine powder . It is incorporated into the suppository base by kneading with it or by trituration in a mortar. Then these masses are rolled into the shape of a cylindrical rod on the rolling tile in presence of lubricants to prevent the adherence of masses. Then cut the rods and made one end to pointed.

PowerPoint Presentation:

DRUG+ADDITIVES FINE POWDER MIXED IN BASES APPLY LUBRICANTS ON ROLLING TILE ABOVE MASSES ARE ROOLED IN CYLINDRICAL SHAPE CUT THE RODS PACKED STORED

(2) AUTOMATIC MACHINE MOLDING:

(2) AUTOMATIC MACHINE MOLDING All the operations in pour molding are done by automatic machines. Using this machine, up to about 10,000 suppositories per hour can be produced. By this the rate of production of suppositories is more higher than hand molding. In this ,there are no chance of air entrapment and contamination of suppositories. In this ,if any mass deposited in mold is not removed during cleaning, so produce overweight suppositories with mold marks.

There are two types of machines used they are following— Rotary Machine- The rate of production of suppositories are about 3500-6000/hr. This machine consists of a turn table in which metal molds are fitted. This table rotates sequentially, the mold gets filled with drug , additives, bases and cooled and ejects the suppositories. Before mass filled in mold ,the lubricant are apply in mold wall. The excess mass is removed by the scraping unit. The cooling system results the solidification of suppositories.

After the cooling the mold is moves towards ejection station , it consists of a stainless steel rod which push out the suppositories from molds. Then completed the ejection process , the empty molds are again moves towards the filling unit for further processes. STEPS INVOLVED IN PROCESS AS FOLLOWING

DRUG+ADDITIVES FINE POWDER MELT BASES + POWER HOPPER LUBRICATED THE MOLDS FILL ABOVE MIXTURE IN MOLD COOLING SYSTEM EJECTION SYSTEM PACKED STORED

(b) LINEAR MACHINE:

(b) LINEAR MACHINE It is similar to rotary machine. Except the rate of production is more higher than rotary machine about 10000/hr. All steps involved is similar to rotary machine. There is no chance of air entrapment and contamination of suppositories as similar to rotary machine. The rate of production is higher than rotary machine.

(3) COMPRESSION MOLDING:

(3) COMPRESSION MOLDING CONSTRUCTION- The compression machine consists of a cylinder, piston , molds, and a metallic stop plate at the bottom. WORKING- When placed the mass in cylinder and apply the pressure . Then mass fulfill in mold move and s remove the suppositories and keep them in cool placed. After cooling release them from compression machine and packed .

PROCEDURE:

PROCEDURE DRUG+ADDITIVES FINE POWDER MIXED WITH BASES LUBRICANTS APPLY IN MOLDS PLACED THE MASSES IN CYLINDER APPLY PRESSURE RELEASE SUPPOSITORY COOLED PACKED STORED

ADVANTAGE-

– It is suitable for thermolabile drugs because in this method no heat is required.

– Rate of production is more.

DISADVANTAGE-

– The main disadvantage is air entrapment occurs during production so oxidation takes place in suppository.

(4) HEAT MOLDING :

(4) HEAT MOLDING In this process the bases are melted and the drugs , additives are mixed in bases. The following methods are involved in this process- Melting the bases Incorporation of the drugs and other additives Filling of mold Cooling and collection of suppositories

Incorporation of drug and additives- the drugs and additives are in solid form , they are converted in fine powder and mixed properly on a warm tile. Triturate the ingredient on warm tile with the sufficient water. These above liquid are mixed in melted bases in half amount after mixing , then added remaining liquid in bases.

FILLING OF MOLDS-

– First the lubricants are apply in molds.

– Then the above masses are introducing in molds.

– During introducing the masses in molds the stirring should be done to prevent the sedimentation of insoluble solids , if they present.

– Overfilling is required to prevent the depression in suppositories.

COOLING AND COLLECTION OF SUPPOSITORIES After the2-3 min . the mass just sets. Then remove the excess mass with warm spatula. Cool the suppositories for 10-15 min. in refrigerators. Then open the mold and collect the suppositories and packed.

MELTING THE BASES DRUGS FINE POWDER TRITURATE WITH WARM WATER LIQUIDS MIXED ½ PARTS OF LIQUIDS MIXING PROPER ADD REMAINS LIQUIDS

CONT…… APPLY THE LUBRICANTS IN MOLD OVERFILLING OF MASSESIN MOLDS REMOVE THE EXTRA MASSES COOLING (10-15MIN) OPEN MOLDS PACKED STORED

PACKING OF SUPPOSITORIES (1)

DISPOSABLE MOLDS-

– These are meant for packing the suppositories.

– These are made of plastics or aluminium foil. :

PACKING OF SUPPOSITORIES (1) DISPOSABLE MOLDS- These are meant for packing the suppositories. These are made of plastics or aluminium foil.

(2) MODERN PACKING MACHINE It is consist of roll of packing material which cut in the required size and rolled around each suppositories.:

(2) MODERN PACKING MACHINE It is consist of roll of packing material which cut in the required size and rolled around each suppositories.

STORAGE CONDITION It is stored at 10-15 0c Used air tight container The suppositories with cocoa butter stored at < 30 0c. The suppositories with glycero-gelatin stored at < 35 0c.

EVALUATION OF SUPPOSITORIES:

EVALUATION OF SUPPOSITORIES Test of appearance(size , shape) Test of physical strength Test of dissolution rate Test of melting range Test of softening time Test of uniformity of drug content

STABILITY PROBLEMS OF SUPPOSITORIES:

STABILITY PROBLEMS OF SUPPOSITORIES BLOOMING- During storage , cocoa butter suppositories sometimes show deposition of white powder on the surface. This result in suppositories of disagreeable appearance. HARDENING- During storage , the suppositories made of fatty bases become hard. I is occurs due to crystallization of bases. This also effect the melting and rate of absorption of drugs.

• Suppositories are solid dosage forms intended for insertion into body orifices where they melt, soften, or dissolve and exert localized or systemic effects.

• They are commonly used rectally and vaginally, and occasionally urethrally.

• Suppositories are prepared in various weights, sizes, and shapes depending on their intended use.

• Rectal suppositories intended for adults usually weigh about 2 g, measure about 1 ‘l2’ in. in length, and are cylindric or bullet-shaped.

• Rectal suppositories for infants and children are proportionately smaller.

• Vaginal suppositories commonly weigh about 5 g and are globular, oviform, or conical.

• Urethral suppositories are:

1. thin and pencil-shaped,

2. weighing approximately 4 g and

3. measuring about 140 mm when intended for males and

4. half the weight and length when intended for females.

1. Ingredients are melted and placed in the suppository mold

2. Suppository mold is separated after it was cool down.

3. Suppositories are removed form the mold

Rectal, vaginal and bladder preparations

SUPPOSITORIES AND PESSARIES

INTRODUCTION

Suppositories are solid unit dosage forms suitable shaped for insertion into the rectum. The bases used either melt when warmed to body temperature, or dissolve or disperse when in contact with mucous secretions. Suppositories may contain medicaments which are intended to exert a systemic effect, either dissolved or dispersed in the base. Alternatively, the medicaments or the base itself may be intended to exert a local action.

Suppositories are prepared by incorporating any medicaments in the base, which may then be shaped by cold compression into moulds. Alternatively, the molten mass is poured at a suitable temperature into moulds and allowed to cool until set.

Pessaries are solid unit dosage forms suitably shaped for insertion into the vagina, and containing medicaments intended to exert a local action. They may be prepared by moulding as described above or, alternatively, they may be compressed as suitably shaped tablets.

PREPARATION OF SUPPOSITORIES AND PESSARIES

Since the preparation of suppositories and pessaries invariably involves some wastage, it is best to calculate for a slight excess, eg. if six suppositories are required, then calculate for eight.

Suppository moulds are calibrated in terms of the weight of theobroma oil, which they will contain; although theobroma oil is now rarely used as a suppository base. Typical sizes are 1g (15 grains), 2g (30 grains), or occasionally 4g (60 grains).

Pessary moulds are similarly calibrated and usually contain 4g (60 grains) or 8g (120 grains). The mould size to be used for official preparations may be specified in the B.P., The Pharmaceutical Codex or B.N.F. Alternatively, the smallest practicable size is used.

Since moulds are filled volumetrically, use of a base whose density differs from that of theobroma oil will result in a difference between the actual and the nominal or calibration weights of the product. In the case of Glycerol Suppository Base, B.P., the moulds will hold 1.2 times their calibration weight and this must be taken into account in the calculation, eg. 8 x 2g (nominal) suppositories, we require 8 x 2 x 1.2 = 19.2g of base.

The volumetric filling of moulds also has implications when a specific amount of an ingredient is required to be incorporated into each suppository or pessary.

Page 1 of 3 Rectal, vaginal and bladder preparations

The amount of base displaced will depend on the “densities” of the ingredient and the base. The amount displaced may be calculated from the displacement value of the medicament. The displacement value of an ingredient is defined as the number of parts by weight of the ingredient which displace one part by weight of theobroma oil. The displacement values for other fatty bases (eg. Witepsol W) are taken to be the same as those quoted for theobroma oil. For Glycerol Suppository Base the displacement values will be 1/1.2 of those values for theobroma oil.

Mould lubrication

Some bases require the use of a mould lubricant, arachis oil in the case of glycerol base and a suitable soap solution or slicone for fatty bases. The inner surfaces of the mould are wiped over with the appropriate lubricant, the mould is assembled and then inverted and any excess lubricant allowed to drain.

Methods of preparation

For oily bases, the required amount of base is weighed and then melted over a water bath. Particular care must be taken with theobroma oil not to use more heat than absolutely necessary since due to its polymorphic properties, even a slight degree of overheating will lower its solidification point.

Glycerol Suppository Base B.P, if available ‘ready-made’, may similarly be weighed and melted. Alternatively, it must be prepared from its constituents according to the method in the B.P. The calculated amount of gelatin is placed in a tared evaporating dish and 1 to 1.5 times the calculated amount of water (to compensate for loss by evaporation) is added. After several minutes the gelatin will have absorbed the water and formed a gel. The glycerol is then added, and the dish and contents are heated on a boiling water bath until all the gelatin dissolves. Stirring is required to assist solution, but care must be taken to avoid incorporating air bubbles, since these will be very difficult to remove. The final product is adjusted to weight.

Any soluble ingredients may be added to the molten base and stirred until dissolved. Insoluble ingredients should be finely powdered, rubbed down with a little of the molten base on a warmed tile, transferred to the dish and thoroughly mixed to ensure a uniform dispersion throughout the base. Mixing continues while the molten mass is cooled until just above its melting point. It is then poured into moulds and allowed to set. It is especially important with insoluble materials that pouring does not take place at too high a temperature. Otherwise particles will settle, and thereby concentrate at the tip of the suppository. When a fatty base is used, then the moulds should be overfilled to allow for the concentration (volume shrinking), which accompanies solidification, and the excess is trimmed off later. Glycerol Suppository Base, B.P. does not contract on solidification and hence the moulds are filled exactly.

Page 2 of 3 Rectal, vaginal and bladder preparations

When used in pessaries, bases containing gelatin should be maintained at 100°C for one hour, replacing any water lost by evaporation, before incorporating the other ingredients.

PACKAGING AND LABELLING OF SUPPOSITORIES

Guidance is given in the B.P. Suppositories should be stored in a cool place. Glass jars are suitable for glycerol-based suppositories. In the practical class, cardboard boxes with separators are available to store the prepared suppositories

v SUPPOSITORIES

1-Introduction:

Suppositories are medicated, solid bodies of various sizes and shapes suitable for introduction into body cavities. The medicament is incorporated into a base such as cocoa butter which melts at body temperature, or into one such as glycerinated gelatin or PEG which slowly dissolves in the mucous secretions. Suppositories are suited particularly for producing local action, but may also be used to produce a systemic effect or to exert a mechanical effect to facilitate emptying the lower bowel.

The ideal suppository base should be nontoxic, nonirritating, inert, compatible with medicaments, and easily formed by compression or molding. It should also dissolve or disintegrate in the presence of mucous secretions or melt at body temperature to allow for the release of the medication. As with the ointment bases, suppository base composition plays an important role in both the rate and extent of release of medications.

2- Methods of preparation :

Suppositories can be extemporaneously prepared by one of three methods.

qHand Rolling is the oldest and simplest method of suppository preparation and may be used when only a few suppositories are to be prepared in a cocoa butter base. It has the advantage of avoiding the necessity of heating the cocoa butter. A plastic-like mass is prepared by triturating grated cocoa butter and active ingredients in a mortar. The mass is formed into a ball in the palm of the hands, then rolled into a uniform cylinder with a large spatula or small flat board on a pill tile. The cylinder is then cut into the appropriate number of pieces which are rolled on one end to produce a conical shape.

Effective hand rolling requires considerable practice and skill. The suppository “pipe” or cylinder tends to crack or hollow in the center, especially when the mass is insufficiently kneaded and softened.

qCompression Molding is a method of preparing suppositories from a mixed mass of grated suppository base and medicaments which is forced into a special compression mold. The method requires that the capacity of the molds first be determined by compressing a small amount of the base into the dies and weighing the finished suppositories. When active ingredients are added, it is necessary to omit a portion of the suppository base, based on the density factors of the active ingredients.

qFusion Molding involves first melting the suppository base, and then dispersing or dissolving the drug in the melted base. The mixture is removed from the heat and poured into a suppository mold. When the mixture has congealed, the suppositories are removed from the mold. The fusion method can be used with all types of suppositories and must be used with most of them.

3- Suppository bases :

Suppository bases may be conveniently classified as according to their composition and physical properties:

· Oleaginous (fatty) bases

· Water soluble or miscible bases (hydrophyllic)

a) Oleaginous Bases include Theobroma Oil and synthetic triglyceride mixtures.

Theobroma Oil or cocoa butter is used as a suppository base because, in large measure, it fulfills the requirements of an ideal base. At ordinary room temperatures of 15° to 25°C (59° to 77°F), it is a hard, amorphous solid, but at 30° to 35°C (86° to 95°F), i.e., at body temperature, it melts to a bland, nonirritating oil. Thus in warm climates, theobroma oil suppositories should be refrigerated.

Particular attention must be given to two factors when preparing suppositories with cocoa butter base. First, this base must not be heated above 35°C (95°F) because cocoa butter is a polymorphic compound and if overheated will convert to a metastable structure that melts in the 25° to 30°C (77° to 86°F) range. Thus, the finished suppositories would melt at room temperature and not be usable.

The second factor is the change in melting point caused by adding certain drugs to cocoa butter suppositories. For example, chloral hydrate and phenol tend to lower the melting point. It may be necessary to add spermaceti or beeswax to raise the melting point of finished suppositories back to the desired range.

The newer synthetic triglycerides consist of hydrogenated vegetable oils. Their advantage over cocoa butter is that they do not exhibit polymorphism. They are, however, more expensive. Some of the bases are single entity formulations. Some of the names may denote a series of bases. In a series, the bases are varied to give a range of melting points. For example, Fattibase® is a single entity base that consists of triglycerides from palm, palm kernel, and coconut oils. Wecobee® is a series of bases. Wecobee FS, M, R, and S are all made from triglycerides of coconut oil.

b) Water Soluble/Water Miscible Bases are those containing glycerinated gelatin or the polyethylene glycol (PEG) polymers.

Glycerinated Gelatin is a useful suppository base, particularly for vaginal suppositories. It is suitable for use with a wide range of medicaments including alkaloids, boric acid, and zinc oxide. Glycerinated gelatin suppositories are translucent, resilient, gelatinous solids that tend to dissolve or disperse slowly in mucous secretions to provide prolonged release of active ingredients.

Suppositories made with glycerinated gelatin must be kept in well-closed containers in a cool place since they will absorb and dissolve in atmospheric moisture. In addition, those intended for extended shelf-life should have a preservative added, such as methylparaben or propylparaben, or a suitable combination of the two. To facilitate administration, glycerinated gelatin suppositories should be dipped in water just before use.

Calibration of Suppository Molds with Glycerinated Gelatin Base

Glycerinated Gelatin Suppositories have the following proportions of glycerin, gelatin, and water. Use 75 g of the suppository base for this calibration exercise.

Ingredients

Percentage

Weight Basis

Amt./Vol. to measure

Glycerin

70%

__________ g

_________ ml

Gelatin

20%

__________ g

_________ g

Purified Water

10%

__________ g

_________ ml

To calibrate the mold with glycerinated gelatin suppository base:

· Clean mold with soap and water.

· Dry the mold.

· Have the mold at room temperature.

· Lubricate the mold with light mineral oil.

· Mix the glycerin and water together and heat on a steam bath or hot plate for 5 minutes. Gently stir in the gelatin to avoid incorporating air in the mixture. After the gelatin has been added, continue heating for another 40 – 50 minutes. Do not allow the temperature to get above 90 – 95°C, as the color will darken.

· Remove from the heat and allow the mixture to cool near the melting point before pouring into the mold.

· Overfill the cavities in the mold, cool at room temperature for 30 minutes, and then place in a refrigerator 15-20 minutes if the suppositories have not completely congealed.

· Carefully remove excess with a hot spatula or knife. Remove suppositories from mold.

· Using only perfect specimens, weigh the suppositories and record the total weight. Calculate the average suppository weight.

Mold #

__________

Total weight for ____ suppositories =

_________ g

Average weight for one suppository =

_________ g

Mold lubricant used

_____________________

Inspection of Final Product

_____________________

N.B.

– Gelatin base is incompatible with many of the substances prescribed in supp. E.g. Tannic acid , Ferric chloride , Gallic acid , and for this another reasons this base is less frequently use than coca butter .

– Glycerin supp. Containing Ichthammol became insoluble on storage

– Gelatoglycerin bases used mainly for preparing supp. Containing boric acid , chloral hydrate , ichthamol , iodine (dissolved by the aid of KI )

Standardization of suppositorise :

The Standardization of any supp. Involves the following determinations:

a- Determination of DISPLACEMENT VALUE of the active ingredients

b- Determination of FRACTURE POINT of the prepared supp. ( the weight under which the supp. Sample collapses under given conditions is taken as a measure of the strength of the supp. Tested .

c- determination of MELTING TIME of the prepared suppository .

d- determination of UNIFORMITY OF WEIGHT of the prepared suppository .

4Preparation of the glycerogelatin bases :

– In a prcelin dish soak the gelatin powder with amount of H2O present in the formula for about 5 – 10 min. till it completely wetted and swelled

– add the amount of glycerin to the soaked gelatin.

– Put the dish on boiling water bath .

– Stirr gently till complete solubility of gelatin and the formulation of a translucent mass, avoid air bubbles formation during stirring

– Pour the translucent mass into mould (previusly lubricated with liquid paraffin or any other oil ) after adding the medicament (if the formula containing medicament ) and – Take care that preferably JUST FILL the cavities because the mass does not contract upon cooling .

4Preparation of Boroglycerin Suppository

Boric acid 7.5 g

Gelatin 15.0 g

Glycerin 62.5 g

Water 15.0 g

Fiat supp. Mitte III

Calculation :-

– The formula gives 100 g of suppository mass.

– To prepare 3 supp. Calculate for 5 .

– If we use mould of 1 g capacity the amounts are as follows :

Boric acid = (1 x 5 x 7.5 ) / 100 = 0.375 g

Gelatin = ( 1 x 5 x 15 ) / 100 = 0.750 g

Glycerin = ( 1 x 5 x 62.5 ) / 100 = 3.125 g

Water = ( 1 x 5 x 15 ) / 100 = 0.750 g

-If we use mould of 2 g capacity the amounts given above multiplied by (2) and so on.

Prepartaion :

– In a porcelin dush soak gelatin in water , then transfer to dish over a water bath .

– Dissolve boric acid in glycerin by the aid of gentle heat .

– Add the dissolved boric acid the gelatin solution and continue heating over a water bath until a clear solution produced and constant wt is attained .

N.B.

– Boric acid reacts with glycerin on heating giving glyceryl borate which has an antiseptic action .

Suppository Vehicles

· Fatty substances

o Cocoa Butter

§ Very effective, but requires tight temperature control to prevent epimerization

o Hard Butter

§ Generic term to describe a class of specialty fats with physical characteristics similar to those found in cocoa butter or dairy butter. Applications include confectionery coatings and centers, coffee whiteners, etc.

§ Derived from palm oil and Shea butter

§ Not really the sames stuff as you put on toast http://www.arrowscientific.com.au/new/mainarticle2.phtml?articleid=b488e37fbb

o Webcobee (aka Fatty Base)

o Witepsol

· Polyethylene Glycol

o Superior drug release to Fatty Substances

Techniques for making Suppositories

· Double Pour Technique

o aka Molding / Fusion

o Typical large scale technique

· Compression

o Not practical for large scale production

· Hand Molded

o Ugh…

Tips for making suppositories

· Make 10% excess

· Refrigerate (10 C) to speed cooling

· Do not freeze, may cause cracking

Four common suppository formulas

1. Glycerated Gelatin

2. Glycerin Suppository

3. Progesterone PEG 400/8000

4. Progesterone PEG 1000/3350

Common Suppository Sizes

Type

Weight(g)

Length (in)

Bougie, Female

Bougie, Male

Pessary

1.5 – 2

Rectal Suppositories, Adult

1-1.5

Rectal Suppositories, Child

ToDo

Definition :- “suppositories are solid dosage form meant to be inserted into body cavity like rectum, urethra, vagina where they melt or soften to release the drugs & exert local or systemic effect.”

Shapes available :

· cone,

· bullet, t

· orpedo.

Advantages :-

1. Alternate dosage form for the drugs with less bioavailability when taken orally.

2. Drugs having bad odour & taste.

3. For treating unconscious & vomiting patients

4. Suitable for administration of drugs which cause gastric irritation

5. For infants & old people who find difficulty in swallowing

6. Administration of drugs which are destroyed by portal circulation

7. Site- specific action on rectal, urethra, etc….

Disadvantages :-

1. Not much acceptable by patient

2. Manufacturing process is difficult

3. Drug which cause irritation to mucous membrane can’t be administered

4. Maintenance of temperature is difficult

5. Leakage of suppository occurs upon insertion into the body cavity at elevated temperature.

Properties of an ideal suppository base :- :

Properties of an ideal suppository base :-

1. Should melt at body temperature or dissolve or disperse in body temperature.

2. Should release any medicament and be compatible with.

3. Should keep it’s shape during handling.

4. Should be non-toxic and non-irritant .

5. Should be stable on storage.

6. Should be easily molded and should not adhere to the mold.

7. Should be stable if heated above its melting point.

8. Should have good emulsifying & wetting properties.

9. Acid value : <0.2 or zero. ; iodine value : <7 ; Saponification value : 200 – 245.

Formulation :-:

Formulation :- Formulation includes ;

· Suppository bases.

· Active ingredients.

· Additives.

Bases :-:

Lipophilic bases (fatty bases) :

These melt at body temperature. Ex. : cocoa butter (Theobromaoil), synthetic base. Hydrophilic base : Dissolves or disperse in rectal separation. Ex. : glycerogelatin, macrogols(PEG), tween & span.

1. Cocoa butter(theobromo oil) :-

Properties:-

1. Natural triglyceride.

2. It exhibits polymorphism.

3. Yellowish-white solid with a chocolate like odour.

4. It is a mixture of glyceryl ester of stearic , palmetic,oleic acid & other fatty acid.

2 . synthetic fats:-

Properties:-

1. Prepared by esterification or hydrogenation of vegetable oils.

2. The first useful product come from the hydrogenation & subsequent heat treatment of vegetable oil such as palm kernal & arachis .

3.surfactant:- Ex. – tween , span.

Property:-

1. Mixture of non-ionic surfactants which are chemically related to PEG.

2. They are used alone or in combination with other base.

4.Glycerogelatin base:-

Properties:-

1. Mixture of glycerin and water made in to a stiff jelly by adding gelatin.

2. According to BP composition of base is, Gelatin –- 14% ,glycerol—70% According to USP ,gelatin—20%,glycerol—70%

3. Gelatin is colorless or pale yellow & available in translucent sheets, granules or powder.

5.Polyethylene glycols(macrogols)

properties:-

1. Long chain polymer of ethylene oxide. They occur as solid and liquid.

2. Liquid have molecular weight ranging from 200-600.

3. Solid have molecular weight more then 1000.

4. Mixture of two or more grades of microgols used as suppository base.

Preparation of suppository:-

Molds:-

Metal device used to get the required shape.

Made up of aluminum , brass, stainless steel, or plastics.

Calibration of mold:-

It is the adjustment of mold to get suppositories of uniform weight, even though different base are used.

It is done prier to suppositories.

A set of suppositories are prepared using only the base.

The average weight of them is calculated & it is taken as the true weight of suppositories prepared using that mold , which is the capacity of mold.

Displacement value:-

The volume of suppository from particular mold is uniform but its weight will vary because the density of medicament usually differ from the density of base .

To prepare product accurately , allowance must be made for the change in density of mass due to added medicament

The most convenient way of making this allowance is to use the displacement value-“ the number of part by the weight of medicament that displace the one part by weight of base”

Methods of preparation:-

· Hand molding

· Automatic machine molding

· Compression molding

· Heat molding

Hand molding:- The rolling tile is lubricated with starch or talcum powder in order to prevent the adherence of mass.

Procedure :-

Advantages:-

Suitable for thermo labile ingredients.

Economical for the manufacture of small number of suppositories.

Disadvantages:- No uniformity in shape & size of suppository. –

Automatic machine molding:- It performs automatically all the operation-mold filling , solidification & removal of suppository.

Two type of machine: Rotary machine (3500-6000 suppositories per hour) Linear machine (up to 10,000 suppositories per hour)

Procedure :-

Advantages:-

The rate of production is high

No chance of air entrapment & contamination of suppository.

Disadvantage:- If any mass deposited in the mold is not removed during cleaning, it result in incomplete closure of molds and produce suppositories of over weight.

Compression molding:- It consist of cylinder, piston, molds, metallic stop plate at the bottom.

Procedure :-

Advantages:-

Suitable for thermo labile drugs.

No possibility of settling of the insoluble solids in base.

Disadvantages:-

Rate of production is low so not suitable for large scale.

Air get entrapped in the mass which leads to oxidation of ingredients.

Heat molding:- method involve following steps.

· Melting the base.

· Incorporation of drug.

· Filling of molds.

· Cooling & collection of suppositories.

Incorporation of drug:

– Solid:-drug and additive powder mixed on warm tile

– Semisolid:-triturate the ingredients on warm tile with water. this decrease the viscosity and give homogenous liquid.

– Liquid:- Volatile liquid:-they can be added to the molten base directly.

– Nonvolatile liquid:- same as semisolid.

Packing of suppositories:- It can be foiled in aluminum ,plastic, paper, tin strip. Modern packing machine: nearly 8000 suppositories can be wrapped per hour.

In packing molding :

In this ,the suppository mass is directly move into the series of molds which are made up of plastic.

After cooling , excess mass is trimmed of . By this technique 12,000 to 15,000 suppositories can be produce per hour.

Disposable molds:-

They are suitable for tropical climate. They are made up of plastic or aluminum . Labeling:- “store in a cool place.” “Not to be taken orally.”

Evaluation of suppositories:–

– Appearance

– Uniformity of weight

– Disintegration

– Test for uniformity of drug content

– Breaking test Softening time

– Test of melting rang

– Test for Dissolution rate

Stability study of suppository:-

Storage :- protected from heat ,preferably by storing in refrigerator.

Stability problem:-

– Active ingrediants and base must be stable at refrigerator temp. as well as room temp. storage condition for at least 2 year.

– Storage stability study are normally conducted at 4 °c and at room temp.(25 ± 3 °c).

– The suppository over wrap foil can also be damaged. Ex. If suppository contain an acid ,the foil wrapping may be attacked and develop e pin hole.

– The softening time test and differential scanning colorimetry cam be used as stability indicating test methods.

Recent development(new trend in suppository) Capsule suppositories Coated suppositories Layer suppositories Tablet suppositories; Compressed tablet Effervescent base tablet.

Depending on a place of introduction suppositories differentiated:

• rectal (suppositoria rectalia), intended for introduction to the rectum;

• vaginal (suppositoria vaginalia), intended for introduction in vagina;

• sticks (bacilli), intended for introduction to motions of fistula, urethra, channel of neck of uterus, acoustic duct and others like that

For the method of preparation suppositories divided into:

• Rolling (hand-pumping0

• pouring.

For the localization procedure:

• local action;

• resorbtion action.

By type of suppositories basis:

• suppositories in hydrophobic bases

• suppositories in hydrophilic bases

Requirements to suppositories:

• Time of melting (for suppositories on hydrophobic bases) – 15 minutes

• Time of dissolution (for suppositories on hydrophilic bases) – 60 minutes

• Length of rectal suppositories must be from 2,5 to 4 centimeters

• A maximal diameter of rectal suppositories is 1,5 centimeters

• Mass of rectal suppositories is from 1,0 to a 4,0 g (middle 3,0)

• Mass of vaginal suppositories must be from 1.5 to a 6,0 gram (middle 4,0)

• Sticks must have a form of cylinder with a sharp end and diameter not more than 1 centimeters.

• Length of sticks must not exceed 10 centimeters, but mass must be from 0,5 to a 1,0 gram.

• Rejections in-bulk suppositories must not exceed ± 5 %. Medicinal matters which are contained in them are guilty to be exactly dosed. Suppositories must have correct and accordingly identical form, homogeneous mass, sufficient hardness (mechanical durability) and fuse at the temperature of body.

• Suppositional mass must be homogeneous, without inclusions, marbling, and sequins.

Disadvantages of suppositories:

• not hygienic of administration

• duration of preparing.

Requirements to the suppositories bases :

• sufficient hardness at a room temperature and ability to fuse (whether to dissolve) at a temperature not higher than 37 °C, that sharply to pass ability from the solid state to the liquid, passing the stage of softening influence – ointment stage; sufficient viscidity, absence of smell, providing of maximal contact between medicinal matters and mucus shell;

• chemical and pharmacological indifference, absence of irritating actions, firmness to the action of external factors (light, heat, moisture, oxygen of air, micro organisms);

• ability easily to acquire the proper form, mixed with the largest possible number of drugs, do not interact with them and be stable during storage;

• easily to free ability medicinal matters, instrumental in the display of them pharmacological action, which depends both on properties of bases and from the method of introduction of medicinal matters in basis;

• presence of the proper reological indexes and optimum structurally mechanical properties.

PRESCRIPTION OF SUPPOSITORIES

Suppositories prescribe in recipes by two methods:

• distributive

• separate.

GENERAL RULES OF PREPARATION SUPPOSITORIES

If mass of suppository in a recipe is not marked, prepare 3,0 grams suppository. In child’s practice mass of suppository is necessarily specified in a recipe is must be from 0,5 to 1,5 gram.

If mass of vaginal suppositories is not marked, 4,0 grams suppository. The size of sticks is guilty to be marked in a recipe.

For preparation of suppositories in the conditions of pharmacy utilize the method of deflation, and at presence of facilities of small mechanization are methods of outpouring and pressing.

Medical substances, soluble in basis, in an amount less than 5% dissolve in the liquid (the same to the type of base),

if them more than 5% – dissolve in part of molten base.

Rp.: Furazolidoni 0,004

Olei Cacao 1,0

M., f. supp.

D. t. d. № 15.

S. 1 suppository into the rectum 10-15 days.

highest single dose Furazolidoni

highest daily dose Furazolidoni

Technology

These suppositories wrapped in a capsule, put in a cardboard box, paste the recipe number and fill the front of WPC.

WCP (Front side)

Date № recipe

Furazolidoni 0,06

Olei Helianthi gtt. I

Olei Cacao 15,0

Lanolini anhydrici q.s.

Massae suppositoriorum 15,06 1,0 N. 15

prepared

checked

Suppositories with substances which entered by the type of solution

• If substances which are soluble in base less than 5% – ground from a few drops of vegetable oil

• if more than 5%, with part of the melted cocoa butter (butter is desirable not to melt if it is normal plasticity)

Rp.: Anaesthesini 0.2

Olei Cacao 2.0

М., f. supp.

D. t. d. N. 10.

S. 1 suppository into the rectum

highest single dose Anaesthesini 0,5

highest daily dose Anaesthesini 1,5

Technology.

These suppositories wrapped in a capsule, put in a cardboard box, paste the recipe number and fill the front of the WCP.

WCP (Front side)

Date № recipe

Anaesthesini 2,0

Olei Cacao 20,0

Lanolini anhydrici q.s.

Massae suppositoriorum 22,0 2,2 N. 10

prepared

checked

Suppositories with substances which entered by the type of emulsion

• If substances which are soluble in water less than 5%- dissolved in a few drops of water and add shaving cocoa butter,

• if more than 5%, enter by the suspension type with a part of the melted cocoa butter by rule of Deryagin ½ the mass of solids.

Rp.: Novocaini 0,1

Olei Cacao q.s.

M. f. supp.

D. t. d. N. 6.

S. To enter in a rectum on a 1 suppository (at pains).

Technology.

WCP (Front side)

Date № recipe

Aquae purificatae q.s.

Novocaini 0,6

Olei Cacao 17,4

Lanolini anhydrici q.s

Massae suppositoriorum 18,0

3,0 N. 6

prepared

checked

ADVANTANGE OF SUPPOSITORY:

ADVANTANGE OF SUPPOSITORY

 It is the alternated dosage form for drugs which have less bioavailability when it is taken orally.

 Drugs having bad odour and taste can be used in suppository form.

 It is suitable for unconscious patients which caot taken drugs orally. It is suitable for drugs which produce irritating effect in GIT.

 It is suitable for infants and old people who find difficulty in swallowing of drugs. It is suitable for the drugs which are destroyed by portal circulation.

DISADVANTAGE OF SUPPOSITORY

 The manufacturing process is more difficult as compare other formulation.

 The drugs which cause irritation to mucous membrane caot be administrated by this form.

 The most important problem is storage condition because it stored at low temp.(10-20 0c ).

 Other than the bases get liquefied.

 Leakage problem is also most critical problem along with suppository after introducing in body cavity at elevated temperature.

TYPES OF SUPPOSITORY:

(B) URETHRAL SUPPOSITORY: