Introduction to Suppositories:
Suppositories are solid dosage form of medicament which is made for insertion into the body cavities. They may be Conical or ovoid medicated solids intended for insertion into several cavities of the body other than the mouth are known as Suppositories. This term was derived from the Latin word suppositious. meaning “ to place under.” They may be inserted in the rectum, vagina, and to a lesser extent, the urethra for local or systemic effects. Rectal and urethral suppositories usually employ vehicles that melt or soften at body temperature, whereas vaginal suppositories, sometimes called pessaries, are also made as compressed tablets that disintegrate in the body fluids exert localized or systemic effects.
Types of Suppositories:
These are meant for insertion into the rectum for producing a systemic effect. The rectal suppositories meant for adults usually weigh 2 gm and are torpedo shape, whereas the suppositories made for children are much smaller in size as compared to the adult suppositories. Children’s suppositories weigh about 1 gm.
The rectal suppositories which are used for systemic effects may contain analgesics, antispasmodic, tranquilizers, and sedative effects. Other than others these are used for antiseptic action, local anesthetic action, lubricating, soothing purposes. The rectal suppositories are used for evacuating the bowel by the irritating mucous membrane of the rectum or by lubricating the membrane.
The vaginal suppositories are also known as Pessaries. They are meant for insertion into the vaginal cavities. They weigh about 3-5 gm and are molded in globular or oviform shape or compressed on a tablet press into conical shapes. The vaginal suppositories are larger than the rectal suppositories. They are used for their local action in the vagina.
These are also called bougies and are of pencil shape. The urethral suppositories are meant for insertion into the urethra. The urethral suppositories intended for males weigh 4 gm each and are 100-150 mm long and those for females are 2 gm each and 60-75 mm in length.
The nasal suppositories are also called nasal bougies or Bulgaria. The nasal suppositories are meant for introduction into the nasal cavity. They are usually prepared with a glycerogelatin base. They have a similar shape as that of the urethral bougies. They weigh about 1 gm and have a length of 9-10 cm.
Ear cones are used for insertion into the ear. They are also known as Auraria. They are used rarely. For the preparation of ear cones generally, theobroma oil is used as a base. They are prepared in urethral bougies to mold and cut according to size.
Advantages of Suppositories:
1. Suppositories can exert a local effect on rectal mucosa.
2. It is used to promote the evacuation of the bowel.
3. It avoids any gastrointestinal irritation.
4. Suppositories can be used in unconscious patients (e.g. during fitting).
5. Suppositories can be used for systemic absorption of drugs and avoid the first-pass metabolism.
6. Babies or old people who cannot swallow oral medication.
7. It is useful for post-operative people who cannot be administered oral medication.
8. A very suitable dosage form for people suffering from severe nausea or vomiting.
Disadvantages of Suppositories:
1. Suppositories have a problem with patient acceptability.
2. In some cases, the total amount of the drug that must be given will be either too irritating or in greater amounts than reasonably can be placed into a suppository.
3. Incomplete absorption may be obtained because suppository usually promotes evacuation of the bowel.
4. Suppositories are not suitable for patients suffering from diarrhea.
Ideal Properties of Suppositories Bases:
1. It should melt at body temperature or dissolves in body fluids.
2. It should be good in appearance.
3. It should be non-toxic and non-irritant.
4. It should be compatible with any medicament.
5. Suppositories should releases medicament readily.
6. It should be easily molded and removed from the mold. It shrinks sufficiently on cooling to release itself from the mold without the need for mold lubricants.
7. It should be stable to heating above the melting point.
8. It should be easy to handle and should retain its shape while handling.
9. It should be stable on storage such that it does not change color, odor, or drug release pattern.
10. Acid value is below 0.2, saponification value ranges from 200 to 245, and iodine value is less than 7.
11. The “water number” is high, i.e., a high percentage of water can be incorporated into it.
Types of Bases:
1. Fatty Bases.
2. Water Soluble or Miscible Bases.
3. Emulsifying Bases.
1. Theobroma oil
2. Emulsified Theobroma oil
3. Hydrogenated bases
They are designed to melt at body temperature.
1. Theobroma Oil (Cocoa butter)
It is a mixture of glyceryl esters of different unsaturated fatty acids.
Cocoa Butter is a triglyceride, yellowish-white, solid, brittle fat, smells and tastes like chocolate. Its melting point is between 30-35°C, its iodine value is "between" 34-38 and its acid value is not higher than 4, because cocoa butter can melt and rancid. So it must be stored in a cool dry place protected from light.
Overheating changes its physical characteristics and it tends to adhere to the mold when solidified. It may exist in four crystalline states.
All four forms are unstable and are converted to stable forms over several days. Thus, extreme care should be exercised while melting and cooling cocoa butter. As in general, the minimal use of heat during the melting process is recommended.
To overcome the drawbacks of cocoa butter, emulsified theobroma oil, hydrogenated palm kernel, and soybean oils have been suggested.
(a) A melting range of 30 – 36°C (solid at room temperature but melts in the body).
(b) Readily melted on warming, rapid setting on cooling.
(c) Miscible with many ingredients.
(a) Polymorphism: When melted and cooled it solidifies in different crystalline forms, depending on the temperature of melting, rate of cooling, and the size of the mass.
(b) If melted at not more than 36°C and slowly cooled it forms stable beta crystals with a normal melting point.
(c) If over-heated then cooled it produce unstable gamma crystals which melt at about 15°C or alpha crystals melting at 20°C.
(d) Cocoa butter must be slowly melted over a warm water bath to avoid the formation of the unstable crystalline form.
(e) Adherence to the mold.
(f) Softening point too low for hot climates.
(g) Melting point reduced by soluble ingredients.
(h) Rancidity on storage.
(i) Poor water-absorbing ability: Improved by the addition of emulsifying agents.
(j)Leakage from the body.
2. Emulsified Theobroma Oil:
When large quantities of aqueous solutions are required to be incorporated then emulsified theobroma oil as a base can be used. There are many agents which are used to form emulsified theobroma oil, for example, 2-3% cetyl alcohol, 4% glyceryl monostearate, 10% Lanette wax, 4% beeswax, and spermaceti up to 12% can be utilized for emulsified theobroma oil suppositories.
3. Hydrogenated Oils:
They are used as a substitute to theobroma oil, many hydrogenated oils are used as a substitute, for example, coconut oil, palm kernel oil, hydrogenated edible oil, a mixture of oleic acid, and stearic acid. They are known as synthetic fat bases.
The synthetic fat bases that have advantages over theobroma oil are as follows:
- Their solidifying points are unaffected by overheating.
- Because of the lower content of unsaturated fatty acids they have good oxidation resistance.
- The difference between melting and setting points is small. Hence, they set quickly, the risk of sedimentation of suspended ingredients is low.
- Lubrication of mold is not necessary because they contract significantly on cooling.
- They are marketed in a series of grades with different melting point ranges, which can be chosen to suit particular products and climatic conditions.
- They produce colorless, odorless, and elegant suppositories.
- They contain a proportion of w/o emulsifying agents, and therefore, their water-absorbing capacities are good.
- Brittle if cooled rapidly, avoid refrigeration during preparation.
- The melted fats are less viscous and more fluid than theobroma oil because of that there is a greater risk of drug particles to sediment during preparation.
Water-Soluble or Water Miscible Base:
(i) Glycerol Gelatin
It is a mixture of glycerin and water which is made into a stiff jelly by the addition of gelatin. The proportion of gelatin can be varied according to the intended use of the preparation.
Gelato-glycerin bases dissolve in the body fluids liberating contained medicaments Gelato-glycerin Mass BP which contains 14% gelatin, 70% glycerin, and water. USP formula contains 20% gelatin together with 70% of glycerin.
For dispensing purposes, good quality powdered gelatin should be used. To control the consistency, glycerin can be partially or wholly substituted by propylene glycol and polyethylene glycols. The incompatibility of some medicaments can be avoided by the use of either Pharmagel A (cationic) or Pharmagel B (anionic). Glycerin suppositories being liable to mold growth, preservatives should be added.
(a) Physiological effect: osmosis occurs during dissolving in the mucous secretions of the rectum, producing a laxative effect.
(b) It can cause rectal irritation due to the small amount of liquid present.
(c) Unpredictable solution time.
(d) Hygroscopic: So, they should be packaged in tight containers and also have dehydrating effects on the rectal and vaginal mucosa leading to irritation.
(e) Microbial contamination likely.
(f) Long preparation time.
(g) Lubrication of the mold is essential.
(ii) Soap Glycerin
In this case, soap is employed instead of glycerin for hardening. Sodium stearate can incorporate up to 95% of glycerin. Sodium stearate (soap) is produced in situ by the interaction of sodium carbonate with stearic acid. Soap glycerin suppositories are however hygroscopic.
(iii) PEG Bases
Different mixtures of polyethylene glycols are marketed under the trade names of Postonals, Carbo waxes, and Macrogols.
Most of the drugs commonly administered in suppository form are compatible with these bases. Polyethylene glycols are however incompatible with phenols and reduce the antiseptic effects of quaternary ammonium compounds.
Massa Esterinum, Witepsol, and Massupol are the trade names under which the emulsifying bases are marketed.
1. Massa Esterinum is a mixture of the mono-, di- and triglycerides of the fatty acids having the formula C11H23COOH to C17H35COOH.
2. Witepsol bases consist of hydrogenated triglycerides of lauric acid with added monoglycerides. These are available in nine grades.
3. Massupol consists of glyceryl esters namely lauric acid and the addition of a very small quantity of glyceryl monostearate.
All these bases are free from the drawbacks of cocoa butter and do not require. lubrication of mould.
Water-dispersible bases essentially consist of surfactants. They melt at body temperature. Some formulae of dispersible bases containing surfactants are outlined below.
Glyceryl monostearate 10, Glyceryl monostearate 15, Tween 60, 40.
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