SUPPOSITORIES | ideal Suppository Base | Coated suppositories |

SUPPOSITORIES

 

Suppositories are solid or semisolid dosage forms, usually medicated for insertion into body cavities like the rectum, vagina, or urethral tract They are designed to melt, disintegrate or dissolve at the body temperature. Suppositories intended for the vagina, urethra, or nasal cavity are also referred to as pessaries, urethral bougies, and nasal bougies, respectively. The distribution of a drug from suppositories may be either local o systemic. Pessaries are also made as compressed tablets, which disintegrate in the body fluids.

 

Historically, suppository dosages form dates back to 2600 B.C. and were reported in the works of Hippocrates and Papyrus Ebers. Theo. _ broma oil and glycerinated gelatin mixtures were recommended a

 

suppository vehicles in 1852 and 1871, respectively. Suppositories account for about. 1% of all medications dispensed today.

 

Advantages of Suppository Medication

When oral administration of a drug is not feasible as in infants of patients suffering from nausea, vomiting, and gastrointestinal disturbances, suppositories serve as an alternate for drug administration. They have been used for a variety of conditions like hemorrhoids and local infections in the vagina and rectum. Drugs like hypnotics, tranquilizers, antispasmodics, etc., are often given as suppositories. This provides the advantage that the biotransformation of drugs in the liver, pH conditions, and gastro-intestinal enzymes are avoided as the portal circulation is bypassed. Oral administration of phenylbutazone and indomethacin may * cause gastric irritation hence these drugs are sometimes administered rectally. Suppositories have also been used for the prolongation of drug action. Absorption of drugs from rectal mucosa directly into the venous

 

circulation may bring about a faster onset of action as compared to oral administration. Undissociated drugs are absorbed more rapidly from gastric mucosa than ionized ones. The rate of diffusion of drugs from the dosage form to the site of absorption depends upon the nature of the medicament, its lipid/water solubility, the physical state of the colon, and the amount and nature of the solids and lipids present in the colon. In general, the presence of surfactants may increase the rate of diffusion unless complexation takes place. It is claimed that suppositories and rectal retention enemas may give drug levels comparable to the intravenous injection provided an allowance is made for a 30 minute lag time.

 

ideal Suppository Base

 

It should possess the following properties:

 

i. It should melt at body temperature or dissolve or disintegrate in body fluids. Higher melting point bases may be necessary for eutectic mixtures. The addition of balsams to suppositories is intended for use in tropical climates.

 

2. It should be inert, non-irritating, and non-sensitizing.

3. It should release the medicament readily.

4. It should be compatible with a broad variety of drugs.

5. It should be stable on storage.

6. It should have wetting and emulsifying properties.

7. It should be able to incorporate a high percentage of water in it

Le. a high water number.

 

On cooling, it should shrink sufficiently to release itself from

 

mold and should be mouldable by pouring or by cold compression.

 

9. Fatty bases should have an acid value below 0.2, saponification value between 200 and 245, iodine value less than 7, and a narrow range between the melting and solidification points.

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Suppository Bases 

Suppository bases can be broadly divided into the following categories:

 

(A) Oleaginous bases; 

Theobroma oil or cocoa butter was introduced as a base in 1852 and has been one of the most widely used bases, it satisfies most of the criteria of an idea] suppository base except that it melts at 32°C i.e, below the body temperature. Overheating alters its physical characteristics and it tends to adhere to the mould When solidified. It may exist in four crystalline states,

 

Alpha form: This form is obtained by sudden cooling of the melted mags to OC. Its melting point is 24°C,

 

Beta form: This form is obtained when cocoa butter is melted at 35 to 36°C and slowly cooled. It melts at 18 to 23°C.

 

Beta dash form; it reverts to B form and melts at 34 to 35°C.

 

Y form: it is obtained by pouring a cool (20°C) cocoa butter into a container before it is solidified and cooled at deep-freeze temperature. k melts at 18°C.

 

All four forms are unstable and are converted to stable forms for several days. Thus extreme care should be exercised while melting and cooling cocoa butter. As a general rule, the minimal use of heat during the melting process is recommended.

 

Cocoa butter can take up to 20 to 30 g of water per 100 g. The incorporation of emulsifiers such as Tween 61 (5 to 10%) increases the water absorption capacity of cocoa butter.

 

Drugs like volatile oils, creosote, phenol, and chloral hydrate lower

 

the melting point of cocoa butter considerably but some wax and spermaceti can be used to correct such a problem.

 

Drawbacks of cocoa butter can be overcome by hydrogenated palm kernel and soybean oils. Palm Kernal oil is particularly suggested for “ae m tropical countries. Completely or partially hydrogenated cottonseed od such as “Cotoflakes’ and ‘Cotomar’ together with hexanediol may be actual.

 

(B) Aqueous Bases

 

(i) Glycerol gelatin; It is a mixture of glycerin and water made into a stiff jelly by the addition of gelatin. The proportion of gelatin can be waned according to the intended use of the preparation.

 

Gelao-glycine bases dissolve in the body fluids liberating contained medicaments. Gelato-glycerin Mass BP contains 14% gelatin, 70% glycerin and water. USP formula contains 20% gelatin together with 70% of glycine. For dispensing purposes, good quality powdered gelatin should be the weed. To control the consistency, glycerin can be partially or wholly substituted by propylene glycol and polyethylene glycol. The incompatibility of some medicaments can be avoided by the use of either Phasmagel A (cationic) or Pharmagel B (anionic).

 

Glycerin suppositories being liable to mold growth, preservatives should be added.

 

(ii) Soup 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, Carbowaxes, and Macrogols, Some important PEG bases used in the preparation of suppositories . are as follows:

The base I: is a low melting, rapidly disintegrating base and requires refrigeration during summer.

 

Base II is much more stable, harder, and gives a slower release.

 

Base III is particularly suitable for drugs having a melting point lowering effect on the base.

 

Base IV contains water and facilitates the incorporation of water-soluble and PEG-insoluble substances.

 

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 effect of quaternary ammonium compounds.

 

(C) Emulsifying bases: 

Massa Esterinum, Witepsol, and Massupol are the trade names under which the emulsifying bases are marketed. Massa Esterinum is a mixture of the mono-, di, and triglycerides of the fatty acids having the formula C; H23COOH to Cy7H35COOH. Witepsol bases consist of hydrogenated triglycerides of lauric acid with added monoglycerides. These are available in 9 grades. Massupol consists of glyceryl esters namely lauric acid with an addition of a very small quantity of glyceryl monostearate.

 

All these bases are free from the drawbacks of cocoa butter and da hot requires any mould lubricant.

 

Water-dispersible bases essentially consist of surfactants. They melt at body temperature. Some formulae of dispersible bases containing Surfactants are outlined below:

 

I Il ll Glyceryl monostearate 10 Glyceryl monostearate 15 Tween 60 4p Tween 61 90 Tween 61 85 Tween 6] 60

 

Types of Suppositories

 

Suppositories: These are intended for insertion into the rectum. may be either cone-shaped with a rounded apex and weighing about 1 g, ¢& torpedo-shaped weighing about 2 g. Torpedo-shaped suppositories are introduced easily and can incorporate a larger amount of medicament because of their size.

 

Pessaries: These are intended for administration into the vagina and are either cone-shaped or wedge-shaped with a rounded apex. They are available in 4 and 8 g sizes.

 

Clotrimazole Pessaries (Clotrimazole Vaginal Tablets) are official in IP 2014.

 

Urethral bougies: These are intended for introduction into the urethra, about 6 cm long and weighing about 1 g. In dispensing practice, urethral bougies are prepared from cocoa butter.

 

Nasal bougies: These are similar to urethral bougies, slightly thinner, not more than 8 cm in size, and weighing about 1.2 g. In dispensing practice nasal bougies are prepared from a gelato-glycerin base.

 

Ear cones: These are rarely used and whenever required they are prepared from cocoa butter.

 

Different shapes and sizes of suppositories are depicted in Fig. 16.1

 

Suppositories can be prepared either by the cold or hot process. Thé cold process consists of either hand shaping or compression. A mold for the preparation of suppositories in the laboratory is shown in Fig. 16.2.

 

1. Cold hand shaping: 

In this method, the powdered impalpable drug is mixed with a part of cocoa butter grated to a small size, in g

mortar. Incorporation of 1 drop of fixed oil per 12 suppositories Remaining cocoa butter is

 

provides additional plasticity to the mass. The amount of heat generated during

 

added by geometric dilution. The situation of the mass in mortar makes the mass plastic, pliable, code

 

sive and easy to roll. The mass is then rolled on a pill tile dusted with starch, with the help of a spatula to the desired length and diameter and

 

then cut approximately to the size.

 

2. Fusion: 

This is the most widely used method. The suppository molds are available in various sizes having 6 to 500 cavities, usually made of aluminum, brass, or nickel-copper alloys. Nowadays Teflon coated molds are available. The moulds are calibrated by adding a sufficient quantity of melted base into the cavities, allowing to cool removing the excess quantity of the base, and weighing the suppositories, After calibration, all the components of the base are melted on a steam bath and the medicament is added. The melted mass is then added into suppository moulds Lubricated, if necessary), allowed to congeal, and kept in the refrigerator for 30 minutes to harden. The top of the suppositories is then trimmed off with a spatula, mould screws are loosened and the suppositories are ejected by pushing them gently from the

bottom. Liquid paraffin and glycerin are commonly used lubricants for suppository molds. A lubricant must be miscible with the suppository base, Glycerin and mineral oil are good lubricants for cocoa butter Suppositories whereas mineral oil is suitable for PEG suppositories.

 

Newer Trends :

 Laxative suppositories prepared as compressed

 

Tablet suppositories: ‘ablets are available in the market. They are designed to disintegrate

 

either by employing effervescent combinations or starch. The COatings of polyethylene glycol protect them and also facilitate their insertion into the rectum. Some vaginal suppositories intended for the treatment of local infections are also available as compressed tablets. Generally, these are almond-shaped for ease of insertion into the vagina.

 

Layered suppositories:

One type of layered suppositories consists, of an outer shell having a melting point of 37 to 38°C and a core melting at 34 to 35°C. Thus each layer may contain a different drug. Multiple layered suppositories can be prepared by adding one layer into the mould, allowing it to congeal, then similarly adding subsequent layers. They can be used for separating the incompatible drugs as wel| as for controlling the release of medicament by varying the melting points of different layers in a controlled manner.

 

Capsule suppositories: 

They consist of soft gelatin capsules filled with liquids or solids and intended for insertion into the rectum or vagina.

 

Coated suppositories: 

Coatings are applied to suppositories for protection as well as to prevent coalescence of adjacent suppositories during storage. Polyethylene glycol, cetyl alcohol, patented polyvinyl alcohol and tween have been applied for coating the suppositories. The coating is applied by dipping the suppository in the solution of coating material until the desired thickness is obtained.

 

Disposable moulds : 

These are most suitable for tropical climates. Disposable moulds made up of plastic materials or aluminum foils have revolutionized the packing of suppositories. Plastic moulds are made of polyvinyl or polyethylene and are attached by stripping materials. Even if the suppository mass melts within the disposable mould yet it remains inside, Such moulds need not be stored at low temperature. AS compared with the cost of processing in conventional moulds, wrapping, and packing the suppositories; disposable moulds are cheaper and elegant. Mould shapes can also be changed at a lower cost. Howevé when the moulds are used, the .patient must be cautioned to reject the plastic mould and withdraw the suppository for insertion.

 

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