Suppositories and inserts

Suppositories and InsertsChapter 12

Suppositories

-Are solid dosage forms intended for insertion into body orifices where they melt, soften, or dissolve and exert local or systemic effects.

-Derived from Latin word supponere, meaning “to place under”.-Are commonly used rectally and vaginally

and occasionally urethrally.

COMPARISON BETWEEN DIFFERENT TYPES OF SUPPOSITORIES

Suppositories Physical Appearance

Size/ Weights Shape

RECTAL=Adult

32 mm (1.5”) long; 2g (w/ base)

Bullet-like Torpedo orLittle finger

=Infants/Children

Half the size & weight of adult supp..

Pencillike

Vaginal(Pessaries)

5g(when cocoa butter is the base)

Globular Oviform orCone-shaped

Suppositories Physical Appearance

Size/ Weights Shape

Urethral(Bougies)=Male

3-66 mm in diameter; 140 mm long4g weight

SlenderPencil-shaped

=Female Half the length & weight of male;70 mm long; 2g

Local action•Rectal suppositories intended for local

action are most frequently used to relieve constipation or the pain, irritation, itching, and inflammation associated with hemorrhoids or other anorectal conditions.

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

•Vaginal suppositories intended for local effects are employed mainly as contraceptives, antiseptics in feminine hygiene, and as specific agents to combat an invading pathogen.•Nonoxynol-9 for contraception, and trichomonacides to combat vaginitis caused by Trichomonas vaginalis, Candida (Monilia) albicans, and other microorganisms.

Systemic action

•For systemic effects, the mucous membranes of the rectum and vagina permit the absorption of many soluble drugs.

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

Advantages over oral therapy of the rectal route of administration:

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

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

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

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

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

Examples of drugs administered rectally

Prochlorperazine and chlorpromazine- for the relief of nausea and vomiting and as tranquilizer

Oxymorphone HCl- for opioid analgesia

Ergotamine tartrate- for the relief of migraine syndrome

Indomethacin- nonsteroidal anti-inflammatory analgesic and antipyretic

Ondansetron- for the relief of nausea and vomiting

Some factors of drug absorption from rectal suppositories

Divided into two main groups:1)Physiologic Factors•Colonic content•Circulation route•pH and Lack of Buffering Capacity of the Rectal

Fluids

2) Physicochemical Factos•Lipid-water solubility•Particle size•Nature of the base

Physiologic Factors

•Colonic content-It is more effective for a drug to absorbed

systematically in an empty rectum than from one that is distended with fecal.

•Circulation route

-Drugs absorbed in the rectum bypass the first pass effect in the liver instead of being absorbed into general circulation.

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

Physiologic Factors

•pH and Lack of Buffering Capacity of the Rectal Fluids

-Rectal fluids are essentially neutral in pH and have no effective buffer capacity, the form in which the drug is administered will not generally be chemically changed by the rectal environment.

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

Physicochemical factors of the drug and suppository base

•Lipid-water solubility-A lipophilic drug that is distributed in a fatty

suppository base in low concentration has less of a tendency to be released into the body fluid, than in a fatty base.

• Particle size-For drugs present in a suppository in the

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

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

•Nature of the base-Base must be capable of melting, softening

or dissolving to release its drug absorption.-If the base interacts with the drug to inhibit

its release, drug reaction will be impaired or prevented.

Suppository bases

Should remain solid at room temperature but soften, melt & dissolve readily at body temperature.

Classification of suppository bases1) Fatty or oleaginous base•Cocoa butter- commonly used because it melts quickly at body

temperature.•Palm kernel oil & Cotton seed oil- have many hydrogenated

fatty acids of vegetable oilOthers:•Plamitic & Stearic acids-is one of the most common saturated

fatty acids found in nature following palmitic acid.

•Wecobee Bases- triglycerides derived from coconut oil

•Witepsol Bases- triglycerides from palm, palm kernel, and coconut oils with self emulsifying glyceryl monostearate and polyoxyl stearate.

2) Water-soluble and water-miscible bases

•Glycerinated gelatin-is most frequently used in the preparation of

vaginal suppositories, where the prolonged localized action of the medicinal agent is usually desired.

•Polyethylene Glycol-used to prepare progesterone vaginal

suppository for premenstrual syndrome.

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

water-miscible materials,-some are preformed emulsions, generally of

the water/oil type, or they may be capable of dispensing in aqueous fluids.

E.g. Polyoxyl 40 stearate

Preparation of suppositories

A. Molding from a meltB. CompressionC. Hand rolling & shaping

A）Preparation by moldingThe steps in molding include•melting the base,•incorporating any required medicaments,•pouring the melt into molds,•allowing the melt to cool and congeal into

suppositories,•removing the formed suppositories from

the mold.

Suppository molds

•Commercially available molds can produce individual or large numbers of suppositories of various shapes and sizes.

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

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

Lubrication of the mold

•Depending on the formulation, suppository molds may require lubrication before the melt is poured to facilitate clean and easy removal of the molded suppositories.

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

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

Calibration of the mold

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

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

Preparing and Pouring the Melt

Using least heat, the weighed suppository base materials is melted over a water bath.

A porcelain casserole is best used because it later permits convenient pouring of melt into the cavities of the mold.

B) Preparation by compression

-may be prepared by forcing the mixed mass of the base and the medicaments into special molds using suppository-making machines.

-In preparation of compression into the molds, the base and the other formulative ingredients are combined by thorough mixing, the friction of the process softening the base into a pastelike consistency.

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

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

Preparation by Hand rolling and Shaping•The oldest and simplest method

of suppository preparation.•Method of choice when only a few

suppositories are to be prepared in a cocoa butter base.

Rectal Suppositories

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

•They are also intended to provide local action within the perianal area.

•They are commonly employed to relieve:-Pruritis ani-Pain sometimes associated with hemorrhoids

Suppositories Commercial Product Active Constituents

Type of Effect

Category and Comments

Bisacodyl Dulcolax (Boehringer-Ingelheim)

10 mg Local Cathartic

Chlorpromazine Thorazine(GlaxoSmithKline)

100 mg Systemic Antiemetic; tranquilizer

Hydrocortisone Anusol-HC (Salix) 25 mg Local Pertusis ani, inflamed hemorrhoids, other inflammatory conditions of the anorectum.

Hydromorphone Dilaudid (Abbott) 3 mg Systemic Analgesic

Indomethacin Indocin 50 mg Systemic Anti-inflammatory

Mesalamine Canasa (Axcan Scandipharm)

500 mg Local Anti-inflammatory

OxymorphoneProchlorperazine

Promethazine HCL

Numorphan (Endo)Compazine (SmithKline Beecham)Phenergan (Wyeth)

5 mg2.5, 5, 25 mg

12.5, 25 mg

SystemicSystemic

Systemic

AnalgesicAntiemetic

Antihistamine, antiemetic, sedative

Examples of Rectal Suppositories

Urethral Suppositories

•Are also called Bougies. They have been used in the treatment of local infections, and a much smaller urethral suppository been introduced for the administration of alprostadil in the treatment of erectile dysfunction.

Vaginal Suppositories

•These preparations are employed principally to combat infections in the female genitourinary tract to restore the vaginal mucosa to its normal state and for contraception.

Product (Manufacturer)

Active Constituents

Cleocin supp(Pfizer) Clindamycin phosphate 100 mg Bacterial vaginosis

Monistat 7 supp (Personal Products)

Miconazole nitrate 100 mg Antifungal for local vuvlvovaginal Candidiasis (moniliasis)

Mycelex-G vaginal contraceptives (Bayer)

Clotrimazole 500 mg Vulvovaginal yeast (Candida) infections

Semicid vaginal contraceptive inserts (Whitehall-Robins)

Nonoxynol-9 100 mg Nonsystemic reversible birth control

Encare contraceptive inserts (Blaire)

Nonoxynol-9 100 mg Nonsystemic reversible birth control

Examples of Vaginal Suppositories

•Nanoxynol-9, a spermicide, is employed for vaginal contraception

•Estrogenic substances as dienestrol are found in vaginal prepareations to restore the vaginal mucosa to its normal state.

Vaginal Inserts

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

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

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

agentmagnesium stearate as a tablet lubricant.

Packaging and storage

Glycerin suppositories and glycerinated gelatin suppositories

-are packaged in tightly closed glass containers to prevent a moisture change in the content of the suppositories.

-stored at temperature below 35 F-can be stored at controlled room temperature

(20 C to 25 C)

Suppositories prepared from a cocoa butter base

-are usually individually wrapped or otherwise separated in compartmentalized boxes to prevent contact and adhesion.

Suppositories containing light-sensitive drugs

-are individually wrapped in an opaque material such as metallic foil.

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

Glycerinated gelatin suppositories are best stored at temperatures below 8C and can routinely be stored at controlled room temperature (2025C).

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