Suppositories and Inserts
Contents Suppositories Some factors of drug absorption from rectal suppositories Suppository bases Preparation of suppositories Type of suppositories Packaging and storage
1. Suppositories Definition: Suppositories are solid dosage forms intended for insertion into body orifices where they melt, soften, or dissolve and exert local or systemic effects. Suppositories are commonly used rectally and vaginally (pessaries) and occasionally urethral (bougies), rarely nasal (bougies) and through ear (ear cones). They have various shapes and weights.
The shape and size of a suppository must be such that it can be easily inserted into the intended orifice without causing undue distension, and once inserted, it must be retained for the appropriate period.
Rectal Suppositories Drugs administered via the rectum are given for a local effect or to achieve a systemic effect. Local effects may include the soothing of inflamed hemorrhoidal tissues, promoting laxation, and enemas. Using rectal administration to achieve systemic activity is preferred when the drug is destroyed in the GI tract, if oral administration is not possible because of vomiting, or the patient is unconscious or incapable of swallowing oral formulations.
Rectal administration has been used to treat a variety conditions such as asthma, nausea, motion sickness, anxiety, and bacterial infections. Suppositories are manufactured in a variety of shapes. Rectal suppositories for adults are tapered at one end and usually weigh about 2 grams. Infant rectal suppositories usually weight about 1 gram or about half that of adult suppositories.
The major disadvantages of rectal suppositories 1.They are not preferred by patients; they are inconvenient. 2.Rectal absorption of most drugs is frequently erratic and unpredictable. 3.Some suppositories "leak" or are expelled after insertion.
Vaginal suppositories are employed as contraceptives, feminine hygiene antiseptics, bacterial antibiotics, or to restore the vaginal mucosa. Vaginal suppositories are inserted high in the vaginal tract with the aid of a special applicator. The suppositories are usually globular, oviform, or cone-shaped and weigh between 3 - 5 grams.
Vaginal Suppositories Vaginal administration has many advantages. 1.Generally there is less drug degradation via this route of administration compared to oral administration 2.The dose can be retrieved if necessary 3.There is the potential of long term drug absorption with various intrauterine devices (IUDs).
Urethral suppositories - called bougies which are pencil shape. Those intended for males weigh 4 gm each and are 100-150 mm long. Those for females are 2 gm each and 60-75 mm in length. Nasal suppositories: - called nasal bougies or buginaria meant for introduction in to nasal cavity. They are prepared with glycero gelatin base. They weigh about 1 gm and length 9-10 cm.
Pharmacological Uses: 1） Local action Rectal suppositories intended for localized 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 or inserts intended for localized effects are employed mainly as contraceptives, antiseptics in feminine hygiene.
2) 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. Examples include paracetamol (acetoaminophen), diclofenac. Normal shapes and weight of rectal suppositories:- For adults weigh 2 gm and are torpedo shape. Children's suppositories weigh about 1 gm.
Among the advantages (Merits) over oral therapy of the rectal route of administration for achieving systemic effects are these: a) Drugs destroyed or inactivated by the pH or enzymatic activity of the stomach or intestines need not be exposed to this destructive environments; b) Drugs irritating to the stomach (or insatiable) may be giving 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 or unconscious patient) e) It is an effective route in the treatment of patients with vomiting episodes. f) Prolong drug release.
Unpredictable absorption Mucosal damage Disadvantages (Limitations)of suppositories: Aesthetic objection Leakage Unpredictable absorption Mucosal damage
2. Some factors of drug absorption from rectal suppositories 1) Physiologic factors Colonic content when deemed desirable, an evacuant enema may be administered and allowed to act before the administration of a suppository of a drug to be absorbed. Diarrhea, colonic obstruction, and tissue dehydration
Circulation route The lower hemorrhoidal veins surrounding the colon receive the absorbed drug and initiate its circulation throughout the body, bypass the liver. Lymphatic circulation also assists in the absorption of rectally administered drugs.
pH and lack of buffering Because 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.
Composition of suppositories Drug (active ingredient) Base Other additives – surfactants, soothing agents, antioxidants, preservatives, anti-settling agents (blend of higher m.p waxes & fatty acids )
2) 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 escape to the surrounding aqueous fluids than would a hydrophilic substance present in a fatty base to an extent approaching its saturation.
Water soluble bases, for example, PEG, which dissolve in the anorectal fluids, release for absorption both water-soluble and oil-soluble drugs. Naturally, the more drug a base contains, the more drug will be available for potential absorption.
Particle size For drugs present in a suppository, 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 The possiblity of chemical and/or physical interactions between the medicinal agent and the suppository base, which could affect the stability and/or bioavailability of the drug. If the base is irritating to the mucous membranes of the rectum, it may initiate a colonic response and prompt a bowel movement, negating the prospect of complete drug release and absorption.
3. The ideal suppository bases One of the first requisites for a suppository base is that (ideal suppository base) it remains solid at room temperature Release medicament readily soon after insertion. Easily melt and dissolve or disperse at body temp. Retain shape while handling moldable, non adhering Non-toxic & non-irritant Stable & compatible
Classification of suppository bases I. Oleaginous (fatty-lipophilic) bases a) Natural - cocoa butter or their substitutes b) Synthetic - witepsol, massuppol II. Hydrophilic (water soluble/miscible) bases a) Natural - glycero gelatin (Glycerinated gelatin) b) Synthetic –PEG- macrogols
1) Fatty or oleaginous base Cocoa butter or Theobroma Oil is defined as the fat obtained from the roasted seed of Theobroma cacao. At room temperature it is a yellowish, white solid having a faint, agreeable chocolate-like odor.
Chemically, it is a triglyceride At ordinary room temperatures of 15 to 25C, it is a hard, amorphous solid Cocoa butter melts between 30C to 36C, it is an ideal suppository base. Readily liquefiable on warming and rapid setting on cooling Cocoa butter exhibits marked polymorphism.
Two factors when preparing suppositories with cocoa butter base Two factors when preparing suppositories with cocoa butter base. First, this base must not be heated above 35C because cocoa butter is a polymorphic compound and if overheated will convert to a metastable structure that melts in the 25 to 30C 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.
Limitations: Polymorphism – unstable gamma/beta forms Adhere to mould due to contractility on solidification Softening point too low for hot climates (beeswax may be added) Batch to batch variation in composition Becomes rancid on storage Immiscible in body fluids and poor water absorption Tendency to leak, immiscibility makes it not suitable for vaginal and urethral route May melt at warmer climates
Synthetic lipophilic bases advantages & disadvantages: - readily available - do not become rancid - chemically more inert - do not exhibit polymorphism - good water absorption and emulsification properties - lubrication can be avoided - white, smooth & odorless - may become brittle & fracture if cooled rapidly - more expensive than cocoa butter
Hydrogenated fatty acids of vegetable oils (palm oil and cottonseed oil) Fat-based compounds containing higher molecular weight fatty acids, such as palmitic and stearic acids with glycerin the (glyceryl monostearate and glyceryl monopalmitate, (Witepsol®) )