SUPPOSITORIES
and

TROCHES

Objectives: This laboratory is designed to give the student practical experience in the extemporaneous preparation of suppository and troche dosage forms. In addition, it will serve to provide hands-on experience in calculations involved in suppository preparation.

Reading Assignments:
Remington's, Chapter 14, pp.851-87; Chapter 45, pp. 891-93. Thompson, "A practical Guide to Contemporary Pharmacy Practice": “Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems”, 8^th. Ed., Chapter 12, pp. 316-335.

Background: The suppository is a solid dosage form intended for insertion into the rectum, vagina, or urethra. Urethral suppositories are encountered in practice occasionally today, but vaginal suppositories are a frequently requested dosage forms. Rectal suppositories are commonly used in the treatment of constipation and for administration of drugs for systemic absorption. Rectal suppositories are used increasingly in geriatric and hospice pharmacy.

The suppository dosage form is a useful drug delivery system in many situations. The rectal route of administration may be a desirable one if the patient cannot take medication orally. Examples include patients who are vomiting, having seizures, or who have obstructions of the upper gastrointestinal tract. Another situation in which the suppository is desirable is when a local effect is needed. Glycerin suppositories are often administered rectally for their hygroscopic nature in relieving constipation. Vaginal preparations for which system side effects are undesirable may be administered in suppository dosage form. Occasionally drugs are not effective orally, and an alternative route of administration is necessary. For example, drugs which exhibit extensive first-pass metabolism may be candidates for a suppository delivery system. When compounding suppositories, it is important to remember that drug absorption from suppositories may be unpredictable. The patient should be carefully monitored for systemic absorption and side effects.

Suppositories are a dosage form that is becoming more common in pharmaceutical compounding.  Drugs that are often encountered in compounding of suppositories used to control nausea include metoclopramide, haloperidol, dexamethasone, diphenhydramine, and benztropine.  Salbutamol can be administered rectally for long-term control of asthma, and morphine for chronic pain can be administered in suppository form to yield a slow-release product. 

Commonly requested by physicians from retail pharmacists are progesterone vaginal suppositories. These are not manufactured commercially, and must be compounded by the pharmacist. Progesterone suppositories are used in the treatment of numerous disorders and symptoms, ranging from premenstrual syndrome to complications with pregnancy. The vaginal suppository is a desirable delivery system because progesterone is extensively metabolized by the liver.    So avoiding the gastrointestinal tract provides a method of drug delivery in which a smaller dose can be used with more efficacy.

Suppository Bases
The characteristics of an ideal suppository base are the same as for an ideal vehicle regardless of administration route.  The base should be non-irritating, have no pharmacological activity, be stable, be compatible with a variety of drugs, and be esthetically pleasing.  It would be desirable to have a base that does not melt at room temperature, nor in tropical climates.
You will recall last semester that you experienced the difficulties inherent in cocoa butter usage.  The polymorphic qualities make it a difficult base to work with.  But otherwise, it is suitable for suppository products for some drugs in which a lipophilic base is desired.  There are a number of commercially available suppository bases that have similar characteristics as the cocoa butter base but have been slightly modified to yield a base that is easier to work with. 
Polyethylene Glycol is another common suppository base.  These bases are made from a combination of different molecular weight polyethylene glycols (as indicated by their "number").  The lower numbered PEGs are liquids, and as the numbers increase, the molecular weights increase, and the compounds are increasingly more solid.  By combining the PEGs, suppositories of varying hardness can be prepared.   Also, a base with a specific melting point can be obtained.
PEG base is not without its problems, however.  The following is a list of substances that are incompatible with PEG base:

Silver salts
Tannic acid
Aminopyrine
Quinine
Ichthammol
Aspirin
Benzocaine
Iodochlorhydroxyquin
Sulfonamides

Some other compounds, including camphor, sodium barbital, and salicylic acid will crystallize out of PEG.  And storage of PEG suppositories is a consideration.  PEG reacts with polystyrene, so suppositories prepared with PEG should be dispensed only in glass or cardboard containers.

So now you are familiar with both lipophilic and hydrophilic choices for suppository bases.  How do you decide?  The following table (adapted from "The Art, Science, and Technology of Pharmaceutical Compounding" by Loyd V. Allen) will give some indication of the release characteristics of drugs in various suppository base formulations, enabling the pharmacist to develop a formulation yielding the desired onset of action.

Drug Base Characteristics	Approximate Drug Release Rate
Oil Soluble Drug; Oily base	Slow release; poor escaping tendency
Water soluble drug: Oily base	Rapid release
Oil soluble drug: Water miscible base	Moderate release
Water miscible drug: Water miscible base	Moderate release; based on diffusion; all components are water soluble

Compounding Suppositories
An excellent reference  for information on the suppository dosage form (and required reading for this lab) is found at http://www.paddocklabs.com/ and performing a search using the keyword  "suppository"

There are three methods of preparing suppositories.  They include hand molding, fusion, and compression.  Preparation of suppositories by the compounding pharmacist is usually accomplished by either molding or fusion.  The fusion method is not appropriate for drugs that are heat sensitive, but it is the method by which most suppositories are made, and the one we will follow in lab, as described in the handout.

Preparing the Mold
Suppository molds are available in a variety of materials and sizes.  Disposable molds are available at a relatively low cost, and will be available in lab for your inspection.  The metal molds with which you are familiar will be used for the preparation of the products this week. 
Molds should be clean and dry.  This step is absolutely mandatory.  If a lubricant is required (and a lubricant is NOT necessary for PEG), only a very small amount should be used.  A vegetable spray may be used, or a cloth with a small amount of mineral oil may be used to apply small amounts of lubricant.

Helpful Hints!

• A small amount (~10%) extra should be calculated to allow for loss
• Mold must be clean and dry
• Drug powders to be incorporated should be triturated to a fine powder to assure uniform mixing with the base, and uniform dosing.
• If disposable molds are used, lines should be marked on them to ensure uniform dosing. 
• PEG base should be heated over a water bath
• Cocoa butter base can be heated in a constant temperature dry bath filled with sand at 37° to avoid overheating

Urethral Suppositories with Inserter

Urethral suppositories are not commercially available at this time. Physicians, especially urologists, may request this specialized dosage form. Preparation of the suppositories in a 1-mL syringe provides a convenient insertion device as well as extremely accurate dosing.

A 1cc tuberculin syringe can be converted to a urethral insertion device in the following manner:

• Pull the plunger back halfway to the end of the syringe.
• Cut off the end of syringe using sharp scissors. (All syringes should be the same size.)
• The liquid PEG mixture can then be drawn into the syringe in the conventional manner. The syringes must be calibrated depending on the vehicle used, just as with vaginal or rectal suppositories.

Stability
Suppositories are considered a non-aqueous dosage form, and thus are quite stable if they are protected from light and heat.  The US Pharmacopeia XXIII/National Formulary XVIII <1161> Pharmacy Compounding Practices provides some guidelines on beyond-use dating.  An appropriate date would be 25% of the time remaining on the expiration date if manufactured dosage forms were used as the source of the drug, or 6 months, whichever is earlier.  If dry powders of USP/NF quality were used, a beyond-use date of 6 months is appropriate.  These guidelines are to be used UNLESS  there is evidence to support a date that is different.