[PHA 619 LEC] Chapter 12 - Suppositories, Inserts, and Medication Sticks

These are solid dosage forms in which one or more APIs are dispersed in a suitable base and molded or otherwise formed into a suitable shape for insertion into body orifices to provide a local or systemic effect.

Suppositories

Suppository came from what Latin word?

Supponere = to place under

Suppositories are generally employed to?

- Promote defecation

- Introduce drugs into the body

- Treat anorectal diseases

They are usually about 32 mm (1.5 inch) long, are cylindrical, and have one or both ends tapered.

Rectal suppositories

What is the weight of rectal suppositories for adult use?

2 g

- Cocoa butter is the base

What is the weight of rectal suppositories for use by infants and children?

- Half the weight and size of the adult suppositories

- More pencil-like shape

Cocoa butter is also known as?

Theobroma oil

These are solid dosage forms inserted into a naturally occurring (nonsurgical) body cavity other than the mouth or rectum, including the vagina and urethra.

Inserts

They are usually globular, oviform, or cone shaped and weigh about 5g when cocoa butter is the base.

Vaginal Inserts

What is the usual weight of vaginal inserts?

5 g

- Cocoa butter is the base

Vaginal inserts are formerly called?

Suppositories or pessaries

These are slender, pencil-shaped suppositories intended for insertion into the male or female urethra.

Urethral inserts

Urethral inserts are also called?

Bougies

What is the length and weight of male urethral suppositories?

- 3 to 6 mm in diameter

- approx. 140 mm long

- 4 g in weight (cocoa butter is the base)

What is the length and weight of female urethral suppositories?

Half the length and weight of the male urethral suppository

- about 70 mm long

- 2 g when made of cocoa butter

These are solid dosage forms inserted into naturally occurring convenient forms for administering topical drugs. They are generally packaged in an applicator tube for topical administration.

Medication sticks

(True/False) Medication sticks are cylindrical in shape and generally range from 10 to 20 g.

False

- 5 to 25 g

(True/False) Rectal administration avoids, at least partially, the first-pass effect and the breakdown of certain drugs that are susceptible to gastric degradation.

True

(True/False) Rectal administration has the ability to administer drugs in smaller doses, has an irritating effect on the oral or gastrointestinal mucosa (if orally taken), and with unpleasant-tasting or smelling drugs.

False

- Administers drugs of LARGER doses

(True/False) The rectal route is useful in children and in patients experiencing nausea and vomiting or when unconscious.

True

(True/False) Rectal administration can achieve a rapid drug effect locally.

False

- SYSTEMICALLY

(True/False) Suppositories may be expensive if made on demand. There is also a perceived lack of flexibility regarding dosage of commercially available suppositories.

True

(True/False) In suppositories, different formulations of a drug with a narrow therapeutic margin can be interchanged without risk of toxicity.

False

- CANNOT be interchanged

(True/False) A pencil-shaped suppository after insertion can leave the anorectal site and ascend to the rectosigmoid and descending colon.

False

- BULLET-shaped suppository

(True/False) Bullet-shaped suppository should not be used at bedtime.

True

(True/False) Defecation may interrupt the absorption process of the drug.

True

(True/False) The absorbing surface area of the rectum is larger than that of the small intestine.

False

- Rectum has SMALLER surface area than small intestine.

(True/False) The fluid content of the rectum is much less than that of the small intestine.

True

(True/False) One of the disadvantages of suppositories is the possibility of degradation of some drugs by the microflora present in the rectum.

True

(True/False) In suppositories, the dose of a drug required may be greater than or less than the dose of the same drug given orally.

True

What are the two factors affecting rectal absorption?

- Anatomic-physiologic

- Physicochemical factors of the drug and the base

Effect of suppositories that once inserted, the suppository base melts, softens, or dissolves, distributing its medicaments to the tissues of the region

Local action

They are commonly employed to relieve pruritus ani of various causes and the pain sometimes associated with hemorrhoids.

Local anesthetic suppositories

They may relieve constipation or the pain, irritation, itching, and inflammation associated with hemorrhoids or other anorectal conditions

Rectal suppositories

They may serve as contraceptives, as antiseptics in feminine hygiene, and as specific agents to combat an invading pathogen

Vaginal suppositories or inserts

They are used for hydration/emollient, antibacterial, sunscreen, antipruritic, and other uses.

Sticks

Effect of suppositories wherein the mucous membranes of the rectum and vagina permit the absorption of many soluble drugs

Systemic action

(True/False) Drugs absorbed rectally can bypass the portal circulation during their first pass into the general circulation.

True

What is the pH of the rectal fluid?

7.2 - 7.4

(True/False) Rectal fluid has a good buffer capacity.

False

- Has a NEGLIGIBLE buffer capacity

(True/False) The form in which the drug is administered will not generally be chemically changed by the rectal environment.

True

(True/False) Adrug will have a greater opportunity to make contact with the absorbing surface of the rectum and colon in the presence of fecal matter.

False

- Greater contact in the ABSENCE of fecal matter (no defecation)

What is usually administered (if needed) to act before the administration of a suppository of a drug to be absorbed?

Evacuant enema

(True/False) A lipophilic drug distributed in a fatty suppository base in low concentration has a greater tendency to escape to the surrounding aqueous fluids than a hydrophilic substance in a fatty base.

False

- LESS tendency to escape

(True/False) The more drug a base contains, the more drug will be available for absorption.

True

(True/False) The smaller the particle, the greater the surface area, the more readily the dissolution of the particle, and the greater the chance for rapid absorption.

True

Why is it preferable to avoid a too fine particle size, especially for high-dose drugs?

Because escessively small particles can raise the viscosity of the melted excipient and cause possible difficulties in flow during production

What happens if the suppository base interacts with the drug to inhibit its release?

drug absorption will be impaired or even prevented.

What happens if the suppository base irritates the mucous membranes of the rectum?

It may initiate a colonic response and prompt a bowel movement, eliminating the prospect of complete drug release and absorption.

What are the ideal characteristics of a suppository base?

- Physically and chemically stable

- Nonirritating

- Nontoxic

- Non-sensitizing

- Chemically and physiologically inert

- Compatible with a variety of drugs

- Stable during storage

- Aesthetically acceptable

What are the three types of suppository bases?

- Fatty/oleaginous

- Water-soluble/water-miscible

- Miscellaneous bases

It is the most frequently employed suppository bases.

Fatty or oleaginous bases

It is a fat obtained from the roasted seed of Theobroma cacao; ideal suppository base.

Cocoa Butter, NF

It is composed of mixed triglycerides of oleic, palmitic, and stearic acids.

Cocoa butter

Melting range of cocoa butter

34-35 C

(True/False) Cocoa butter suppositories do not melt at body temperature but rather dissolve slowly in the body's fluids.

False

- Polyethylene glycol suppositories

It is composed of triglycerides from palm, palm kernel, and coconut oils with self-emulsifying glyceryl monostearate and polyoxyl stearate.

Fattibase

Melting range of fattibase

35.5 - 37 C

It is a homogenelus blend of PEGs and polysorbate 80.

Polybase

Melting range of polybase

60 - 71 C

These are eutectic mixtures of mono-, di-, triglycerides derived from natural vegetable ils, each type having slightly different properties.

Suppocire OSI

Melting point of Suppocire OSI

33 - 35 C

These are triglycerides derived from coconut oil.

Wecobee W

Melting point of Wecobee W

31.7 - 32.8

These are triglycerides of saturated fatty acids C12-C18 with varied portions of the corresponding partial glycerides.

Witepsol H15

Melting range of Witepsol H15

33 - 35 C

What are the examples of water-soluble and water-miscible bases?

- Glycerinated gelatin suppositories

- Polyethylene glycol suppositories

These are slower to soften and mix with the physiologic fluids than is cocoa butter. It provides a slower release, hygroscopic, and may have a dehydrating effect and irritate the tissues upon insertion.

Glycerinated gelatin suppositories

These do not melt at body temperature but rather dissolve slowly in the body's fluids. It provides slower release of the medication from the base once the suppository has been inserted.

Polyethylene glycol suppositories

What formulation variables are generally considered?

- nature and form of the active principle

- physical state, particle dimensions, and specific surface of the product

- solubility of the drug in various bases

- presence or absence of adjuvants added to the active principle

- nature and type of dosage form in which the active principle is incorporated

- pharmaceutical procedures used in the preparation of the dosage form

It causes the drug to diffuse more slowly through the base to reach the mucosal membrane for absorption.

Viscosity

(True/False) The release rate of the drug may be slowed if the viscosity of the base is very low.

False

- Very HIGH

(True/False) Brittleness in suppositories results when the percentage of non-base materials exceeds about 35%.

False

- exceeds about 30%

This condition causes fat and cocoa butter suppositories to crack.

Shock Cooling

(True/False) Suppositories can be placed in a freezer.

False

- may cause shock cooling

(True/False) Bases, excipients, and active ingredients generally occupy more space at lower temperatures than at higher temperatures.

False

- LESS space

What is the approximate drug release rate of an oil-soluble drug in an oily base?

- Slow release

- Poor escaping tendency

What is the approximate drug release rate of a water-soluble drug in an oily base?

Rapid release

What is the approximate drug release rate of an oil-soluble drug in a water-miscible base?

Moderate release

What is the approximate drug release rate of a water-soluble drug in a water-miscible base?

- Moderate release

- based on diffusion

- all water soluble

What are the two methods of preparing suppositories?

- Molding

- Hand rolling / shaping

It is the method of preparing suppositories that is most frequently employed on both on a small scale and on an industrial scale.

Molding

What are the steps in molding suppositories?

1. Melting the base

2.I incorporating any required medicaments

3. Pouring the melt into molds

4. Allowing the melt to cool and congeal into suppositories

5. Removing the formed suppositories from the mold

(True/False) The final step in the calibration of a mold is to prepare molded suppositories from base material alone.

False

- FIRST step

Method of preparing suppositories that is seldomly used due to ready availability of suppository molds of accommodating shapes and sizes; thus, there is little requirement for today's pharmacist to shape suppositories by hand.

Hand Rolling and Shaping

What method are manufactured suppositories generally prepared?

Melt fusion method

(True/False) Increased solubility of the active in the base can improve product homogenity.

True

What are some quality control procedures listed in the USP/NF for manufactured suppositories and inserts?

- Identification

- Assay

- Loss on drying

- Disintegration

- Dissolution

- Stability

- (For compounded suppositories) Calculations of theoretical and actual weight and weight variation, color, hardness, surface texture, and overall appearance

What is observed during stability check for quality control in suppositories and inserts?

Excessive softening and oil stains on packaging

These suppositories are packaged in tightly closed glass containers to prevent a change in moisture content and stored at controlled room temperature.

Glycerin or glycerinated gelatin suppositories

Controlled room temperature

20-25 C (68-77 F)

These suppositories are individually wrapped; separated in compartmented boxes to prevent contact and adhesion stored below 30°C (86°F) and preferably in a refrigerator.

Prepared from cocoa butter base

Refrigerator temperature

2-8 C (36-46 F)

These suppositories are stored at usual room temperatures.

Prepared from base of polyethylene glycol

These suppositories are individually wrapped in an opaque material such as a metallic foil.

Containing light-sensitive drugs

Changes in the odor of suppositories may be caused by?

Fungal contamination

- ex. vegetable extracts

Changes in the color of suppositories may be caused by?

Discoloration due to oxidation

- ex. tartrazine yellow aq. solution

Changes in the shape of suppositories may be caused by?

Incorrect temperature during storage

- ex. essential oils

Changes in the surface condition of suppositories may be caused by?

Whitening

- ex. vegetable extracts or caffeine base suppositories

Changes in the weight of suppositories may be caused by?

Loss of volatile substances

- ex. camphor, methol