Pharmaceutics Ii (Test 1): Suppositories

Front 1

What is a suppository?

Back 1

A solid dosage form intended to be inserted into various body orifices where they melt, dissolve, or disperse to exert local or systemic effects.

Front 2

Name the possible sites of insertion for suppositories.

Back 2

1. Commonly rectal or vaginal

2. Occasionally urethral

Front 3

Sizes of rectal suppositories for children vs. adults?

Back 3

Adult = 2g

Children = 1g

Front 4

The possible shapes of rectal suppositories?

Back 4

Bullet, finger, or torpedo

Front 5

Size of vaginal pessaries?

Back 5

5 g

Front 6

Shape of vaginal pessaries?

Back 6

Globular, oviform. More rounded than rectal suppositories.

Front 7

Size of urethral bougies for males verses females?

Back 7

Males = 4 g

Females = 2 g

Front 8

Shape of male bougies?

Back 8

Pencil shaped. 3-6 mm diameter and 140 mm long.

Front 9

Suppositories are used to attain what kind of effect?

Back 9

Either Local or Systemic.

Front 10

Some local effects of rectal suppositories?

Back 10

1. Pain, irritation, itching, inflammation associated with steroids

2. Local anesthetic, vasoconstrictor, astringent, analgesic, soothing, emollients, protective agents.

3. Relief of constipation

Front 11

Give 2 examples of rectal suppositories used for constipation relief?

Back 11

1. Glycerin

2. Bisacodyl

Front 12

Some local effects of vaginal suppositories?

Back 12

1. Contraceptives

2. Antiseptic

3. Antifungal

4. Yeast infection

Front 13

Some local effects of urethral suppositories?

Back 13

1. Antibacterial

2. Anesthetic before preparation for urethral examination.

Front 14

The systemic effects of rectal suppositories involves these steps?

Back 14

Absorption involves 2 steps:

1. Release of drug from vehicle, diffuse through the mucosa

2. Drug transports through the veins, lymph vessels and into systemic fluids or tissues

Front 15

Suppositories are useful alternatives to the oral route of administration for these medications?

Back 15

1. Aminophyline and theophyline for asthma.

2. Prochlorperazine and chlorpromazine for relief of nausea/vomiting, and as a tranquilizer.

3. Aspirin and acetaminophen for analgesic and antipyretic (reduce fever) effects.

Front 16

5 advantages of rectal suppositories?

Back 16

1. Avoid first pass effect (So avoid losing drug through liver processing)

2. Avoid possible drug inactivation by GI pH or enzymatic activity

3. Drugs will not irritate stomach (ex. Aspirin, Indomethacin diclofenac)

4. Patients who are not able to swallow

5. Patients who are vomiting

Front 17

List 3 disadvantages of suppositories?

Back 17

1. Un-comfort

2. Variation of absorption

3. Irritation to mucous membranes by some bases or drugs.

Front 18

Elaborate on how variation in absorption is a possible disadvantage of suppositories?

Back 18

The rectum is 15-20 cm long. There is variation in blood vessel distribution. So absorption depends on where it is inserted. Blood vessels tend to congregate in the center.

Front 19

Basic composition of suppositories?

Back 19

1. Active drug

2. Base

3. Additive

Front 20

2 general factors that affect the absorption of suppositories?

Back 20

1. Physiological factors

2. Physiochemical factors

Front 21

List 4 points about the physiology of the rectum?

Back 21

1. Rectum is 15-20 cm

2. 2-3 mL of mucus

3. Not mobile in resting state, no villi or microvilli

4. High viscularization (High blood flow)

Front 22

List 3 physiological factors that may affect the absorption of suppositories?

Back 22

1. Colonic content

2. Circulation route

3. pH and lack of buffering capacity.

Front 23

Explain how colonic content can affect the absorption of suppositories?

Back 23

If it is empty verses distended with fecal matter affects absorption. Fecal matter can remove drug. Also diarrhea and colonic obstruction due to tumorous growth can affect absorption.

Front 24

How does the circulation route affect the absorption of suppositories?

Back 24

It can bypass the portal circulation and be circulated by hemorrhoidal veins and lymphatic circulation.

Front 25

How does pH and lack of buffering capacity affect the absorption of suppositories?

Back 25

pH is neutral. So no chemical change will happen to the drug.

Front 26

What are the physiochemical factors that must be considered when considering the drug for a suppository?

Back 26

1. Lipid water solubility

2. Particle size

Front 27

Would you want a lipophilic drug in an oleaginous base for a suppository?

Back 27

No. The drug would be more attracted to the base and would not be absorbed.

Front 28

What is the nature of the ideal base for a suppository? (5)

Back 28

1. The base should be nontoxic and not irritable to the mucous membrane.

2. It should be compatible with the variety of drugs that are used in suppositories.

3. It should melt or dissolve in rectal fluids.

4. It should be stable on storage, it should not bind or otherwise interfere with the release and absorption of drug substances (ie. it should be inert)

5. It should be easy to handle and be cost effective.

Front 29

Name 3 problems that may be encountered with the base of a suppository?

Back 29

1. Base may interact with the drug

2. Base does not release the drug

3. Base irritates the mucous membrane and promotes bowel movement.

Front 30

Name the 3 classes of Supp. Bases.

Back 30

1. Fatty or Oleaginous (hydrophobic) bases

2. Water soluble and water miscible bases

3. Misc. bases (combo of lipophylic and hydrophilic)

(This class will focus on 1 and 2)

Front 31

Fatty or Oleaginous bases are the ? ? used bases.

Back 31

The most frequently used.

Front 32

How do fatty and oleag. bases melt at body temperature?

Back 32

They allow quickly. This allows the drug to be released and absorbed.

Front 33

Are fatty and oleag. bases irritating at all?

Back 33

No, they are mild and non-irritating.

Front 34

Fatty or Oleag. bases allow for a rapid release of what kind of drugs?

Back 34

They allow for a rapid release of water soluble drugs.

Front 35

What is basically the most ideal base used for suppositories?

Back 35

Cocoa butter. It is the most commonly used.

Front 36

Besides Cocoa butter, list some examples of fatty or oleaginous bases used in the preparation of suppositories?

Back 36

1. Hydrogenated Fatty Acids of vegetable oil (palm kernel oil or cottonseed oil)

2. Glycerin and High MW fatty acids, Glyceryl monostearate and glyceryl monopalmitate.

Front 37

Where does cocoa butter come from?

Back 37

It is natural, from the roasted seed of theobroma cacao.

Front 38

What is the color of Cocoa butter?

Back 38

It is a yellowish-white solid.

Front 39

At what temperature does Cocoa butter melt at?

Back 39

It melts at 30-36 degrees celsius. This is a little below body temperature.

Front 40

Cocoa butter is a triglyceride. What does this mean?

Back 40

It is composed of a combo of glycerin and one or more different FAs)

Front 41

Cocoa butter, NF exhibits ? ? ? and commonly exists in ? forms.

Back 41

It exhibits different crystal forms and commonly exists in four forms.

Front 42

Cocoa butter is a polymorph. What does this mean?

Back 42

It has different crystal forms but the same chemical constitution. This has an effect on the m.p. It becomes an issue when we overheat cocoa butter.

Front 43

Does cocoa butter require lubrication when it is the base for a supp.?

Back 43

No, Because it is fatty/oleaginous.

Front 44

Name 3 additives that are added to Cocoa butter bases?

Back 44

1. Phenol

2. Camphor

3. Chloral Hydrate

These are all added for other purposes but they all happen to lower m.p.

Front 45

What may be added to cocoa butter bases to thicken them?

Back 45

1. Beeswax

2. Cetyl Ester Wax

Front 46

Substances that are said to be polymorphic exist in what state?

Back 46

They exist in different crystalline forms.

Front 47

The different crystalline forms of a polymorphic substance have what differences between forms?

Back 47

They differ in melting points and solubility.

Front 48

How must cocoa butter be melted?

Back 48

Slowly and evenly. Not at a high temp.

Front 49

What occurs if cocoa butter is overheated?

Back 49

If overheated lower M.P. crystals will form on cooling and the mix may not solidify at room temperature.

Front 50

When overheated what form of cocoa is derived?

Back 50

Alpha form is derived. It has a low m.p.

Front 51

What form of Cocoa butter do we aim for in preparations?

Back 51

We want the Beta form. It is the most stable for our purposes.

Front 52

What is the melting point of the Beta form of cocoa butter? What is the m.p. of the Alpha form?

Back 52

Beta Form = 30-36

Alpha Form = 22

Front 53

List 6 disadvantages of cocoa butter?

Back 53

1. Polymorphism

2. Poor water absorptive power

3. Pitting due to contraction on cooling

4. Rancidity (40% of FAs are unsaturated, lends to chemical instability)

5. Softens at low temperatures (28-30)

6. Batch to batch variability due to natural origin.

Front 54

Due to Cocoa butter limitations, what is available?

Back 54

Many combinations of FATS and WAXES are available to be used as substitutes.

Front 55

List 3 examples of Cocoa butter substitutes?

Back 55

1. Fattibase

2. Wecobee bases

3. Witepsol bases

Front 56

Why is the cocoa butter substitute Fattibase desirable?

Back 56

It is more stable than cocoa butter because it is not made of unsaturated fats. It is saturated.

Front 57

Name 6 Advantages of Cocoa butter substitutes over cocoa butter?

Back 57

1. No polymorphism

2. Higher M.P. range possible (33-37.5)

3. Rancidity corrected (Due to the fact that the substitutes are mostly saturated rather than unsaturated fats)

4. More reproducible

5. Better contraction (So better looking)

6. Enhanced ability for water uptake.

7. Rapidly solidify

Front 58

List 2 bases that are water-soluble and water-miscible?

Back 58

1. Gycerinated gelatin

2. Polyethylene glycols (PEG)

Front 59

What is Gycerinated gelatin and what is it composed of?

Back 59

It is a base that is both water soluble and water miscible. It is composed of 10% Drug solution + 70% Glycerin + 20% Pharmagel A or B.

Front 60

What are Pharmagel A and Pharmagel B?

Back 60

They are different sources of gelatin. A is from acid hydrolysis of skin. B is from base hydrolysis of bone.

Front 61

Cocoa butter tends to ? ? orifice.

Back 61

Tends to leak from the orifice.

Front 62

What kind of suppositories are glycerinated gelatins used for?

Back 62

They are commonly used for vaginal supp's. It is slower to soften and mix with physiological fluids.

Front 63

What is the difference between Glycerinated gelatins used for vaginal suppositories verses those used for urethral supp's?

Back 63

Urethral suppositories using glycerinated gelatin have more gelatin than the vaginal variety. Urethal are composed of 20% drug solution, 60% gelatin, and 20% glycerin.

Front 64

Does glycerinated gelatin display the property of poymorphism like cocoa butter does?

Back 64

No

Front 65

What needs to be done to a glycerinated gelatin supp. before insertion?

Back 65

It needs to be moisturized with water before insertion. Otherwise, it could cause irritation by absorbing fluid.

Front 66

Glycerinated Gelatins tend to have a ? dissolution. This makes them best suited for a ? effect.

Back 66

They tend to have a slow dissolution that is best suited for a local effect.

Front 67

What needs to be done to glycerinated gelatins if they are not intended for immediate use?

Back 67

They need to be preserved. Parabens may be used to accomplish this. Refrigeration is reqd for these.

Front 68

What may overheating of glycerinated gel supps lead to?

Back 68

It may lead to a release of volatile toxic vapors.

Front 69

What is polyethylene glycol?

Back 69

It is another example of a base that is water soluble and miscible. Also referred to as PEG, Carbowax. It is commonly used.

Front 70

What is PEG composed of?

Back 70

It is a polymer of ethylene oxide and water.

Front 71

What is the M.W. of PEG?

Back 71

Range from 300-8000

Front 72

Which varieties of PEG are clear liquid at room temperature?

Back 72

PEG 300, 400, and 600

Front 73

PEGs that are <1000M.W. are ?. PEGs that are >1000M.W. are ?.

Back 73

PEGs less that have a mw less than 1000 or liquid. PEGs that have a mw greater than 1000 are wax-like solids whose hardness increases with mw.

Front 74

Are PEGs water soluble?

Back 74

Yes, but dissolution is slow.

Front 75

Do PEGs require a preservative?

Back 75

Yes, Paraben can be used to preserve.

Front 76

Remember, the term PEG is interchangeable with what?

Back 76

Polyethylene glycol or Carbowax

Front 77

Name 7 advantages of water-soluble/water-miscible bases?

Back 77

1. mp~40C (This makes them easier to handle)

2. Slowly melt and release. (An advantage if you desire a slower release)

3. Ratio adjustment for a suitable base. ie, you can combine PEGs with different mw until you get the type of base you desire.

4. Not sticky

5. Appropriate for hydrophilic and lipophilic drugs

6. High viscosity

7. Easy storage

Front 78

Name 5 disadvantages of water-soluble/water-miscible bases?

Back 78

1. High mw PEG has a slow release of ~25-30 minutes.

2. Tendency to sting. This is because they absorb water from the mucous membrane. This is why they need to be dipped in water before insertion.

3. Contraction on cooling. They get cavitation at the ends like the pitting of cocoa butter.

4. They interact with polystyrene. This limits the molds that can be used.

5. They are incompatible with many drugs.

Front 79

Give 2 examples of drugs that water-soluble/water-miscible bases are incompatible with?

Back 79

1. Aspirin degrades faster in PEG than in cocoa butter

2. Indomethacin and PEGs

Front 80

List the 3 methods of suppository preparation?

Back 80

1. Molding

2. Compression

3. Hand rolling

Front 81

What is molding aka?

Back 81

Fusion

Front 82

List the 5 steps of molding?

Back 82

1. Melt the base using minimum heat in water bath.

2. Incorporate medication

3. Pour into the mold

4. Allow to cool. May be refrigerated.

5. Remove from the mold

Front 83

How would you incorporate a volatile drug into a mold?

Back 83

If a drug is volatile or thermo-labile it should be added at the CONGEALING point.

Front 84

How should a supp. prep. be poured into a mold?

Back 84

In a continous stream with stirring. Over filling should be avoided.

Front 85

How should a supp. be removed from a mold?

Back 85

Usually with no pressure applied.

Front 86

What is not involved in the method of compression?

Back 86

No heating involved. You are forcing the base and the medication into a special mold.

Front 87

How does the base soften in the method of compression if heat is not applied?

Back 87

It is softened by friction. Mortar and pestle may be used.

Front 88

What are two advantages of the method of compression for supp. making?

Back 88

1. May use heat-labile medication

2. No medication can precipitate at the bottom of the mold

Front 89

What are the 2 disadvantages of using compression to make supps?

Back 89

1. Requires the use of a special machine.

2. LImitation of the suppository shape.

Front 90

What 2 bases are commonly used in the compression method of making supps?

Back 90

PEG and cocoa butter

Front 91

What is the most common way of making supps?

Back 91

Fusion (molding)

Front 92

What is the historic method of making supps?

Back 92

Hand-rolling

Front 93

What does the process of hand rolling help avoid?

Back 93

Helps to avoid the necessity of heating cocoa butter.

Front 94

How is a "plastic-like mass" formed in the process of hand rolling supps?

Back 94

You would triturate cocoa butter and the active ingredient in a mortar.

Front 95

What size and shape are supp. molds available in?

Back 95

A variety of shapes and sizes.

Front 96

What are supp. molds commonly comprised of?

Back 96

1. Aluminum

2. Stainless steel

3. Brass

4. Plastic

5. Rubber

6. Foil paper

Front 97

What base does not need lubrication when it is molded?

Back 97

PEG and Cocoa butter do not need lubrication. This is because they contract.

Front 98

What type of base needs a lubricated mold? What is an option for lubrication?

Back 98

Glycerinated gel bases may need a lubricated mold. You may use mineral oil to achieve this.

Front 99

Each mold is capable of holding specific volumes. What size is desired for adults? What size is desired for children?

Back 99

Adults = 2g

Children = 1g

Front 100

What is the reason for calibrating molds?

Back 100

To account for the fact that bases and drugs have different sizes and densities.

Front 101

In the calibration of a mold, Active drug with ? ? ? volume is considered insignificant.

Back 101

Active drug with < 100 mg of drug is insignificant.