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What are suppositories?
- Solid dosage forms intended for insertion to the rectum, vaginal cavity or urethra
- Systemic or local effects
- Liquefies after insertion
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How large are infant rectal suppositories?
1 gram
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How large are adult rectal suppositories?
2 grams
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What is the shape of rectal suppositories?
Cylindrical and tapered at one or both ends
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What is the shape of vaginal suppositories?
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What is the weight of most Vaginal suppositories?
3-5 grams
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What are vaginal suppositories also called?
Pessaries
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What are urethral suppositories also called?
Bougies
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What is the shape of urethral suppositories?
Pencil shaped
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What situations are rectal suppositories indicated for?
- Oral route not available
- The drug is not useful when applied orally
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What are the disadvantages of rectal suppositories?
- Slow/incomplete absorption
- Intra/inter subject variation
- Local irritation
- Difficult to manufacture
- Long prep time
- Stringent storage conditions
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What are rectal suppositories intended for?
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What are rectal suppositories used for systemically?
- Analgesics
- Antispasmodics
- Tranquilizers and Sedatives
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What are the physiological factors that affect suppository absorption?
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What are the Physicochemical factors that affect suppository absorption?
- Solubility
- Concentration
- Particle size
- Partition coefficient
- Degree of ionization
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What are the Physiochemical factors that affect suppository absorption?
- Melting point
- Solubility
- Reactivity
- Polymorphism
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Describe the Retum:
- 5-20 cm in length
- 2-3mL of mucous fluid prior to defecation
- No villi or microvilli
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What three physiological issues can effect rectal suppository absorption?
- Tissue dehydration
- Colonic obstruction
- Diarrhea
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When using a systemic suppository, what must be done prior to insertion?
Evacuation
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Why is evacuation needed prior to use of systemic suppositories?
To increase absorption
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How can evacuation be carried out?
Evacuation enema
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Why is it advisable to keep the suppository in the lower part of the rectum?
To avoid the upper hemorrhoid vein, as it leads to portal circulation
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What part of the rectum should patients be advised to put the suppository in and why?
- The lower part (nearest to anus)
- To avoid portal circulation
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What percent of drug administered rectally goes directly into circulation?
50-70%
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What are the names of the Hemorrhoid veins?
Upper, middle and lower
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What veins absorb rectal suppository drugs?
Hemorrhoid veins
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What happens to rectal drugs after absorption?
- Available for systemic effect
- Some pass portal circulation
- NO LIVER
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What is the pH of rectal fluids?
7-8
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What is the effective buffer capacity of the rectal fluids?
None
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The rectal mucosa is preferentially permeable to what type of drugs?
Unionized
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How can rectal absorption be enhanced physiologically?
By changing the pH to one where the most drug is unionized
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When selecting a base and determining the release of the drug from that base, what factors should you evaluate?
The Lipid water partition coefficient
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A lipophilic drug will not release well in the hydrophilic rectal fluids if it is in what type of base?
Fatty base
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What type of drugs can be used in suppository Fatty bases?
Water soluble salts
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What type of base would you use for a lipophilic drug or a hydrophilic drug?
Water soluble base
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What is the most common water soluble suppository base?
PEG
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What is the rate limiting step suppository absorption?
- Partitioning of the drug from the suppository base
- NOT THE RATE AT WHICH THE DRUG CREATES A SOLUTION IN THE RECTAL FLUIDS
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Will the rate of absorption continue to rise with higher rectal concentration?
No, plateaus
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What happens to the suppository base after insertion?
Melts or softens
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What can affect the melting or softening of suppository bases?
The exipients
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What are the properties of an ideal suppository base (7)?
- Melts at 37.5 degrees C in presence of mucous secretiosn
- Easy to handle, doesn't break or melt
- Does not leak from rectum
- Stable in storage
- Non-irritating
- Compatible
- No meta-stable forms
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What are the three classifications of suppository bases?
- Oleaginous
- Water soluble
- Water dispersible
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Give two examples of oleaginous bases:
- Cocoa butter (Theobroma oil)
- Cocoa butter substitutes
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Give two examples of Water soluble bases:
- Polyethylene glycol mixes
- Glycerinated gelatin
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Give two examples of Water dispersible bases:
- Polyethylene glycol derivatives
- Cocoa butter substituted with surfactants
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Describe the appearance of Cocoa butter:
yellowish white with chocolate scent
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What is Cocoa butter composed of?
Glycerol esters of various FAs
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What is the most widely used rectal suppository base?
Cocoa butter
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Why is Cocoa butter so widely used?
It meets most of the requirements of an ideal base
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What are the four main advantages of Cocoa butter?
- Melts at 30-36 degrees C
- Rapid melting and cooling
- Non-irritating
- Miscible with many drugs
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What is the disadvantage of Cocoa butter/Oleaginous bases?
- Polymorphism
- Adherence to the mold
- Softening point to low for hot climates
- Poor water absorption
- Melting point lowered by soluble exipients
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Describe how Water soluble bases work:
- Do not melt at body temperature
- Dissolve in body secretions
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What is Glycerol suppository base B.P. made of?
- 14% gelatin
- 70% Glycerol
- QS 100% with water
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What is glycerol-geltin base U.S.P. composed of?
- 20% gelatin
- 70% Glycerol
- QS 1005 with water
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What type of base is Hygroscopic?
Glycerinated gelatin bases
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What is Hygroscopic?
Tendency to absorb water
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What are polyethylene glycols composed of?
Ethylene oxide and water of various lengths
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What do the numerical designations after PEG indicate?
The average MW
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What PEG MWs are clear colorless liquids?
300, 400 and 600
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What PEG MWs are Semisolids?
600-1000
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What PEG MWs are wax-like white solids?
Over 1000, increasing hardness as MW increases
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What is the melting point for most PEGs?
50 degrees C
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If PEG bases melt at 50 degrees C, how is the drug released at body temperature?
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You can blend different MW PEGs together to alter what characteristics?
- Melting point
- Physical Characteristics
- Dissolution rate
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What is the iodine value?
The grams of iodine that react with 100 grams of Fat or unsaturated material
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Why is the iodine value important?
- Correlates with:
- Decomposition by moisture, acids and oxygen
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What is the solidification value for a suppository base?
The time it takes to solidify once cooled
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What is the Melting range for a suppository base?
Initiation and endpoint of melting
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What are the possible type of suppository base orgin?
Natural or synthetic
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What is the acid value of a suppository base?
The mg of potassium hydroxide needed to neutralize the free acid in 1 gram of base
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What relative Acid Value is good for suppositories?
Low
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Why is a low Acid Value good for suppository bases?
- Complicate formulation work
- React with ingredients
- Cause irritation
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What is the water number for a suppository base?
The grams of water that can be incorporated into 100 grams of Fatty base
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How can you increase the Water number of a fatty suppository base?
Addition of surfactants
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What are the four methods of suppository manufacture?
- Hand Molding
- Compression molding
- Pour molding
- Automatic molding
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What is the oldest and simplest method for making suppositories?
Hand molding
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Describe Hand molding:
- Trituration of drug and base
- Rolled into a cylinder with steel blade spatula
- Divided
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What type of prescription could you use hand Molding for?
- Few suppositories needed
- Cocoa butter base
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What is the process of Compression Method of suppository molding?
- Make a paste of the base and ingredients
- Compress in a die
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What do you need to determine prior to compression molding?
The compressibility of the base in the dies
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What is the most commonly used method for suppository production?
Pour molding
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Describe the technique of pour molding:
- Base is melted
- Ingredients are added
- Suppositories are cooled
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What is the output of a rotary automatic molding machine?
3,500-6,000 suppositories per hour
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What type of suppositories need to be refrigerated?
Cocoa butter and glycerinated gelatin
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What type of suppositories can be stored at room temperature?
PEG
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What type of molds can suppositories be stored in?
Metal or Plastic
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What are the advantages of disposable plastic suppository molds?
- Cheap to change mold shape
- No need to expensive molds or wrappings
- Eliminate the wrapping process
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What are the five tests that should be performed on Suppositories?
- Melting range test
- Liquefaction test for rectal suppositories
- Disintegration test in-vitro
- Stability testing
- Breaking test
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