Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PH2107 go iawn > Rectal drug delivery > Flashcards

Rectal drug delivery Flashcards

1
Q

What is a rectal drug delivery?

A

A solid dosage form that is inserted into the body through the rectum as a suppositry which will then elt, soften or dissolve.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the approx length of suppositories?

A

32mm

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the weight range of suppositories?

A

1g to 4g depending on the density of the suppository base.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is a base?

A

A solid or semi-solid base.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the drug content range of suppositories?

A

from <0.1% to 4%. Generally 1.5 to 2 times the oral dose but can be equivalent.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are the advantages of rectal drug delivery?

A
  1. can treat local conditions like haemorroids, fissures etc
  2. Can also treat systemic conditions if the patient is unable to swallow/unconcious/vomiting.
  3. Usefull if the oral medication has unacceptable taste
  4. PArtial avoidance of hepatic metabolism
  5. Avoidance of parenteral route in children.
  6. difficult to abuse and overdose i.e. cannot insert 20 suppositories
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What can be contained in Suppositories to treat local conditions?

A
  1. Can contain soothing agents like Mild astringents (bismuth subgallate), Vasoconstrictors (adrenaline), or local anaesthetics (lignocaine).
  2. Can contain Cortiosteroids but only used short-term e.g hydrocortisone to treat proctitis
  3. Evacuants - bisacodyl, glycerin
  4. Antimicrobials - sulphasalazine
  5. Mesalazine for ulcerative colitis.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are the disadvantages of Suppositories?

A
  1. Administration issues - not the easiest
  2. Slow and incomplete absorption thereofre slower onset of action
  3. Inter and intra subject variation
  4. Formulation is difficult.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How to use suppositories?

A
  1. in necessary, go to toilet to empty bowles
  2. wash hands
  3. remove any foil or plastic wraping from the suppository
  4. Either squat or lie on side with one leg straight and one bent
  5. gently but firmly push the suppository with the tappered end first into the rectum. push far enough so that it doesn’t slip out
  6. Colse your leg and sit still for a few minutes. Avoid emptying bowel for at least one hour (unless supp is a laxative)
  7. Wash hands again.
    May be best to insert at night as there might be some leakage from the suppository so would be uncomfortable during the day.
    Some supps can stain clothes.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the storage instructions for most supps?

A

Store in a cool, dark place but not in the fridge unless specifically instructed. If they get too warm, they will melt and not be firm enough to insert. (they melt at body temp 37)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What governs the drug absorption from the rectum?

A

Physiological and physiochemical factors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the Physiological factors affecting absorption?

A

1) Colonic content
2) Circulation route
3) pH and lack of buffering capacity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How does colonic content affect absorption?

A
  • greater absorption when there is no fecal matter there therefore an evacuant enema may be used prior to administration. Diarrhoea, or a tumour or tissue dehydration may also affect absorption.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

How does Circulation route affect absorption?

A

Drugs via rectal delivery will partly avoid first-pass metabolism (50-70%) therefore drugs metabolised by the liver orally may be more effective.
The drug can be absorbed into the rectal veins.
Placement of the supp therefore affects metabolism and whether the drug reaches the liver or not (if placed too high, much more of drug will reach liver).
Lymphotrphic delivery is also possible - lymphatic vessels are more porous than blood vessels, so is an opportunity for large drug molecules to be delivered this way.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How does pH and lack of buffering capacity affect absorption?

A

Rectal fluids are pH 7-8, and there is no effective buffering capacity. Therefore durgs will determine the pH of the environment.
Weaker acids and bases are absorbed better than stronger, highly ionised ones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are the physiochemical factors affecting absorption?

A

1) Drug solubility in lipid and water

2) Drug particle size

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How does Drug solubility in lipid and water affect absorption?

A

Lipohilic drugs are less readily released if the base is also lipophilic.
Water soluble bases readily dissolve in anorectal fluids , therefore hydrophilic drugs are more readily released.
The rate of drug absorption cannot e increased above a certain concentration.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

How does drug particle size affect absorption of the drug?

A

Particle size affects dissolution and absorption

Decreased size = increased dissolution = increased rate of absorption.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are the important properties of a base?

A

Must be capable of melting, softening or dissolving at body temperature
Must not be irritating as could initiate a bowel movement (unless its purpose is laxative)
Campatibiltiy of drug with base must be ascertained.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the rate limiting step of drug delivery in the rectum?

A

The partitioning of the drug from the melted base and not the rate of solution od drugs in body fluid.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

How are drugs released from a lipohilic base?

A

The base melting in the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How are drugs released from a hydrophilic base?

A

Base dipersing in the mucus

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What affects the release of drugs from the base?

A 
Affinity of the drug for the vehicle
Solubility of the drug in rectal fluids
Particle size
Spreading of the vehicle
Interactions between drug and vehicle i.e. lipophilic drug is released slowly from lipophilic base.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What determines the rate of transfer of drug across the mucosa?

A

Determined by partitioning and diffusion.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What happens during transfer across mucosa?

A

Drug needs to dissolute, diffuse through ucus layer and then into and through the epithelium of the rectal wall by passive diffuion

26
Q

What affects the transfer across the mucosa?

A
  • Lipophilicity which is pH dependant for weak acids and bases and buffer solutions can increase absorption.
    Site of absorption
    Absorption enhancers
27
Q

How do absorption enhancers work?

A

Surfactants work by decreaseing the surface tension of the vehicle and mucus barrier and increase membrane permeability by interacting with the phospholipids e.g. cetomacrogols

28
Q

What is used to decrease absorption?

A

Phenolics

29
Q

Suppositry bases: what are the ideal properties of a base?

A
  • Rapid release of drug in active form
  • Patient acceptibility
  • Ease of manufacture
  • Stability during storage
30
Q

What is the ideal properties of a base for rapid release of drug from base?

A
  • Either melts at body temp (lipophilic base) or dissolves in rectal fluids (hydrophilic base) to release the drug within 10 minutes
  • Must also be no incompatibility between the drug and base
  • Must have good wetting and emulsifying properties.
31
Q

What is the ideal properties of a base for patient acceptibility?

A
  • Not toxic, sensitising or irritant to rectal mucosa
  • Capable of being handled and firm enough for easy application
  • Bland i.e. base has no unwanted therapeutic action
32
Q

What are the ideal properties of a base for ease of manufacture?

A
  • Easily moulded by pouring
  • Adequate shrinkage allowing easy removal from the mould without lubricant.
  • Good suspending power (viscosity) for heavy insoluble medications
  • Stable above melting point
  • Higher melting point bases can be used for drugs that lower the melting point or when formulating drugs in tropical climates.
  • Lower melting point bases can be used with drugs that increase the melting point of the base or if adding large quantities of solids.
33
Q

What are the ideal properties of a base for stability during storage?

A

-Iodine value below 7 to decrease decomposition
-Acid value below 0.2 to decrease reactivity and irritation
Small interval between melting and solidification point to decrease sedimentation

34
Q

What are the two types of vehicles that act as bases?

A

1) Vehicles that melt (hydrophobic)

2) Vehicles that dissolve/disperse (hydrophilic)

35
Q

What type of base is Theobroma oil (coca butter)

A

A vehicle that melts.

Solid at RT, then melts at body temp between 30-36.

36
Q

What are the substances known to exist in more than one crystalline form known as? What are the barriers of These?

A

Polymorphic substances.
They generally have different melting points and solubilities eventhough they are chemically identical.
We need to use the polymorph with the most favourable properties.

37
Q

WHat type of base are Hard Fats e.g. Witepsol

What is an advantage of using these?

A

These are vehicles that melt as they are hydrophibic. They are semi-synthetic mixtures of glycerides and are prepared from natural vegetable oils by hydrogenation and fractionation.
Pros: Small interval between melting and solidification point therefore decreased sedimentation. is a gould mould release: Less polymorphism therefore with less range of melting points available. Stable to oxidation and hydrolysis.

38
Q

What type of base is Glycerinated Gelatin suppository base?

Pros and COns

A

Vehicle that DISSOLVES (hydrophilic). A mixture of gelatin and glycerin that dissolves in the rectal secretions. Purified water is present so preservation is required.
Pros: dissolves slowly for prolonged action. Used more often in pessaries
Cons: Hygroscopic: may produce slight dehydration of the rectal mucosa which is not favourable.
Also requires preservation (due to water) and cool storage.

39
Q

What type of base is Polyethene Glycol base?

Pros and Cons

A

A vehicle that DISSOLVES. it is available as a liquid or a solid form.
There are different Molecular weight PEGs which means that there are different solubilities and melting points. the higher the melting point, the less soluble in water.
Pros: useful for fat soluble drugs, can be altered to prepare a base with a specific melting point or one that will overcome the adverse characteristics
Cons: Hygroscopic (will produce slight dehydration of the rectal mucosa), irritant so must be dipped in water first

40
Q

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

A

Slow release due to poor escaping tendancy (high affinity of drug to base)

41
Q

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

A

Rapid release - low affinity of drug to base

42
Q

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

A

Moderate release

43
Q

What is the approximate drug release of a water miscible drug in an water miscible base?

A

Moderate release- based on diffusion and all components are water soluble.

44
Q

What are the differnt ways of creating a suppository?

A

1) Moulding
2) Compression
3) Hand rolling

45
Q

What is the ‘moulding method’?

A

What we did in LAB

1) Melt base at lowest possible heat
2) incorporate ingredients
3) Pour into mould and overfill
4) allow to cool
5) remove any excess due to contraction
6) remove from mould

46
Q

How is the drug prepared to be added to melted base?

A

1) break down to uniform, small particle size
2) The maximum quantity of drug/excipient to be incorporated is 30% of the blank weight of the suppository
3) liquids may pccupy too much volume to be easily incorprated
4) if a large amount of liquid is to be incorporated into an oily base, may be neccessary to make a w/o emulsion

47
Q

What is the mixing/ incorporating and pouring process?

A

Sufficient mixing to obtain a uniform distribution of the drug but not too long to result in either drug or base deterioration
Poured into the mould at room temperature
Slowly fill the mould avoiding any air bubbles, leaving a small excess of materials on the top of the mould.

48
Q

What is the finishing process of cooling and after this?

A

Set for 15-30 minutes at RT, then refrigirate for an additional 30 minutes (not fridge straight away as will affect polymorphic properties).
To remove excess, dip blade of spatula in warm water to scrape off the excess.
REmove carefully and label.

49
Q

What is the ‘compression’ method?

When is it used

A

Incorporate ingredients vigorously
Force into mould using compression machinery
Remove from mould
Compression method is suitable for bases that can be formed into suppositories under pressure, Useful for heat liable drugs and where there is a large amount of insoluble material.

50
Q

What is the ‘hand rolling and shaping method’?#

WHen is it normally used?

A

Historical method, requires coniderable skill, but avoids heat so is useful for heat-liable material.
Generally used with coca butter which can be easily manipulated, shaped and handeled at room temperature.
1) coca butter is grated
2) drug is added
3) mixed with mortar and pestle or a tile and spatula
4) Shape into a long cylinder
5) cut into the desired lenght and round the tips
6) Package and label

51
Q

Why are calcualtions required for preparing suppositoreis

A

Drug will displace some of the base which is the displacement value, so will affect the calibration of the base due to the moulds being filled VOLUMETRICALLY.

52
Q

What is the displacement value?

A

The number of parts by weight of the drug that displaces 1 part by weight of the base (exept glycerol suppository base)

53
Q

WHat si the equation?

A

Wheight of base requried = weight of suppository - (weight of active / displacement value)

54
Q

Probelms in suppository preparation:

A 
Moisture in supps
Hygroscopicity
Incompatibilities
Viscocity
Brittleness
Volume contraction
Rancidity
55
Q

Why should moisture be avoided in suppositories?

A

Water should be avoided as it

  • accelerates oxidation of fats
  • crystallizes materials on evaporation
  • increases reactions between ingredients
  • assists bacterial growth
56
Q

What is Hygroscopicity?

A

Causes slight rectal dehydration which causes irritancy.

57
Q

Why is viscosity so important in suppository preparation?

A

Controlls sedimentation
to control the viscosity, either adjust temperature or add a viscosity enhancer e.g. alumminium monosterate or increase fatty acid chain length.

58
Q

WHy is brittleness a probelm in preparing suppos?

A

May cause snapping on insertion or removal from package. can be induced by rapid cooling which is why they are not put straight into fridge. Can be reduced by Tweens.

59
Q

Why is volume contraction a problem?

A

Requried to eject the suppository from mould

Undesirable at base of suppository

60
Q

Why is rancidity an issue in prep?

A

Resistance of fatty acid to oxidation measured by quantity of peroxide. MAy requrei and antioxidant.

61
Q

What are some of the quality control rules of supps by BP?

A

-Appearance including odur, colour, surface, and shape.
-Wehight: BP limts that no more than 2 >5% deviation from average weight
None deveiate >10% from average weight.
(WEigh 20 supps together then individually)
-Disintegration time: complies with BP disintegration test for supps and pessaries. DOes not affect MR supps.
-Mechanical strength for handling
-COntnet uniformity
-Drug release

62
Q

Suppository MOULDS:

A

made form plasitc or metal
Care must be taken when cleaning or drying
Lubrication mwy be required
Calibration may be required

PH2107 go iawn (18 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions