Dosage form design I

Question 1

What are some rationales for drug design?

Answer 1

• Adding starch or lactose to enlarge the volume of the drug to ensure tablet is a compressible size
• colouring powder to make it more appealing to patients
• alter properties of tablet to ensure controlled release which would require less frequent administration from patient,
• base our drug design on the stability that is available to us
• formulating certain dosage forms for the convenience of the patient (e.g. tablets vs. suspensions)

Question 2

why does there need to be rationale behind drug design?

Answer 2

biologically active entities are rarely administered as pure chemical substances due to issues with patient acceptability, therapeutic issues, toxicity, stability, etc. so they are given as a formulated preparation

these can vary from simple solutions to complex drug delivery devices

these are designed to help patients take and adhere to their medications

Question 3

what do we aim to improve in all dosage forms?

Answer 3

taste
appearance
stability
availability
absorption

Question 4

why do we need to improve availability in dosage forms?

Answer 4

you can only give some dosage forms to a certain age group

e.g. kids under 5 can’t really swallow tablets and may need suspensions which requires the right taste and colour.

Question 5

why do we need to improve absorption in dosage forms?

Answer 5

Every drug must be absorbed into the body in order to have effect. we aim to enhance this.

e.g. Q10 is a drug which stimulates heart or organ function with little oxygen. It is very suitable for heart disease patients. However, it is poorly water soluble. If we want to enhance the bioavailability of Q10 we need to enhance its solubility. this can be done with microemulsions.

Question 6

what makes up a drug?

Answer 6

the active compound and all its additives/excipients

Question 7

What are the major components of a tablet?

Answer 7

active ingredient which is usually powder. This is usually a very small amount.

starch (cheap and common additive) used to make the tablet normal sized and compressible

other additives including buffer, flavourant, colourant, preservative, lubricant, thickener, etc.

Question 8

What do we sometimes replace powder with?

Answer 8

granules

Question 9

what is the dry method of making granules?

Answer 9

place powder directly into machine to form the pretablets

we cut this up to form the dry granules

we then compress these into tablets

Question 10

What is the wet method of making granules?

Answer 10

mix powder and starch uniformly and then add water.

this is then seived through and collected to make the granules

Question 11

What must occur if the granules are to be put into capsules?

Answer 11

they must be dried using temperature control

this depends on the type of compound you are using

Question 12

Why is the transdermal patch used as a controlled release medicament?

Answer 12

It utilises a polymer to create a rate controlling membrane between the drug and our skin.

Question 13

what are the main components of the transdermal patch?

Answer 13

Drug is contained in the patch.
Rate controlling membrane determines how much drug is released and goes into our blood stream
Adhesive layer keeps the patch on our skin

The drug is gradually released through the membrane, epdiermis, dermis and enters the blood vessels into the systemic circulation

Question 14

what is a dosage form?

Answer 14

the clinical package in which a drug is presented to a patient

Question 15

What are the two large families that pure powders belong to?

Answer 15

crystal (structured) in which atoms are arranged into a neat lattice. These have a high MP, BP and stability. This makes them difficult to dissolve

amorphous (irregularly dispersed). These have a low MP, BP and stability but are highly soluble

Question 16

what properties do liquid crystals have?

Answer 16

some of liquids and some of crystals. They have some (but not all) of their atoms arranged neatly.

Question 17

what is used to tell the difference between crystal, amorphous and liquid crystal powders?

Answer 17

a polarised microscope

Question 18

What are the two different types of liquid dosage forms?

Answer 18

oily based and water based

Question 19

What are the three major components of emulsions?

Answer 19

oil phase
water phase
surfactant/emulsifying agent

Question 20

What are the criteria that dosage forms must reach?

Answer 20

stability
reliability
convenience
palatability
effectiveness

Question 21

What kind of stability criteria must dosage forms have?

Answer 21

tablets should have 2 years shelf life minimum
suspenesions = 3 months
eye drops = 1 month

Question 22

what kind of reliability criteria must dosage forms have?

Answer 22

tablets of the same kind should be produced with the same pharmacological function as other tablets. e.g. you can’t have one which causes therapeutic effect and one which doesn’t

Question 23

what kind of convenience criteria must dosage forms have?

Answer 23

tablets should be packaged in such a way that they are easy to administer and can be taken wherever the patient is.

Question 24

What kind of palatabile criteria must dosage forms have?

Answer 24

oral dosage forms must be edible.

unfortunately 99% of active compounds are bitter so we have to mask this (and sometimes the colour as well)

Question 25

What kind of effectiveness criteria must dosage forms have?

Answer 25

the drug must meet its claimed therapeutic effect

Question 26

What are the major factors affecting the dosage form design process

Answer 26

``` physical form of the drug various physicochemical propertieis target site method of manufacture routes of administration ```

Question 27

how does the physical form of the drug affect the dosage design process?

Answer 27

some drugs may be in crystalline or amorphous form crystalline compounds are not very good as they are poorly water soluble before you formulate further, you should first convert the crystalline compound into an amorphous form to enhance drug solubility otherwise you will waste time and money further down the line when you discover it is not very soluble

Question 28

how do physicochemical properties of the drug affect the dosage design process?

Answer 28

Melting point: is a good indication of solubility (e.g. 270 degrees = not very soluble) pka: will indicate if the drug is acidic or basic logP: tells us the lipophilicity of the drug. (>3 = poorly water soluble)

Question 29

how does the target site affect the dosage design process?

Answer 29

We may have to design the drug in such a way that it is not broken down and released before it reaches the target site. e.g. potential oral form of insulin. We would want it to be absorbed in the colon as there are no enzymes which would break it down. This would mean we have to carefully design the carrier system to ensure it survives along the GIT to reach the colon

Question 30

how does the method of manufacture affect the dosage design process?

Answer 30

We have to decide which methods to use e.g. the wet vs. dry method to make granules

Question 31

how does the route of administration affect the dosage design process?

Answer 31

routes of administration determines the type of characteristics we would enhance in a dosage form e.g. if the drug was to be administered as an injection, it would have to be in liquid form. if the drug was to be adminsitered as an eye drop, we might want to enhance the viscosity to make it stay longer

Question 32

what are some of the excipients used?

Answer 32

``` solubiliser thickener preservative modifying the solution improving compressability suspender ```

Question 33

What are some reasons to add excipients?

Answer 33

may need to enlarge drug volume to ensure proper formulation | excipients need to be inert and must not react with active compound

Question 34

What is an example of a solubiliser?

Answer 34

bile salt which can enhance solubility for the compound

Question 35

what is an example of a thickner?

Answer 35

can add certain polymers which thickens the solution to apply to the ear and eye to make it stay as long as possible

Question 36

what is an example of a preservative?

Answer 36

benzyl paraben, alcohol. these prolong the shelf life

Question 37

what is an example of a modifier?

Answer 37

bile salt for fast dissolution | viscosity for slow dissolution

Question 38

what is an example of an excipient which improves the compressability?

Answer 38

lubricants are often used so when you compress the tablets they do not stick to the machinery. this ensures an accurate dose and size of each tablet

Question 39

what is an example of a suspender?

Answer 39

suspending agent.. these can be natural or modified. this prevents the active ingredient from sedimenting at the bottom

Question 40

Why must the dosage design be predictable, reproducible and able to produce a therapeutic response?

Answer 40

you need to plan how to formulate the dosage form down to the fine detail this plan needs to be reproducible so the next person can make the same product. This allows you to upscale and sell it the dosage form must be able to produce a therapeutic response as that is what drugs are for.