Dosage form design I Flashcards
What are some rationales for drug design?
- 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)
why does there need to be rationale behind drug design?
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
what do we aim to improve in all dosage forms?
taste appearance stability availability absorption
why do we need to improve availability in dosage forms?
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.
why do we need to improve absorption in dosage forms?
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.
what makes up a drug?
the active compound and all its additives/excipients
What are the major components of a tablet?
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.
What do we sometimes replace powder with?
granules
what is the dry method of making granules?
place powder directly into machine to form the pretablets
we cut this up to form the dry granules
we then compress these into tablets
What is the wet method of making granules?
mix powder and starch uniformly and then add water.
this is then seived through and collected to make the granules
What must occur if the granules are to be put into capsules?
they must be dried using temperature control
this depends on the type of compound you are using
Why is the transdermal patch used as a controlled release medicament?
It utilises a polymer to create a rate controlling membrane between the drug and our skin.
what are the main components of the transdermal patch?
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
what is a dosage form?
the clinical package in which a drug is presented to a patient
What are the two large families that pure powders belong to?
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
what properties do liquid crystals have?
some of liquids and some of crystals. They have some (but not all) of their atoms arranged neatly.
what is used to tell the difference between crystal, amorphous and liquid crystal powders?
a polarised microscope
What are the two different types of liquid dosage forms?
oily based and water based
What are the three major components of emulsions?
oil phase
water phase
surfactant/emulsifying agent
What are the criteria that dosage forms must reach?
stability reliability convenience palatability effectiveness
What kind of stability criteria must dosage forms have?
tablets should have 2 years shelf life minimum
suspenesions = 3 months
eye drops = 1 month
what kind of reliability criteria must dosage forms have?
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
what kind of convenience criteria must dosage forms have?
tablets should be packaged in such a way that they are easy to administer and can be taken wherever the patient is.
What kind of palatabile criteria must dosage forms have?
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)
What kind of effectiveness criteria must dosage forms have?
the drug must meet its claimed therapeutic effect
What are the major factors affecting the dosage form design process
physical form of the drug various physicochemical propertieis target site method of manufacture routes of administration
how does the physical form of the drug affect the dosage design process?
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
how do physicochemical properties of the drug affect the dosage design process?
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)
how does the target site affect the dosage design process?
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
how does the method of manufacture affect the dosage design process?
We have to decide which methods to use e.g. the wet vs. dry method to make granules
how does the route of administration affect the dosage design process?
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
what are some of the excipients used?
solubiliser thickener preservative modifying the solution improving compressability suspender
What are some reasons to add excipients?
may need to enlarge drug volume to ensure proper formulation
excipients need to be inert and must not react with active compound
What is an example of a solubiliser?
bile salt which can enhance solubility for the compound
what is an example of a thickner?
can add certain polymers which thickens the solution to apply to the ear and eye to make it stay as long as possible
what is an example of a preservative?
benzyl paraben, alcohol. these prolong the shelf life
what is an example of a modifier?
bile salt for fast dissolution
viscosity for slow dissolution
what is an example of an excipient which improves the compressability?
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
what is an example of a suspender?
suspending agent.. these can be natural or modified. this prevents the active ingredient from sedimenting at the bottom
Why must the dosage design be predictable, reproducible and able to produce a therapeutic response?
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.
