formulations -water

explain what happens when you take a solid dosage form

If you take a tablet dosage form it enters the gi tract and the tablet will

1.disintegrate

2.from the smaller bits of tablet which are disperesed the API will dissolve out of the solid form into the liquid

3if you have a non-dissocating dosage form the API will go straight into the gi

the drug has to be in a solution for what reasons.

-it will have no effect if you cannot get the drug to dissolve into the fluid of the GI tract

-if the drug is not in the solution It will NOT pass through the gi walll and wont reach the receptors that it has to attach to

The drug HAS to be in a solution before it can be absorbed

-it will simply pass through the body

where does adsorbtion usually take place

the absorption occurs mainly in the small intestine

-largest surface area and microvilli

the faster the rate of dissolution ...

, the faster the rate of absorption

what is the advantage of the drug bein in a solution for administration

You can leapfrog some of the process that you must undergo in a solid s=dosage form

If the drug is already in the solution it can skip the dissolution step and can be moire quickly adsorbed as it is already present in the solution

what are the 2 types of liquid dosage forms

suspension and solutions

what is the drug in a solution

FULLY DISSOLVED

what is a suspension

-the drug is presented in a finely disperesed

how does a suspension still have an advantage over the solid dosage form

Small sized particles dissolve more rapidlfy

what is the critical thing you have to do

AQUEAOUS SOLUBILITY of the drug in water

If the drug at the conc you want to get in the solution is very solubule it is very easy to make the slution

advantages of oral dosage forms -swallowing

Liquids are easier to swallow than tablets/capsules

(infant, paediatric, geriatric and some psychiatric patients can't swallow solid dosage forms)

advantages of oral dosage forms -

badly behaved patients

Some patients administered oral liquids to prevent them placing tablets/capsules under the tongue and not swallowing them at time of administration

advantages of oral dosage forms - dose strength

Offer a wide variety of dosage forms and dosage strengths-you can alter the dose given by altering the liquid

advantages of oral dosage forms -

low potency

The bulk of some preparations make oral liquids more feasible/more suitable product

-if you have a low potency drug and a lot needs to be given in a single dose it may not be able to be given in a tablet and they may need to take 2/3 large tablets

advantages of oral dosage forms -theraputic response

Faster therapeutic response than with solid dosage form-no need to wait for disintegration and dissolution

advantages of oral dosage forms -

git irritation

Reduced irritation of GIT by certain drugs if admin. as solution due to immediate dilution by gastric contents

disadvantage of oral dosage forms -

transport

Liquids are bulky - inconvenient to transport and store

disadvantage of oral dosage forms -stability

Stability may be poorer (e.g. by hydrolysis) than if formulated as solid dosage form

disadvantage of oral dosage forms -

bacteria

Aqueous liquids

- suitable media for micro-organism growth

- need to incorporate a preservative

-liquid formulations are more prone to bacterial growth

disadvantage of oral dosage forms -

paient dosage

Accurate dosage requires patient to use a 5/2.5ml spoon or volumetric dropper/graduated syringe-the pateint/carrer has a responsibility

disadvantage of oral dosage forms -

taste

The taste of a drug will be more pronounced when in solution than when in solid form - use sweeteners and flavours to make more palatable

define a liquid oral prepration

Liquid preparations for oral use are usually solutions, emulsions(can be oral liquid formulations,topical formulations such as creams comprised of an oily phase and a water phase with a dispersion of one in the other,the API can be in the water or the oily phase) or suspensions containing one or more active substances in a suitable vehicle; they may, however, consist of liquid active substances used as such (oral liquids). Ph Eur, BP

what is the most commoly used liquid in oral liquid preparations

water

why is water used in most oral liquid preprations

Lack of toxicity-very inert

- Physiological compatibility

- Ability to dissolve/(suspend) a wide range of materials

what can water also be used for in the pharma industry

cleaning pipes and vesels

water without qualification

this means either potable water (drinking water)freshly drawn direct from the public supply and suitable for drinking or freshly boiled and cooled 'Purified Water BP'. The latter should be used if the public supply is from a local storage tank or if the potable water is unsuitable for a particular preparation.

water BP

The BP states that Purified Water BP is to be used in this case.

Purified Water BP is equivalent to Purified Water Ph Eur [European Pharmacopoeia])

what is potable water

drinking water

potable water must be ...

Must be palatable, safe to drink, clear, colourless, odourless and tasteless, free from toxic substances, pathogenic organisms and excessive amounts of certain other materials.

what are there restricitions on in potable water

arsenic, barium, cadmium, chromium, copper, cyanide, lead, selenium, fluoride and nitrates.

when can potable water not be used

i) Precipitates may be formed when hard water* is used.

(ii) The colour of some pharmaceutical mixtures varies due to variation in water pH (which is affected by presence of salts).

(iii) The calcium* present can affect the gelling power/viscosity of some gelling/suspending agents, e.g. pectin and alginate dispersions.

what are the types of impurites found in water

Fully dissolved impurities

Particulate matter:

• Colloidal matter:

microfunghi

what are fully dissolved impurities

organic e.g. carbohydrates and inorganic e.g. salts.

what is particulate matter

this includes suspended solids of various types.

what is collodial matter

particles from about 0.005 to 0.2 µm (i.e. 5 to 200 nm) which tend not to sediment.

They are so small they don't settle under gravity but they are held in the liquid by brownian motion holding the molecules in the suspension

define purified water

Water for the preparation of medicinal products other than those that are required to be both sterile and apyrogenic, unless otherwise justified and authorised.

define "apyrogenic"

"apyrogenic" = free from pyrogens. A pyrogen is a substance that causes fever/febrile reaction.

what is purified water in bulk

A clear, colourless, odourless and tasteless liquid

how do you get purified water in bulk

prepared from suitable potable water either by distillation or by treatment with ion-exchange materials or any other suitable method.

what is purified water in bulk used for

nonparenteral liquid preparations and in other pharmaceutical applications, such as the cleaning of nonparenteral product-contact components and equipment.

what are the tests on purified water in bulk

aerobic count

organic carbon

nitrates

aerobic count specification

Total viable aerobic count of no more than 100 micro-organisms per milliliter (100 CFU(colony forming units)/ml)

organic carbon

Total organic carbon (limit of 0.5 mg/L) or oxidisable substances S.cm-1 ) measures the amount of ions in the water

what are endotoxins

* Endotoxins are part of the outer membrane of the cell wall of Gram-negative bacteria and are released upon cell lysis.

THEY ARE NOT MICROORGANISIMS

are endotoxins pyrogenic

can be pyrogenic - cause a febrile reaction (and low blood pressure, increased heart rate, low urine output) if they get into the blood stream.

what is purified water in containers

It is Purified Water in Bulk that has been filled and stored in conditions designed to assure the required microbiological quality and is free from any added substances.

what are the tests carried out for purified water in containers

- Acidity or alkalinity

- Oxidisable substances

- Residue on evaporation (not more than 0.001%)

- Limit tests for chlorides, sulphates, ammonium, calcium and magnesium, bacterial endotoxin content (if for use in the manufacture of dialysis solutions)