L2 Preformulation Flashcards
Post 1990 formulation leads found through….
High throughput screening(HTS)
Four sources of lead identification pre 1990
Seredipity
Tradition remedies eg. Atropine
Rational design (analogues of knows)
Natural products
Three reasons introducing oral activity is unpredictable in HTS?
Increasing Mr
Decreasing solubitliy
Increasing lipophilicity
Size of assay in automated HTS?
1microL
How many samples can we assay in automated HTS each day?
Thousands
Automated HTS measures mainly …. But also (3)
Pharmacological activity (major)
Pharmacokinetics
Metabolism
Toxicity
How do we optimise the chemical lead?
testing a range of selected compounds in in vitro and in vivo (animal) studies (Pharmacological and toxipharmacological assessment) (2 – 3 years).
For a range of possible compounds with similar pharmacological and toxicological profiles ……… properties will govern the selection criteria for lead identification.
Pharmaceutical
We can only ever make statements of correlation between
Attributes and functionality
define preformulation
Preformulation is the physicochemical characterisation of the properties of the compounds.
Aim of preformulation?
The overall objective of preformulation testing is to generate information useful to the formulator in developing stable and bioavailable dosage forms that can be mass produced
Produce a mathematical model for drug behaviour when formulated
To provide an initial working model of behaviour of dosage form in vitro and in vivo
API
Active pharmaceutical ingredient
Why understand the solubility and stability of the API? (2)
Increase shelf life and inhibit decomposition of the product
How much compound is provided for preformulation studies?
Very little (eg 50mg)
