Bioequivelence Flashcards
what is pharmaceutical equivelence
- contain the same active ingredients
- same dosage form and route of administration
- identical in strength or concentration
describe what occurred in the phenytoin toxicity study
- same dose per capsule
- normal batches were made with CaSO4
- some batches made with lactose
describe what occurred with levothyroxine sodium tablets
- 58 adverse drug reactions
- patients were switching brands
- inconsistencies between batches from same manufacturer
how is bioavailability measured on a graph
area under the curve
what is bioequivelence
2 medicinal products containing the same active substance that are pharmaceutically equivalent or pharmaceutical alternatives and their bioavailabilities after administration in the same molar dose lie within acceptable predefined limits
- these limits are set to ensure comparable in vivo performance
what are the stages that occur after taking a tablet
- disintegration
- dissolution
- diffusion
what is disintegration dependent on
- formulation dependent
- excipients
- diluents
- binders
- disintegrants
- lubricants
- coatings - processes
- mixing
- granulation
- drying
- compaction
- coating
what factors impact dissolution
- water solubility of the drug
- particle size
- salt form
- crystal form
what can cause biological variation between patients
- body weight
- gender
- age
- disease state
- genetic differences
- nutrition and hydration
- other drugs
- stress
- time of administration
what is absolute bioavailability
comparison between blood levels achieved in IV dosing and oral dosing
what is relative bioavailability
comparison between blood levels achieved in standard formulation and in test formulation
when are dosage forms bioequivelent
if their bioavailability doesn’t differ significantly after administration
what are the EMA guidelines on bioequivelence
- acceptance intervals of 80-125%
- 90-111% for narrow therapeutic index drugs - requires 90% confidence intervals between test and reference formulations
what is the biopharmaceutical classification system
- class I
- high solubility
- high permeability - class II
- low solubility
- high permeability - class III
- high solubility
- low permeability - Class IV
- low solubility
- low permeability
what is defined as good or poor water solubility
- soluble >10mg/ml over the physiological pH range
- poorly soluble < 1mg/ml over physiological pH range
describe the effects of Class I drugs in the biopharmaceutical classification system
- dissolution and absorption are rapid
- not generally a problem for bioequivelence
- eg. propanolol, diazepam
describe the effects of Class II drugs in the biopharmaceutical classification system
- dissolution is slow (particle size)
- absorption is rapid
- eg. amiodarone, digoxin
describe the effects of Class III drugs in the biopharmaceutical classification system
- rapid dissolution
- slow absorption
- low log P values may affect permeability
- eg. atenolol, ranitidine
describe the effects of Class IV drugs in the biopharmaceutical classification system
- slow dissolution and absorption
- make prodrugs if possible
- eg. furosemide, allopurinol
outline the formulation approaches that deal with low solubility
- alternative salt forms
- metastable crystalline polymorphic forms
- co-crystals
- complex formation
- cosolvents
- solubilisation by surfactants
- amorphous forms
what structural modifications can be made to deal with low permeability
make a prodrug
- eg. aciclovir has low permeability, valaciclovir has greater bioavailability than aciclovir
what are biosimilars
biological medicine that is similar to another biological medicine that has already been authorised for use
- made from a biological source, such as bacterium or yeast
what are some exceptions to the generic medicines in the NHS
- drugs with narrow therapeutic index
- some antiepileptics
- some modified release products
- certain drug administration devices
- some multi ingredient products
- biosimilars
- special needs- intolerance to excipients
