increasing the permeability Flashcards
why are the majority of immediate release drugs are in the oral form?
– Higher patient compliance than other routes
and other dosage forms.
– Simple and convenient administration.
– Fast and cost-effective manufacturing
compared to other dosage forms
what is the BCS
a mean of classifying drugs based
on their solubility and permeability.
what does the absorption need to happen?
– The drug must be in molecular form.
– The drug must have sufficient permeability to cross
the plasma membrane of epithelial cells.
When a rapid onset of action is required from a solid
dosage form:
↑ solubility & ↑ dissolution + ↑ permeability.
what are the BCS classes
class 1 high solubility and permeability
class 2 low solubility and high permeability
class 3 high solubility and low permeability
class 4 low solubility and permeability
what are the two factors that affect the BCS classes
- Solubility: the drug substance is considered highly
soluble if:
– The highest dose strength is soluble in < 250 ml
water over a pH range of 1 -7. - Permeability: the drug substance is considered highly
permeable if:
– The absorption in humans is > 90% of an
administered dose
remember
permeability is KD\h
rate of absorption = PAC
what does the passive absorption of the drug depends on
– The drug concentration (Cd)
– The area of absorptive tissue (A)
– The physicochemical properties of the drug (K
& D).
we can predict the bad drug absorption based on the rule of 5, what is the rule of 5?
poor absorption might happen if the drug have
- More than five hydrogen bond donor groups
- A molecular weight over five hundred (500
Daltons) - A partition coefficient over five (log P)
- A sum of nitrogen and oxygen atoms in the
molecule over ten (2 times five)
the rule of 5 is a prediction and drugs with active transport wont follow it
ok
what is class 1 (high , high)
– Most suitable for immediate release dosage forms
– The absorption rate is higher than elimination rate
– With the addition of appropriate excipients and suitable
formulation procedure delayed, sustained and
controlled dosage forms can be developed.
what is class 2 (bad solubility high permeability)
– Limited bioavailability due to poor solubility and/or poor
dissolution.
– Special formulation approaches are used to improve the
solubility or the dissolution rate of such drugs
what are class 3 and 4
– Very challenging
– Permeability of such drugs can not be
changed by formulation approaches
– If a high dose is required (high plasma
concentration) it is not possible to develop
these drugs.
– If high dose is required, the best option is to
optimize the chemical structure (and thus
physicochemical properties) to improve the
absorption a new chemical entity has to be
synthesized and developed.
give examples on some class 4 and 3 drugs
• Class IV
– HCTZ : maximum dose =100 mg/day and oral bioav =
~ 55% (variable, formulation and dose dependent)
– Taxol: Given IV, oral bioav = 6.5%
– Cyclosporine: maximum dose = 5 mg/kg/day
(psoriasis) and oral bioav = ~ 30% (10 – 60%)
• Class III
– Acyclovir : maximum dose = 800 mg x 5 daily and oral
bioav = ~ 10 -20%. (solubility = 2.5 mg/ml)
– Captopril: maximum dose =300 mg and oral bioav = ~
70 - 75%. (solubility = 160 mg/ml, short t0.5)
– Cimetidine: maximum dose = 800 mg and oral bioav
= ~ 60 - 70%. (the HCL salt is freely soluble in water,
short t0.5)
in the case of digoxin and griseovulvin
– Both drugs are BCS class II
– It is much easier to solve the solubility (and dissolution)
problem of digoxin compared to Griseofulvin.
– A complete intestinal absorption is expected when
digoxin is micronized, but it is not the case for
Griseofulvin