Absorption Models of Drug Delivery

Abstract

The absorption of drugs. ‘was. studied -using two
absorption models, the goldfish and excised skin. The
method of drug analysis was high performance liquid
chromatography (HPLC).

The technique used for monitoring goldfish absorption
was an improvement over the earlier reported pharmacological
endpoints of turnover and death time by employing HPLC
analysis of the bathing media. Using a series of n-alkyl
salicylate esters the absorption rate constants were
directly correlated to the octanol/water partition
coefficients “of “the «esters: The fish were able to
metabolise hydrocortisone=2l—acetate and hydrocortiso—n2]ebutyrate
but did not affect hydrocortisone—l17— butyrate.
The effect of bathing media pH on the absorption of
phenylbutazone was studied using fixed and nonisopH methods.
The resultant absorption-pH profiles obey the pH-partition
hypothesis.

The penetration of a series of p-aminobenzoic acid
esters was monitored through excised human skin and silastic
membranes. An aqueous’ propylene glycol vehicle ensured
rapid penetration of the higher esters while a lipophilic
vehicle, white soft paraffin, resulted in slower penetration
of the longer chained esters. An attempt was made to
correlate percutaneous absorption of these drugs with
reported turnover times for goldfish, a reasonable linear
relationship resulted with correlation coefficients better
than 0.9 7.

The penetration of ibuprofen and naproxen was monitored
through *,excised "rat, 4 skin. Ibuprofen suspensions and
solutions were used to study the effect of vehicle pH on
penetration rates. For the solutions the pH effect was
related to the degree of ionisation of the drug and more
importantly to the degree of saturation of the solution. If
suspensions of ibuprofen were used no effect on penetration
was noted. except at extreme pH values. The effect of
increasing concentration of a cosolvent, propylene glycol,
was studied and the increase in penetration related to an
increase in soluba 11 ty; and reduction of partition
coefficient. N,N-dimethylamides were formulated in the
ibuprofen and naproxen suspensions and
N,N-dimethyldecanamide increased steady state flux two and
ten fold respectively. This increase in flux was related to
an increase in skin partition of the drug and penetration
rate of the enhancer, N,N-dimethyldecanamide.

Date of Award	1986
Original language	English