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 acidesters 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 betterthan 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 wasrelated 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 theibuprofen 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	Oct 1986
Original language	English
Awarding Institution	Aston University