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.