Comparison of different absorption enhancers on the intranasal absorption of isosorbide dinitrate in rats.

The objective of this work was to study the influence of different absorption enhancers on the intranasal absorption of isosorbide dinitrate (ISDN). First of all, an in situ nasal perfusion technique in rats was used to investigate the effect of pH, concentration of drug solution and different absorption enhancers on the intranasal absorption of ISDN. The absorption enhancers investigated include hydroxypropyl-beta-cyclodextrin (HP-beta-CD), chitosans (CS) of different molecular weight, and poloxamer 188. All of them enhanced the intranasal absorption of ISDN remarkably. It was found that poloxamer 188 had better permeation enhancing effect than that of HP-beta-CD and CS of the same concentration. Thereafter, in vivo behaviors of the selected formulations were studied in rats and the pharmacokinetic parameters were calculated and compared with that of intravenous injection. Both in situ and in vivo studies demonstrated that poloxamer 188 played a key role in promoting intranasal absorption of ISDN. In nasal ciliotoxicity test, all the absorption enhancers investigated showed good safety profiles. Taking both enhancing effect and safety into account, we suggest poloxamer 188 is the most promising as an intranasal absorption enhancer.