Optimization of Systemic Nasal Delivery of Progesterone using Polyacrylic Acid Based Gels

Abstract

In this study, CDs significantly enhanced the nasal absorption of progesterone in rabbits. From these results it is suggested that the absorption enhancing effect is mediated through the solubility enhancing and permeation enhancing properties of the CDs. Similar results have been reported by Henry131 et al in which dimethyl-and#946;-cyclodextrin is used in nasal product containing 17-and#946;-estradiol. The solubilized 17-and#946;-estradiol gave significantly higher nasal bioavailability in rabbits as compared to non-suspension formulations. A similar work by Merkus145 et al demonstrated that formulation in which dimethyl-and#946;-cyclodextrin was used to solubilize progesterone for nasal delivery has been tested in human volunteers and has been shown to result in blood levels of progesterone comparable to those after intravenous administration. In addition to the solubilizing and stabilizing effects of the cyclodextrins, these materials may also have an absorption enhancing effect on the nasal membrane. Gu72 et al investigated the solubilization of prostaglandin with hydroxypropyl and#946;-cyclodextrin. The complex first increased the solubility and stability of the drug which lead to increase in bioavailbility to 25% on nasal administration. In this study the effect of the CDs on the integrity of nasal mucosa was evaluated and found to be safe. This was similarly demonstrated in the study by Kazunori121 et al who showed that there was no tissue damage with 1.5% and#946;-cyclodextrin and 10% hydroxypropyl and#946;-cyclodextrin. This work stives to show the effect of the method of addition of CDs on the absorption enhancement properties on the nasal mucosa. The progesterone absorption-enhancing effect of CDs showed a trend towards its method of addition either as a complex or as a physical mixture. In this study detailed characterizations of the formulations along with toxicological and bioavailability studies are carried out in animals which has been promising. However there is a tendency for the absorption promoting effect to be different in larger animals.