Grace, Rathnam (2009) Optimization of Systemic Nasal Delivery of Progesterone using Polyacrylic Acid Based Gels. Doctoral thesis, The Tamilnadu Dr. M.G.R. Medical University, Chennai.
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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-β-cyclodextrin is used in nasal product containing 17-β-estradiol. The solubilized 17-β-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-β-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 β-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% β-cyclodextrin and 10% hydroxypropyl β-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. Gels have been used for quite a long time as drug carriers and recent advances in gel and polymer technology have attracted researchers’ interest in these polymeric systems. The nasal route was no exception. The nasal route for administration of gels for systemic delivery of progesterone is proved to be an effective mode of drug delivery. The increased bioavailability of progesterone following nasal instillation of the gel formulation using bioadhesive PAA polymers along with beta cyclodextrin and hydroxypropyl beta cyclodextrin, together with observed minor toxicity demonstrate the potential of these nasal gels to systemically deliver the hormone. PAA polymers are a promising drug delivery system for the steroidal hormone progesterone, which enhances nasal residence time owing to increased viscosity and mucoadhesive characteristics; furthermore PAA polymers along with absorption enhancers beta cyclodextrin and hydroxypropyl beta cyclodextrin exhibit permeation enhancing effect. Gels for nasal delivery require careful study because of the special delivery required. According to this work the formulative approaches for improving nasal delivery of progesterone consist in the use of suitable absorption enhancers. As cyclodextrins were chosen for absorption enhancement, the method of addition is important to the study. Statistical optimization reveals that addition of cyclodextrins as an inclusion complex with the drug in the gels significantly affects the absorption profile. In vivo studies in rabbits for nasal absorption of progesterone show a rapid increase in plasma levels and promising bioavailability values. Hence the formulations represent a promising and novel tool for the nasal delivery of progesterone and can be used instead of injectables for the administration of the hormone. As drugs and biotechnology markets continue to grow, in the future we should expect a range of novel nasal products to escalate in the market. It is envisaged that these products will be used in crisis management as well as in treatment of long term conditions. Most of the drugs which will be available as nasal products in the future, are those, which at present are given as injections or have a low bioavailability and display unwanted pharmacological effects due to inappropriate dosing regimen. 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. Accordingly, investigations in humans are necessary in order to prove the pharmaceutical performance and allow excellence of clinical outcome.
| Item Type: | Thesis (Doctoral) |
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| Uncontrolled Keywords: | Optimization, Systemic nasal delivery, Progesterone, Polyacrylic acid based gels. |
| Subjects: | PHARMACY > Pharmacy Practice |
| Depositing User: | Devi S |
| Date Deposited: | 22 Jun 2017 10:42 |
| Last Modified: | 16 Sep 2022 01:36 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/259 |
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