Nasal delivery of levonorgestrel for contraception: an experimental study in rats

Abstract

Objective: To ascertain the nasal bioavailability of Levonorgestrel and change formulation components to provide long-term effective concentrations of the drug in blood. An experimental study was conducted on rats to reduce dose and/or frequency of drug administration to reduce expected side effects reported in humans.

Design: In vivo study in rats.

Setting: Centre of Relevance & Excellence in new drug delivery systems, Pharmacy Dept., G.H. Patel Budg., Faculty of Technology and Engineering, M.S. University of Baruda, Fatehgunj, Vadodara, Gujarat, India.

Animal(s): Rats of proven fertility.

Intervention(s): Formulations containing 10-microg of levonorgestrel were administered in rats via the nasal route. Similarly, a 10-microg drug suspension was administered orally. The influence of the mucoadhesive agents chitosan and carbopol 934p on nasal absorption of the drug was also evaluated.

Main outcome measure(s): Plasma drug concentration and pharmacokinetics.

Result(s): Relative bioavailabilities of 29.93%, 32.14%, and 25.97% were observed after nasal administration of plain drug, physical mixture, and liposomal formulations, respectively. Mucoadhesive agents in nasal formulations were found to produce a threefold increase in drug bioavailability. Bioavailability was improved from 29.93% to 101.70% and 99.42%, respectively, for chitosan (0.5%) and carbopol 934p (0.5%) formulations, with a significantly improved plasma half life from 7.0 hours to 55.7 hours and 52.9 hours, respectively. Pharmacodynamic studies indicate that the dosing interval can be changed from daily oral administration to nasal administration once every 2 days without changing the dose.

Conclusion(s): Levonorgestrel with mucoadhesive agents administered nasally in rats is superior for maintaining effective drug concentrations over an extended period of time when compared with the presently available orally administered form.