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


METHODS
In vivo study in rats.


METHODS
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.


METHODS
Rats of proven fertility.


METHODS
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.


METHODS
Plasma drug concentration and pharmacokinetics.


RESULTS
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.


CONCLUSIONS
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.
Shahiwala
Aliasgar
A
Pharmacy Department, Faculty of Technology and Engineering, M.S. University of Baroda, Kalabhavan, Vadodara-390 001, Gujarat, India.
Misra
Ambikanandan
A
D000042:Absorption / Q000187:drug effects; D000180:Acrylic Resins; D000277:Adjuvants, Pharmaceutic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002686:Chitin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D048271:Chitosan; D003271:Contraceptive Agents, Female / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage; D005260:Female; D006207:Half-Life; D016912:Levonorgestrel / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D008081:Liposomes; D009296:Nasal Cavity / Q000378:metabolism; D011145:Polyvinyls / Q000008:administration & dosage; D051381:Rats
D000180:Acrylic Resins; D000277:Adjuvants, Pharmaceutic; D003271:Contraceptive Agents, Female; D004337:Drug Carriers; D008081:Liposomes; D011145:Polyvinyls; C006912:carboxypolymethylene; D002686:Chitin; D016912:Levonorgestrel; D048271:Chitosan