Optimization of self-nanoemulsifying systems for the enhancement of in vivo hypoglycemic efficacy of glimepiride transdermal patches.
OBJECTIVE
To optimize and use of glimepiride (GMD)-loaded self-nanoemulsifying delivery systems (SNEDs) for the preparation of transdermal patches.


METHODS
Mixture design was utilized to optimize GMD-loaded SNEDs in acidic and aqueous pH media. Optimized GMD-loaded SNEDs were used in the preparation of chitosan (acidic) and hydroxypropyl methyl cellulose (HPMC) (aqueous) films. The prepared optimized formulations were investigated for ex vivo skin permeation, for in vivo hypoglycemic activity and for their pharmacokinetic parameters using animal model.


RESULTS
The optimized formulations showed flux value of (2.88 and 4.428 μg/cm(2)/h) through rat skin for chitosan and HPMC films, respectively. The pattern of GMD release from both formulations was in favor of Higuchi and approaching zero order models. The n values for Korsmeyer-Peppas equation were characteristic of anomalous (non-Fickian) release mechanism. Moreover, HPMC patches have shown significant reductions (p < 0.05) in blood glucose levels; (213.33 ± 15.19) mg/100 ml from the base-line measurement after 12 h of application.


CONCLUSIONS
Optimized GMD SNEDs patches were found to improve GMD skin permeability and the essential pharmacokinetic parameters. Further extensive pre/clinical studies are necessary prior to use transdermal GMD as a valuable alternative to peroral dosage forms with improved bioavailability, longer duration of action and more patient convenience.
King Abdulaziz University, Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Jeddah-21589 , Saudi Arabia +966 599120686 ; +966 26951696 ; oaahmed@kau.edu.sa , osama712000@gmail.com.
Osama A A
OA
Ahmed
Mohsen I
MI
Afouna
Khalid M
KM
El-Say
Ashraf B
AB
Abdel-Naim
Alaa
A
Khedr
Zainy M
ZM
Banjar
D000279:Administration, Cutaneous; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D004655:Emulsions / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D065347:Hypromellose Derivatives; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects; D013453:Sulfonylurea Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D057968:Transdermal Patch
D004655:Emulsions; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D065347:Hypromellose Derivatives; C057619:glimepiride; D008747:Methylcellulose; D048271:Chitosan
chitosan; glimepiride; hydroxypropyl methyl cellulose; mixture design; self-nanoemulsifying delivery systems; transdermal film