Development of the ambroxol gels for enhanced transdermal delivery.
Ambroxol is an expectoration improver and mucolytic agent that has been used to treat acute and chronic disorders. However, ambroxol needs to be administered percutaneously in order to avoid systemic adverse effects, such as headache, drowsiness, dizziness, and insomnia, which can occur after oral administration. The aim of this study was to develop a gel preparation containing a permeation enhancer to enhance the delivery of ambroxol. The ambroxol gels were prepared using hydroxypropyl methylcellulose (HPMC) and poloxamer 407. The release characteristics of the drug from the gels were examined according to the receptor medium, drug concentration, and temperature. The rate of drug permeation into the skin was enhanced by incorporating various enhancers such as the ethylene glycols, the propylene glycols, the glycerides, the non-ionic surfactants, and the fatty acids into the gels. The permeation study through mouse skin was examined at 37 C. The rate of drug release increased with increasing drug concentration and temperature. Among the enhancers used, propylene glycol mono caprylate showed the best enhancing effects. The estimated activation energy of release (Ea), which was calculated from the slope of a log P versus 1000/T plot, was 14.80, 14.22, 13.91, and 12.46 kcal/mol for ambroxol loading doses of 2, 3, 4, and 5%, respectively. The results of this study show that the gel preparation of ambroxol containing a permeation enhancer could be developed for the enhanced transdermal delivery of ambroxol.
Cho
Cheong-Weon
CW
College of Pharmacy, Chungnam National University, Daejeon, Korea.
Choi
Jun-Shik
JS
Shin
Sang-Chul
SC
D000279:Administration, Cutaneous; D000551:Ambroxol / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D004337:Drug Carriers / Q000737:chemistry; D005026:Ethylene Glycols / Q000737:chemistry; D005079:Excipients / Q000737:chemistry*; D005100:Expectorants / Q000737:chemistry / Q000493:pharmacokinetics*; D005227:Fatty Acids / Q000737:chemistry; D005782:Gels; D005989:Glycerides / Q000737:chemistry; D065347:Hypromellose Derivatives; D066298:In Vitro Techniques; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D020442:Poloxamer / Q000737:chemistry; D011409:Propylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption; D013696:Temperature
D004337:Drug Carriers; D005026:Ethylene Glycols; D005079:Excipients; D005100:Expectorants; D005227:Fatty Acids; D005782:Gels; D005989:Glycerides; D011409:Propylene Glycols; D020442:Poloxamer; D000551:Ambroxol; D065347:Hypromellose Derivatives; D008747:Methylcellulose