In vitro and in vivo evaluation of a hydrogel-based prototype transdermal patch system of alfuzosin hydrochloride.
The first-line therapy for moderate to severe benign prostatic hyperplasia is the oral therapy by alfuzosin hydrochloride. Unfortunately, the oral therapy of alfuzosin is associated with several route-specific systemic side-effects. The current study was aimed to develop a prototype transdermal patch system for alfuzosin using a hydrogel polymer and optimize the drug delivery through the skin for systemic therapy. The prospective of different chemical enhancers (polyethylene glycol (PEG 400), isopropyl myristate, propylene glycol, menthol and L-methionine; 5% w/v) and iontophoresis (0.3 mA/cm(2)) in the alfuzosin delivery across the full thickness rat skin was assessed in vitro. In vivo iontophoretic studies were carried out using selected patch system (PEG 400) for a period of 6 h in Sprague-Dawley rats. Passive permeation studies indicated that the incorporation of chemical agents have moderate effect (~4- to 7-fold) on the alfuzosin skin permeability and reduced the lag time. Combined approach of iontophoresis with chemical enhancers significantly augmented the drug transport (~ 43- to 72-fold). In vivo pharmacokinetic parameters revealed that the iontophoresis (transdermal patch with PEG 400) significantly enhanced the C(max) (~ 3-fold) and AUC(0-α) (~ 4-fold), when compared to control. The current study concludes that the application of iontophoresis (0.3 mA/cm(2)) using the newly developed agaorse-based prototype patch with PEG 400 could be utilized for the successful delivery of alfuzosin by transdermal route.
Nair
Anroop B
AB
M. M. College of Pharmacy, M. M. University, Ambala, India.
Vaka
Siva Ram Kiran
SR
Gupta
Sumit
S
Repka
Michael A
MA
Murthy
S Narasimha
SN
D000279:Administration, Cutaneous; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000818:Animals; D004867:Equipment Design; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D007478:Iontophoresis; D008297:Male; D011470:Prostatic Hyperplasia / Q000188:drug therapy; D011799:Quinazolines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D057968:Transdermal Patch
D058668:Adrenergic alpha-1 Receptor Antagonists; D011799:Quinazolines; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; C047638:alfuzosin