Enhanced bioavailability of buspirone from reservoir-based transdermal therapeutic system, optimization of formulation employing Box-Behnken statistical design.
The purpose of the present study was to develop and optimize reservoir-based transdermal therapeutic system (TTS) for buspirone (BUSP), a low bioavailable drug. A three-factor, three-level Box-Behnken design was employed to optimize the TTS. Hydroxypropyl methylcellulose, D: -limonene and propylene glycol were varied as independent variables; cumulative amount permeated across rat abdominal skin in 24 h, flux and lag time were selected as dependent variables. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The statistical validity of polynomials was established, and optimized formulation factors were selected by feasibility and grid search. Validation of the optimization study with seven confirmatory runs indicated high degree of prognostic ability of response surface methodology. BUSP-OPT (optimized formulation) showed a flux 104.6 microg cm(-2) h(-1), which could meet target flux. The bioavailability studies in rabbits showed that about 2.65 times improvement (p < 0.05) in bioavailability, after transdermal administration of BUSP-OPT compared to oral solution. The ex vivo-in vivo correlation was found to have biphasic pattern and followed type A correlation. Reservoir-based TTS for BUSP was developed and optimized using Box-Behnken statistical design and could provide an effective treatment in the management of anxiety.
National Facilities in Engineering and Technology with Industrial Collaboration Centre, University College of Pharmaceutical Sciences, Kakatiya University, Warangal, 506 009, Andhra Pradesh, India.
Ramesh
R
Gannu
Chinna Reddy
CR
Palem
Shravan Kumar
SK
Yamsani
Vamshi Vishnu
VV
Yamsani
Madhusudan Rao
MR
Yamsani
D000279:Administration, Cutaneous; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D002065:Buspirone / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003627:Data Interpretation, Statistical; D004337:Drug Carriers / Q000138:chemical synthesis*; D015195:Drug Design; D051381:Rats; D012867:Skin / Q000737:chemistry / Q000378:metabolism*; D012869:Skin Absorption
D014151:Anti-Anxiety Agents; D004337:Drug Carriers; D002065:Buspirone