Bioavailability enhancement of baclofen by gastroretentive floating formulation: statistical optimization, in vitro and in vivo pharmacokinetic studies. (June 2013)

• Record Type: Journal Article
• Authors: Thakar, Krishna; Joshi, Garima; Sawant, Krutika K.
• Is Part Of: Drug development and industrial pharmacy. Volume 39:Number 6(2013:Jun.)
• Page Start: 880
• Page End: 888
• Publication Date: 2013-06
• Subjects: Pharmaceutical chemistry -- Periodicals; Pharmaceutical industry -- Periodicals; Drug Industry -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615.05
• DOI: 10.3109/03639045.2012.709249
• Languages: English
• ISSNs: 0363-9045

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic>Objectives</italic>: The study was aimed to improve bioavailability of baclofen by developing gastroretentive floating drug delivery system (GFDDS).</p> <p> <italic>Methods</italic>: Preliminary optimization was done to select various release retardants to obtain minimum floating lag time, maximum floating duration and sustained release. Optimization by 3<sup>2</sup> factorial design was done using Polyox WSR 303 (X<sub>1</sub>) and HPMC K<sub>4</sub>M (X<sub>2</sub>) as independent variables and cumulative percentage drug released at 6 h (Q6h) as dependent variable.</p> <p> <italic>Results</italic>: Optimized formulation showed floating lag time of 4–5 s, floated for more than 12 h and released the drug in sustained manner. <italic>In vitro</italic> release followed zero ordered kinetics and when fitted to Korsemeyer Peppas model, indicated drug release by combination of diffusion as well as chain relaxation. <italic>In vivo</italic> floatability study confirmed floatation for more than 6 h. <italic>In vivo</italic> pharmacokinetic studies in rabbits showed <italic>C</italic><sub>max</sub> of 189.96 ± 13.04 ng/mL and <italic>T</italic><sub>max</sub> of 4 ± 0.35 h for GFDDS. The difference for AUC<sub>(0–T)</sub> and AUC<sub>(0–∞)</sub> between the test and reference formulation was statistically significant (<italic>p</italic> > 0.05). AUC<sub>(0–T)</sub> and AUC<sub>(0–∞)</sub> for GFDDS was 2.34 and 2.43 times greater than the marketed formulation respectively.</p> <p> <italic>Conclusion</italic>: GFDDS provided prolonged gastric residence and showed significant increase in bi oavailability of baclofen.</p> </abstract>