Baclofen novel gastroretentive extended release gellan gum superporous hydrogel hybrid system: in vitro and in vivo evaluation.
Baclofen is a centrally acting skeletal muscle relaxant with a short elimination half-life, which results in frequent daily dosing and subsequent poor patient compliance. The narrow absorption window of baclofen in the upper gastrointestinal tract limits its formulation as extended release dosage forms. In this study, baclofen extended release superporous hydrogel (SPH) systems, including conventional SPH, SPH composite and SPH hybrid (SPHH), were prepared aiming to increase the residence of baclofen at its absorption window. The applicability of different polymers, namely, gellan gum, guar gum, polyvinyl alcohol and gelatin, was investigated in preparation of SPHH systems. The prepared SPH systems were evaluated regarding weight and volume swelling ratio, porosity, mechanical properties, incorporation efficiency, degree of erosion and drug release. In vivo assessment was performed in dogs to evaluate gastric residence time by X-ray studies. In addition, the oral bioavailability of baclofen relative to commercially available Lioresal® immediate release tablets was also investigated. The novel baclofen gellan SPHH cross linked with calcium chloride was characterized by optimum mechanical properties, acceptable swelling properties as well as extended drug release. It also exhibited a prolonged plasma profile when compared to twice daily administered Lioresal®.
a Department of Pharmaceutics and Industrial pharmacy, Faculty of Pharmacy , Cairo University , Cairo , Egypt and.
Ibrahim A
IA
El-Said
a Department of Pharmaceutics and Industrial pharmacy, Faculty of Pharmacy , Cairo University , Cairo , Egypt and.
Ahmed A
AA
Aboelwafa
b Department of Pharmaceutical technology , National Research Center , Cairo , Egypt.
Rawia M
RM
Khalil
a Department of Pharmaceutics and Industrial pharmacy, Faculty of Pharmacy , Cairo University , Cairo , Egypt and.
Omaima N
ON
ElGazayerly
D000818:Animals; D001418:Baclofen / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002122:Calcium Chloride / Q000737:chemistry; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D004285:Dogs; D005079:Excipients; D018755:GABA Agonists / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D020100:Hydrogels; D007408:Intestinal Absorption; D011135:Polysaccharides, Bacterial; D016062:Porosity; D013607:Tablets; D013718:Tensile Strength
D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D005079:Excipients; D018755:GABA Agonists; D020100:Hydrogels; D011135:Polysaccharides, Bacterial; D013607:Tablets; C048288:gellan gum; D001418:Baclofen; D002122:Calcium Chloride
Baclofen; dogs; gastroretentive; gellan gum; pharmacokinetics; superporous