title: QbD-Oriented Development and Characterization of Effervescent Floating-Bioadhesive Tablets of Cefuroxime Axetil.
abstract: The objective of the present studies was systematic development of floating-bioadhesive gastroretentive tablets of cefuroxime axetil employing rational blend of hydrophilic polymers for attaining controlled release drug delivery. As per the QbD-based approach, the patient-centric target product profile and quality attributes of tablet were earmarked, and preliminary studies were conducted for screening the suitability of type of polymers, polymer ratio, granulation technique, and granulation time for formulation of tablets. A face-centered cubic design (FCCD) was employed for optimization of the critical material attributes, i.e., concentration of release controlling polymers, PEO 303 and HPMC K100 LV CR, and evaluating in vitro buoyancy, drug release, and ex vivo mucoadhesion strength. The optimized formulation was embarked upon through numerical optimization, which yield excellent floatation characteristic with drug release control (i.e., T 60% > 6 h) and bioadhesion strength. Drug-excipient compatibility studies through FTIR and P-XRD revealed the absence of any interaction between the drug and polymers. In vivo evaluation of the gastroretentive characteristics through X-ray imaging and in vivo pharmacokinetic studies in rabbits revealed significant extension in the rate of drug absorption (i.e., T max, K a, and MRT) from the optimized tablet formulation as compared to the marketed formulation. Successful establishment of various levels of in vitro/in vivo correlations (IVIVC) substantiated high degree of prognostic ability of in vitro dissolution conditions in predicting the in vivo performance. In a nutshell, the studies demonstrate successful development of the once-a-day gastroretentive formulations of cefuroxime axetil with controlled drug release profile and improved compliance.
authors.affiliation: Maharishi Markandeshwar College of Pharmacy, Maharishi Markandeshwar University, Mullana, Ambala, Haryana, 133 207, India.|Department of Pharmacy, MCP College, Jalandhar City, Punjab, 144 008, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Bansal
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, UGC Center for Excellence in Nano Applications, Panjab University, Chandigarh, 160 014, India.
authors.forename: Sarwar
authors.initials: S
authors.lastname: Beg
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, UGC Center for Excellence in Nano Applications, Panjab University, Chandigarh, 160 014, India.
authors.forename: Babita
authors.initials: B
authors.lastname: Garg
authors.affiliation: Maharishi Markandeshwar College of Pharmacy, Maharishi Markandeshwar University, Mullana, Ambala, Haryana, 133 207, India. abhaypharmacy@gmail.com.
authors.forename: Abhay
authors.initials: A
authors.lastname: Asthana
authors.affiliation: Maharishi Markandeshwar College of Pharmacy, Maharishi Markandeshwar University, Mullana, Ambala, Haryana, 133 207, India.
authors.forename: Gyati S
authors.initials: GS
authors.lastname: Asthana
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, UGC Center for Excellence in Nano Applications, Panjab University, Chandigarh, 160 014, India. bsbhoop@yahoo.com.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Singh
mesh_terms: D000269:Adhesives / Q000737:chemistry* / Q000378:metabolism*; D000818:Animals; D002444:Cefuroxime / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry; D005753:Gastric Mucosa / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D011108:Polymers / Q000737:chemistry; D011817:Rabbits; D012995:Solubility; D013607:Tablets / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D000269:Adhesives; D003692:Delayed-Action Preparations; D005079:Excipients; D011108:Polymers; D013607:Tablets; D002444:Cefuroxime; C040738:cefuroxime axetil
keywords: drug release; gastroretentive; mucoadhesion; quality by design; x-ray imaging