title: QbD-enabled systematic development of gastroretentive multiple-unit microballoons of itopride hydrochloride.
abstract: The objectives of present studies were to develop the systematically optimized multiple-unit gastroretentive microballoons, i.e. hollow microspheres of itopride hydrochloride (ITH) employing quality by design (QbD)-based approach. Initially, the patient-centric QTPP and CQAs were earmarked, and preliminary studies were conducted to screen the suitable polymer, solvent, solvent ratio, pH and temperature conditions. Microspheres were prepared by non-aqueous solvent evaporation method employing Eudragit S-100. Risk assessment studies carried out by constructing Ishikawa cause-effect fish-bone diagram, and techniques like risk estimation matrix (REM) and failure mode effect analysis (FMEA) facilitated the selection of plausible factors affecting the drug product CQAs, i.e. percent yield, entrapment efficiency (EE) and percent buoyancy. A 3(3) Box-Behnken design (BBD) was employed for optimizing CMAs and CPPs selected during factor screening studies employing Taguchi design, i.e. drug-polymer ratio (X1), stirring temperature (X2) and stirring speed (X3). The hollow microspheres, as per BBD, were evaluated for EE, particle size and drug release characteristics. The optimum formulation was embarked upon using numerical desirability function yielding excellent floatation characteristics along with adequate drug release control. Drug-excipient compatibility studies employing FT-IR, DSC and powder XRD revealed absence of significant interaction among the formulation excipients. The SEM studies on the optimized formulation showed hollow and spherical nature of the prepared microspheres. In vivo X-ray imaging studies in rabbits confirmed the buoyant nature of the hollow microspheres for 8 h in the upper GI tract. In a nutshell, the current investigations report the successful development of gastroretentive floating microspheres for once-a-day administration of ITH.
authors.affiliation: a Department of Pharmacy , MCP College , Jalandhar City , Punjab , India .
authors.forename: Sanjay
authors.initials: S
authors.lastname: Bansal
authors.affiliation: b Department of Pharmaceutics , University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University , Chandigarh , India .
authors.forename: Sarwar
authors.initials: S
authors.lastname: Beg
authors.affiliation: c  M.M. College of Pharmacy, Maharishi Markandeshwar University , Mullana-Ambala , Haryana , India , and.
authors.forename: Abhay
authors.initials: A
authors.lastname: Asthana
authors.affiliation: b Department of Pharmaceutics , University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University , Chandigarh , India .
authors.forename: Babita
authors.initials: B
authors.lastname: Garg
authors.affiliation: c  M.M. College of Pharmacy, Maharishi Markandeshwar University , Mullana-Ambala , Haryana , India , and.
authors.forename: Gyati Shilakari
authors.initials: GS
authors.lastname: Asthana
authors.affiliation: b Department of Pharmaceutics , University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University , Chandigarh , India .
authors.forename: Rishi
authors.initials: R
authors.lastname: Kapil
authors.affiliation: b Department of Pharmaceutics , University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University , Chandigarh , India .|d UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles & Nanocomposites (Biomedical Sciences), Panjab University , Chandigarh , India.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Singh
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000592:standards; D001593:Benzyl Compounds / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000592:standards; D002152:Calorimetry, Differential Scanning; D018360:Crystallography, X-Ray; D003692:Delayed-Action Preparations; D004304:Dosage Forms; D004334:Drug Administration Schedule; D004337:Drug Carriers; D004339:Drug Compounding; D065569:Gastrointestinal Absorption; D005765:Gastrointestinal Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000592:standards; D005769:Gastrointestinal Motility; D041981:Gastrointestinal Tract / Q000000981:diagnostic imaging / Q000378:metabolism*; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D008956:Models, Chemical; D015233:Models, Statistical; D010316:Particle Size; D011109:Polymethacrylic Acids / Q000737:chemistry*; D033362:Powder Diffraction; D011786:Quality Control; D011817:Rabbits; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards; D013696:Temperature
chemical_list: D001549:Benzamides; D001593:Benzyl Compounds; D003692:Delayed-Action Preparations; D004304:Dosage Forms; D004337:Drug Carriers; D005765:Gastrointestinal Agents; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; C102254:itopride
keywords: Formulation by design (FbD); gastroretention; hollow microspheres; hydrodynamically balanced; quality by design (QbD)