title: Gastroretentive inorganic-organic hybrids to improve class IV drug absorption.
abstract: Therapeutic efficacy of some orally administered molecules is often conditioned by their solubility in physiological fluids as well as their absorption. The last aspect becomes more limitative and conditioning drug plasmatic profiles when the active ingredient is preferentially absorbed in a specific region of the gastrointestinal tract. A case is represented by furosemide (FURO) preferentially absorbed in the stomach, site in which, because of its acidic nature, is poorly soluble. To solve this problem new oral solid formulations have been developed. The inorganic-organic hybrid MgAl-HTlc-FURO has been formulated in tablet in which floating and mucoadhesion properties have been combined. Swellable (Methocel K4, Methocel K15, Methocel K100 M, hydroxypropyl methyl cellulose) or swellable/erodible polymers (Methocel E50 LV, Methocel K100 LV), used to obtain the floating, were combined to Carbopol(®) (971P or 974P) to confer mucoadhesion capacity. Prepared tablets were deeply characterized in terms of hydration capacity, erosion %, buoyancy lag time/floating time and mucoadhesion. The most suitable tablets selected from these preliminary tests, submitted to in vitro release studies, showed a sustained release of FURO. This is useful to maintain the therapeutic concentrations for a long time, in comparison to conventional dosage forms, thanking to the enhancement of formulation residence time in the stomach.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Perugia, Via del Liceo 1, Perugia 06123, Italy. Electronic address: luana.perioli@unipg.it.
authors.forename: Luana
authors.initials: L
authors.lastname: Perioli
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Perugia, Via del Liceo 1, Perugia 06123, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Pagano
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000268:Adhesiveness; D000284:Administration, Oral; D000818:Animals; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D016503:Drug Delivery Systems; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry*; D005665:Furosemide / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D005753:Gastric Mucosa / Q000378:metabolism; D065347:Hypromellose Derivatives / Q000737:chemistry; D008747:Methylcellulose / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D012995:Solubility; D013552:Swine; D013607:Tablets
chemical_list: D000179:Acrylates; D003692:Delayed-Action Preparations; D005079:Excipients; D011108:Polymers; D013607:Tablets; C492577:carbopol 971P; C117167:carbopol 974P NF; D065347:Hypromellose Derivatives; D005665:Furosemide; D008747:Methylcellulose
keywords: Floating; Gastric retention; Inorganic–organic hybrids; Mucoadhesion; Sustained release