title: Laminated sponges as challenging solid hydrophilic matrices for the buccal delivery of carvedilol microemulsion systems: Development and proof of concept via mucoadhesion and pharmacokinetic assessments in healthy human volunteers.
abstract: Carvedilol (CVD) suffers from low absolute bioavailability (25%) due to its limited aqueous solubility and hepatic first-pass metabolism. Hydroxypropyl methylcellulose (HPMC) laminated buccal sponges loaded with CVD microemulsions (CVD-ME) were exploited to surmount such limitations. Six pseudoternary-phase diagrams were constructed using Capmul® MCM C8/Capmul® PG8, Tween® 80, propylene glycol and water. Six CVD-ME systems (0.625% w/v) were incorporated into HPMC core sponges backed with Ethocel® layers. The sponges were preliminary evaluated via FT-IR, DSC and XRD. The surface pH, morphology and in vitro drug release studies were evaluated. In vivo mucoadhesion and absorption studies of the best achieved laminated sponges (F4) were assessed in healthy volunteers. CVD-ME systems displayed nano-spherical clear droplets. The sponges showed interconnecting porous matrices through which CVD was dispersed in amorphous state. No intermolecular interaction was detected between CVD and HPMC. The surface pH values were almost neutral. The sponges loaded with CVD-ME systems showed more sustained-release profiles than those loaded with CVD-powder. Compared to Dilatrend® tablets, the significantly (P<0.05) higher bioavailability (1.5 folds), delayed Tmax and prolonged MRT(0-∞) unraveled the dual-potential of F4 sponges for water-insoluble drugs, like CVD, in improving drug oral bioavailability and in controlling drug release kinetics via buccal mucosa.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Abd-Elbary
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Misr University for Science and Technology (MUST), Giza, Egypt.
authors.forename: Amna M A
authors.initials: AM
authors.lastname: Makky
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address: mina_ebrahim@yahoo.com.
authors.forename: Mina Ibrahim
authors.initials: MI
authors.lastname: Tadros
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Misr University for Science and Technology (MUST), Giza, Egypt.
authors.forename: Ahmed Adel
authors.initials: AA
authors.lastname: Alaa-Eldin
mesh_terms: D000268:Adhesiveness; D000278:Administration, Buccal; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D000328:Adult; D001682:Biological Availability; D002227:Carbazoles / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D000077261:Carvedilol; D018592:Cross-Over Studies; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004655:Emulsions; D064368:Healthy Volunteers; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D009061:Mouth Mucosa; D011412:Propanolamines / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D004655:Emulsions; D011412:Propanolamines; D000077261:Carvedilol
keywords: Buccal delivery; Carvedilol; Laminated sponges; Solidification of microemulsions