title: II. Technological approaches to improve the dissolution behavior of nateglinide, a lipophilic insoluble drug: co-milling.
abstract: Nateglinide is an oral antidiabetic agent that should be administered 10-30 min before the meal, but it shows low and pH-dependent solubility that may reduce its oral bioavailability. To improve nateglinide dissolution rate, the active was co-milled with three different super-disintegrants or with some hydrophilic excipients, in 1:1, 1:2, and 1:4 drug to carrier ratio (w:w). The three super-disintegrants were crosslinked polyvinylpyrrolidone (PVPC), sodium starch glycolate (SSG) and crosslinked carboxymethyl cellulose (CMCC). The three hydrophilic excipient were amorphous silica (AS), mannitol (M) and Poloxamer (PO). A strong enhancement of drug dissolution rate was obtained from the nateglinide:super-disintegrant co-milled systems in 1:4 ratio, which can be explained by a combination of several factors: an increase in wettability, due to the hydrophilic nature of the carriers, a possible reduction of particle size and a more intimate dispersion of the drug onto the carrier, as a result of the mechanical treatment.
authors.affiliation: Department of Drug Sciences, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy.
authors.forename: Lauretta
authors.initials: L
authors.lastname: Maggi
authors.forename: Giovanna
authors.initials: G
authors.lastname: Bruni
authors.forename: Mariarosa
authors.initials: M
authors.lastname: Maietta
authors.forename: Andrea
authors.initials: A
authors.lastname: Canobbio
authors.forename: Andrea
authors.initials: A
authors.lastname: Cardini
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Conte
mesh_terms: D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003510:Cyclohexanes / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers; D005079:Excipients / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry*; D007700:Kinetics; D008353:Mannitol / Q000737:chemistry; D000077715:Nateglinide; D010316:Particle Size; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D020442:Poloxamer / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry; D012995:Solubility; D013213:Starch / Q000031:analogs & derivatives / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D003510:Cyclohexanes; D004337:Drug Carriers; D005079:Excipients; D007004:Hypoglycemic Agents; D020442:Poloxamer; D008353:Mannitol; D000077715:Nateglinide; D010649:Phenylalanine; D012822:Silicon Dioxide; D013213:Starch; C048390:sodium starch glycolate; D011205:Povidone; D002266:Carboxymethylcellulose Sodium
keywords: Co-milling; Dissolution rate; Hydrophilic swellable polymers; Insoluble drug; Nateglinide; Superdisintegrant