title: I. Technological approaches to improve the dissolution behavior of nateglinide, a lipophilic insoluble drug: nanoparticles and co-mixing.
abstract: Nateglinide is a non-sulphonylurea insulinotropic oral antidiabetic agent. The main problem in formulating an oral dosage form is its low solubility in aqueous media. This problem is particularly critical for an anti-diabetic drug because it should be administered just before the meals and be quickly bioavailable to cover the post-prandial glycemic peak. In this work, some technological approaches have been studied to improve the dissolution rate of nateglinide. Furthermore, two different polymorphs of nateglinide (H and B) have been tested to evaluate the influence of the crystal habitus on the dissolution behavior of the drug. The results have clearly demonstrated that wettability plays a key role in the dissolution behavior of nateglinide. As a matter of fact the physical dispersion of the drug with colloidal silica or hydrophilic swellable polymers strongly enhances the dissolution rate of nateglinide. The two polymorphs tested did not show significant differences in terms of dissolution behavior.
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: D000284:Administration, Oral; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D003510:Cyclohexanes / Q000008:administration & dosage / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000737:chemistry*; D007700:Kinetics; D053758:Nanoparticles; D036103:Nanotechnology; D000077715:Nateglinide; D010649:Phenylalanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D003510:Cyclohexanes; D005079:Excipients; D007004:Hypoglycemic Agents; D011108:Polymers; D000077715:Nateglinide; D010649:Phenylalanine
keywords: Co-mixing, silica; Dissolution rate; Hydrophilic swellable polymers; Insoluble drug; Nateglinide