title: Nanosizing of a drug/carrageenan complex to increase solubility and dissolution rate.
abstract: In this study, we present a novel approach of nanosizing a drug/polymeric complex to increase both solubility and dissolution rate of poorly water-soluble compounds. A hydrophilic polymer, lambda-carrageenan, was first complexed with a model poorly water-soluble compound to increase the compound's aqueous solubility. The compound/carrageenan complex was further nanosized by wet-milling to enhance the dissolution rate. By complexing with carrageenan, the compound became amorphous in the complex. Using additional carrageenan as a stabilizer for nanosizing, a nanosuspension of a compound/carrageenan complex with a median particle size of about 0.3 microm was successfully developed. The particle size of the nanosuspension did not increase significantly during the lyophilization process and was stable for at least 39 days at room temperature after lyophilization. This approach of nanosizing a drug/carrageenan complex increased the aqueous solubility of the compound from less than 1 microg/mL to 39 microg/mL. In addition to increasing aqueous solubility, a nanosized compound/carrageenan complex had a faster dissolution rate than the complex, the free compound, and the nanosuspension of the free compound.
authors.affiliation: ALZA Corporation, 1900 Charleston Road, Mountain View, CA 94039, USA. wdai2@alzus.jnj.com
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Dai
authors.forename: Liang C
authors.initials: LC
authors.lastname: Dong
authors.forename: Yan-Qiu
authors.initials: YQ
authors.lastname: Song
mesh_terms: D002152:Calorimetry, Differential Scanning; D002351:Carrageenan / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients; D005612:Freeze Drying; D007700:Kinetics; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000008:administration & dosage*; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D005079:Excipients; D004364:Pharmaceutical Preparations; D002351:Carrageenan