Tailoring the release rates of fluconazole using solid dispersions in polymer blends.
Formulations of the drug Fluconazole with different release characteristics were prepared by dispersing the active pharmaceutical ingredient (API) in various polymeric carriers, and especially in polymer blends. Fluconazole was tested as a model drug with low solubility in water. First solid dispersions in pure polymers were studied. Use of pure polyvinylpyrrolidone (PVP) as carrier even for high drug load (30 wt%) resulted in rapid release. The drug release rates decreased by increasing the API content. The dissolution rate enhancement was attributed to drug amorphization, particle size reduction, and possible improvement of the drug wetting characteristics. Hydroxypropyl methylcellulose (HPMC) gave solid dispersions, from which the release rates of the drug varied from immediate to sustaining. As the drug amount increased, the rates became higher. Similar behavior also was found when Chitosan was used as carrier, with much more controlled rates close to those for sustained release. These differences were mainly attributed to the limited solubility and swelling of HPMC and Chitosan in aquatic media. To study the effectiveness of polymer blends in adjusting the release rates of the drug, solid dispersions in PVP/HPMC and PVP/Chitosan miscible blends were studied. The release rates of Fluconazole were adequately adjusted by differentiating the weight ratio of the polymers in the blends. PVP/HPMC blends with high PVP content can be used for immediate release formulations but PVP/Chitosan blends are inappropriate for such formulations and can only be used for controlled release.
Papageorgiou
George Z
GZ
Laboratory of Organic Chemical Technology, Chemistry Department, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Bikiaris
Dimitrios
D
Kanaze
Feras I
FI
Karavas
Evangelos
E
Stergiou
Anagnostis
A
Georgarakis
Emmanouil
E
D000935:Antifungal Agents / Q000737:chemistry*; D048271:Chitosan / Q000737:chemistry; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D015725:Fluconazole / Q000737:chemistry*; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D017155:Wettability
D000935:Antifungal Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011108:Polymers; D065347:Hypromellose Derivatives; D015725:Fluconazole; D008747:Methylcellulose; D048271:Chitosan; D011205:Povidone