In vitro and in vivo evaluation of a fast-disintegrating lyophilized dry emulsion tablet containing griseofulvin.
Development of a fast-disintegrating lyophilized dry emulsion (LDE) tablet that enhanced the in vitro dissolution and in vivo absorption of griseofulvin (GF) is presented. The LDE tablets were prepared by freeze-drying o/w emulsions of GF, a drug for which bioavailability is known to be enhanced by fat co-administration. Oil-in-water emulsions were prepared using a gelatin solution (2%, w/v) as the water phase and medium chain triglycerides (Miglyol) or sesame oil as the oil phase. In addition, different emulsifiers were evaluated. The influence of formulation parameters on the disintegration and in vitro dissolution of GF from LDE tablets along with other tablet characteristics were investigated. A significant influence of the emulsifier type on the tablet disintegration time was seen (p<0.01). Results obtained from dissolution studies showed that LDE tablets of GF improved the dissolution rate of the drug compared to the plain drug. The extent of absorption of GF from a selected LDE tablet formulation as compared to an immediate release conventional tablet as reference after single oral dose (125mg) administration was determined in four healthy subjects using a randomized crossover design. In this study, the rate of absorption of GF from LDE tablet was faster than that from the reference tablet and had significantly higher (p=0.02) peak plasma concentration (more than three times higher) and shortened time to C(max) by 4h (p=0.014). The extent of absorption expressed by AUC was 85% larger as compared to the commercial tablet. Stability results, after 6 months storage of LDE tablets at 25 degrees C and 60% relative humidity, showed a slight increase in disintegration time and residual moisture content, while results from dissolution studies showed slightly slower initial drug release.
Ahmed
Iman Saad
IS
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr-El-Eini St., Cairo, Egypt. Iman.Saad@Lycos.com
Aboul-Einien
Mona Hassan
MH
D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D018592:Cross-Over Studies; D003902:Detergents / Q000737:chemistry; D004655:Emulsions; D005612:Freeze Drying; D005780:Gelatin / Q000737:chemistry; D006118:Griseofulvin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D065347:Hypromellose Derivatives; D016014:Linear Models; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D013607:Tablets; D014867:Water / Q000737:chemistry
D000935:Antifungal Agents; D003902:Detergents; D004655:Emulsions; D013607:Tablets; D014867:Water; D006118:Griseofulvin; D065347:Hypromellose Derivatives; D005780:Gelatin; D008747:Methylcellulose