In Vitro & In Vivo Characterization of Tableted Spray-Congealed Lipid Microparticles for Extended Release of Vildagliptin

Abstract

Vildagliptin (VG), a drug used for treatment of type 2 diabetes, is soluble in water and currently marketed as an instantaneous release tablet that is administered twice daily. VG is not available as an extended release dosage form. The aim of this project therefore, was to design an extended release oral drug delivery for VG that can be administered once daily by producing solid lipid microparticles using the Spray Congealing technique (SC). The SC is an environmentally friendly microparticles (MP) preparation process that can be utilized to produce MP without using any solvent. Drug with or without Carbomer® was dispersed in the melted lipid carriers and atomized through the two fluid nozzle of the Buchi® spray congealer leading to form MP loaded with VG. The produced VG loaded MP were characterized for their morphological features, yield, content and thermal properties. VG/MP were then pressed into tablets and their in vitro and in vivo release studies were investigated. Determination of VG in samples was done using validated High Pressure Liquid Chromatography HPLC-UV and Liquid Chromatography Mass Detector LC/MS methods of analysis for in vitro and in vivo studies respectively. VG microparticles were spherical in shape with a yield of 76 %. The drug content in the microparticles was found to be 98.8 %. The in vitro dissolution studies showed that VG was released from the tableted particles in an extended-release fashion for up to 24 hours when compared to the immediate-release VG marketed tablets. Moreover, no changes in the release profile were observed upon the storage of the formula for 6 months at 4 oC. The in vivo pharmacokinetics studies using mixed breed dogs reported a Cmax, Tmax, T1/2 and mean residence time of 118ng/ml, 3.4 h, 5.27 h and 9.8 h respectively for the tested formulation prepared by SC with a significant difference when compared to those of the reference immediate-release marketed drug (147 ng/ml, 1 h, 2.16 h and 2.8 h respectively). The mean area under the curve (AUC) values for the test and the reference were not significantly different as indication of comparable bioavailability. The IVIVC studies resulted in level A correlation with a correlation coefficient of 0.965. On the other hand, the multiple level C correlation showed a linear correlation for different pharmacokinetic parameters with the dissolution parameters. In conclusion, SC technology was successfully utilized for designing a once daily extended release drug delivery system of VG.