Comparative Pharmacokinetic Evaluation of Controlled Release Matrix Tablet of Milnacipran Hydrochloride in Rabbit
Gautam Singhvi, Abhishek Shah, Sri R. Nalla and Ranendra N. Saha
Affiliation: Department of Pharmacy, Industrial Research Laboratory, Birla Institute of Technology and Science, Pilani, Rajasthan, Pin: 333 031, India.
Keywords: Controlled release, in-vitro, in-vivo, milnacipran, pharmacokinetic.
Milnacipran hydrochloride (MIL) is a selective serotonin and norepinephrine dual reuptake inhibitor used for
the treatment of depression and fibromyalgia. The aim of present work was to carry out comparative pharmacokinetics
evaluation of in-house developed oral controlled release (CR) and marketed immediate release (IR) tablet formulation of
MIL. Three prototype CR formulations (i) MIL with HPMC 100K, single hydrophilic polymeric matrix tablet [MSH], (ii)
MIL with HPMC 100K and sodium CMC, binary hydrophilic polymeric matrix tablet [MBH] and (iii) MIL with hydrophilic
and hydrophobic wax polymeric matrix tablets using HPMC 100K and paraffin wax [MHW] were formulated. One
optimized formulation from each prototype formulation was selected for in-vivo study in rabbits. In-vivo plasma concentration
data were obtained from 6 healthy male New Zealand albino rabbits after administration of IR and CR tablets of
MIL. Plasma samples were analyzed by in-house developed RP-HPLC method. Remarkable differences in plasma drug
profile were observed between IR and CR formulations, expressed by lower Cmax, delayed Tmax and extended MRT values
for CR tablets. The mean Cmax and Tmax values from CR tablets were found to be 480.28 ± 31.27 to 586.53 ± 15.24 ng/mL
and 8 to 10 h respectively whereas for IR formulation these were 1075.25± 50.38 ng/mL and 1 h respectively. The MRT
was found twice in CR formulation than IR formulation. Level A in-vitro and in-vivo correlation was also established for
developed CR formulations with correlation coefficient 0.896 to 0.930, which indicates a fair correlation between in-vitro
release and in-vivo absorption of MIL from dosage form.
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