[Design and development of hydroxypropyl methycellulose (HPMC) based polymeric films of methotrexate: physicochemical and pharmacokinetic evaluations].
The present investigation was aimed to evaluate the possibility of using different concentrations and polymeric grades of hydroxypropyl methylcellulose (K4M, K15M and K100M) for transdermal delivery of methotrexate, an immunosuppressant drug for rheumatoid arthritis. The matrix films were evaluated for their physicochemical characterization followed by in vitro and in vivo evaluation. Selected formulations were subjected for their in vivo studies on healthy rabbits following balanced incomplete block design. The relevance of difference in the in vitro dissolution rate profile and pharmacokinetic parameters (C(max), t(max), AUC((s)), t(1/2), K(el), and MRT) were evaluated statistically. The thickness and weight of the patch increased with the increase in polymeric grade and content. Fourier transform infrared spectroscopy and differential scanning calorimetry results confirm that there is no interaction between drug and polymer used. X-ray diffraction study reveals an amorphous state of drug in the matrix films. The in vitro drug release followed Higuchi kinetics (r=0.972-997; p<0.001) as its coefficient of correlation values predominates over zero order and first order release kinetics. In vitro dissolution profiles and pharmacokinetic parameters showed a significant difference between test products (p<0.01), but not within test products. A quantitatively good correlation was found between per cent of drug absorbed from the transdermal patches and AUC((s)). A significant in vitro/in vivo correlation was observed when per cent drug released was correlated with serum drug concentration. Out of the various formulations made, the selected formulations are better in their in vitro dissolution and pharmacokinetic characteristics and thus hold potential for transdermal delivery.
Chandak
Ashok R
AR
Department of Pharmaceutical Sciences, Birla Institute of Technology, Jharkhand, India.
Verma
Priya Ranjan Prasad
PR
D000279:Administration, Cutaneous; D000818:Animals; D001682:Biological Availability; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D016503:Drug Delivery Systems; D065347:Hypromellose Derivatives; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008727:Methotrexate / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008747:Methylcellulose / Q000031:analogs & derivatives*; D011817:Rabbits
D007166:Immunosuppressive Agents; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D008727:Methotrexate