Development and Evaluation Controlled Release Diclofenac Sodium Matrix Tablets

Abstract

In vitro release profiles were studied for the matrix controlled release Diclofenac sodium tablets (MT20, MT33, MT34) in comparison with Voltaren retard (V.R) a well known marketed Diclofenac sodium controlled release tablets from Novartis® (Switzerland). Percentage release of Diclofenac sodium was studied in gradient pHS (1.2, 2.1, 4.2, 5.5, 6.5, 6.7, & 7.2) in accordance with gastric pHS, which are varying from pH one to eight. The study included the release profiles and evaluated the kinetics of diffusion and diffusion exponents. Analysis of new controlled release oral drug delivery systems using, C8 (Eurosphere-100 (5 µm) 4.6 mm ID x 250 mm) and C18 (Eurosphere-100 (5 µm) 4 mm ID x 100 mm) columns was carried out. The mobile phase was phosphate buffer/methanol. Spectrophotometric detection was at 272 nm. Percentages of content for the different matrices were evaluated. Based on t-test no significantdifference was found between content measurements using C8 and C18 columns at p′-value of 0.05. (Observed t-value was 0.062 compared to the theoretical value of 2.15. Content analysis showed good precision and accuracy with C8 rather than C18. In vivo performance and bio-equivalence of controlled release matrix tablets (MT33) containing gum Arabic and Guar gum was compared to a standard control drug Voltaren retard in healthy male volunteers. The study design was randomized cross-over study. Blood samples were collected at pre-determined periods, up to 12 hours and one sample was taken after 24 hours. High performance liquid chromatographic (HPLC) analysis was done for both sample and control. Parameters such as Cmax,Tmax, AUC0-24, iii Keland MRT0-24. AUMC 0-t, AUMC 0-∞were obtained. The bioequivalence of both formulationswas evaluated which showed no difference in prolonged action in vivo performance between controlled matrix tablets (MT33 ) containing gum Arabic and guar gum compared to a standard control drug ; Voltaren retard in healthy volunteers. Accelerated stability study for six months was performed for controlled release matrix tablets (MT20, MT33, MT34, MT33p, MT34p) containing natural gums (gum Arabic, guar gum), semi-synthetic gum (Xanthan gum), Eudragit L100 (methacrylic acid and methyl methacrylate), and Hydroxypropylmethylcellulose. Microbiological tests for matrices were evaluated by comparing preserved and non preserved tablets. Content was found to be 90-105% in all the five matrix formulae. Applying out of trend stability rules (OOT), the best formula was MT33 which contain guar gum 15% and gum Arabic 15%. No changes in physical appearance and organoleptic properties were observed. No microbiological growth (bacteria or fungi) was observed in both preserved and non-preserved controlled release formulae.