Application of design of experiment for polyox and xanthan gum coated floating pulsatile delivery of sumatriptan succinate in migraine treatment

Abstract

Migraine follows circadian rhythm in which headache is more painful at the awakening time. This needs administration of dosage form at night time to release drug after lag period when pain gets worse. Sumatriptan succinate is a drug of choice for migraine. Sumatriptan succinate has bitter taste, low oral bioavailability, and shorter half-life. Present work deals with application of design of experiment for polyox and xanthan gum in development of press coated floating pulsatile tablet. Floating pulsatile concept was applied to increase gastric residence of the dosage form. Burst release was achieved through immediate release tablet using crospovidone as superdisintegrant (10%). Pulse lag time was achieved using swellable polymer polyox WSR 205 and xanthan gum. 3(2) experimental design was applied. Optimized formulation was evaluated for physical characteristics and in-vitro and in-vivo study. From results, it can be concluded that optimized batch F8 containing polyox WSR205 (72.72%) and xanthan gum (27.27%) of total weight of polymer has shown floating lag time of 55 ± 2 sec, drug content of 100.35 ± 0.4%, hardness of 6 ± 0.1 Kg/cm(2), and 98.69 ± 2% drug release in pulse manner with lag time of 7 ± 0.1 h. Optimized batch showed prolong gastric residence which was confirmed by in-vivo X-ray study.

Figure 1

IR spectra of optimized batch F8, xanthan gum, polyox WSR205 and Sumatriptan succinate.

Figure 2

DSC spectra of (A) sumatriptan succinate, (B) polyox WSR205, (C) xanthan gum, and (D) optimized batch F8.

Figure 3

Swelling indices profile of factorial batches F1–F9 of polyox WSR205 and xanthan gum.

Figure 4

Dissolution profile of factorial batches F1–F9 of polyox WSR205 and xanthan gum.

Figure 5

Contour plot and response surface plot showed relationship in between hardness and % of polymer.

Figure 6

Contour plot and response surface plot showed relationship in between swelling index and % of polymer.

Figure 7

X-ray graph of optimized batch F8 (polyox WSR205 and xanthan gum).