FORMULATION AND EVALUATION OF BILAYER TABLET OF ALMOTRIPTAN MALATE AND DICLOFENAC POTASSIUM

Migraine is a chronic neurological disorder characterized by recurrent moderate to severe headaches often in association with a number of autonomic nervous system symptoms. The word derives from the Greek ἡμικρανία (hemikrania), "pain on one side of the head", from ἡμι- (hemi-), "half", and κρανίον (kranion), "skull".Typically the headache affects one half of the head, is pulsating in nature, and lasts from 2 to 72 hours. That affects approximately 17% of adult women and 6% of adult men. It is most common among people age 25 to 55, though it can affect children and teens as well. Migraine is about three times more prevalent in women than men; roughly one in five women and one in 16 men suffer from migraine Associated symptoms may include nausea, vomiting, and sensitivity to light, sound, or smell.

                  The objective of present study was to formulate and evaluate bilayer tablet of Almotriptan malate (AM) and Diclofenac potassium (DP) for the effective treatment of migraine. The combination of almotriptan malate and diclofenac potassium is used as almotriptan malate establishes the immediate release layer (initialdose) and diclofenac potassium as the sustained release layer (maintenance dose) respectively. The bilayer tablets of AM and DP was particularly designed to minimize the risk of rebound migraine and improve the therapeutic efficacy and to prolong the release of drug and patient compliance. Formulation variables for immediate release layer include sodium starch glycolate and crospovidone as super disintegrants and micro crystalline cellulose as filer. HPMC K100, HPMC K15, was used as sustained release polymers. The result of in-vitro release data showed that HPMC K15 and HPMC K100 combination can sustain the drug release up to 12hrs. From these studies HPMC K15 and HPMCK100 combination has been selected for further studies of bilayer tablet. Almotriptan malate and diclofenac potassium bilayer tablet were prepared by direct compression method. The hardness of the bilayer tablets was 6.30±0.17kg/cm². The thickness of the bilayer tablets was 5.19±0.10mm. The drug content of Almotriptan malate and Diclofenac potassium was 98.10±0.90 (SR) and 98.84±0.09 (IR). The in-vitro drug release of bilayer tablets have Almotriptan malate immediate release was within 45minutes and Diclofenac release from the tablets was found sustained over 12 hours with Zero order equation to analyze the release pattern of the drug from the polymeric system. The value of “n” were in the range of 8.0454, indicating the drug release followed Super case-II transport diffusion, possibly owing to chain distanglement and swelling of hydrophilic polymer. The Fourier transform infrared spectroscopy (FT-IR) analyses indicated that there was absence of any chemical interaction between the drugs and excipients.

The results of Accelerated stability studies showed that all parameters were within the expected specifications and there was no significant changes observed from initial to 2month, indicating good stability.

                Thus, the objective of bilayer drug delivery system of anti-migraine drug almotriptan malate and diclofenac potassium with sustained release profile was achieved.