Patent EA-000276-B1 (EA)
Title: Valaciclovir tablets containing colloidal silicon dioxide
Inventor: CARTER BARRY HOWARD
IPC: A61K47/34
Filed: 1996-01-19
Abstract: 1. A tablet comprising at least about 50% w/w valaciclovir or a salt thereof, a filler, a binding agent, a lubricant and about 0.05 to about 3% w/w colloidal silicon dioxide wherein the valaciclovir or a salt thereof is present within the granules of the tablet, the lubricant and silicon dioxide being present extragranularly; wherein the friability of the tablet does not exceed 1%, the hardness is at least 9 kPa, and the ejection force does not exceed 1000 Newtons. 2. A tablet as claimed in Claim 1 wherein the colloidal silicon dioxide is present in an amount of about 0.1% to about 0.5% w/w. 3. A tablet as claimed in Claims 1 or 2 wherein the filler is ceilulostic filler and is present in an amount of about 3% w/w to about 30% w/w. 4. A tablet as claimed in Claim 3 wherein the filler is ceilulostic filler and is present at about 5% to about 15% w/w. 5. A tablet as claimed in Claim 4 wherein the filler is ceilulostic filler and is present at about 10%w/w. 6. A tablet as claimed in any of the preceding Claims 5 wherein the ceilulostic filler represents microcrystalline cellolose. 7. A tablet as claimed in any of the preceding Claims, wherein the particle size of the ceilulostic filler is about 20 to about 300 mkm. 8. A tablet as claimed in any one of the preceding Claims wherein the binding agent is present at about 1% to about 5% w/w. 9. A tablet as claimed in any one of the preceding Claims wherein the binding agent is methylcellulose or povidone. 10. A tablet as claimed in Claim 9 wherein the binding agent is povidone. 11. A tablet as claimed in Claim 10 wherein the povidone is povidone K90 grade. 12. A tablet as claimed in any one of the preceding Claims wherein the lubricant is present at about 0.1% to about 2.0% w/w. 13. A tablet as claimed in Claim 12 wherein the lubricant is a stearate derivative. 14. A tablet as claimed in Claim 13 wherein the lubricant is magnesium stearate and is present at about 0.1% to about 1.0% w/w. 15. A tablet as claimed in any one of the preceding Claims wherein the valaciclovir or its salt thereof is present at about 65% to about 85% w/w. 16. A tablet as claimed in any one of the preceding Claims comprising valaciclovir hydrochloride. 17. A tablet as claimed in Claim 16 wherein the valaciclovir hydrochloride is anhydrous crystalline form including substantially a d spacing pattern as follows: d spacing pattern (in Angstroms): 10.20 +- 0.08, 8.10 +- 0.06. 7.27 +- 0.06, 6.08 +- 0.05. 5.83 +- 0.03, 5.37 +- 0.02, 5.23 +- 0.02, 4.89 +- 0.02, 4.42 +- 0.02, 4.06 +- 0.02, 3.71 +- 0.02, 3.39 +- 0.02, 3.32 +- 0.02, 2.91 +- 0.02, 2.77 +-0.02. 18. A tablet as claimed in any one of the preceding Claims wherein the tapped bulk density of valaciclovir or salt thereof is about 0.1 to about 0.9g/cc. 19. A tablet as claimed in any one of the preceding Claims, which further includes a disintegrating agent present at about 0.5% to about 20% w/w. 20. A tablet as claimed in Claim 19 wherein the disintegrating agent is a non-ionic disintegrating agent. 21. A tablet as claimed in Claim 20 wherein the disintegrating agent is crospovidone present at about 0.5% to about 7% w/w. 22. A tablet as claimed in Claim 1comprising about 65% to about 85% w/w anhydrous crystalline valaciclovir hydrochloride including the d spacing diffraction pattern of Claim 16, about 0.5% to about 5% w/w of povidone, about 3% to about 30% w/w of a cellulostic filler, about 0.5 to about 7% w/w of a non-ionic disintegrating agent, about 0.1% to about 1.0% of a stearate lubricant and about 0.1% to about 0.5% w/w of colloidal silicon dioxide, wherein the valaciclovir hydrochloride is present intragranularly; and wherein the cellulostic filler, stearate lubricant and colloidal silicon dioxide are present extragranularly. 23. A tablet as claimed in any one of Claims 1 to 22, which is film, coated. 24. A process of treatment of a herpes virus infection in a human comprising administering to the host one or more tablets as claimed in any one of the preceding Claims to administer an effective anti-herpes viral amount of valaciclovir or a salt thereof. 25. A process for preparing a tablet comprising at least about 50% w/w valaciclovir or a salt thereof, a binding agent, a lubricant, and about 0.05 to about 3.0% colloidal silicon dioxide, wherein the friability of the tablet does not exceed 1% the hardness is at least 9 kPa and the ejection force does not exceed 1000 N; said process comprising forming granules which include valaciclovir or a salt thereof and then blending the lubricant and colloidal silicon dioxide and at least a portion of the ceilulostic filler with said granules. 26. A process according to Claim 25 wherein comprising forming granules by mixing said valaciclovir or salt optionally a binding agent or a portion thereof, and optionally the filler or a portion thereof; granulating with a granulating solution to form granules or dissolving the binding agent or a portion in the granulating solution before adding to valaciclovir; drying the granules; blending the granules with the lubricant, colloidal silicon dioxide, and optional filler or a portion thereof; and then compressing the blended mixture to form a tablet. 27. A process according to Claim 25 wherein comprising ceilulostic filler in a tablet is about 3% to 30% w/w, granules are formed by mixing valaciclovir or a salt thereof, and optionally the filler or a portion thereof; granulating with a granulating solution to form granules or dissolving the binding agent or a portion in the granulating solution before adding to valaciclovir; drying the granules; blending the granules with the lubricant, colloidal silicon dioxide, and optional filler or a portion thereof; and then compressing the blended mixture to form a tablet. The patent is valid in all Contracting States except AM and MD.