Vitamin D content uniformity in pharmaceutical dosage forms

A method of manufacturing calcium carbonate/vitamin D tablets comprising:

• forming a premix comprising a layer of calcium carbonate, a layer of vitamin D/silicon dioxide and another layer of calcium carbonate;
• sieving and blending the premix to form a first vitamin D/calcium carbonate granulation mixture;
• adding calcium carbonate to said first vitamin D/calcium carbonate granulation mixture such that there is a layer of calcium carbonate granulation, a layer of said first granulation mixture, and another layer of calcium carbonate, to form a second vitamin D/calcium carbonate granulation mixture;
• sieving and blending the second vitamin D/calcium carbonate granulation mixture;
• and,
• forming tablets from a composition comprising the second vitamin D/calcium carbonate granulation mixture.

A pharmaceutical tablet of calcium carbonate and vitamin D produced by the process comprising:

• forming a premix comprising a mixture of vitamin D granulation and silicon dioxide;
• adding a calcium carbonate granulation to said premix to form a first vitamin D/calcium carbonate granulation mixture;
• mixing and sieving the first vitamin D/calcium carbonate granulation mixture;
• blending the first vitamin D/calcium carbonate granulation mixture in a V blender;
• dividing the first vitamin D/calcium carbonate granulation mixture into four equal portions and adding calcium carbonate each portion to form a second vitamin D/calcium carbonate granulation mixture;
• blending the second vitamin D/calcium carbonate granulation mixture in a V blender;
• and,
• pressing a composition comprising the second vitamin D/calcium carbonate granulation mixture into a tablet.

A pharmaceutical tablet of calcium carbonate and vitamin D produced by the process comprising:

• forming a premix comprising a layer of calcium carbonate, a layer of vitamin D/silicon dioxide and another layer of calcium carbonate;
• sieving and blending the premix to form a first vitamin D/calcium carbonate granulation mixture;
• adding calcium carbonate to said first vitamin D/calcium carbonate granulation mixture such that there is a layer of calcium carbonate granulation, a layer of said first granulation mixture, and another layer of calcium carbonate, to form a second vitamin D/calcium carbonate granulation mixture;
• sieving and blending the second vitamin D/calcium carbonate granulation mixture;
• and,
• forming tablets from a composition comprising the second vitamin D/calcium carbonate granulation mixture.

A method of manufacturing vitamin D and a second nutritional or pharmaceutical active tablets comprising:

• forming a premix comprising a mixture of vitamin D granulation and silicon dioxide;
• adding a second nutritional or pharmaceutical active granulation to said premix to form a first vitamin D/second nutritional or pharmaceutical active granulation mixture, wherein the second nutritional or pharmaceutical active component has a particle size ratio to the vitamin D of at least 1.4;
• mixing and sieving the first vitamin D/second nutritional or pharmaceutical active to said premix to form a first vitamin D/second nutritional or pharmaceutical active granulation mixture;
• blending the first vitamin D/to said premix to form a first vitamin D/second nutritional or pharmaceutical active granulation mixture in a V blender;
• dividing the first vitamin D/second nutritional or pharmaceutical active granulation mixture into four equal portions and adding calcium carbonate to each portion to form a second vitamin D/second nutritional or pharmaceutical active granulation mixture;
• blending the second vitamin D/second nutritional or pharmaceutical active granulation mixture in a V blender;
• and,
• forming tablets from a composition comprising the second vitamin D/second nutritional or pharmaceutical active granulation mixture;
• wherein a match in D50 values between vitamin D and second nutritional is preferably ±40%.