IES65615B2 - Pharmaceutical processing - Google Patents

Abstract

Tablets are produced by directly compressing a mixture formed by dry blending an active pharmaceutical agent such as oxybutynin chloride, direct compression lactose, a lubricant such as magnesium stearate and an inhibitor such as a cross povidone based product. The inhibitor prevents interaction between the direct compression lactose and the active pharmaceutical ingredient.

Description

Pharmaceutical Processing The invention relates to a method for producing tablets of an active pharmaceutical ingredient.

There are two main techniques for formulating tablets of pharmaceutically active compounds - wet granulation and direct compression.

Direct compression is preferred for active ingredients which react adversely with aqueous media. However, there are problems in producing satisfactory tablets by direct compression techniques. These include blending/unblending, poor flow characteristics, poor compressibility of tablet ingredients and low colour potential.

This invention is therefore directed towards providing an improved method for producing tablets of an active pharmaceutical ingredient.

According to the invention there is provided a method for producing tablets of an active pharmaceutical ingredient comprising the steps of: mixing the active pharmaceutical ingredient, a lubricant, direct compression lactose, and an amount of an inhibitor to substantially prevent interaction between the direct compression lactose and the active pharmaceutical ingredient; and * directly compressing the mixture thus formed to form * tablets. - 2 In one embodiment of the invention, the inhibitor is a starch product or a derivative of a starch product such as carboxymethyl starch.

In another embodiment of the invention, the inhibitor is a cross-povidone based product.

Preferably the formulation includes a lubricant and the method includes the step of mixing the ingredients except the lubricant; subsequently adding the lubricant; and further mixing the ingredients.

Any suitable lubricant may be used such as stearic acid salts e.g. magnesium, calcium or zinc stearate. Other suitable lubricants include glyceryl monostearate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, light mineral oil, mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulphate, sodium stearyl fumarate, stearic acid and talc.

Most preferably mixing is performed using a dry blending technique.

The invention also provides tablets of an active pharmaceutical ingredient whenever prepared by a method according to the invention.

The invention will be more clearly understood from the following description thereof given by way of example only.

We have found that if tablets are produced by a direct compression technique using a lubricant and direct compression lactose, there are unfavourable interactions with the pharmaceutically active ingredient in the tablet formulation resulting in unacceptably low assay figures.

I We have overcome this problem by including an inhibitor in the formulation to substantially prevent such interactions. We have also found that by mixing the ingredients except the lubricant and subsequently adding the lubricant and further mixing of the ingredients leads to the production of tablets with satisfactory hardness, dissolution and tabletting qualities.

Mixing using a dry blending technique is also preferred since the avoidance of granulating solutions confers active ingredient stability, the elimination of applied heating stages, particle size uniformity.

In each case, the formulation is a direct compression formulation. The ingredients were weighed out and all the ingredients except the lubricant (in these cases magnesium stearate) were added to a receptacle and dry blended for about 6 minutes. The magnesium stearate was then added and the mixture was blended for a further 2 minutes. Tablets were then formed from the blend by conventional direct compression techniques.

EXAM-1 A batch of tablets were prepared by direct compression. Each tablet had the following composition:- mg Oxybutynin chloride 119 mg DC Lactose 43 mg microcrystalline cellulose 12 mg c ro s povidone 1 mg magnesium stearate The tablets gave an assay of 97.9%.

EXAMPLE 2 A batch of tablets were prepared by direct compression. Each tablet had the following composition. mg Bumetanide 5 237.5 mg DC Lactose mg microcrystalline cellulose 25 mg crospovidone 2.5 mg magnesium stearate The tablets gave an assay of 97.4%.

EXAMPLE 3 A batch of tablets were prepared by direct compression Each tablet had the following composition. mg Bumetanide 237.5 mg DC Lactose 80 mg microcrystalline cellulose mg maize starch 2.5 mg magnesium stearate The tablets gave an assay of 98.2%.

EXAMPLE_4_ A batch of tablets were prepared by direct compression Each tablet had the following composition:- 2.5 mg Indapamide 82.75 mg DC Lactose 4 mg carboxymethyl starch 25 0.75 mg magnesium stearate The tablets gave an assay of 100.4%.

The invention is not limited to the embodiments hereinbefore described which may be varied in detail.

Claims (5)

1. ΓΤΑΤΜΚ

1. A method for producing tablets of an active pharmaceutical ingredient comprising the steps of: mixing the*active pharmaceutical ingredient, 5 a lubricant, direct compression lactose, and an amount of an inhibitor to substantially prevent interaction between the direct compression lactose and the active pharmaceutical ingredient; and 10 directly compressing the mixture thus formed to form tablets.

2. A method as claimed in claim 1 wherein the method includes the step of mixing the ingredients except the lubricant; subsequently adding the lubricant; 15 and further mixing the ingredients, preferably the mixing is performed using a dry blending technique.

3. A method as claimed in any preceding claim wherein the inhibitor is a starch product or a derivative 20 thereof, alternatively the inhibitor is a crosspovidone based product.

4. A method of producing tablets of an active pharmaceutical ingredient substantially as hereinbefore described with reference to the 25 examples.

5. Tablets of an active pharmaceutical ingredient whenever prepared by a method as claimed in any preceding claim.