Tablet diluents mixing

The first stage in the wet granulation process is often a dry mixing stage in which the active component is mixed with a diluent. Many drugs need to be administered in doses of only a few milligrams or even less, yet a tablet that weighs less than about 50 mg is difficult for the patient to handle conveniently. It is therefore... 

The key component here is the diluent. This must not only possess those properties which are necessary for satisfactory tablet formulation, but also retain those properties when mixed with the other constituents of the formulation such as the active ingredient. 

Several authors have listed the attributes of the ideal direct compression diluent. " However, it must always be borne in mind that the diluent will invariably form part of a multicomponent mixture. At the very least, the diluent will be mixed with the active ingredient, and almost invariably a lubricant will also be present. The greater the proportion of active ingredient in the formulation, the less influence the diluent will have on the properties of the tablet. 

By definition, direct compression diluents are intended to be mixed with other ingredients. Therefore, not only should the pressure-tablet strength profile of the diluent be determined, but also should those of mixtures of the diluent with an active ingredient. The capacity of a direct compression diluent is the proportion of another ingredient that can be mixed with it while still obtaining tablets of acceptable quality. The definition of acceptable will depend on the purpose for which the tablets are required. 

The magnitude of the effect that a given active ingredient will have on tablet properties will clearly depend on the tabletting properties of that substance. If it is also capable of direct compression, then the effect will not be great. If, however, it is a substance that is difficult to compress into tablets, then it will cause a marked deterioration in tablet quality when mixed with the diluent. Therefore, for a reliable test of capacity, the direct compression diluent should be mixed with a standard substance and tabletted under standardized conditions. The pressure-strength profiles of the mixtures can then be constructed. Paracetamol and ascorbic acid have been used as standards. 

Ten tablets were weighed and finely powdered. A quantity of powder equivalent to one tablet, containing 500 mg of metformin HCI and 5 mg of glibenclamide, was transferred to a 100-mL volumetric flask 50 mL of acetonitrile was then added and sonication was applied for 5 min. After sonication, 20 mL of buffer was added and further sonication was applied for 20 min with swirling. The solution was cooled to ambient temperature and diluted to the desired volume with the diluent and mixed well. The solution was filtered through Whatman filter paper 41. The first 5-mL portion of the filtrate was rejected and then 1 mL of the filtered solution was transferred into a 50-mL volumetric flask and diluted with the dUuent. 

The sample is sonicated for 20 minutes and cooled to room temperature. After dilution to volume with water/acetonitrile diluent, the sample is mixed and centrifuged to remove any dispersed solids. The solution is then appropriately diluted depending upon tablet strength and the resultant solution is injected into the HPLC system. Tablets must contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of indapamide (34). 

Uses Emulsifier, thickener, colloidal stabilizer, binder for foods binder, diluent, absorbenL and disintegrant in pharmaceutical tablets food pkg. emulsifrer and encapsulant for oils in dry food mixes film-former opacifier, bodying agent in nonaq. cosmetic creams Re latrxy FDA 21 CFR 155.130,169.150,169.179,172.892,175.105, 178.3520,182.90... 

Properties Wh. powd., odorless, tasteless insol. in water, alcohol, ether, chloroform Hazardous Decomp. Prods. Heated to decomp., emits acrid smoke and irritating fumes Uses Emulsifier, thickener, colloidal stabilizer, binder for foods binder, diluent, absorbent, and disintegrant in pharmaceutical tablets food pkg. emulsifier and encapsulant for oils in dry food mixes film-former opacifier, bodying agent in nonaq. cosmetic creams Regulatory FDA 21CFR 155.130, 169.150, 169.179, 172.892, 175.105, 178.3520, 182.90 Manuf./Distrib. A.E. Staley Mfg. http //www.tateandlyle.com, ADM http //www.admworld.com, Ashland http //www.ashchem.com, Avebe BV Cerestar Int l. 

When a patient cannot swallow tablets or capsules, has a feeding tube, or requires a lower dose of the active substance than present in a commercial product, the pharmacist should find a way to administer the active substance. Sections 37.6.2 and 37.8.3 discuss various strategies to modify conventional (fast-release) tablets or capsules, such as the opening and emptying of a capsule, or pulverisation of a tablet and subsequently mixing it with a diluent or liquid. 

Otsuka M, Gao J, Matsuda Y. Effects of mixer and mixing time on the pharmaceutical properties of theophylline tablets containing various kinds of lactose as diluents. Drug Dev Ind Pharm 1993 19(3) 333-348. 

Sample preparation Sonicate powdered tablet containing 500 mg metformin and 30 mg pioglitazone with 100 mL 100 mM HCl for 10 min with intermittent shaking, add 40 mL MeCN, sonicate for 25 min with intermittent shaking, cool to room temperature, add 10 mL MeCN, make up to 200 mL with 100 mM HCl, mix well, centrifuge at 10 000 rpm for 10 min. Mix a 2 mL aliquot with 1 mL 250 p,g/mL IS in MeCN 100 mM HCl 25 75, make up to 50 mL with diluent, inject an aliquot. (The diluent was MeCN 5 mM disodium hydrogen phosphate 30 70, adjusted to pH 2.3 with HCl.)... 

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