Tablet diluents substances

Tablet diluent Inert substance used as filler to create desired bulk, flow properties, and compression characteristics in preparation of tablets Dibasic calcium phosphate, kaolin, lactose, mannitol, microcrystalline cellulose, powdered cellulose, precipitated calcim carbonate, sorbitol, starch...

At about the same time, two materials were introduced that were specifically designed to act as tablet diluents and would not require preliminary treatment. These were spray-dried lactose and microcrystalline cellulose, introduced in 1962 and 1964, respectively. These two substances can be said to have initiated the direct compression revolution. Since that time, a wide range of direct compression tablet diluents has become available. The properties of some of these materials will be reviewed later in this article. 

Powdered cellulose is used as a tablet diluent and a hard gelatin capsule filler see Table I. In both contexts it acts as a bulking agent to increase the physical size of the dosage form for formulations containing a small amount of active substance. 

Tablet and capsule diluents inert substances incorporated to increase the bulk, to make the tablet or capsule of practical size. 

Take, for example, dextrose. When dextrose is used as a sweetener in baked goods, it is a food ingredient and subject to the requirements of food products. When dextrose is used as a sweetener or diluent in tablet, capsule, or liquid preparations, it is an excipient. When it is used in the manufacture of sterile dextrose injection, it is an active drug substance and an API but now... 

An inert substance is frequently added to increase the bulk of a tablet for processing and handling. The lower weight limit for formulation of a tablet is usually 50 mg. Ideally, diluents should be chemically inert, nonhygroscopic, and hydrophilic. Having an acceptable taste is important for oral formulations, and cost is always a significant factor in excipient selection. 

The true direct compression process as described earlier almost invariably applies to formulations containing potent active ingredients and where the direct compression properties derive from the diluent. A few substances do possess adequate flow and cohesive properties without the need for pretreatment. These are usually crystalline inorganic salts such as sodium chloride and potassium chloride. Direct compression forms of less potent active ingredients are available e.g., paracetamol and ascorbic acid. These can be directly compressed into tablets, perhaps after the addition of a lubricant. However, such substances are more accurately described as pre-granulated, in that the granulation process—either wet granulation or precompression—has been carried out by the excipient manufacturer. 

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. 

This constraint, in the case of mixture-amount problems where the proportion of active substance is allowed to vary, is one which is particularly relevant to pharmaceutical formulation. We take a formulation where the percentage of drug substance is between 5 and 50%. This variation is compensated for by a change in the percentage of diluent (for simplicity we assume a single diluent). The tablet mass is varied from 100 to 200 mg, so the design space is square as shown in figure 9.28c (broken lines). 

Mixture design was used to help in formulation of a sustained release tablet, based on a hydrophilic cellulose polymer, which swells in the presence of water, and so impedes the release of the soluble active substance. Drug release is by a combination of diffusion and erosion. The formulators wished to examine the effect of changing the proportions of polymer, and of the different diluents (9). The constraints on the formulation are given in table 10.8. Other components (drug substance, lubricant) are to be considered as fixed, at least for the time being. 

The formulation of an inert matrix tablet for a soluble drug substance (dosed at 5 mg per tablet) was investigated (18). It was based on 2 acrylic polymers and 3 diluents, as shown in table 10.14. Polymer A is of low permeability, polymer B relatively permeable. 

Products and Uses It is in chewing gum, confectionery, candy eggs (shell), tablet form food supplements, fruits, and vegetables as a color diluent and as a masticatory substance in chewing gum base. 

It is usually not possible to prepare a capsule, oral powder or tablet from an active substance without the addition of any excipients. Firstly, the volume of the active substance is often very small a diluent is necessary in order to handle the powder mixture. Secondly, the active substance may not have good flow properties these can be improved by addition of a glidant. Another reason to use excipients is that a preparation, consisting only of an active substance, may not disintegrate well in the gastro-intestinal tract a disintegrating agent can improve this. Many excipients combine a number of such functions so the number of different excipients can be limited and the potential interactions between materials can be minimised [12]. The next sections... 

Fig. 4.2 Nifedipine contents in single-dose powders or capsules that were meant to contain nifedipine 1 mg as active substance (from crushed tablets Adalat 10 mg retard) and microcrystalline cellulose (MCC) as a diluent. The batch size was 50 single-dose powder or capsules and no excess tablets were used. Capsules number 4 (80 mg MCC), 3 (130 mg MCC) and 1 (200 mg MCC) are compared to oral...

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. 

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