Tablet excipients

Binding agent directly compressible tablet excipient tablet and capsule diluent tablet and capsule filler. 

Chauve G, Raverielle F, Marchessault RH. Comparative imaging of a slow-release starch excipient tablet evidence of membrane formation. Carbohydr Polym 2007 70(l) 61-67. 

Glyceryl di/tristearate excipient, tablets Acacia Agar Dextrates Glyceryl pal mitate/stearate Hyd roxypropyl methylcellulose Sucrose polystearate excipient, veterinary medicine Sulfanilamide excipient, veterinary preps. 

Stability is one of the main advantages of solid dosage forms compared to liquid ones. There is no need for preservatives or other excipients (e.g. antioxidants) to enhance stability. Capsules, cachets and powders can be prepared with few and safe excipients. Tablets, capsules... 

Bioavailability, Bioequivalence, and Pharmacokinetics. Bioavailabihty can be defined as the amount and rate of absorption of a dmg into the body from an adrninistered dmg product. It is affected by the excipient ingredients in the product, the manufacturing technologies employed, and physical and chemical properties of the dmg itself, eg, particle size and polymorphic form. Two dmg products of the same type, eg, compressed tablets, that contain the same amount of the same dmg are pharmaceutical equivalents, but may have different degrees of bioavailabihty. These are chemical equivalents but are not necessarily bioequivalents. For two pharmaceutically equivalent dmg products to be bioequivalent, they must achieve the same plasma concentration in the same amount of time, ie, have equivalent bioavadabihties. 

The availabihty of spray-dried lactose, microcrystaUine cellulose, and other excipients allows for the use of granular rather than powdered phases. This eliminates some of the problems of particle segregation according to size (demixing) and even flow to the die. Direct compression eventually may be the preferred method of tablet preparation. 

Lactose occurs in milk, mainly free, but to a small extent as a component of higher oligosaccharides. Cow and goat milks contain about 4.5% lactose human milk contains about 7.0%. Lactose is used as an excipient in tablets to provide bulk and rapid disintegration. It is also used in some food products where it contributes body with only about 40% the sweetness of sucrose and enhances colors and flavors. 

The analysis of a pharmaceutical tablet (6) requires sample preparation that is little more complex as most tablets contain excipients (a solid diluent) that may be starch, chalk, silica gel, cellulose or some other physiologically inert material. This sample preparation procedure depends on the insolubility of the excipient in methanol. As the components of interest are both acidic and neutral, the separation was achieved by exploiting both the ionic interactions between the organic acids and the adsorbed ion exchanger and the dispersive interactions with the remaining exposed reverse phase. 

To remove the excipient, the tablet was ground to a powder and a weighed portion treated with a known volume of a mixture of 5% glacial acetic acid in methanol. The slurry was well stirred to ensure all the active ingredients were dissolved and the mixture was filtered. 

The different salts, esters, ethers, isomers, mixtures of isomers, complexes or derivatives of an active substance shall be considered to be the same active substance, unless they differ significantly in properties with regard to safety and/or efficacy, in which case additional safety and efficacy data are required. The same qualitative and quantitative composition only applies to the active ingredients. Differences in excipients will be accepted unless there is concern that they may substantially alter the safety or efficacy. The same pharmaceutical form must take into account both the form in which it is presented and the form in which it is administered. Various immediate-release oral forms, which would include tablets, capsules, oral solutions and suspensions, shall be considered the same pharmaceutical form for this purpose. 

Assay 90-110% of label claim (pick 20 tablets at random grind and mix weigh an amount of powder corresponding to five tablets dissolve compound sample and centrifuge excipients run a HPLC analysis on an aliquot of the supernatant), and... 

Figure 4.50. Cumulative dissolution results. Two experimental tablet formulations were tested against each other in a dissolution test in which tablets are immersed in a stirred aqueous medium (number of tablets, constructional details and operation of apparatus, and amount of medium are givens). Eighty or more percent of the drug in either formulation is set free within 10 minutes. The slow terminal release displayed by formulation B could point towards an unwanted drug/excipient interaction. The vertical bars indicate ymean - with Sy 3%. A simple linear/exponential model was used to approximate the data for the strength 2 formulation. Strengths I and 3 are not depicted but look very similar.

Figure 4.52. Coefficients of variation that reflect both tablet to tablet and analytical variability. For formulation B, particularly strengths 2 and 3, the drop in CV with higher cumulative release (a - b) is marked, cf. Fig, 4.50. When the dissolution rate is high, individual differences dominate, while towards the end analytical uncertainty is all that remains. The very low CVs obtained with strength 3 of formulation A ( 0.7-0.8%, data offset by +10% for clarity) are indicative of the analytical uncertainty. Because content uniformity is harder to achieve the lower the drug-to-excipient ratio, this pattern is not unexpected.

The Cadila system [13] has been designed to formulate tablets for drugs based on their physical (solubility, hydroscopicity, etc), chemical (functional groups), and biologically interrelated (dissolution rate) properties. The system first identifies the desirable properties for optimum compatibility with the drug, selects those excipients that have the required properties, and then recommends proportions based on the assumption that all tablet formulations comprise at least one binder, one disintegrant, and one lubricant. Other... 

Incompatibilities have also been observed in solid dosage forms. A typical tablet contain binders, disin-tegrants, lubricants and fillers. Compatibility screening for a new drug should consider two or more excipients from each class. Serajuddin et al. have developed a drug-excipient compatibility screening model to predict interactions of drug substances with excipients [49],... 

Most formulations are composed of one or more medicaments plus a variety of excipients. Irrespective of the type of tablet, general criteria for these raw materials are necessary. In order to produce accurate, reproducible dosage forms, it is essential that each component be uniformly dispersed within the mixture and that any tendency for component segregation be minimized. In addition, the processing operations demand that the mixture be both free-flowing and cohesive when compressed. 

In many products it seems highly probable that there exists a narrow range of optimum moisture contents that should be maintained. More specifically, the effect of moisture on MCC-containing tablets has been the subject of an investigation that demonstrates the sensitivity of this important excipient to moisture content [10]. These researchers found that differences exist in both the cohesive nature and the moisture content to two commercial brands of MCC. A very useful report on the equilibrium moisture content of some 30 excipients has been compiled by a collaborative group of workers from several pharmaceutical companies and appears in the Handbook of Pharmaceutical Excipients [11,12],... 

Because of the nature of modern pharmaceutical systems, formulators have made more complete investigations of the materials they use. This interest has identified several materials that may have more than one use in tableted systems. The type of effect that an excipient will produce is often dependent upon the concentration in which it is used. For example, Table 5 lists some multiuse excipients and the corresponding concentration ranges required for their various applications. 

Table 5 Some Multiple-Use Excipients for Tablet Formulation... 

The influence of the actual manufacturing process can also affect the contribution of the diluent to the final characteristics of the product. For instance, Shah et al. [45] demonstrated that the release of drug from tablets formulated with soluble excipients may be more... 

Few tablets intended for oral administration are totally soluble in aqueous media, but if such a product is needed, then soluble excipients are employed. These include dextrose, lactose, mannitol, and sodium chloride, with the last of these sometimes acting as its own lubricant. Urea may also be used, but due to its known pharmacological effects, it is less desirable than the other soluble compounds cited. 

For most tablets, it is necessary to overcome the cohesive strength introduced into the mass by compression. It is therefore common practice to incorporate an excipient, called a disintegrant, which induces this process. Several types, acting by different mechanisms, may be distinguished (a) those that enhance the action of capillary forces in producing a rapid uptake of aqueous liquids, (b) those that swell on contact with water, (c) those that release gases to disrupt the tablet... 

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