Filler/binders requirements

However, some excipients have multiple functions. For example, microcrystalline cellulose can function as a filler, a binder, and a disintegrant. As seen in Table 7.3, a typical low-dose formulation could include more than 85% filler—binders. Thus, physical and chemical properties for these specialty excipients are extremely important in a low-dose formulation for manufacturability, product performance, and longterm stability. Because the poor physicomechanical properties of components are not altered during manufacture as they are in the wet or dry granulation process, critical material properties and their impact on product quality attributes should be well characterized and understood.23 Discussion in this section will focus on fillers-binders. For those requiring more information on excipients, several excellent books and review articles are available in the literature.24-27... 

There are many commercially available direct compression filler-binders. The most commonly used filler-binders include spray-dried lactose, mannitol, microcrystalline cellulose, pregelatinized starch, and dibasic calcium phosphate. Many factors affect the selection of a filler-binder for a direct compression tablet formulation. The most important requirements for a directly compressible filler-binder used in a low-dose formulation are listed below ... 

Certainly, not a single excipient meets all the optimum requirements. Therefore, it is common to use a combination of two filler-binders in order to obtain a formulation with excellent tableting properties. 

Formulation design is based on the physical, chemical, and biopharmaceutical properties of a drug substance. A formulation for direct compression is composed of active pharmaceutical ingredients and other inactive ingredients such as fillers, binders, dis-integrants, flow aids, and lubricants. Simplicity is the basis of good formulation design. Minimally, a direct compression tablet formulation must meet requirements for manufacturability, uniformity of dose, physical and chemical stability, appropriate dmg release profiles, and bioavailability. In addition, the formulation must meet many quality standards and special requirements to ensure the efficacy and safety of the product. 

For a two-level factorial design, only two excipients can be selected for each factor. However, for the filler-binder, a combination of brittle and plastic materials is preferred for optimum compaction properties. Therefore, different combinations such as lactose with MCC or mannitol with starch can count as a single factor. Experimental responses can be powder blend flowability, compactibility, blend uniformity, uniformity of dose unit, dissolution, disintegration, and stability under stressed storage conditions. The major advantage of using a DOE to screen prototype formulations is that it allows evaluation of all potential factors simultaneously, systematically, and efficiently. It helps the scientist understand the effect of each formulation factor on each response, as well as potential interaction between factors. It also helps the scientist identify the critical factors based on statistical analysis. DOE results can define a prototype formulation that will meet the predefined requirements for product performance stability and manufacturing. 

FillerlBinders. Filler/binders are used in direct compression of tablets. The requirements they have to fulfill are summarized by Khan and Rhodes. " An important factor in the evaluation of filler/binders is... 

The art of mixing various size fractions is empirical, aimed at minimizing the amount of binder required to produce an adequate density. As a rule, binder requirements increase with decreasing size of filler particle. 

Part of the FPC system requirements specified by CEN EN 13108-21 (2008) is inspection and testing on incoming constituent materials and on finished bituminous mixture (delivered product). As constituent materials, the following are distinguished aggregates, filler, binders, additives and reclaimed asphalt. 

The development of excipients of new chemical composition requires extensive toxicology tests. This is a costly preposition and so, in the last three decades, only a few such new excipients have been introduced in the market [23], Therefore, improved filler-binders have mainly been generated via physical manipulation of existing excipient materials, i.e., as the physical mixture of GRAS (generally regarded as safe) materials [24]. 

Making paper without pollution requires that each part of the process be nonpolluting. The chemicals most commonly used in the production of pulp are NaOH and Na2 S. In modem paper mills, sulfur-containing by-products are scmbbed from the plant exhaust, and the aqueous sodium hydroxide is reclaimed and recycled. The fillers used to make paper opaque—titanium dioxide, calcium carbonate, and kaolin (a clay)—are natural, nonpolluting minerals. The polymer binders and sizers are relatively easy to recapture from the aqueous waste stream. 

Cementitious materials use a hydraulically setting cement such as Portland cement as a binder with a filler material of good insulation properties, e.g., verminculite, perlite, etc. Concrete us frequently used for fireproofing because it is easily installed, readily available, is quite durable and generally economical compared to other methods. It is heavy compared to other materials and requires more steel to support that other methods. 

Typical liquid systems require doses between 10 and 50 kGy. They consist of binders (prepolymers) with acrylic (H2C=CH-CO-0-) double bonds in the main chain (polymaleates and polyfumarates) and of monomers, usually acrylates used as reactive thinners. Other ingredients added to the formulation may be pigments, dyes, fillers, flatting agents, and additives to improve film and surface properties and attain the required performance criferia. ... 

Such techniques have been tried with solid propellants, but reproducible results depend on attaining complete binder-filler release and adequately measuring the binder sol fraction. Preliminary swelling studies to determine a solvent system and conditions which do not degrade the propellant are required. Common extraction techniques are used to determine the sol fraction. This determination is then applied as a correction when computing crosslink density. The force-deformation relationship for swollen rubbers is... 

The inhibition of composite propellants is somewhat easier than that of DB propellants. The binders used for composite propellants (with or without fillers) have been reported for inhibition of composite propellants. Such inhibition systems possess stronger bonds with composite propellants and prove to be more compatible coupled with better shelf-life of the inhibited propellants. However, epoxy or novolac epoxy resin with or without inert fillers is generally preferred for the inhibition of composite propellants due to a combination of properties possessed by them. The inhibition is usually done by casting technique and inhibition thickness is usually required on higher side in order to make the missions successful. In India, thread winding technique or inhibitor sleeve technique is preferred where 2.5-3.0mm inhibition thickness is sufficient as against 3.5-4.0 mm in case of inhibition by casting technique . 

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