Tableting process properties

Since the viscoelastic properties of the solid undergo a significant change as the solid undergoes a transition from the amorphous to rubbery states (due to elevation of temperature at constant moisture content or to an increase in moisture content at constant temperature), one also expects marked changes in the processing properties of these solids as this transition occurs. Some properties that are likely to be affected include tablet compaction [76], gelatin capsule... 

To modify processing properties for the manufacture of finished dosage forms (tablets, capsules, parenterals, etc.)... 

Successful scale-up of the tableting process also requires control of the raw materials used in compaction. Typically, pharmaceutical excipients vary in their physicochemical properties, which result in batch-to-batch variations. The tableting process, especially direct compression processes where there is limited raw material alteration before compaction, is susceptible to raw material variation, which may be magnified upon scale-up. Compaction science affords the ability to fingerprint raw materials, including the drug substance, to determine if the same compaction properties will be observed from batch to batch. This also allows for a rational approach for determining alternate vendor sources of the same materials. 

It was demonstrated that dimensional analysis of the tableting process can produce a scientifically reliable way of predicting tablet properties across the range of materials and with diverse compaction mechanisms. A theoretically sound scale-up method is thus readily available for tableting equipment of different capacity. The method can be readily expanded to include other materials and tablet presses and other target quantities, such as tablet stability (disintegration) and bioavailability (dissolution). 

Microcrystalline Cellulose. Microcrystalline cellulose is a purified, partially depolymerized cellulose that occurs as a white, odorless, tasteless, crystalline powder composed of porous particles. It is widely used in pharmaceutical dosage forms, primarily as a filler-binder in oral tablets and capsules with both wet granulation and direct compression processes. Microcrystalline cellulose was marketed first in 1964 by the FMC Corporation under name Avicel PH in four different particle size grades, each with different properties.37 Addition of Avicel into a spray-dried lactose-based formulation overcame compressibility problems. At the same time, the lactose enhanced the flowability of the Avicel products available at that time. The direct compression tableting process became a reality, rather than a concept, partially because of the availability of Avicel. As of 2007, Avicel PH is commercially available in 10 types with different particle size, density, and moisture grades that have different properties and applications (Table 7.6).38 Other brands of microcrystalline cellulose are also available on the pharmaceutical market, including Pharmacel 101 and 102 from DMV International and Emcocel 50 M and 90 M from JRS Pharma. 

A tableting process depends on the physical parameters, as e.g. mean particle diameter dp, bulk density (porosity), flow behaviour (lubricating ability) of the powder, which depends also on humidity. These physical properties can be replaced by the lumped parameter powder compressibility K [136],... 

The aim of any tabletting process is to produce tablets that are of satisfactory quality. Virtually all tablet properties e.g., porosity, physical strength, disintegration... 

Most direct compression diluents are available from only one source, but a few can be obtained from more than one manufacturer. If multiple sources are available, they will be offered under individual registered names. For example, microcrystalline cellulose is available under a number of brand names such as Avicel (FMC Corporation), Emcocel (Edward Mendell), and Vivacel (J. Rettenmaier). Chemical properties of such materials will be similar if not completely identical, especially if there are pharmacopeial standards for identity and purity. However, it cannot be assumed that products from different manufacturers will have the similar physical properties which will govern their performance in the tabletting process. 

The amount of clearance (space) between interacting parts like punch/die and barrel/turret guide, depends on the tolerance range (deviation from theoretical dimensions due to practical manufacturing reasons) of tooling dimensions. The clearance between the die wall and the punch tip affects the tableting process as well as the mechanical properties of the finished product while the powder is compressed, air needs to be released, and when the compressed tablet is moved upwards within the die bore, friction on the die walls is affected by the clearance. 

Measurement of physical parameters (compaction, ejection and residual forces) in the tabletting process and the effect on the dissolution rate. Drug Dev Ind Pharm 1986 12 1329-1346. Baichwal AR, Augsburger LL. Variations in the friction coefficients of tablet lubricants and relationship to their physicochemical properties. J Pharm Pharmacol 1988 40 569-571. 

Schiller M, von der Heydt H. Marz F. Schmidt PC. Enhanced processing properties and stability of film-coated tablets prepared from roller-compacted and ion-exchanged Eschscholtzia califomica Cham. Dry extracts. STP Pharm Sci 2003 13 111-7. 

The free base of amonifide has undesirable processing properties, including high porosity, low compressibility, and bad flow properties. Replacing the free base with its dihydrochloride salt improved its processing in direct tablet compression. ... 

We have a list of possible additives (excipients) for a tablet. In formulating the tablet we want to know how its properties vary when changing the relative proportions of the excipients. In particular, we want to know which of these excipients will have the greatest effect on the measured properties of the tablet and the tableting process when changing their proportions. 

The compressional behavior of four polymorphs of mannitol (the a, P, and 5 forms, as well as one unidentified phase) has been studied [57]. It was found that the compressibility of the a-phase is superior, and fortunately this phase is the major form in most commercial products. The particle shape was found to exert an influence upon the compressibility properties granulated powders show better behavior than native crystalline powders. It was reported that no polymorphic transitions took place under the compression stresses used during the tableting process. 

Chem. Descrip. PEG-6 NF, FCC CAS 25322-68-3 EINECS/ELINCS 220-045-1 Uses Pharmaceuticals (carrier tor ointments for antiseptics and other medicaments, plasticizer in tablet coatings, base for suppositories, carrier, solvent, suspending agent in liq. preps., vehicle in gelatin capsules) thickener defoamer in fermentation and foal processing Properties Clear vise, liq. sol. in water m.w. 300 sp.gr. 1.125 dens. 9.36 Ib/gal f.p. -IOC vise. 69cSt flash pt. (PMCC) >400 F ref. index 1.463 sp. heat 0.508 cal/g/°C... 

Tablet Excipients. One of the important goals in tableting process is to produce tablets which are uniform in weight and strong enough to withstand the rigors of processing and packaging. It is also equally important that the tablets break down and dissolve upon administration for the release of the drug. Tablets with such desirable pharmaceutical properties can be prepared by using various types of polymeric excipients. It is the excipients that determine the compressibility, hardness, hygroscopy, friability, lubricity, stability, and dissolution rate of the prepared tablets.

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