**4. MCC as pharmaceutical excipients**

According to the International Pharmaceutical Excipient Council (IPEC), excipients are the process aids or any substances other than the active pharmaceutical ingredient that are included in pharmaceutical dosage forms. The functionalities of excipient are to impart weight, consistency, and volume which allow accuracy of dose, improve solubility, and in the end increase stability. It can also be proposed to enhance bioavailability, modifying drug release and used in product quick identification, increase patient acceptability, and facilitate dosage form design.

Excipients classified as:

1.Primary excipients: diluents (filler), binders (adhesives), disintegrants, lubricants, antiadhesives, glidants

2.Secondary excipients: coloring agents, flavors, sweeteners, coating agents, plasticizers wetting agents, buffers, and adsorbents

Diluents are incorporated into tablet or capsule dosage forms to increase dosage form volume or weight and can also be referred as fillers. Direct compression binders are functional even at low use levels and offer superior tabletability [1]. Some diluents, such as microcrystalline cellulose, can also be considered as dry binders since they improve the compactibility or tabletability of the compression mix.

Microcrystalline cellulose, according to many publications, is an excipient of outstanding merit and remains the most widely used direct compression excipient serving as a strong dry binder, tablet disintegrant, an absorbent, filler or diluent, a lubricant, and anti-adherent.

MCC is generally considered as the diluent having the best binding properties and is recognized as one of the preferred DC binders [44, 76]. It is used as a binder/ diluent in oral tablet and capsule formulations including both wet granulation and direct compression processes. It also has some lubricant and disintegrant properties which is useful in direct tableting. Small amounts of MCCs are able to efficiently bind other materials, especially poorly tabletable active pharmaceutical ingredients. MCC exhibits a high dilution potential, whereas the broad particle size range provides optimum packing density and coverage of other materials [44, 54].

MCC has been the most favorite diluent among others due to its low bulk density. Excipient having low bulk density and large particle size distribution will exhibit a high dilution potential on a weight basis, optimum packing density, and coverage of drug and other excipient materials [77].

MCC is commercially available in different particle sizes, density, and moisture grades that have different properties and applications. The most widely pronounced grades are Avicel PH 101 and Avicel PH 102 (FMC Corporation, Princeton, NJ, USA). PH stands for the pharmaceutical grade of MCC. Avicel PH 101 is the original grade of MCC, while PH 102 is available as a partially agglomerated product with a larger particle size distribution and slightly better fluidity. Both grades show no significant difference in the compressibility [78].

#### **4.1 MCC as directly compressible filler**

MCC has been very well known as the most compressible of all direct compression fillers which has the highest dilution potential and capacity. It is defined as the amount of active ingredient that a diluent can successfully carry in the direct compression method. This property can be explained by the basis of the physicochemical nature of MCC particles, which are held together by hydrogen bonds. MCC particles are deformed plastically under compaction forces to yield an extremely large number of clean surfaces brought in contact during this deformation, forming a strong compact even under low compression forces [78].

Direct compression (DC) is the tableting process of a blend of ingredients without a preliminary granulation or agglomeration process. Despite involving only few process steps, product design in DC can be challenging because of the numerous competing objectives [79]. Direct compression requires increased performance, quality, and consistency from the starting ingredients including excipients [44, 56, 80, 81]. The use of poorly controlled or inadequately specified raw materials may lead to several challenges in DC, such as poor flowability and inconsistent tablet weight, unsatisfactory tablet strength, lack of content uniformity or segregation, and dissolution failure [56, 82, 83]. Among several requirements, the compression mix has to flow to ensure a consistent tablet weight; it has to compress and compact into robust tablets. Overall, as a direct compression filler, Avicel promotes efficient

**49**

*Microcrystalline Cellulose as Pharmaceutical Excipient DOI: http://dx.doi.org/10.5772/intechopen.88092*

particle size approximating 200 mm [58, 85].

ness and color stability.

enable improved flow.

order to design robust formulations.

**4.2 MCC as wet granulation filler**

dry blending of ingredients and produces tablets with high hardness levels and low friability levels with excellent compression. It produces tablets of superior white-

Lately, MCC can be considered as the most widely used diluent in the direct compression and wet granulated tablet making procedures. MCC type 102, having a median particle size of about 100 mm (D50 value measured by laser diffraction), presents acceptable flow properties required for successful high-speed tableting [2, 84]. However due to the low bulk density of MCC, its mass flow is less than that of other common and denser excipients such as direct compression grades of lactose or dibasic calcium phosphates [43, 44, 59, 82]. Avicel grades (Avicel PH-102 SCG, Avicel HFE-102, Avicel PH-200, Avicel PH-302) provide excipient solutions to many challenges of direct compression formulations including improved flow, better compressibility, and accommodation of moisture-sensitive actives [78]. The larger particle size grades generally provide better flow properties, while lowmoisture grades are used for moisture-sensitive materials. Higher-density grades have improved flowability. Flowability may be improved by selecting coarser grades of MCC with a larger number of aggregates, such as MCC type 200 with a median

The difference between these common excipients is less pronounced on a volumetric basis [86], which determines die fill. Another approach may be to combine MCC with other free flowing excipients or glidants [59, 62, 87]. Gamble et al. observed that the particle size distributions of coarser grades of MCC do not scale up proportionally [58]. MCC types 101, 102, and 200 all have primary particles of about 50 mm but differ in the number of larger aggregated particles. These aggregates, accounting for a large volume/mass fraction but a low number fraction,

During compression, MCC plastically deforms and therefore maximizes the area of interparticle bonding [88]. Mechanical interlocking of irregularly shaped and elongated MCC particles has also been suggested to enhance tabletability [44, 60, 75]. The plasticity of MCC is the main reason of its exceptional binding properties. However, compared to brittle excipients, MCC is more lubricant sensitive. For a constant number of revolutions, tabletability may also decrease with increasing blender sizes and decreasing loadings in the blender [89]. The viscoelastic behavior of MCC also explains its strain rate sensitivity (SRS), which refers to the greater elastic effects at higher tableting speeds where there is insufficient compaction time for plastic deformation [90]. The strain rate sensitivity of viscoelastic excipients has to be taken into account by the formulation scientists in

MCC is one of the types of filler which is water insoluble having swelling tendencies and excellent water imbibing or wicking action. Other filler examples with the same property are calcium pectinate and sodium alginate. This property makes MCC as also an excipient of choice for wet granulation. Both Avicel PH 101 and Avicel PH 102 can be used advantageously as fillers in wet granulation in a concentration of 5.15%. When used as filler in wet granulation method, the wicking action of MCC promotes rapid wetting of the powder mix. Another advantage offfered by using MCC as wet granulation filler is the ability to retain water, which makes the wet mass less sensitive to overwetting due to an excess of granulating fluid. The milling of the wet mass will be much easier due to less clogging of the screen; hence it will produce a more uniform granules. Drying process also will be more homogeneous, and the case of hardening can be reduced. Case hardening is a phenomenon

*Pharmaceutical Formulation Design - Recent Practices*

lubricant, and anti-adherent.

plasticizers wetting agents, buffers, and adsorbents

coverage of drug and other excipient materials [77].

significant difference in the compressibility [78].

a strong compact even under low compression forces [78].

**4.1 MCC as directly compressible filler**

2.Secondary excipients: coloring agents, flavors, sweeteners, coating agents,

Diluents are incorporated into tablet or capsule dosage forms to increase dosage form volume or weight and can also be referred as fillers. Direct compression binders are functional even at low use levels and offer superior tabletability [1]. Some diluents, such as microcrystalline cellulose, can also be considered as dry binders since they improve the compactibility or tabletability of the compression mix. Microcrystalline cellulose, according to many publications, is an excipient of outstanding merit and remains the most widely used direct compression excipient serving as a strong dry binder, tablet disintegrant, an absorbent, filler or diluent, a

MCC is generally considered as the diluent having the best binding properties and is recognized as one of the preferred DC binders [44, 76]. It is used as a binder/ diluent in oral tablet and capsule formulations including both wet granulation and direct compression processes. It also has some lubricant and disintegrant properties which is useful in direct tableting. Small amounts of MCCs are able to efficiently bind other materials, especially poorly tabletable active pharmaceutical ingredients. MCC exhibits a high dilution potential, whereas the broad particle size range provides optimum packing density and coverage of other materials [44, 54]. MCC has been the most favorite diluent among others due to its low bulk density. Excipient having low bulk density and large particle size distribution will exhibit a high dilution potential on a weight basis, optimum packing density, and

MCC is commercially available in different particle sizes, density, and moisture grades that have different properties and applications. The most widely pronounced grades are Avicel PH 101 and Avicel PH 102 (FMC Corporation, Princeton, NJ, USA). PH stands for the pharmaceutical grade of MCC. Avicel PH 101 is the original grade of MCC, while PH 102 is available as a partially agglomerated product with a larger particle size distribution and slightly better fluidity. Both grades show no

MCC has been very well known as the most compressible of all direct compression fillers which has the highest dilution potential and capacity. It is defined as the amount of active ingredient that a diluent can successfully carry in the direct compression method. This property can be explained by the basis of the physicochemical nature of MCC particles, which are held together by hydrogen bonds. MCC particles are deformed plastically under compaction forces to yield an extremely large number of clean surfaces brought in contact during this deformation, forming

Direct compression (DC) is the tableting process of a blend of ingredients without a preliminary granulation or agglomeration process. Despite involving only few process steps, product design in DC can be challenging because of the numerous competing objectives [79]. Direct compression requires increased performance, quality, and consistency from the starting ingredients including excipients [44, 56, 80, 81]. The use of poorly controlled or inadequately specified raw materials may lead to several challenges in DC, such as poor flowability and inconsistent tablet weight, unsatisfactory tablet strength, lack of content uniformity or segregation, and dissolution failure [56, 82, 83]. Among several requirements, the compression mix has to flow to ensure a consistent tablet weight; it has to compress and compact into robust tablets. Overall, as a direct compression filler, Avicel promotes efficient

**48**

dry blending of ingredients and produces tablets with high hardness levels and low friability levels with excellent compression. It produces tablets of superior whiteness and color stability.

Lately, MCC can be considered as the most widely used diluent in the direct compression and wet granulated tablet making procedures. MCC type 102, having a median particle size of about 100 mm (D50 value measured by laser diffraction), presents acceptable flow properties required for successful high-speed tableting [2, 84]. However due to the low bulk density of MCC, its mass flow is less than that of other common and denser excipients such as direct compression grades of lactose or dibasic calcium phosphates [43, 44, 59, 82]. Avicel grades (Avicel PH-102 SCG, Avicel HFE-102, Avicel PH-200, Avicel PH-302) provide excipient solutions to many challenges of direct compression formulations including improved flow, better compressibility, and accommodation of moisture-sensitive actives [78]. The larger particle size grades generally provide better flow properties, while lowmoisture grades are used for moisture-sensitive materials. Higher-density grades have improved flowability. Flowability may be improved by selecting coarser grades of MCC with a larger number of aggregates, such as MCC type 200 with a median particle size approximating 200 mm [58, 85].

The difference between these common excipients is less pronounced on a volumetric basis [86], which determines die fill. Another approach may be to combine MCC with other free flowing excipients or glidants [59, 62, 87]. Gamble et al. observed that the particle size distributions of coarser grades of MCC do not scale up proportionally [58]. MCC types 101, 102, and 200 all have primary particles of about 50 mm but differ in the number of larger aggregated particles. These aggregates, accounting for a large volume/mass fraction but a low number fraction, enable improved flow.

During compression, MCC plastically deforms and therefore maximizes the area of interparticle bonding [88]. Mechanical interlocking of irregularly shaped and elongated MCC particles has also been suggested to enhance tabletability [44, 60, 75]. The plasticity of MCC is the main reason of its exceptional binding properties. However, compared to brittle excipients, MCC is more lubricant sensitive. For a constant number of revolutions, tabletability may also decrease with increasing blender sizes and decreasing loadings in the blender [89]. The viscoelastic behavior of MCC also explains its strain rate sensitivity (SRS), which refers to the greater elastic effects at higher tableting speeds where there is insufficient compaction time for plastic deformation [90]. The strain rate sensitivity of viscoelastic excipients has to be taken into account by the formulation scientists in order to design robust formulations.
