**4.5 Particle size**

Particle size greatly affects a number of quality parameters like dissolution rate, solubility, bioavailability, content uniformity, and lack of grittiness. Application of particle size study during preformulation stage is described as follows:


A number of methods are available to determine particle size, which are as follows:


Apart from particle size, particle shape plays an important role during preformulation phase as the shape of particle may influence surface area, flow properties, and compaction force. A drug particle may exist in different forms like spherical,

**15**

*Preformulation Studies: An Integral Part of Formulation Design*

angular, acicular, needle, oval, or rough. It is a well-accepted fact that a spherical particle has the maximum area and uniform flow property. The maximum surface area ensures the better solubility. For topical products that are working as abrasives, irregular particle shape is more preferred. **Table 3** provides idea about various methods, which can control particle shape and size and provide better results

Density can be defined as ratio of mass of a substance to its volume, which greatly depends on particle size distribution and shape. The main problem arises during determination of bulk volume is the voids, which can be interparticulate, open, and closed intraparticulate. So by considering the presence of different types

• True density: It is defined as total volume of solids excluding all space

greater than molecule diameter. True density can be measured with helium

• Bulk density: It is defined as total volume occupied by entire powder mass. It can be determined by placing previously sieved powder bulk into a graduated cylinder and measuring the volume in milliliters. Division of original weight

• Tapped density: It is determined by placing graduated cylinder containing known weight of sample on tapped density apparatus and is operated for the fixed number of taps until a constant volume is attained. Ratio of total amount of substance taken to the final constant volume gives idea about tapped density.

One needs to gain knowledge about the size and type of dosage form and is the most critical parameter for the low potency drugs. In most of the cases, two types of

• With drugs having low density, the bulk becomes more and hence capsule formulation is quite difficult to formulate as capsule can incorporate limited

• In development of tablet formulation, low-density drug creates difficulties as they are having low compressibility and hardness in tablet is difficult to

• If the difference of density is more between drug substances and excipient

Flow property of material can be affected by a number of factors including frictional forces, surface tension forces, electric forces, and van der Waals forces. Efficient flow of drug substance powder is needed for effective tablet formulation. The main reason behind inclusion of this parameter in preformulation is its linkage with other physical parameters like hygroscopicity and particle size and shape. Importance of flow property is even more when dose loading is more.

is more, homogeneity in the formulation is difficult to achieve.

*DOI: http://dx.doi.org/10.5772/intechopen.82868*

of void volume, various densities are proposed.

and attended volume gives idea about bulk density.

density are studied, namely, bulk density and tapped density. Following problems can be addressed related to density:

needed to design a formulation.

**4.6 Density and porosity**

pycnometer.

volume.

achieve.

**4.7 Flow properties**

angular, acicular, needle, oval, or rough. It is a well-accepted fact that a spherical particle has the maximum area and uniform flow property. The maximum surface area ensures the better solubility. For topical products that are working as abrasives, irregular particle shape is more preferred. **Table 3** provides idea about various methods, which can control particle shape and size and provide better results needed to design a formulation.
