**4.6 Density and porosity**

*Pharmaceutical Formulation Design - Recent Practices*

**Process Affected properties**

Encapsulation Particle shape and size

Precipitation Surface area, particle size, shape

*Utilization of different salts to give environment with different RH.*

Chemical reaction Surface area and particle shape

*Use of different process to control particle size, shape, and surface area.*

Crystallization Particle shape, size, crystalline/amorphous nature

**Substance used % RH achieved** Silica gel 0% Potassium acetate 20% Calcium chloride 30% Potassium bromide 85% Water 100%

Particle size greatly affects a number of quality parameters like dissolution rate, solubility, bioavailability, content uniformity, and lack of grittiness. Application of

• When solubility is major issue, one may significantly improve the solubility by

• In case of suspension, particle size is the most important parameter, which determines the stability and quality of formulation. Too much reduction in the particle size leads to generation of charged particle and hence unstable system.

• Due to nonuniform particle size distribution, there is significant risk associ-

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

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,

particle size study during preformulation stage is described as follows:

ated with content uniformity in case of potent formulations.

• Surface area determination by nitrogen adsorption method

reducing the particle size (increased surface area).

On other hand, larger particle size leads to caking.

**14**

follows:

• Microscopy

• Sedimentation rate

• Coulter counter method

**4.5 Particle size**

**Table 5.**

**Table 4.**

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 of void volume, various densities are proposed.


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 density are studied, namely, bulk density and tapped density.

Following problems can be addressed related to density:

