**4.7 Flow properties**

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.

**Table 6** gives outline on correlation of flow properties of a material with moisture uptake at different humidity levels.


Normally, flow property of solid drug substance can be measured by Hausner ratio, Carr's index, and angle of repose, and in case of liquids or semisolid, rheology and thixotropy. Carr's compressibility index can be represented by the following formula.

$$\text{xotropy. Carr's compressibility index can be represented by the following formula}$$

$$\text{Carr's compressibility index} = \frac{\text{Tapped density - Bulk density}}{\text{Tapped density}} \times 100.\tag{3}$$

Hausner's ratio can be represented by the following equation:

$$\text{Hausner's ratio can be } \texttt{Teprecium} \text{ and by the following equation:}$$

$$\texttt{Hausner's ratio} = \frac{\texttt{Tapped density}}{\texttt{Bulk density}}.\tag{4}$$

**Table 7** provides the correlation between Carr's index, Hausner's ratio, and flowability.

Another way of measuring flow property is angle of repose, which provides the idea resistance to the movement of particle. It can be represented by the following formula:

$$
\tan \Theta = \mathcal{Z}h/D \tag{5}
$$

**17**

*Preformulation Studies: An Integral Part of Formulation Design*

It is the maximum angle that can be obtained between height of pile and a horizontal plane. It gives a brief idea about internal cohesive and frictional levels. There

Excipients are added along with the active pharmaceutical ingredient in formulations. Most excipients possess biological activity but having role in administration, mediating the release of the active component, and providing stability against degradation. However, inappropriate excipients can also give rise to inadvertent and/or unintended effects, which can affect the chemical nature, the stability, and the bioavailability of the API, and consequently, their therapeutic efficacy and safety. So study about interaction between active ingredient and inactive ingredient can provide idea about type of incompatibility and the justification behind the

are basically two types of methods that are available, which are as follows:

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

Static angle of repose

1.Fixed funnel method

2.Fixed cone method

2.Tilting box method

Dynamic angle of repose

1.Rotating cylinder method

**5. Drug excipient compatibility**

inactive ingredient selection [14].

**5.1 Physical incompatibility**

• Change in organoleptic properties of formulation.

• Decreased potency of active ingredient.

• Generation of toxic degradation product.

• Changes in in vivo performance of formulation, that is, dissolution.

• Change in physical appearance of formulation, that is, color, phase conversion.

In general, one can say that drug-excipient incompatibility may result in change in

In such an instance, active pharmaceutical ingredient and excipients interact without undergoing changes involving like breaking or formation of new bonds. The resulting drug product retains its original chemical properties but may involve changes such as alteration in physical properties. Such interaction results in changes like change in color, odor, flow properties, and sedimentation rate. Such an example of physical incompatibility is between tetracycline and calcium carbonate. It results in formation of insoluble complex with calcium carbonate, leading to slower dis-

physical, chemical, microbiological, or therapeutic properties of formulation.

solution and decreased absorption in the gastrointestinal tract [15].


#### **Table 6.**

*Correlation between relative humidity, moisture uptake, and flowability.*


#### **Table 7.**

*Correlation between Carr's index, Hausner's ration, and flowability.*

*Preformulation Studies: An Integral Part of Formulation Design DOI: http://dx.doi.org/10.5772/intechopen.82868*

It is the maximum angle that can be obtained between height of pile and a horizontal plane. It gives a brief idea about internal cohesive and frictional levels. There are basically two types of methods that are available, which are as follows:

Static angle of repose

*Pharmaceutical Formulation Design - Recent Practices*

uptake at different humidity levels.

property of drug.

flowability.

formula:

**Table 6** gives outline on correlation of flow properties of a material with moisture

• In case of hygroscopic material, flow property of drug tends to deteriorate as

• Irregular particle size and nonuniform shape can also disturb normal flow

Carr's index, and angle of repose, and in case of liquids or semisolid, rheology and thixotropy. Carr's compressibility index can be represented by the following formula. Carr� <sup>s</sup> compressibility index <sup>=</sup> Tapped density <sup>−</sup> Bulk density \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ Tapped density <sup>×</sup> 100. (3)

**Table 7** provides the correlation between Carr's index, Hausner's ratio, and

Another way of measuring flow property is angle of repose, which provides the idea resistance to the movement of particle. It can be represented by the following

tanθ = 2*h*/*D* (5)

40 0.35 Base of powder adheres to the container

**Relative humidity (%) Moisture uptake (%) Flowability** 0.30 Free flowing 0.24 Free flowing 0.27 Less free flowing

80 0.62 Cake formation

**Carr's index Hausner's ratio Flowability** 5–15 1.05–1.18 Excellent 12–16 1.14–1.20 Good 18–21 1.22–1.26 Fair-passable 23–35 1.30–1.54 Poor 33–38 1.50–1.61 Very poor Greater than 40 Greater than 1.67 Very very poor

*Correlation between Carr's index, Hausner's ration, and flowability.*

*Correlation between relative humidity, moisture uptake, and flowability.*

Normally, flow property of solid drug substance can be measured by Hausner ratio,

Bulk density . (4)

the presence of absorbed moisture increases cohesiveness.

Hausner's ratio can be represented by the following equation:

Hausner� <sup>s</sup> ratio <sup>=</sup> Tapped density \_\_\_\_\_\_\_\_\_\_\_\_

**16**

**Table 7.**

**Table 6.**


Dynamic angle of repose

