**4.4 Prediction of behavior of a new pharmaceutical ingredient (APIs and excipients)**

SeDeM-ODT expert system has been applied for the determination of suitability of new powdered substances for direct compression. The powder substance may be a new API or excipients which are intended to be used in formulation of compact solid dosage forms.

Sune-Negre et al. used the SeDeM method to characterize an active product ingredient in powder form (API SX-325) and to determine whether it is suitable for direct compression [12], applying the profile to the SeDeM diagram. Twelve parameters were determined for the powdered raw material according to the standard protocols, presented as SeDeM diagram, indicating suitability of the material for direct compression. Findings of the study implied deficient rheological characteristics and poor stability. The product was declared hygroscopic on the basis of SeDeM profile and tended to capture moisture, worsening rheological characteristics and impairing its stability. Various precautionary measures were suggested for prevention of negative effects like drying of the material and tablet preparation in an environment of controlled humidity (relative humidity below 25%).

Sune-Negre et al. applied SeDeM expert system for characterization of 51 directly compressible excipients [12]. On the basis of the results, directly compressible excipients were classified into different groups with different rheological and compressibility capability, and a periodic table of directly compressible excipients was developed, as shown in **Figure 6**.

They showed that the best excipient for direct compression should have an index of good compressibility of 8.832 [12]. SeDeM expert system has been applied for the

where CP is the % of corrective excipient, RE is the mean-incidence radius value (compressibility) of the corrective excipient, R is the mean-incidence radius value to be obtained in the blend, RP is the mean-incidence radius value (compressibility) of the API to be corrected, and R is the 5 as 5 is the minimum value that is regarded

**Figure 4** presents a strategy for the development of orally disintegrating tablets

as necessary in order to achieve good compression [14].

**substances**

**Figure 4.**

*Advanced Functional Materials*

strength after taste masking.

**180**

by direct compression by applying the proposed equation (Eq. (10)).

*Strategy proposed by SeDeM expert system to develop orally disintegrating tables [14].*

**4.3 Elucidation of the effect of processing on characteristics of powder**

SeDeM-ODT expert system has been applied for elucidation of the effect of processing parameters on characteristics of powder substance. Amjad et al. applied SeDeM-ODT expert system for predicting the effect of taste masking on the rheological characteristics, mechanical strength, and disintegration behavior of highly water-soluble drug (Itopride HCl) [31]. Itopride HCl is a bitter-tasting, highly water-soluble drug with poor rheological characteristics. Taste of Itopride HCl was masked by water-based wet granulation technique using HPMC as taste masking polymer. Itopride HCl powder was the subjected characterization as per SeDeM-ODT expert system, before and after taste masking, and results were compared (**Figure 5**) to evaluate the effect on rheological characteristics, disintegration behavior, and mechanical strength. Dimension factor and flowability/powder flow factors were below the acceptable limit. Comparison of results before and after taste masking showed that taste masking significantly improved the mechanical strength and rheological characteristics and decreased the disintegration behavior of powder. It was concluded that in order to formulate by direct compression, the formulation will require large amount of disintegrant to overcome increase in mechanical

Amjad [32] has applied SeDeM-ODT expert system for the optimization of process variables of roller compaction. He studied ribavirin powder and powder


characteristics [35]. For example, various disintegrants and diluents were characterized on the basis of the expert system [13], and the suitable one is selected for a particular formulation. Various parameters are determined according to the SeDeM expert system, deficiencies are defined, and an adequate substance can be selected to get a final blend suitable for direct compression. In a study [11] several lactose were characterized and differentiated on the basis of SeDeM expert system.

*SeDeM-ODT Expert System: A Solution to Challenges in Characterization of Pharmaceutical…*

*SeDeM diagram of different batches of glucosamine sulfate [35].*

*DOI: http://dx.doi.org/10.5772/intechopen.92444*

SeDeM-ODT expert system is a novel tool for the characterization of powder substances on the basis of their physical parameters. The system has been successfully applied for the determination of rheological characteristics, mechanical strength, and disintegration behavior of pharmaceutical powders (APIs and excipi-

dispersibility. SeDeM-ODT expert system facilitates the process of excipient selection and calculation of their relative proportion in oral solid dosage form. A data base can be developed for various excipients which will help in the selection of excipients having desired characteristics. It avoids extra experimentation for optimization of various characteristics of powder blend, reducing the cost and time span of formulation development process. This method characterizes the individual components of a formulation and applies a mathematical analysis to determine the exact amount of each ingredient in the final formulation. This innovative tool is consistent with the current requirements of regulatory health authorities such as the FDA and ICH, whereas data generated on the basis of the system can contribute to the concept of Quality by Design. SeDeM-ODT expert system has certain limitations, and misleading results are possible in certain cases. Suitability of material for direct compression is decided on the basis of index of good compressibility value, which is based on "r" values of the individual parameters. Substances having high "r" values will raise IGC value and vice versa. So suitability of a material should not be judged on the basis of IGC value. The incidence factor value should be considered, and outliers in "r" value of the individual factors, if present, should be properly addressed. Overall SeDeM-ODT expert system is an unmatched tool for material characterization at pre-formulation level and has significantly decreased

ents) and determination of suitability for direct compression and bucco-

time span and cost of pharmaceutical formulation development process.

**5. Conclusions**

**183**

**Figure 7.**

#### **Figure 6.**

*Correction of "compressibility" and "flowability" of APIs with excipient [12].*

determination of reproducibility of various batches of pharmaceutical ingredients (APIs and excipients). Various batches were characterized according to the SeDeM expert system, and reproducibility was estimated on the basis of consistency of the results [13].
