**6. Conclusion**

It can be concluded that preformulation is a proactive phase that deals with transformation of new chemical entity into a safe, effective, and most importantly stable pharmaceutical formulation.

**19**

**Author details**

Pinak Patel

provided the original work is properly cited.

Smt. S.M. Shah Pharmacy College, Mehemdabad, India

\*Address all correspondence to: pinakqa@gmail.com

*Preformulation Studies: An Integral Part of Formulation Design*

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

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

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

*Pharmaceutical Formulation Design - Recent Practices*

In such incompatibility, there is interaction of active pharmaceutical ingredient and excipient through chemical degradation pathway. The chemical reaction involves bond breakage or new bond formation to produce an unstable chemical entity. Chemical reaction may take place as hydrolysis, oxidation racemization, and Maillard reactions. The resulting changes are more deleterious than physical incompatibility. This type of incompatibility can be assessed by chromatographic studies. One of the classical examples of chemical incompatibility is exhibited by reaction of lactose with amino group of active pharmaceutical ingredient referred to as "Maillard reaction" and results into darkening of formulation with characteristic odor. Classical example is of a bronchodilator aminophylline, in which ethylenediamine moiety is reduced by lactose and as a result brown discoloration appeared in samples containing 1:5 (w/w) mixtures of aminophylline and lactose after storing at

Such interaction is also referred to as biopharmaceutical interaction, but it differs from previously discussed incompatibilities in a way that interaction will take place once the formulation is administered into the body. Such type of incompatibility is associated with alteration in drug absorption in the body. In other way, one can say that interaction is taking place between excipient, active component, and physiological fluid. One of the classical examples of such incompatibility is interaction of enteric coated polymers, when administered along with antacids. In such an event, they dissolve prematurely and release the drug that is liable to acid degradation or may cause adverse effect in GI, that is, gastric bleeding associated

There are specific methods that are employed to determine the existence of incompatibility between excipient and the active pharmaceutical ingredient. Out of all analytical techniques, thermal methods of analysis can provide most positive outcome. In association with thermal methods of analysis, spectroscopic techniques like X-ray diffraction and infrared spectroscopy can provide sideline assistance. High-performance liquid chromatography and thin-layer chromatography provide the more suitable way of studying chemical incompatibilities and provide qualita-

It can be concluded that preformulation is a proactive phase that deals with transformation of new chemical entity into a safe, effective, and most importantly

**5.2 Chemical incompatibility**

60°C for 3 weeks [16].

with NSAIDs [17].

**6. Conclusion**

**5.3 Therapeutic incompatibility**

tive and quantitative assessments.

stable pharmaceutical formulation.

**18**
