Qualitative and quantitative analyses of a pharmaceutical formulation produced by hot melt extrusion using Raman spectroscopy

In the pharmaceutical industry, Hot Melt Extrusion (HME) is a recent technique used to integrate poor water soluble drugs in pharmaceutical formulations. Indeed, more and more active pharmaceutical ingredients (API) belong to the Biopharmaceutical Classification System (BCS) II and IV. Their integration in pharmaceutical solid forms is a big deal. HME processes increase the bioavailability and the solubility of those API by encompassing them in a polymeric carrier and by forming solid dispersions [1]. Moreover, in 2004, the FDA’s guidance initiative promoted the usefulness of Process Analytical Technology (PAT) tools when developing a manufacturing process. Vibrational spectroscopy is an appropriate PAT tool to analyze extrudates [2 – 3]. In this case, Raman spectroscopy, which belongs to vibrational spectroscopy, was used to analyze itraconazole extrudates qualitatively and quantitatively.
During HME, the main objective is to develop solid dispersions by converting a crystalline API in an amorphous one, in order to improve its solubility and bioavailability [4]. According to Raman spectra, it is possible to identify the polymorphic form of the components in the extrudates by integrating or rationing the Raman bands that are characteristic of the API or by calculating the width at half intensity of some bands [5].
After determining the polymorphic form of the API, a quantitative method was developed in order to measure the ratio between the API and the polymer. Finally, chemical imaging was performed on extrudates to identify the distribution of the homogeneity of the API inside the polymer [6].
In conclusion, Raman spectroscopy is an appropriate tool to follow an extrusion process. By qualitative and quantitative analyses it is possible to determine the composition, the polymorphic form, the homogeneity, and the concentration of pharmaceutical matrices according to Raman fingerprint.

References:
[1] S. Shah et. al., Int J Pharm 453 (2013) 233 – 252.
[2] L. Saerens et. al., Anal Chem 85 (2013) 5420 – 5429.
[3] T. De Beer et. al., J Pharm Biomed Anal 48 (2008) 772 – 779.
[4] A. Sarode et. al., Eur J Pharm Sci 48 (2013) 371 – 384.
[5] E. Widjaja et. al., Eur J Pharm Sci 42 (2011) 45 – 54.
[6] J. M. Amigo, Anal Bioanal Chem 398 (2010) 93 – 109.