The development of an inline Raman spectroscopic analysis method as a quality control tool for hot melt extruded ramipril fixed-dose combination products

Abstract

, Y. (2019). The development of an inline Raman spectroscopic analysis method as a quality control tool for hot melt extruded ramipril fixed-dose combination products.

The development and validation of a quality by design based process analytical tool for the inline quantification of Ramipril during hot-melt extrusion

“…Extrusion was performed at various conditions as outlined in Table 2. An in-house designed, 2 mm diameter die was fitted to the end of the barrel to accommodate the inline Raman probe (Andrews et al, 2019). The extrudates produced were collected and stored in bags for further analysis.…”

“…Linearity was observed with a goodness of fit (R 2 ) of 0.9999. RMP-DKP concentration was then normalised to the concentration of RMP using Equation 1 (Andrews et al, 2019):…”

“…10 μL of each sample was injected to the column using an auto-sampler. The mobile phase consisting of an aqueous solution of 0.1M sodium perchlorate adjusted to pH 2.5 using phosphoric acid (mobile phase A), and acetonitrile (mobile phase B) was pumped to the system under gradient mode at varied flow rates between 0.8 and 1.5 mL/min (Andrews et al, 2019). Detection was achieved using a UV detector at a wavelength of 210nm.…”

“…In our previous work, the feasibility of utilizing hot melt extrusion (HME) as a continuous processing platform for the thermolabile drug Ramipril (RMP) was demonstrated (Andrews et al, 2019). Offline HPLC and LC-MS were used as reference methods to quantify RMP and its degradation product ramipril-diketopiperazine (RMP-DKP).…”

Development and Validation of an in-line API Quantification Method Using AQbD Principles Based on UV-Vis Spectroscopy to Monitor and Optimise Continuous Hot Melt Extrusion Process

“…To minimise day to day variability, KOL readings from each experiment day were used to normalise the transmittance spectra of the samples. Studies with Raman and NIR use other common pre-processing techniques such as derivatives [30], standard normal variate transformation [32] and multiple scatter correction [36]. These techniques can be complex to implement [37] and for the UV-Vis were not required.…”