Development of an analytical method for crystalline content determination in amorphous solid dispersions produced by hot-melt extrusion using transmission Raman spectroscopy: A feasibility study.

The development of a quantitative method determining the crystalline percentage in an amorphous solid dispersion is of great interest in the pharmaceutical field. Indeed, the crystalline Active Pharmaceutical Ingredient transformation into its amorphous state is increasingly used as it enhances the solubility and bioavailability of Biopharmaceutical Classification System class II drugs. One way to produce amorphous solid dispersions is the Hot-Melt Extrusion (HME) process.

Critical review of surface-enhanced Raman spectroscopy applications in the pharmaceutical field.

Surface-enhanced Raman spectroscopy (SERS) is a sensitive analytical tool used in the pharmaceutical field in recent years. SERS keeps all the advantages of classical Raman spectroscopy while being is more sensitive allowing its use for the detection and the quantification of low-dose substances contained in pharmaceutical samples. However, the analytical performance of SERS is limited due to the difficulty to implement a quantitative methodology correctly validated.

Global approach for the validation of an in-line Raman spectroscopic method to determine the API content in real-time during a hot-melt extrusion process.

Since the Food and Drug Administration (FDA) published a guidance based on the Process Analytical Technology (PAT) approach, real-time analyses during manufacturing processes are in real expansion. In this study, in-line Raman spectroscopic analyses were performed during a Hot-Melt Extrusion (HME) process to determine the Active Pharmaceutical Ingredient (API) content in real-time. The method was validated based on a univariate and a multivariate approach and the analytical performances of the obtained models were compared.

Continuous production of itraconazole-based solid dispersions by hot melt extrusion: Preformulation, optimization and design space determination.

The purpose of this work was to increase the solubility and the dissolution rate of itraconazole, which was chosen as the model drug, by obtaining an amorphous solid dispersion by hot melt extrusion. Therefore, an initial preformulation study was conducted using differential scanning calorimetry, thermogravimetric analysis and Hansen's solubility parameters in order to find polymers which would have the ability to form amorphous solid dispersions with itraconazole. Afterwards, the four polymers namely Kollidon VA64, Kollidon 12PF, Affinisol HPMC and Soluplus, that met the set criteria were used in hot melt extrusion along with 25wt.

Monitoring of anatabine release by methyl jasmonate elicited BY-2 cells using surface-enhanced Raman scattering.

A new application of surface-enhanced Raman scattering (SERS) in the field of plant material analysis is proposed in this study. The aim was to monitor the release of anatabine by methyl jasmonate (MeJa) elicited Bright Yellow-2 (BY-2) cells. Gold nanoparticles (AuNps) were used as SERS substrate.

A simple calibration approach based on film-casting for confocal Raman microscopy to support the development of a hot-melt extrusion process.

When developing a new formulation, the development, calibration and validation steps of analytical methods based on vibrational spectroscopy are time-consuming. For each new formulation, real samples must be produced and a "reference method" must be used in order to determine the Active Pharmaceutical Ingredient (API) content of each sample. To circumvent this issue, the paper presents a simple approach based on the film-casting technique used as a calibration tool in the framework of hot-melt extrusion process.

From near-infrared and Raman to surface-enhanced Raman spectroscopy: progress, limitations and perspectives in bioanalysis.

Over recent decades, spreading environmental concern entailed the expansion of green chemistry analytical tools. Vibrational spectroscopy, belonging to this class of analytical tool, is particularly interesting taking into account its numerous advantages such as fast data acquisition and no sample preparation. In this context, near-infrared, Raman and mainly surface-enhanced Raman spectroscopy (SERS) have thus gained interest in many fields including bioanalysis.

Active content determination of pharmaceutical tablets using near infrared spectroscopy as Process Analytical Technology tool.

The aim of this study was to develop Near infrared (NIR) methods to determine the active content of non-coated pharmaceutical tablets manufactured from a proportional tablet formulation. These NIR methods intend to be used for the monitoring of the active content of tablets during the tableting process. Firstly, methods were developed in transmission and reflection modes to quantify the API content of the lowest dosage strength.

A simple approach for ultrasensitive detection of bisphenols by multiplexed surface-enhanced Raman scattering.

Bisphenol A (BPA) is well known for its use in plastic manufacture and thermal paper production despite its risk of health toxicity as an endocrine disruptor in humans. Since the publication of new legislation regarding the use of BPA, manufacturers have begun to replace BPA with other phenolic molecules such as bisphenol F (BPF) and bisphenol B (BPB), but there are no guarantees regarding the health safety of these compounds at this time. In this context, a very simple, cheap and fast surface-enhanced Raman scattering (SERS) method was developed for the sensitive detection of these molecules in spiked tap water solutions.

Optimization of a pharmaceutical tablet formulation based on a design space approach and using vibrational spectroscopy as PAT tool.

The aim of the present study was to optimize a tablet formulation using a quality by design approach. The selected methodology was based on the variation of the filler grade, taking into account the particle size distribution (PSD) of active pharmaceutical ingredient (API) in order to improve five critical quality attributes (CQAs). Thus, a mixture design of experiments (DoE) was performed at pilot scale.

Thorough characterization of a Self-Emulsifying Drug Delivery System with Raman hyperspectral imaging: a case study.

Newly developed drugs often have poor bioavailability due to their poor water solubility (BCS class 2 drugs). It is therefore necessary to develop new strategies to enhance their solubility and their activity, among which, Self-Emulsifying Drug Delivery System (SEDDS). The efficacy of the drugs contained in these preparations is mainly affected by the solid state and the particle size of the active pharmaceutical ingredient (API).

Vibrational spectroscopy and microspectroscopy analyzing qualitatively and quantitatively pharmaceutical hot melt extrudates.

Since the last decade, more and more Active Pharmaceutical Ingredient (API) candidates have poor water solubility inducing low bioavailability. These molecules belong to the Biopharmaceutical Classification System (BCS) classes II and IV. Thanks to Hot-Melt Extrusion (HME), it is possible to incorporate these candidates in pharmaceutical solid forms.

Data processing of vibrational chemical imaging for pharmaceutical applications.

Vibrational spectroscopy (MIR, NIR and Raman) based hyperspectral imaging is one of the most powerful tools to analyze pharmaceutical preparation. Indeed, it combines the advantages of vibrational spectroscopy to imaging techniques and allows therefore the visualization of distribution of compounds or crystallization processes. However, these techniques provide a huge amount of data that must be processed to extract the relevant information.

A new criterion to assess distributional homogeneity in hyperspectral images of solid pharmaceutical dosage forms.

During galenic formulation development, homogeneity of distribution is a critical parameter to check since it may influence activity and safety of the drug. Raman hyperspectral imaging is a technique of choice for assessing the distributional homogeneity of compounds of interest. Indeed, the combination of both spectroscopic and spatial information provides a detailed knowledge of chemical composition and component distribution.

Development of a quantitative approach using surface-enhanced Raman chemical imaging: first step for the determination of an impurity in a pharmaceutical model.

This publication reports, for the first time, the development of a quantitative approach using surface-enhanced Raman chemical imaging (SER-CI). A pharmaceutical model presented as tablets based on paracetamol, which is the most sold drug around the world, was used to develop this approach. 4-Aminophenol is the main impurity of paracetamol and is actively researched in pharmaceutical formulations because of its toxicity.

Determination of 4-aminophenol in a pharmaceutical formulation using surface enhanced Raman scattering: from development to method validation.

A surface enhanced Raman scattering (SERS) method able to quantify 4-aminophenol in a pharmaceutical formulation based on acetaminophen, also called paracetamol, was developed and, for the first time, successfully validated. In this context, silver nanoparticles were synthesized according to the method described by Lee-Meisel and used as SERS substrate. The repeatability of the silver colloid synthesis was tested using different methods to characterize the size and the zeta potential of silver nanoparticles freshly synthesized.