Extraction of information about structural changes in a semisolid pharmaceutical formulation from near‐infrared and Raman images by multivariate curve resolution–alternating least squares and ComDim

Abstract

Solid dispersions are an interesting option to improve the solubility of Class II (high permeability, low water solubility) drugs of the Biopharmaceutical Classification System without the use of organic solvents. However, structural changes (polymorphism) may be present in both active pharmaceutical ingredients (API) and excipients, which require evaluation during pharmaceutical development. Thus, the aim of this work was to demonstrate the feasibility of using Raman and near-infrared (NIR) mapping associated with multivariate curve resolution-alternating least squares (MCR-ALS) and common components and specific weights analysis (CCSWA or ComDim) chemometric methods to assess the solid dispersions of atorvastatin calcium in Gelucire ® 48/16 under controlled (3.0 ± 1.0 C, sealed flask) and accelerated (33.0 ± 1.0 C, 75% of relative humidity, open flask) aging conditions. MCR-ALS allowed the identification of the amorphous and crystalline fractions of the drug within the solid dispersion, which is not easily achieved by traditional techniques such as differential scanning calorimetry and X-ray diffraction, especially for semisolid formulations. ComDim results indicated that Raman seemed more sensitive to the presence of the API, whereas NIR was found to be more sensitive to alterations in the spectra of the excipient. The use of the ComDim method is not yet widespread in the pharmaceutical area; therefore, this paper shows its potential to support pharmaceutical development in preformulation stages for stability studies.

Development of Gelucire® 48/16 and TPGS Mixed Micelles and Its Pellet Formulation by Extrusion Spheronization Technique for Dissolution Rate Enhancement of Curcumin

“…Gelucire® 48/ 16 is a PEG 32 ester comprised of a mixture of stearic and palmitic acid monoesters and diesters. It can be used alone or combined with other oils, surfactants, or solvents for solubility and bioavailability enhancement of poorly water-soluble drugs (20,21). Gelucire® 48/16 forms micellar solutions and can be used alone or in combination with other miscible lipid-based excipients for solubility enhancement of drugs.…”

Development of a Versatile Lipid Core for Nanostructured Lipid Carriers (NLCs) Using Design of Experiments (DoE) and Raman Mapping

“…This is especially important when mixing semi-solid lipophilic and medium polarity or hydrophilic excipients. Chemical images based on spectroscopic techniques (for example, NIR, MIR, and Raman) are important tools for assessing the homogeneity of mixtures [ 14 , 15 , 16 ] and can indicate heterogeneities at a microscopic level, allowing stability issues to be foreseen.…”

Comparing the Performance of Raman and Near-Infrared Imaging in the Prediction of the In Vitro Dissolution Profile of Extended-Release Tablets Based on Artificial Neural Networks

“…In the past 15 years, both NIR and Raman imaging have been used in the analysis of pharmaceutical tablets to measure their active ingredient content [ 12 , 13 ], to characterize the size of components [ 14 , 15 ], to measure the coating thickness of film-coated tablets [ 16 , 17 ], to characterize the distribution of polymorphic forms of a drug [ 18 , 19 ], to detect changes after storage under stress [ 20 , 21 ], to recognize counterfeit products [ 22 , 23 ], to identify the components of a formulation [ 24 ] and to predict the dissolution profile of tablets [ 6 , 25 , 26 ]. It is evident that both techniques are capable of great things; however, the aforementioned works provide little help in deciding which imaging method is worth using to achieve a specific goal.…”

“…It was found that the two techniques yield generally similar results, although, in distribution maps obtained by Raman imaging, the boundaries of particles are clearer and Raman imaging is a better choice for components with low concentrations. Mitsutake et al [ 24 ] compared the capability of Raman and NIR imaging in the analysis of solid dispersions; Raman was more sensitive to the active ingredient, while NIR was more sensitive to the excipient. However, to our knowledge, there are no works in the literature where Raman and NIR imaging are compared using several hundred samples.…”