Application of Partial Least-Squares (PLS) modeling in quantifying drug crystallinity in amorphous solid dispersions

Rumondor, Alfred C. F.; Taylor, Lynne S.

doi:10.1016/j.ijpharm.2010.07.049

Cited by 59 publications

(30 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Togkalidou et al 32) studied ATR-IR spectroscopy coupled with robust chemoinformatic techniques for the online measurement of two pharmaceutical compounds in aqueous phase. Rumondora and Taylor 33) compared two kinds of calculation and model-building methods for the quantification of the ratio of crystalline drug and amorphous polymer in a dispersed solid. These reports show that multivariate regression methods, such as PLS and PCA, are useful tools to extract interesting pieces of information from complicated experimental data set.…”

Section: Quantitative Analysis Of Pharmaceutical Bulk Powders By Pls mentioning

confidence: 99%

Quantification of Pharmaceutical Compounds Based on Powder X-Ray Diffraction with Chemometrics

Otsuka

Itô

Matsumura

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

We propose an approach for the simultaneous determination of multiple components in pharmaceutical mixed powder based on powder X-ray diffraction (PXRD) method coupled with chemometrics. Caffeine anhydrate, acetaminophen and lactose monohydrate were mixed at various ratios. The samples were analyzed by PXRD method in the ranges of 2θ 5.00-30.0 and 35.0-45.0 degrees. Obtained diffractograms were analyzed by conventional peak intensity method, multi curve resolution (MCR)-alternating least squares (ALS) method and partial least squares (PLS) method. Constructed PLS models can most accurately predict the concentrations among different methods used. Each regression vector of PLS correlates not only to the compound of interest but also to the coexisting compounds. The combination of PXRD and PLS methods is concluded to be powerful approach for analyzing multi components in pharmaceutical formulations.Key words powder X-ray diffraction; partial least square; pharmaceutical formulationThe polymorphs and pseudo-polymorphs (hydrates and solvates) of pharmaceuticals exhibit different physicochemical properties such as solubility, dissolution rate, stability and hygroscopicity. These properties strongly relate to the pharmaceutical properties in their dosage forms such as specific bioavailability, efficacy, stability and toxicity.1) Pharmaceutical regulations are, therefore, required for producing appropriate bulk drugs, the crystalline modifications of which (i.e., polymorphism) are well specified or precisely controlled. 2)Powder X-ray diffraction (PXRD) analysis is the most frequently used method for identifying crystalline modifications and for determining their contents in bulk powders.3) Any crystals have their own PXRD patterns. Pharmaceutical formulations are, in general, composed of multiple components including excipients. PXRD is, therefore, useful to identify crystalline compounds in the formulation and to determine their amounts in a non-contact and non-destructive fashion. 4,5) However, PXRD method has large relative errors, typically around ±5%. Such shortcoming of PXRD method is serious when two or more components having broad and overlapping X-ray diffraction peaks are contained in one formulation.Regulatory authorities such as the U.S. Food and Drug Administration and the International Conference on Harmonization have requested to use Process Analytical Technology (PAT) in order to reduce the production risk of inferior pharmaceuticals.6) Since the introduction of guidelines for PAT, online and real-time analysis have increasingly been accepted in pharmaceutical industry as a tool for monitoring and controlling manufacturing process. Non-contact methods, such as PXRD analysis, near infrared (NIR) spectroscopy and terahertz spectroscopy have been paid attention as important tools for PAT. 6) Chemoinformatics are employed by pre-formulation scientists for the quantitative and qualitative analyses of NIR because they can provide ideal means for extracting quantitative information from complex spectra of mult...

show abstract

Section: Quantitative Analysis Of Pharmaceutical Bulk Powders By Pls mentioning

confidence: 99%

Quantification of Pharmaceutical Compounds Based on Powder X-Ray Diffraction with Chemometrics

Otsuka

Itô

Matsumura

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

show abstract

“…However, it should be taken into account that the degree of crystallinity for the Gris/carrier systems cannot be quantified with higher accuracy since detection limits of 5% crystallinity or lower have been reported when amorphous/crystalline mixtures are analysed by powder Xray diffractometry (21). The disappearance of a melting peak in the DSC profile in general indicates that the drug is present in amorphous state or that it is dissolved in the solid state (22).…”

Section: Discussionmentioning

confidence: 99%

Griseofulvin/Carrier Blends: Application of Partial Least Squares (PLS) Regression Analysis for Estimating the Factors Affecting the Dissolution Efficiency

et al. 2011

View full text Add to dashboard Cite

Abstract. The main aim of the present study was to estimate the carrier characteristics affecting the dissolution efficiency of Griseofulvin (Gris) containing blends (BLs) using partial least squares (PLS) regression analysis. These systems were prepared at three different drug/carrier weight ratios (1/5, 1/10, and 1/20) by the solvent evaporation method, a well-established method for preparing solid dispersions (SDs). The carriers used were structurally different including polymers, a polyol, acids, bases and sugars. The BLs were characterised at the solid-state by spectroscopic (Fourier transform infrared spectroscopy), thermoanalytical (differential scanning calorimetry) and X-ray diffraction studies and their dissolution behaviours were quantified in terms of dissolution efficiencies (log DE/DE Gris ). The correlation between the selected descriptors, including parameters for size, lipophilicity, cohesive energy density, and hydrogen bonding capacity and log DE/DE Gris (i.e., DE and DE Gris are the dissolution efficiencies of the BLs and the pure drug, respectively) was established by PLS regression analysis. Thus two models characterised by satisfactory coefficient of determination were derived. The generated equations point out that aqueous solubility, density, lipophilic/hydrophilic character, dispersive/polar forces and hydrogen bonding acceptor/donor ability of the carrier are important features for dissolution efficiency enhancement. Finally, it could be concluded that the correlations developed may be used to predict at a semiquantitative level the dissolution behaviour of BLs of other essentially neutral drugs possessing hydrogen bonding acceptor groups only.

show abstract

“…Quantification of the crystallinity in amorphous formulations using PXRD is a well-known technique. The intensity and area of diffraction peaks increase proportionally with an increase in crystallinity [161][162][163][164]. A more challenging aspect is to quantify nanocrystals in an amorphous material.…”

Section: X-ray Diffraction Techniquesmentioning

confidence: 99%

Pharmaceutical solvates, hydrates and amorphous forms: A special emphasis on cocrystals

Healy

Worku

Kumar

et al. 2017

Advanced Drug Delivery Reviews

272

189

View full text Add to dashboard Cite

a b s t r a c t a r t i c l e i n f oActive pharmaceutical ingredients (APIs) may exist in various solid forms, which can lead to differences in the intermolecular interactions, affecting the internal energy and enthalpy, and the degree of disorder, affecting the entropy. Differences in solid forms often lead to differences in thermodynamic parameters and physicochemical properties for example solubility, dissolution rate, stability and mechanical properties of APIs and excipients. Hence, solid forms of APIs play a vital role in drug discovery and development in the context of optimization of bioavailability, filing intellectual property rights and developing suitable manufacturing methods. In this review, the fundamental characteristics and trends observed for pharmaceutical hydrates, solvates and amorphous forms are presented, with special emphasis, due to their relative abundance, on pharmaceutical hydrates with single and two-component (i.e. cocrystal) host molecules.

show abstract

Application of Partial Least-Squares (PLS) modeling in quantifying drug crystallinity in amorphous solid dispersions

Cited by 59 publications

References 34 publications

Quantification of Pharmaceutical Compounds Based on Powder X-Ray Diffraction with Chemometrics

Quantification of Pharmaceutical Compounds Based on Powder X-Ray Diffraction with Chemometrics

Griseofulvin/Carrier Blends: Application of Partial Least Squares (PLS) Regression Analysis for Estimating the Factors Affecting the Dissolution Efficiency

Pharmaceutical solvates, hydrates and amorphous forms: A special emphasis on cocrystals

Contact Info

Product

Resources

About