Analysis of Structural Variability in Pharmaceutical Excipients Using Solid-State NMR Spectroscopy

Abstract

Abstract. Polysaccharide-based excipients comprise the majority of most solid dosage forms and can vary dramatically in terms of structural and functionally related properties. Analytical methods for characterizing these important formulation components are crucial. Solid-state NMR spectroscopy (SSNMR) can provide a wealth of information on these materials while offering the advantages of nondestructive sample preparation and selectivity. The overall objective of this work is to identify SSNMR parameters that can be used to detect differences among these excipients. Excipients were obtained from a wide range of suppliers and analyzed as received; 13 C SSNMR spectra were acquired using a Chemagnetics CMX-300 spectrometer operating at approximately 75 MHz. The resolution of SSNMR signals of many excipients allows for positive identification of the major form present. Alginic acid and sodium alginate can be differentiated based on carbonyl peak position. Analysis of relative peak intensities provides insight into the purity of a carrageenan sample compared to known standards. The SSNMR spectrum of starch can be used to identify the source and to quantitate the amorphous and crystalline content. Relaxation values and peak areas of starch derivatives can be related to the degree of hydrolysis, providing an alternative method for determining dextrose equivalent. Differences in peak intensities and relaxation time values of HPMC samples can be correlated to the amount of methoxy subsituent groups. Important characteristics of excipients such as form identification, structural differences, crystalline and amorphous content, and water content variations can be detected using SSNMR spectroscopy.

35Cl dynamic nuclear polarization solid-state NMR of active pharmaceutical ingredients

“…110-135 ppm), e CP ( 13 C) = 32, is less than that of the solvent. Finally, there are features that correspond to various types of excipient molecules, including polysaccharides (20-40 ppm), synthetic polymers (60-75 ppm) and stearates (100-110 ppm), 69,97,98 which have enhancements ranging from 12 to 50. Overlapping signals from the API and excipient make it challenging to determine the phase of an API in 13 C NMR spectra even without the use of DNP; 21 however, the differences in the DNP-enhancement such as those observed in the spectra of isox can further complicate the analysis.…”

Solid state nuclear magnetic resonance studies of hydroxypropylmethylcellulose acetyl succinate polymer, a useful carrier in pharmaceutical solid dispersions

“…[25][26][27] Solid-state nuclear magnetic resonance (NMR) has been demonstrated as one of the most informative analytic technique used in the field of pharmaceutical sciences. [28,29] NMR allows the structural characterisation of drugs [30] and excipients, [31] identification of drug polymorphs, [32] understanding of molecular mobility and physical stability of solid dispersions, [33] and the study and identification of specific intramolecular interactions in the solid dispersion. [34] The knowledge of the accurate assignments of the NMR signals in the HPMC-AS polymer used for ASDs plays a crucial role in understanding HPMC-AS-API interactions and is required to study the overall stability and dynamics of the ASD.…”

Excipients functionality: Importance and compendial status

“…source-to-source variability) (12,14). To se posebno odnosi na ekscipijense mineralnog, biljnog, životinjskog i mikrobiološkog porekla, čije karakteristike mogu značajno da variraju, zavisno od porekla i/ili sezone prikupljanja sirovina (15,16). Iz ovih razloga, proizvodnja ekscipijenasa obično uključuje niz postupaka koji imaju za cilj da se eliminiše varijabilnost izazvana razlikama u polaznim sirovinama.…”