Quantitation of a polymorphic mixture of an active pharmaceutical ingredient with solid state 13C CPMAS NMR spectroscopy

Virtanen, Tommi; Maunu, Sirkka Liisa

doi:10.1016/j.ijpharm.2010.04.017

Cited by 46 publications

(26 citation statements)

References 30 publications

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“…The overall characterization and quantitation of pharmaceutical polymorphs and related forms (solvates) in the solid phase can be accomplished by cross‐polarization (CP) magic‐angle spinning (MAS) nuclear magnetic resonance (CPMAS NMR) spectroscopy. Numerous application studies on pharmaceutical solids using SSNMR have been reported5–13 and reviewed 12,13. Technically, it is relatively easy to handle a powdered sample of a drug and subject it to SSNMR measurement.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Application of 13C CPMAS NMR for Qualitative and Quantitative Characterization of Carvedilol and its Commercial Formulations

Zielińska–Pisklak

Pisklak

Wawer

2012

Journal of Pharmaceutical Sciences

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Section: Introductionmentioning

confidence: 99%

“…The assignment of resonances, especially for polymorphs, is a more difficult task. However, the most valuable data are obtained by combining SSNMR, X‐ray diffraction crystal structure analysis, and theoretical calculations of NMR shielding constants 7–11…”

Section: Introductionmentioning

confidence: 99%

Application of 13C CPMAS NMR for Qualitative and Quantitative Characterization of Carvedilol and its Commercial Formulations

Zielińska–Pisklak

Pisklak

Wawer

2012

Journal of Pharmaceutical Sciences

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“…Certas técnicas de caracterização no estado sólido são frequentemente empregadas para identifi cação e elucidação estrutural em sólidos farmacêuticos 86 . Entre elas, podemos citar técnicas microscópicas, como a microscopia eletrônica de varredura (MEV), as quais permitem a descrição do hábito cristalino, fornecendo informações morfológicas valiosas para a triagem de modifi cações cristalinas 87,88 , técnicas térmicas por calorimetria exploratória diferencial (CED) e termogravimetria (TG) 89,90 , técnicas espectroscópicas por absorção na região do infravermelho (IV) 91 , espalhamento Raman 92 , e ressonância magnética nuclear (RMN) 93 , e técnicas cristalográfi cas por DRX 94,95 .…”

Section: Técnicas De Caracterização De Polimorfos De Fármacosunclassified

Aplicações Tecnológicas do Polimorfismo Farmacêutico

Martins

2010

Rev. Proc. Q.

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Sólidos farmacêuticos podem apresentar diferentes arranjos arquitetônicos de suas estruturas cristalinas. Este fenômeno é conhecido como polimorfi smo e, no caso dos fármacos, pode impactar sobre propriedades farmacotécnicas e farmacocinéticas. Em última análise, o emprego de uma forma polimórfi ca inadequada no estágio de formulação ou qualquer transformação entre fases durante o processamento e estocagem pode resultar em inefi cácia farmacêutica ou até mesmo em toxicidade. Isto destaca que o conhecimento das possíveis formas polimórfi cas que um fármaco pode apresentar é essencial para assegurar o comportamento reprodutível dos medicamentos e sua segurança. Por outro lado, a engenharia de cristais moleculares, fundamentada na síntese supramolecular racional de novas formas cristalinas, é uma atraente alternativa para melhoramento de perfi s farmacêuticos sem a necessidade de quebrar ou formar ligações covalentes. O presente trabalho tem como fi nalidade apresentar os principais aspectos relacionados ao polimorfi smo, às estratégias de engenharia de cristais moleculares e às técnicas de caracterização e controle de qualidade de polimorfos de fármacos. Palavras-chave: sólidos farmacêuticos, polimorfi smo, engenharia de cristais moleculares.Pharmaceutical solids can present different crystal structure assemblies. Such phenomenon is defi ned as polymorphism and can impact on pharmacotechnical and pharmacokinetic features of drugs. The use of a wrong polymorph for incorporation into drug formulations or phase transformations during processing and storage can lead to pharmaceutical ineffectiveness or even toxicity. This means that the knowledge of all polymorphs of a drug is crucial to ensure a reproducible behavior of medicines and safety. On the other hand, crystal engineering of molecular solids, which is based on rational supramolecular synthesis of novel crystal forms, is an attractive alternative to improve pharmaceutical properties without either cleaving or forming covalent bonds. This work aims to present the main issues related to polymorphism, crystal engineering strategies and solid state techniques for characterization and quality control of drug polymorphs.

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“…The 13 C ssNMR spectrum represents the finger-print of a material. It is likely that two polymorphs may have different spectra due to differences in chemical environment (4)(5)(6). Similar to the XRPD, the 13 C ssNMR has advantage of being nondestructive.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Univariate and Multivariate Models of 13C SSNMR and XRPD Techniques for Quantification of Nimodipine Polymorphs

et al. 2015

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Abstract. The focus of the present investigation was to explore the use of solid-state nuclear magnetic resonance ( 13 C ssNMR) and X-ray powder diffraction (XRPD) for quantification of nimodipine polymorphs (form I and form II) crystallized in a cosolvent formulation. The cosolvent formulation composed of polyethylene glycol 400, glycerin, water, and 2.5% drug, and was stored at 5°C for the drug crystallization. The 13 C ssNMR and XRPD data of the sample matrices containing varying percentages of nimodipine form I and form II were collected. Univariate and multivariate models were developed using the data. Least square method was used for the univariate model generation. Partial least square and principle component regressions were used for the multivariate models development. The univariate models of the 13 C ssNMR were better than the XRPD as indicated by statistical parameters such as correlation coefficient, R 2 , root mean square error, and standard error. On the other hand, the XRPD multivariate models were better than the 13 C ssNMR as indicated by precision and accuracy parameters. Similar values were predicted by the univariate and multivariate models for independent samples. In conclusion, the univariate and multivariate models of 13 C ssNMR and XRPD can be used to quantitate nimodipine polymorphs.

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Quantitation of a polymorphic mixture of an active pharmaceutical ingredient with solid state 13C CPMAS NMR spectroscopy

Cited by 46 publications

References 30 publications

Application of 13C CPMAS NMR for Qualitative and Quantitative Characterization of Carvedilol and its Commercial Formulations

Application of 13C CPMAS NMR for Qualitative and Quantitative Characterization of Carvedilol and its Commercial Formulations

Aplicações Tecnológicas do Polimorfismo Farmacêutico

Comparison of Univariate and Multivariate Models of 13C SSNMR and XRPD Techniques for Quantification of Nimodipine Polymorphs

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