Characterization of tautomeric forms of ranitidine hydrochloride: thermal analysis, solid-state NMR, X-ray

Mirmehrabi, Mahmoud; Rohani, Sohrab; Murthy, K. S. Keshava; Radatus, Bruno

doi:10.1016/j.jcrysgro.2003.08.061

Cited by 70 publications

(94 citation statements)

References 9 publications

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“…Furthermore, one of the advantages of ss-NMR is that it is very sensitive to minor conformational changes but is insensitive to particle size. In a ss-NMR study of ranitidine hydrochloride, the authors showed that form II of the drug exhibits molecular disorder crystals and contains two tautomers, nitronic acid and enamine (91). Molecular disorder was attributed to ranitidine hydrochloride solved intermolecular bonding (89).…”

Section: Ss-nmrmentioning

confidence: 99%

Methods of amorphization and investigation of the amorphous state

Einfalt¹,

Planinšek²,

Hrovat³

2013

Acta Pharmaceutica

117

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.g., polymorphs) provides pharmaceutical scientists with an opportunity to select the preferred form of the material to be used in a formulation. This is very useful since critical properties, such as particle morphology and dissolution properties, are frequently different in the different physical forms of a material. The amorphous form of pharmacologically active materials has received considerable attention because, in theory, it represents the most energetic solid state of a material, and should thus provide the biggest advantages in terms of dissolution rate and bioavailability (1). However, the amorphous form also shows various disadvantages, such as lower physical stability compared to crystals.The structure of an amorphous solid is usually described as possessing a crystal--like short-range molecular arrangement, but lacking a long-range order. As illustrated by Fig. 1, the immediate environment of a molecule (m) in an amorphous solid may not differ significantly from that in a crystal (e.g., similar number of and distance to nearest neighbors), but an amorphous solid lacks any long-range transational-orientational symmetry that characterizes a crystal (1). However, this is only true when we are dealing The amorphous form of pharmaceutical materials represents the most energetic solid state of a material. It provides advantages in terms of dissolution rate and bioavailability. This review presents the methods of solid--state amorphization described in literature (supercooling of liquids, milling, lyophilization, spray drying, dehydration of crystalline hydrates), with the emphasis on milling. Furthermore, we describe how amorphous state of pharmaceuticals differ depending on the method of preparation and how these differences can be screened by a variety of spectroscopic (X-ray powder diffraction, solid state nuclear magnetic resonance, atomic pairwise distribution, infrared spectroscopy, terahertz spectroscopy) and calorimetry methods.

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Section: Ss-nmrmentioning

confidence: 99%

Methods of amorphization and investigation of the amorphous state

Einfalt¹,

Planinšek²,

Hrovat³

2013

Acta Pharmaceutica

117

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“…The precise structure of form I is not known, however, it is thought to be more ordered than form II and to contain stronger intramolecular bonds. [4] Although the structural differences between forms I and II are ill defined, their presence is obvious throughout the 200-1700 cm −1 spectral region of the Raman spectra (Fig. 1).…”

Section: Resultsmentioning

confidence: 99%

“…The polymorphism observed in ranitidine hydrochloride is largely due to the nitroethenediamine moiety of the molecule. [4] The two polymorphs are equivalent in terms of bioavailability and therapeutic efficacy, [5] though the stability of the two forms under different conditions remains unclear. It has been suggested that form II is more stable than form I on the basis of its higher melting point; however, Miremehrabi et al [6] have shown that manual grinding in a mortar and pestle and tableting does not cause polymorphic conversion.…”

Section: Introductionmentioning

confidence: 99%

Pharmaceutical polymorphs quantified with transmission Raman spectroscopy

McGoverin

Hargreaves

Matousek

et al. 2011

J Raman Spectroscopy

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The quantification of polymorphs in dosage forms is important in the pharmaceutical industry. Conventional Raman spectroscopy of solid-state pharmaceuticals may be used for this, but it has some limitations such as sub-sampling and fluorescence. These problems can be mitigated through the use of transmission Raman spectroscopy (TRS). The efficacy of TRS measurements for the prediction of polymorph content was evaluated using a ranitidine hydrochloride test system. Four groups of ranitidine hydrochloride-based samples were prepared: three containing form I and II ranitidine hydrochloride and microcrystalline cellulose (spanning the ranges 0-10%, 90-100% and 0-100% form I fraction of total ranitidine hydrochloride), and a fourth group comprising form I ranitidine hydrochloride (0-10%) spiked commercial formulation. Transmission and conventional Raman spectroscopic measurements were recorded from both capsules and tablets of the four sample groups. Prediction models for polymorph and total ranitidine hydrochloride content were more accurate for the tablet than for the capsule systems. TRS was found to be superior to conventional backscattering Raman spectroscopy in the prediction of polymorph and total ranitidine hydrochloride content. The prediction model calculated for form I content across the 0-100% range was appropriate for process control [ratio of prediction to deviation (RPD) equal to 14.62 and 7.42 for tablets and capsules, respectively]. The 10% range calibrations for both form I and total ranitidine hydrochloride content were sufficient for screening (RPDs greater than 2.6). TRS is an effective tool for polymorph process control within the pharmaceutical industry.

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“…In aqueous and/or more polar solvents the intramolecular hydrogen bonds are expected to be weakened or disrupted and thereby lead to the nitronic acid tautomer which is Form 2 in the solid state. 5 The first polymorphic form, Form 1, was discovered in 1978 by Allen and Hanbury Ltd. of the Glaxo group, 6 and it had poor filterability and drying characteristics. The second polymorphic form, Form 2, was also patented by the Glaxo group 7 in 1985.…”

Section: Introductionmentioning

confidence: 99%

“…Mirmehrabi et al showed that significant amounts of strongly polar solvents favor the production of Form 2. 9 In another study, 10 Mirmehrabi et al demonstrated a systematic approach for improving the filterability and solid density of Form 1 in reactive crystallization of RAN-HCl by manipulating the operating conditions such as temperature, pH, and pattern of reactant addition. This study focuses on the recrystallization of two anhydrous polymorphs of RAN-HCl and the effect of various solvent systems on the polymorphic generation.…”

Section: Introductionmentioning

confidence: 99%

Polymorphic Generation through Solvent Selection: Ranitidine Hydrochloride

Trifkovic

Rohani

Mirmehrabi³

2006

Org. Process Res. Dev.

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The fundamental processes of crystal nucleation and growth are strongly dependent on the solvents used in the crystallization process. Consequently, the product quality is also affected by the choice of solvent used in the process. In this study, several solvents were used, and their impact on the polymorphic generation of ranitidine hydrochloride (RAN-HCl) was studied using two different recrystallization modes. The solid-state FTIR and UV spectrophotometer were used for characterization and quantification of two polymorphic forms of RAN-HCl. It was found that methanol concentration greater than 10 wt % at nucleation onset favored formation of Form 2. The best results with respect to the solid bulk density were achieved with acetonitrile as an antisolvent.

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Characterization of tautomeric forms of ranitidine hydrochloride: thermal analysis, solid-state NMR, X-ray

Cited by 70 publications

References 9 publications

Methods of amorphization and investigation of the amorphous state

Methods of amorphization and investigation of the amorphous state

Pharmaceutical polymorphs quantified with transmission Raman spectroscopy

Polymorphic Generation through Solvent Selection: Ranitidine Hydrochloride

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