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Related Concept Videos

Recrystallization: Solid–Solution Equilibria01:10

Recrystallization: Solid–Solution Equilibria

Recrystallization is a purification technique used to separate impurities from solid compounds. In this technique, no chemical reactions occur. Instead, it exploits physical properties only, specifically, the solubility differences between the desired compound and impurities, either at a single temperature or at different temperatures, and under other selected conditions. The solid-solution equilibrium (solubility equilibrium) of each component in the solution represents a binary phase...
2° Amines to N-Nitrosamines: Reaction with NaNO201:20

2° Amines to N-Nitrosamines: Reaction with NaNO2

Secondary amines react with nitrous acid to form N-nitrosamines, as depicted in Figure 1. Nitrous acid, a weak and unstable acid, is formed in situ from an aqueous solution of sodium nitrite and strong acids, such as hydrochloric acid or sulfuric acid, in cold conditions. In the presence of an acid, the nitrous acid gets protonated. The subsequent loss of water results in the formation of the electrophile known as nitrosonium ion.
Racemic Mixtures and the Resolution of Enantiomers02:30

Racemic Mixtures and the Resolution of Enantiomers

A racemic mixture, or racemate, is an equimolar mixture of enantiomers of a molecule that can be separated using their unique interaction with chiral molecules or media. Racemic mixtures are denoted by the (±)- prefix. This ‘optical rotation descriptor’ applies to the whole solution of a racemic mixture rather than a specific stereoisomer. Enantiomers typically have the same physical and chemical properties. Hence, they are not easily separable. However, enantiomers can exhibit different...
Preparation of Amines: Reductive Amination of Aldehydes and Ketones01:38

Preparation of Amines: Reductive Amination of Aldehydes and Ketones

Carbonyl compounds and primary amines undergo reductive amination first to produce imines, followed by secondary amines in the same reaction mixture, using selective reducing agents like sodium cyanoborohydride or sodium triacetoxyborohydride. Reductive amination produces different degrees of substitution of amines depending on the starting amine substrate.
Precipitation Processes01:12

Precipitation Processes

The experimental conditions in a gravimetric analysis should be optimized to maximize the particle size and purity of the obtained precipitate. Ideally, the concentration of the precipitating reagent should be low with effective stirring to maintain low relative supersaturation for the growth of large crystals. In homogeneous precipitation, the precipitant is slowly generated by a chemical reaction in the solution to avoid local reagent excesses. For example, urea decomposes gradually to...
Crystal Growth: Principles of Crystallization01:25

Crystal Growth: Principles of Crystallization

Crystallization is a phase transformation process in which crystals are precipitated from a supersaturated solution or formed from other sources. During crystallization, atoms or molecules arrange themselves into a well-defined, rigid crystal lattice to minimize energy.
Initiating crystallization involves manipulating the concentration of the solute and the temperature of the solution. Since crystal growth occurs when the ratio of concentration and solubility of the solute in the solvent – the...

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Related Experiment Video

Updated: Jun 21, 2026

A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s
07:38

A General Method for Detecting Nitrosamide Formation in the In Vitro Metabolism of Nitrosamines by Cytochrome P450s

Published on: September 25, 2017

Recrystallization can stop nitrosamine formation in ranitidine hydrochloride.

Jianchao Xu1, Yijing Huang1, Jon Selbo2

  • 1Department of Industrial and Molecular Pharmaceutics, Purdue University, West Lafayette, IN, 47907, USA.

Journal of Pharmaceutical Sciences
|June 19, 2026
PubMed
Summary

Controlling crystal quality by recrystallization can significantly reduce N-nitrosodimethylamine (NDMA) formation in ranitidine hydrochloride. High-quality crystals with fewer reactive species inhibit NDMA, offering a new strategy against drug contamination.

Keywords:
Cryogenic millingCrystal defectNDMANitrosaminePhysical stabilityRanitidine hydrochlorideRecrystallization

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06:18

Syntheses, Crystallization, and Spectroscopic Characterization of 3,5-Lutidine N-Oxide Dehydrate

Published on: April 24, 2018

Area of Science:

  • Pharmaceutical Sciences
  • Chemical Engineering
  • Materials Science

Background:

  • Nitrosamines, including N-nitrosodimethylamine (NDMA), are carcinogenic contaminants found in various products.
  • NDMA is a significant concern in pharmaceuticals like ranitidine hydrochloride due to its carcinogenicity.
  • Solid-state reactive species (SSRS), such as crystal defects, drive NDMA formation in solid-state ranitidine hydrochloride.

Purpose of the Study:

  • To investigate the impact of crystal quality on NDMA formation in ranitidine hydrochloride.
  • To demonstrate the efficacy of recrystallization in inhibiting NDMA formation.
  • To explore the role of oxygen in the degradation of ranitidine hydrochloride.

Main Methods:

  • Recrystallization of ranitidine hydrochloride to control crystal quality.
  • Storage of different ranitidine hydrochloride samples (as-received, cryoground, recrystallized) under controlled conditions (60°C, <2% RH).
  • Assessment of NDMA formation under varying oxygen concentrations (vacuum, nitrogen, air, oxygen-rich).

Main Results:

  • Well-controlled recrystallization yielding high-quality crystals significantly reduced NDMA formation compared to as-received material.
  • Cryoground samples exhibited increased reactivity, while subsequent recrystallization restored stability.
  • NDMA formation was minimal under vacuum/nitrogen, elevated in air, and highest in an oxygen-rich environment.

Conclusions:

  • Reducing SSRS through well-controlled crystallization is a highly effective method to inhibit nitrosamine formation in ranitidine hydrochloride.
  • This approach offers a potential alternative or complementary strategy to antioxidants and pH modification for minimizing nitrosamine contamination.
  • Crystal quality is a critical factor influencing the stability and degradation pathways of drug substances like ranitidine hydrochloride.