Ganguly · AAPS PharmSciTech 2003 · in vitro stability and physicochemical study · n=?

Evaluation of the stability of creatine in solution prepared from effervescent creatine formulations.

Cited 20 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Bench research evaluating in vitro physicochemical stability with no human participants.

PubMed 12916907 · doi:10.1208/pt040225 · record verified 2026-08-29

What was done

Researchers evaluated the stability and crystallization of creatine solutions prepared by dissolving effervescent di-creatine citrate powders in deionized water (pH 6.2) and storing them at room temperature (25°C) and under refrigerated conditions (4°C) for 45 days. Creatine concentration over time was determined via high-performance liquid chromatography (HPLC). Formed crystals were characterized using differential scanning calorimetry (DSC) and x-ray diffractometry (XRD), and intrinsic dissolution and saturated solubility were compared across di-creatine citrate, creatine, and creatine monohydrate.

What was found

Crystals formed only in refrigerated samples starting at day 7 and were identified as creatine monohydrate. Over 45 days, creatine degraded by 90% at room temperature and by 80% under refrigeration. Solution pH at room temperature increased from 3.6 to 4.5 during storage, whereas refrigerated pH remained stable. The intrinsic dissolution rate constants ranked in decreasing order: di-creatine citrate > creatine > creatine monohydrate.

Why it matters

Liquid preparations of effervescent di-creatine citrate are unstable for long-term storage, as the compound rapidly degrades at room temperature and precipitates as less-soluble creatine monohydrate under refrigeration.

Limits

This is an in vitro bench study without human physiological, pharmacokinetic, or bioavailability data. The abstract does not report sample sizes, replicate numbers, statistical variance, intermediate degradation time points, or specific degradation products such as creatinine.

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