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AAPS PharmSciTech. 2003 June; 4(2): 119–128.
Published online 2003 May 12. doi:  10.1208/pt040225
PMCID: PMC2750587

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

Abstract

The objectives of this study were to determine the cause of the crystallization in a large volume creatine supplement solution made from effervescent powders containing di-creatine citrate, and to characterize these crystals using thermal analyses and x-ray diffractometry. Creatine effervescent powders were dissolved in deionized water (pH 6.2) and stored both at room temperature (RT) (25°C) and refrigerated condition (4°C) over a period of 45 days. Creatine concentration was determined using high-performance liquid chromatography (HPLC). Intrinsic dissolution and saturated solubility of creatine, creatine monohydrate, and di-creatine citrate in water were determined and compared. Crystal growth was detected only in the refrigerated samples on the seventh day of storage. Differential Scanning Calorimetry (DSC) and x-ray diffraction (XRD) studies revealed that the crystals formed were of creatine monohydrate. Ninety percent creatine degradation was observed within 45 days for RT samples. However, at refrigerated condition this degradation was 80% within the same time period. The pH of the RT samples also increased from 3.6 to 4.5 during storage. No such increase was observed in the case of refrigerated samples. The intrinsic dissolution rate constants of the compounds decreased in the following order: dicreatine citrate>creatine>creatine monohydrate. In conclusion, di-creatine citrate used in effervescent formulation dissociates to creatine in aqueous solution and eventually crystallizes out as creatine monohydrate. Significant decrease in solubility and effect of pH contribute to this crystallization process.

Keywords: Di-creatine citrate, creatine, creatine monohydrate, creatinine, stability, effervescent creatine

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Green AL, Simpson EJ, Littlewood JJ, Macdonald IA, Greenhaff PL. Carbohydrate ingestion augments creatine retention during creatine feeding in humans. Acta Physiol Scand. 1996;158:195–202. doi: 10.1046/j.1365-201X.1996.528300000.x. [PubMed] [Cross Ref]
2. Volek JS, Kraemer WJ. Creatine supplementation: its effect on human muscular performance and body composition. J Strength Cond Res. 1996;10:200–210. doi: 10.1519/1533-4287(1996)010<0200:CSIEOH>2.3.CO;2. [Cross Ref]
3. Persky AM, Brazeau GA. Clinical pharmacology of the dietary supplement creatine monohydrate. Pharmacol Rev. 2001;53:161–176. [PubMed]
4. Willot CA, Young ME, Leighton B, et al. Creatine uptake in isolated soleus muscle: kinetics and dependence on sodium, but not on insulin. Acta Physiol Scand. 1999;166:99–104. doi: 10.1046/j.1365-201x.1999.00539.x. [PubMed] [Cross Ref]
5. Dash AK, Miller DW, Huai-Yan H, Camazzo J, Stout Evaluation of creatine transport using Caco-2 monolayers as an in vitro model for intestinal absorption. J Pharm Sci. 2001;90:1593–1598. doi: 10.1002/jps.1109. [PubMed] [Cross Ref]
6. Budavari S, O Neil MJ, Smith A, Heckelman PE, editors. The Merck Index. 1 th ed. Rathway, NJ: Merck & Co, Inc; 1989. pp. 402–403.
7. Creatine Edge and Creatine Clear [package insert]. Omaha, NE: FSI Nutrition. US patent 5,925,378. July 20, 1999.
8. Edgar G, Shiver HE. The equilibrium between creatine and creatinine, in aqueous solutions: the effect of hydrogen ion. J Am Chem Soc. 1925;47:1179–1188. doi: 10.1021/ja01681a040. [Cross Ref]
9. Cannan RK, Shore A. The creatine-creatinine equilibrium: the apparent dissociation constants of creatine and creatinine. Biochemistry. 1928;22:920–929. [PubMed]
10. Dash AK, Mo Y, Pyne A. Solid-state properties of creatine monohydrate. J Pharm Sci. 2002;91:708–718. doi: 10.1002/jps.10073. [PubMed] [Cross Ref]
11. Dash AK, Sawhney A. A simple LC method with UV detection for the analysis of creatine and creatinine and its application to several creatine formulations. J Pharm Biomed Anal. 2002;29:939–945. doi: 10.1016/S0731-7085(02)00167-X. [PubMed] [Cross Ref]
12. Wood J, Syarto J, Letterman H. Improved holder for intrinsic dissolution rate studies. J Pharm Sci. 1965;54:1068–1068. doi: 10.1002/jps.2600540730. [PubMed] [Cross Ref]
13. Martin A. Physical Pharmacy. 4th ed. Philadelphia, PA: Lea & Febiger; 1993. pp. 212–250.
14. Grant DJW, Brittain HG. Solubility of pharmaceutical solids. In: Brittain HG, editor. Physical Characterization of Pharmaceutical Solids. New York, NY: Marcell Dekker, Inc.; 1995. pp. 321–386.
15. Ganguly S, Carnazzo J, Dash AK. Evaluation of the solution stability of creatine in large volume supplements [abstract] AAPS PharmSci. 2002;4:R–6248.

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