Published by GMPriority Pharma
Date: July 2025

Abstract

Recent consumer-facing communications have attributed visible crystallisation in liquid magnesium supplements to the natural byproduct of liposomal encapsulation, further implying that the absence of chemical stabilisers reflects a more desirable, “natural” formulation. These claims are both scientifically inaccurate and potentially misleading.

This paper explores the true causes of crystallisation in magnesium-containing nutraceuticals, corrects misunderstandings about liposomal formulation science and underscores the importance of accuracy and transparency in health product communications.

A technical review of magnesium bioavailability, encapsulation chemistry and pH interactions is presented, with a focus on best practices for ensuring product safety, stability and consumer trust.

Introduction

Liposomal delivery systems are widely used in the nutraceutical and pharmaceutical industries to enhance the bioavailability of active compounds that are otherwise poorly absorbed through the gastrointestinal tract. Magnesium, a mineral with relatively low oral bioavailability in standard forms, has seen increased application in liposomal form for use in paediatric and adult populations.

However, the emergence of crystallisation in certain liquid liposomal magnesium products and the attribution of this phenomenon to the encapsulation process itself, raises critical questions regarding formulation integrity, scientific literacy and consumer safety.

Liposomal Encapsulation: Function and Limits

 – Overview of Liposomal Technology

Liposomal encapsulation involves entrapping an active compound within the aqueous core or lipid bilayer of a vesicle formed from phospholipids.

Properly designed, liposomes:

• Improve the absorption of hydrophilic and lipophilic nutrients
• Protect actives from degradation in the GI tract
• Can reduce gastrointestinal side effects

Magnesium, being a highly water-soluble, charged ion, is typically encapsulated in the aqueous interior of liposomes or adsorbed onto the liposome surface through ion-pairing techniques.

Importantly, liposomal encapsulation does not inherently cause the precipitation or crystallisation of magnesium compounds.

Crystallisation in Liquid Magnesium Products

 – The Chemistry of Crystallisation

Crystallisation occurs when the concentration of dissolved solute (in this case, magnesium) exceeds its solubility limit, or when environmental conditions,  such as pH shifts, temperature changes or evaporation, favour nucleation and crystal growth.

In magnesium supplements, crystallisation is typically a result of:

• Incorrect solubilisation of magnesium salts (e.g., Mg citrate, chloride)
• High product alkalinity, which can drive precipitation of magnesium hydroxide
• Insufficient use of stabilising excipients, such as solubility-enhancing agents, chelators or buffering systems
• Lack of preservatives or pH adjusters, leading to microbial changes that alter pH

 – Misconceptions Regarding Liposomal Carriers

Recent public statements have attributed visible crystallisation to “alkaline properties of magnesium reacting with the carriers.” However, phospholipid-based liposomes are neutral to slightly acidic in most formulations and do not typically introduce sufficient alkalinity to cause precipitation, especially not visible crystalline formations.

The primary cause of magnesium crystal formation in a liquid suspension is typically poor compatibility of the magnesium source with the chosen solvent system, often exacerbated by inadequate buffering or stabilisation protocols.

Formulation Science vs. “Chemical-Free” Marketing

 – Misuse of “Natural” Claims

The implication that crystallisation is acceptable, or even desirable, because it reflects a more “natural” product is scientifically unsubstantiated. Comparisons to the crystallisation of honey or pulp in juice are invalid. Honey crystallises due to the saturation of glucose, and juice sediments due to insoluble plant solids, neither are analogous to ionic mineral solutions.

Furthermore, the claim that preventing crystallisation requires loading products with “chemical additives” ignores the fact that potassium sorbate, which is third-party proven to be present in the brand in question, is itself a synthetic chemical preservative, commonly used to prevent microbial growth.

The dichotomy presented between “natural variability” and “chemical over-processing” is both misleading and inconsistent with good manufacturing and formulation practice (GMP and GFsP).

Implications for Consumer Safety and Product Performance

Crystallisation in a magnesium product – especially if progressing over time in opened bottles – can pose several issues:

• Inaccurate dosing: Solids settling at the bottom lead to inconsistency across servings.
• Physical discomfort: Ingesting sharp or large crystals may cause irritation to the mouth or throat.
• Reduced absorption: Precipitated forms are less bioavailable than dissolved magnesium.
• Microbial risk: Product instability may be indicative of broader formulation degradation.

Recommending that consumers “use the product within 25 days” after opening to avoid these effects is a workaround not a solution. A stable, well-formulated liquid magnesium supplement should maintain its integrity across its stated shelf life under proper storage conditions.

Best Practices in Liposomal Magnesium Formulation

GMPriority Pharma magnesium formulations are designed using the following principles:

• Solubility profiling of the magnesium salt selected
• Proper pH balancing and buffering to ensure long-term stability
• Use of bioavailable, fully solubilised forms of magnesium
• Transparent labeling of all excipients, including preservatives and emulsifiers
• Rigorous testing for phase separation, precipitation and crystal formation
• Shelf-life stability studies under ICH guidelines

Our R&D team works closely with analytical chemists, toxicologists and formulation scientists to ensure that our products meet or exceed pharmaceutical-grade standards for stability, safety and efficacy.

Conclusion

The crystallisation of magnesium in a liposomal product is not an inherent feature of liposomal delivery. The crystallisation of magnesium in a liposomal product is a sign of suboptimal formulation. While natural variation can occur in colour, flavour or viscosity due to botanical ingredients, the formation of visible crystals in a magnesium supplement reflects a preventable formulation issue, not a beneficial property.

At GMPriority Pharma, we are committed to:

• Evidence-based formulation
• Transparent consumer education
• Avoidance of misleading marketing claims
• Safe, effective and stable magnesium delivery systems

We encourage all manufacturers in the supplement industry to maintain scientific rigour, especially when educating customers on product properties that may affect safety and performance.

Contact & Technical References

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This white paper is a publication of GMPriority Pharma. ©2025

All technical content is peer-reviewed by our in-house R&D and QA teams. Reproduction permitted with proper citation.