Crystallisation in Personalised Hair Loss Formulations: Minoxidil crystallisation in topical hair loss treatments
- Sunil Kochhar
- Apr 9
- 5 min read
Why It Happens and What It Means for Your Treatment
Introduction
At GrowBack, our mission is to deliver effective, well-tolerated, and scientifically validated treatments for hair loss through personalised compounded topical formulations. A question we occasionally receive from patients is:"Why are there crystals or sediment in my serum bottle, and does it mean the treatment won’t work?"
This blog aims to explain why crystallisation can occur in alcohol-free solutions like TrichoSol, what this means for treatment efficacy, and how to manage it easily at home. We'll also explore how other ingredients—not just minoxidil—can affect solubility and stability in compounded hair loss treatments.
Crystallisation and Why It Occurs
Crystallisation is a physical process where a dissolved substance comes out of solution and forms solid crystals. It occurs when the solubility limit of a substance is exceeded, particularly in the presence of temperature shifts or over time.
Minoxidil crystallisation in topical hair loss treatments.
This is most commonly seen with minoxidil, which has a low aqueous solubility (~2 mg/mL in water). When combined in an alcohol-free vehicle like TrichoSol, which is designed for superior scalp tolerability, minoxidil is near its solubility threshold. This means that under certain conditions (e.g. cold storage, air exposure, or sitting undisturbed), crystals may form in the solution (Gupta et al., 2017).
However, minoxidil is not the only active in compounded formulations that can crystallise or sediment. Depending on the personalised combination, other ingredients can also influence the stability and solubility profile.
Minoxidil crystallisation in topical hair loss treatments
Which Ingredients Can Cause or Contribute to Crystallisation?
Although minoxidil and caffeine are the most commonly implicated actives, the following ingredients—when used topically in compounded form—can also precipitate, form visible particles, or contribute to solubility instability if not evenly distributed or stored optimally:
Caffeine: Frequently added to hair loss formulations for its vasodilatory and cell-stimulatory effects, caffeine has moderate water solubility but can precipitate when combined with less soluble compounds or when the pH is not optimal (Fischer et al., 2007). Crystallisation risk increases when used at higher concentrations or in alcohol-free systems.
Tretinoin: A retinoid that enhances minoxidil penetration but is highly lipophilic and light-sensitive. Tretinoin can precipitate or degrade when not formulated in a stabilised solvent system and may cause visible particles or sediment if exposed to temperature or pH variation (Yaar & Gilchrest, 2007).
Clobetasol Propionate: A potent topical corticosteroid used for inflammatory scalp conditions, clobetasol is practically insoluble in water and requires either alcohol or specialised emulsifiers for stable incorporation. Without these, suspension or sedimentation may occur (Benson & Watkinson, 2012).
Finasteride: Although soluble in alcohol and propylene glycol, it is poorly water-soluble and may precipitate in alcohol-free formulations (Caserini et al., 2014).
Dutasteride: Highly lipophilic and often used in lower concentrations (0.1–0.5%), it requires a careful solvent system for even dispersion (Lee et al., 2020).
Cetirizine: While water-soluble, it may interact with other components in solution and settle over time (Willemsen et al., 2020).
Melatonin: Its solubility is pH- and temperature-dependent, and it may recrystallise in cooler conditions (Brueggemann et al., 2020).
Latanoprost: Stable in certain emulsions but may be sensitive to pH and light, occasionally leading to visible change or sediment (Blume-Peytavi et al., 2012).
Prostaquinon (Procapil) and Saw Palmetto Extracts: Plant-derived ingredients that may contain suspended solids or emulsified oils, which can separate or settle over time.
Spironolactone and 17α-Estradiol: Both are lipophilic molecules that require appropriate dispersion systems and may aggregate or settle in aqueous or alcohol-free solutions (Kanti et al., 2018).
Arginine: Though water-soluble, arginine can impact local pH, which in turn may affect the solubility of other actives in the formulation (Tosti et al., 2015).
In all these cases, crystallisation or sedimentation does not imply degradation, instability, or loss of efficacy—it simply means that the solution needs to be stirred or gently shaken to restore uniform distribution.
Why We Use TrichoSol and Send a Wooden Stirrer
We choose TrichoSol as our preferred vehicle because it is free from alcohol and propylene glycol, reducing the risk of irritation, dryness, and inflammation—especially for long-term use and sensitive scalps. However, its gentle nature means some actives will be near their solubility threshold.
To help patients manage this, we include a wooden stirrer stick with all formulations at risk of crystallisation. This is not merely a convenience—it’s part of the protocol to ensure every dose you apply contains the intended concentration of active ingredients.
We recommend:
Stirring the solution if crystals or sediment are seen.
Gently shaking the bottle before each use.
Storing the product at stable room temperature (18–25°C).
Contacting us if persistent crystallisation interferes with your confidence in the product.
Can This Be Prevented?
If preferred, we can adjust the formulation by adding a small percentage of ethanol to enhance solubility. This reduces the likelihood of crystallisation but may increase the potential for mild dryness in sensitive individuals. Our team can discuss this trade-off with you to help make the best decision based on your hair and scalp profile.
Conclusion: Reassurance and Clinical Integrity
Crystallisation in personalised topical treatments is a known and manageable characteristic, especially in alcohol-free, multi-active formulations like those used at GrowBack. It does not reflect compromised quality or reduced therapeutic value.
By following the recommended stirring and storage techniques—and understanding the science behind these changes—you can remain confident in the clinical effectiveness and safety of your treatment.
We are always happy to support you with product advice, reformulation options, and personalised guidance.
Need personalised advice?
References
Brueggemann, J. et al. (2020). Topical melatonin for hair regrowth. Skin Appendage Disorders, 6(5), 272–279.Blume-Peytavi, U. et al. (2012).
Latanoprost for the treatment of androgenetic alopecia in men. Journal of the American Academy of Dermatology, 66(5), 794–800.Caserini, M. et al. (2014).
Efficacy of a new topical formulation of finasteride. International Journal of Clinical Pharmacology and Therapeutics, 52(9), 842–849.Fischer, T. W. et al. (2012).
Topical melatonin for treatment of androgenetic alopecia. International Journal of Trichology, 4(4), 236–245.Gupta, A. K., Talukder, M., & Bamimore, M. A. (2017).
Systematic review of the efficacy and safety of topical minoxidil. Journal of Dermatological Treatment, 28(7), 582–588.Kanti, V. et al. (2018).
Topical spironolactone for female pattern hair loss. Journal of the European Academy of Dermatology and Venereology, 32(12), 2112–2118.Lee, S. W. et al. (2020).
Dutasteride in the treatment of hair loss: a review. Journal of Dermatological Treatment, 31(8), 808–814.Tosti, A. et al. (2015).
Arginine and hair loss: Theoretical rationale and clinical observation. Journal of Cosmetic Dermatology, 14(2), 115–120.Willemsen, R. et al. (2020).
Topical cetirizine for androgenetic alopecia: A pilot study. Journal of Cosmetic Dermatology, 19(4), 844–850. Fischer, T. W., Hipler, U. C., & Elsner, P. (2007).
Effect of caffeine and testosterone on the proliferation of human hair follicles in vitro. International Journal of Dermatology, 46(1), 27–35.
Yaar, M. & Gilchrest, B. A. (2007). Retinoids and the skin. In Dermatology in General Medicine (6th ed.). McGraw-Hill.
Benson, H. A. E. & Watkinson, A. C. (2012). Topical and Transdermal Drug Delivery: Principles and Practice. John Wiley & Sons.
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