A new preprint study conducted by researchers at Emplicure provides promising evidence that bioceramic calcium sulfate-based nicotine pouches may offer faster and more efficient nicotine delivery than conventional cellulose-based formats. The findings, currently hosted on Research Square, could shape future innovations in nicotine pouch design and regulation.
The study, titled Comparative study of calcium sulfate and cellulose-based nicotine pouch on pharmacokinetics, pulse rate and nicotine extraction, was authored by Dr. Anna Franzén and colleagues. It represents one of the first direct clinical comparisons between novel calcium sulfate pouch formulations and established commercial products.
Study Design
The research utilized a randomized, crossover pharmacokinetic study involving 12 habitual snus or nicotine pouch users. Each participant used:
- SERATEK® 3 mg and 6 mg pouches (calcium sulfate-based)
- ZYN® 6 mg pouches (cellulose-based)
Participants underwent a single 30-minute usage session per product, with follow-up assessments extending up to 8 hours post-use. Primary outcomes included:
- Nicotine plasma concentration (Cₘₐₓ, AUC₀–₃₀ min, AUC₀–∞)
- Time to peak concentration (Tₘₐₓ)
- Pulse rate response
- Residual nicotine content and extraction efficiency
Key Findings
- Faster Nicotine Absorption:
SERATEK pouches produced significantly higher plasma nicotine levels within the first 5 minutes than ZYN (p < 0.05), indicating a more rapid onset of effect. - Enhanced Early Exposure:
AUC₀–₃₀ min was significantly higher for SERATEK 6 mg pouches compared to ZYN 6 mg (p = 0.034). Peak concentration (Tₘₐₓ) occurred approximately 10 minutes earlier. - Higher Extraction Efficiency:
SERATEK users extracted an average of 56% of nicotine, compared to 43% for ZYN, suggesting more complete nicotine release during use. - Stronger Physiological Response:
SERATEK 6 mg was associated with a faster and more pronounced early pulse rate increase, peaking at +12 bpm in the first 5 minutes (p = 0.0032). - Comparable Overall Exposure:
Total nicotine exposure (AUC₀–∞) over 8 hours was similar across all products, indicating comparable safety profiles over time.
Mechanism: Role of Calcium Sulfate
The enhanced performance of SERATEK pouches may be attributed to the alkaline nature of calcium sulfate (pH ~7.7), which increases the availability of free-base nicotine—improving both solubility and mucosal absorption. This contrasts with the more neutral pH environment of cellulose-based matrices.
In addition to its delivery profile, the calcium sulfate matrix supports tighter packing and more efficient release, suggesting a promising future for bioceramic technologies in oral nicotine products.
GINN Perspective
This study contributes important data to the scientific foundation underpinning nicotine pouch development. The findings are relevant to several GINN priorities:
- Product innovation: Supports industry exploration of alternative carriers that optimize delivery without increasing dosage.
- Public health impact: Offers a pathway for lower-milligram products to remain effective in smoking cessation and substitution efforts.
- Regulatory frameworks: Demonstrates the need to assess carrier materials and extraction efficiency when reviewing product submissions—not just nicotine content.
GINN strongly supports continued research into the pharmacokinetics, safety, and user behavior associated with novel nicotine pouch formulations. We encourage manufacturers to adopt transparent clinical testing protocols and regulators to incorporate delivery efficiency metrics into their evaluation processes.
Conclusion
Emplicure’s comparative analysis of bioceramic versus cellulose nicotine pouches represents a significant advancement in the field. The demonstrated faster onset, greater extraction, and comparable overall exposure of calcium sulfate-based pouches may offer consumers more satisfying and effective alternatives—particularly for adult smokers seeking non-combustible nicotine products.
As innovation accelerates in the nicotine pouch category, GINN remains committed to fostering evidence-based dialogue between researchers, manufacturers, and regulators to ensure consumer safety, product efficacy, and public trust.
Citation:
Franzén A., Loof J., Birgersson U., et al. (2025). Comparative study of calcium sulfate and cellulose-based nicotine pouch on pharmacokinetics, pulse rate and nicotine extraction. Research Square preprint. https://doi.org/10.21203/rs.3.rs-5953198/v1
