Low Nitrite Microcrystalline Cellulose (MICCEL-LN)

Why Low Nitrite MCC Matters in Pharmaceuticals

Nitrosamines are classified as genotoxic impurities and are considered probable human carcinogens, which has led to increased scrutiny by global regulatory authorities such as the US FDA and EMA. In pharmaceutical formulations, nitrosamines can form when nitrites react with secondary or tertiary amines under specific processing or storage conditions.

Since excipients can contribute trace-level nitrites to drug products, excipient selection has become a critical part of nitrosamine risk assessments. Using a low nitrite microcrystalline cellulose such as MICCEL-LN helps pharmaceutical manufacturers reduce excipient-related risk and strengthen overall nitrosamine control strategies in oral solid dosage formulations.

What is MICCEL-LN – Low Nitrite MCC Grade

MICCEL-LN is a low nitrite grade of microcrystalline cellulose (MCC) developed specifically to support nitrosamine risk mitigation in pharmaceutical formulations. It is manufactured using carefully controlled processes that eliminate the use of nitrosating agents and minimize potential sources of nitrogen-related impurities.

Derived from natural, nitrogen-free raw materials, MICCEL-LN offers a low inherent risk of nitrosamine formation while delivering the functional performance expected from pharmaceutical-grade MCC.

Nitrosamine Risk Mitigation Approach

MICCEL-LN is developed using a comprehensive, risk-based approach aligned with current regulatory expectations for nitrosamine control. Risk mitigation begins at the raw material level and continues throughout the manufacturing process. Key elements of the MICCEL-LN nitrosamine risk mitigation strategy include controlled sourcing of raw materials, thorough evaluation of potential impurity contributors, and the absence of secondary and tertiary amines across the manufacturing process.

The use of reverse-osmosis (RO) treated process water further supports impurity control and consistency. The overall risk assessment approach aligns with IPEC Excipient Nitrosamines Risk Evaluation guidelines, providing additional confidence for regulatory and quality teams.

Analytical Data & Compliance

Extensive analytical testing supports the low-nitrite profile of MICCEL-LN at both raw material and finished product stages.

Seven commercial batches of MICCEL-LN were analyzed using ion chromatography, with all results confirming nitrite levels consistently below 50 ppb. This demonstrates strong control over nitrite content in the finished product and highlights the effectiveness of manufacturing controls and process water quality in maintaining low impurity levels.

Sr. No.	Name of Raw Material	Nitrite content
1.	Wood Pulp	BLQ(< 50 ppb)
2.	Hydrochloric Acid	113 ppb
3.	Ammonia	BLQ(< 50 ppb)

Sr. No.	Batches of MICCEL-LN	Nitrite content	Remark
1.	Seven batches are analyzed for nitrite	BLQ(<50 ppb)	All the 7 batches showing the nitrite results below 50 ppb
2.		BLQ(<50 ppb)
3.		BLQ(<50 ppb)
4.		BLQ(<50 ppb)
5.		BLQ(<50 ppb)
6.		BLQ(<50 ppb)
7.		BLQ(<50 ppb)

Sr. No.	Water sample Batch No.	Nitrite content	Remark
1.	Process Water	BLQ(< 50 ppb)	Water nitrite results are below 50 ppb and well below the limits suggested by WHO Guideline
2.	Purified Water	BLQ(< 50 ppb)

Manufacturing Controls & Safety Assurance

MICCEL-LN is manufactured under strict controls designed to minimize nitrosamine risk throughout production. These controls are embedded into process design, material selection, and equipment management. Key manufacturing and safety measures include the absence of secondary or tertiary amines, no use of nitrogen-containing or recycled solvents, and no chloramines used during equipment cleaning.

Dedicated equipment is used exclusively for cellulose manufacturing, and ammonium salts, amides, and primary amines are excluded from the process.These controls ensure consistent quality, traceability, and suitability for sensitive pharmaceutical applications.

Applications of MICCEL-LN

Oral Solid Dosage Formulations

MICCEL-LN is suitable for tablets and capsules where microcrystalline cellulose is used as a filler, binder, or disintegrant, while supporting low nitrite requirements.

Nitrosamine-Sensitive APIs

This low-nitrite MCC grade is ideal for formulations containing APIs that are sensitive to nitrosamine formation, helping reduce excipient-related risk.

High-Risk Regulatory Markets (US & EU)

MICCEL-LN supports products intended for markets with stringent regulatory expectations around nitrosamine risk assessment and impurity control.

Sensitive Pharmaceutical Formulations

It is well suited for formulations requiring tighter control over excipient impurities without compromising functional performance.

Standard MCC Applications with Enhanced Safety Focus

MICCEL-LN can be used wherever standard MCC is required, offering the same functional benefits with added assurance for nitrite control.

Lifecycle Management and Reformulation Projects

MICCEL-LN is suitable for reformulation or lifecycle management initiatives where existing products require enhanced control of nitrosamine risk due to evolving regulatory guidance.

Frequently Asked Questions

What is MICCEL-LN?

MICCEL-LN is a pharmaceutical-grade microcrystalline cellulose with consistently low nitrite levels, developed to support nitrosamine risk mitigation in oral solid dosage formulations.

Why is low nitrite MCC important in pharmaceuticals?

Nitrites can contribute to nitrosamine formation under certain conditions. Using a low-nitrite MCC helps reduce excipient-related risk and supports regulatory compliance.

How is nitrite content controlled in MICCEL-LN?

Nitrite levels are controlled through nitrogen-free raw materials, absence of nitrosating agents, RO-treated process water, and routine ion chromatography testing of finished batches.

Is MICCEL-LN suitable for regulated markets like the US and EU?

Yes, MICCEL-LN is designed to meet evolving regulatory expectations and aligns with industry guidance for nitrosamine risk evaluation.

Can MICCEL-LN replace standard MCC grades?

MICCEL-LN offers the same functional benefits as standard MCC while providing additional assurance for formulations where nitrosamine risk control is required.