Pharmaceutical-grade microcrystalline cellulose (MCC)

01

Choose the grade by particle size, bulk density and moisture

IFF gives an average particle size of 50 µm (typ.) for Avicel PH-101, 100 µm (typ.) for PH-102 and 200 µm (typ.) for PH-200, each with moisture content between 3 and 5%. It positions PH-101 for wet granulation, extrusion spherization and tablet compression, and PH-102 and PH-200 for direct compression and dry granulation/roller compaction, with the larger PH-200 particles giving enhanced flow. Loose bulk density is 0.28–0.33 g/ml for PH-102 and 0.29–0.36 g/cc for PH-200. [1] [2] [3]

Asahi Kasei's Ceolus PH table lists average particle size and bulk density of 50 µm and 0.29 g/cm³ (PH-101), 90 µm and 0.30 g/cm³ (PH-102) and 170 µm and 0.35 g/cm³ (PH-200), with angles of repose of 45°, 42° and 36° and loss on drying 2.0–6.0%; higher-density PH-301 and PH-302 are listed at 0.41 and 0.43 g/cm³. It states the values are basic reference only and not specifications. [4]

JRS lists Vivapur average particle size by laser diffraction and bulk density: 101 at 65 µm and 0.26–0.31 g/mL, 102 at 130 µm and 0.28–0.33 g/mL, and 200 at 220/250 µm and 0.31–0.37 g/mL. Its grades 103, 112 and 200 XLM are described as having very low moisture content (< 1.5 %) for water-sensitive actives, and 301 and 302 as having increased bulk density and improved flow. [5]

Editorial calculation: for the 101 grade the three makers give 50 µm (IFF and Asahi Kasei) and 65 µm (JRS, laser diffraction), and for the 200 grade 170 µm, 200 µm and 220/250 µm. The figures are not directly comparable unless the method is the same, so require the supplier to state the particle size method and d10, d50 and d90 ranges. [1] [4] [5] [6]

Give the supplier the grade or equivalent (PH-101, PH-102, PH-200 type or high-density/low-moisture variants), process (wet granulation, direct compression, roller compaction, spheronization), particle size limits and method (sieving or laser diffraction with d10/d50/d90), bulk density range, loss on drying range, pharmacopoeias to be met, nitrite or elemental impurity statements needed, microbial limits, packaging, and annual quantity.

02

Check the pharmacopoeia tests and supplier limits

The USP 35–NF 30 Microcrystalline Cellulose monograph, as reproduced by DrugFuture, requires: degree of polymerization not greater than 350 (from intrinsic viscosity in cupriethylenediamine); conductivity of the supernatant not exceeding that of the water by more than 75 µS/cm; pH 5.0–7.5; loss on drying NMT 7.0% at 105 °C for 3 h, or as labelled; residue on ignition NMT 0.1%; heavy metals NMT 10 ppm; water-soluble substances NMT 12.5 mg (0.25%); ether-soluble substances NMT 5.0 mg (0.05%); total aerobic count NMT 1000 cfu/g and molds and yeasts NMT 100 cfu/g. Labelling must state nominal loss on drying, bulk density and degree of polymerization, and d10, d50 and d90 where particle size distribution is stated. [6]

Supplier specifications can be tighter. IFF's Avicel PH-102 specification lists loss on drying 3–5%, pH 5.5–7.0, residue on ignition max 0.05%, heavy metals max 0.001%, degree of polymerization max 350, conductivity max 75 μS/cm, total aerobic plate count max 100 cfu/g and mold and yeast max 20 cfu/g. Its PH-200 sheet marks loss on drying 2.0–5.0% and pH 5.5–7.0 as more restrictive than compendium; its PH-101 sheet limits the +60 mesh (250 microns) fraction to max 1.0% and the +200 mesh (74 microns) fraction to max 35%. [2] [3] [1]

Pharmacopoeia listings: Asahi Kasei lists Ceolus PH under JP Microcrystalline Cellulose, USP/NF Microcrystalline Cellulose and Ph. Eur. Cellulose, Microcrystalline; JRS lists Vivapur under Ph. Eur., NF, JP, E 460(i) and FCC. [4] [5]

Editorial calculation: IFF's heavy metals limit of max 0.001% equals 10 ppm, the same as the USP 35 limit, and its water-soluble substances limit of 12.0 mg per 5 g is 0.24%, inside the USP 12.5 mg (0.25%). The reviewed monograph text is the USP 35–NF 30 edition, so ask the supplier which current edition and elemental impurity statement it certifies against. [2] [6]

03

Grade table, certificate, particle size method and regulatory files to ask each supplier for

When requesting quotations, ask each supplier for the grade table, certificate of analysis, specification with compendial and in-house limits, particle size method, regulatory file references, stability and retest period, and samples.

04

Particle size, bulk density, loss on drying, degree of polymerization, conductivity and microbial limits

The last three rows are compendial tests and the first three are grade choices: USP–NF fixes degree of polymerization, conductivity and microbial limits for every grade, while particle size and density separate PH-101, 102 and 200. [6]

05

Particle size and method, bulk density, moisture, pH and compendial limits for an MCC order

Particle size only compares on one method: IFF and Asahi Kasei give 50 µm for the 101 grade, JRS 65 µm by laser diffraction, so name the method with the limit. [4] [5]

06

Send the grade, process and compendia together

Paste it into your enquiry below or into an email to a maker, then replace every bracket.

Grade: [PH-101; PH-102; PH-200 type; other]
Process: [wet granulation; direct compression; roller compaction]
Particle size: [d50; d10/d90; method]
Bulk density: [g/mL range]
Moisture: [LOD range]
Compendia: [USP/NF; Ph. Eur.; JP; edition]
Quantity: [kg per year; packaging]

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