NISSO HPC Application Guide: Choosing the Right Grade for Your Formulation

Hydroxypropyl Cellulose is not a one-grade material.

Within the NISSO HPC portfolio, viscosity ranges from very low-viscosity SSL to very high-viscosity VH, with different particle-size options and application ranges. A grade considered for high-shear granulation may therefore be very different from one considered for controlled-release matrix tablets.

The practical starting point is to look at viscosity, particle size, processing method and intended application together.

This guide brings these factors into one practical overview to help formulation, R&D and procurement teams navigate the NISSO HPC portfolio and understand the technical properties behind its different grades.

NISSO HPC at a Glance

NISSO HPC is Hydroxypropyl Cellulose, a modified cellulose obtained by reacting propylene oxide with cellulose. The presence of hydroxypropoxy groups prevents hydrogen bonding between hydroxyl groups on the cellulose chain, thereby making HPC soluble.

NISSO HPC was first sold in Japan in 1969 and was listed in the Japanese Pharmacopeia (JP) by 1971. It was designated as a food additive in 2005, and manufacturing has been fully IPC GMP compliant since 2010.

Key features of NISSO HPC include:

• Exceptional binding force
• Solubility in water and most organic solvents
• Chemically inert and virtually non-reactive behavior
• Multiple viscosity grades and particle-size options
• Minimal lot-to-lot variability
• 5-year shelf life
• No additives such as silica
• Conformity with JP, USP and EP

NISSO HPC is used across pharmaceutical, food, cosmetic and industrial applications.

From Granulation to Controlled Release: One HPC Portfolio, Different Roles

NISSO HPC covers several processing and application areas, including:

• Granulation
• Coating
• Thickening
• Direct compression / dry granulation
• Hot melt processing
• Solubility enhancement
• Controlled-release matrix tablets
• Industrial applications including sintering

The important distinction is that these applications do not all use the same part of the grade range.

Lower-viscosity grades appear across several granulation, direct-compression, coating and solubility-enhancement applications, while the higher-viscosity region is positioned for controlled-release matrix tablets. Hot melt processing spans a particularly broad section of the grade range.

The first question in an HPC project should therefore not simply be “Can we use HPC?” but rather “Which NISSO HPC grade and powder form should we evaluate for this process?”

Understanding the NISSO HPC Grade Range

NISSO HPC is available in eight principal viscosity grades.

NISSO HPC Viscosity Grades

The progression from SSL to VH represents a substantial change in both viscosity and molecular weight.

For formulation work, the specific NISSO HPC grade therefore matters considerably more than specifying “HPC” alone.

Matching NISSO HPC Grades to the Processing Method

The application matrix provides a useful first view of where different sections of the NISSO HPC portfolio are positioned.

High-Shear Granulation

For high-shear granulation, the application range extends approximately from SSL through L.

Fluidized-Bed Granulation

For fluidized-bed granulation, the range extends more broadly from approximately SSL through LMM.

Direct Compression and Dry Granulation

For direct compression and dry granulation, the range extends approximately from SSL through L.

Hot Melt Processing

Hot melt processing covers the broadest range shown in the matrix, extending approximately from SSL through VH.

Film Coating

For film coating, the range extends approximately from SSL through LMM.

Solubility Enhancement

For solubility enhancement, the application range is concentrated around SSL through SL.

Controlled-Release Matrix Tablets

For controlled-release matrix tablets, the application range shifts toward the higher-viscosity region, approximately M through VH.

The matrix provides a useful starting point for grade screening, while the final selection still needs to be evaluated in the intended formulation and process.

Particle Size Adds Another Selection Variable

Viscosity is only one part of the NISSO HPC portfolio. Different powder forms are also available.

• Regular Powder (40 mesh): generally D50 150–190 μm

• Fine Powder (100 mesh): D50 80–110 μm

• Super Fine Powder (330 mesh): D50 20 μm

For SSL Regular Powder, the matrix includes a specific footnote indicating a particle size of 85 μm.

Particle-Size Distribution Reference Values

Regular powder is shown as available across SSL through VH. Fine powder is available for selected grades including SL, L, M, H and VH, while super-fine powder is shown for SSL.

These particle-size options provide another technical distinction between products within the NISSO HPC range.

Powder Characteristics Beyond Particle Size

NISSO HPC is also characterized through bulk density, compressibility and angle of repose.

For regular powder grades SSL, SL, L, M and H:

• Aerated bulk density ranges from 0.38 to 0.44 g/mL

• Packed bulk density ranges from 0.50 to 0.55 g/mL

• Compressibility ranges from 16% to 32%

• Angle of repose ranges from 43° to 46°

Fine and super-fine powder forms show different values. For example:

SSL-SFP: Aerated bulk density 0.18 g/mL | Packed bulk density 0.33 g/mL | Compressibility 46% | Angle of repose 53°

SL-FP: Aerated bulk density 0.31 g/mL | Packed bulk density 0.47 g/mL | Compressibility 33% | Angle of repose 47°

L-FP: Aerated bulk density 0.33 g/mL | Packed bulk density 0.46 g/mL | Compressibility 28% | Angle of repose 42°

M-FP: Aerated bulk density 0.38 g/mL | Packed bulk density 0.49 g/mL | Compressibility 23% | Angle of repose 44°

H-FP: Aerated bulk density 0.36 g/mL | Packed bulk density 0.49 g/mL | Compressibility 25% | Angle of repose 43°

These measurements provide additional characterization of the different NISSO HPC powder forms beyond particle size alone.

Solubility: More Than Simply Water-Soluble

NISSO HPC dissolves in water at room temperature and in the majority of polar organic solvents.

Testing with 2% HPC-L shows soluble systems in a broad range of solvents, including:

• Water

• Methanol

• Ethanol

• Isopropyl alcohol

• n-Butanol

• Cyclohexanone

• THF

• Cellosolve

• Butyl cellosolve

• Glacial acetic acid

• Formic acid

• DMF

• DMSO

• Pyridine

• Methyl chloride

• Chloroform

• Benzene:Methanol (1:1)

• Toluene:Ethanol (3:2)

• Glycerin:Water (3:7)

The same test identifies several systems as difficult to dissolve, including tert-butanol, cyclohexanol, propylene glycol, acetone, dioxane and lactic acid.

Ethyl acetate and butyl acetate are reported as insoluble under the stated test conditions.

The data also shows that solution viscosity and appearance vary according to solvent. Selected 2% HPC-L viscosity values include:

Water: 6.3 mPa·s

Ethanol: 6.9 mPa·s

Isopropyl alcohol: 13.1 mPa·s

Propylene glycol: 276.0 mPa·s

Cyclohexanol: 397.0 mPa·s

Lactic acid: 416.0 mPa·s

Solubility should therefore be considered together with the characteristics of the selected solvent system.

How Concentration and Temperature Change HPC Solution Behavior

An aqueous HPC solution appears clear and smooth, while viscosity decreases as temperature increases.

Solution viscosity also increases as HPC concentration increases. This behavior is shown in both aqueous and ethanol systems, with the magnitude depending on the selected grade.

Temperature produces another characteristic response. Beginning around the cloud-point region, the aqueous solution becomes hazy and viscosity decreases abruptly as thermal precipitation occurs.

This process is completely reversible.

Cloud Point: Why Grade and Concentration Matter

The reported gelation temperatures vary by grade and concentration:

Reported Gelation Temperatures

The cloud point is inversely related to HPC viscosity: as HPC viscosity increases, the observed cloud-point temperature decreases.

This temperature-dependent behavior should be considered when evaluating aqueous HPC systems that will undergo heating or cooling.

Viscosity Across Different pH Conditions

The effect of pH was evaluated using 2% HPC solutions at 20°C.

The graph covers SSL, SL, L, M and H, with the plotted viscosity profiles remaining relatively stable across the tested pH conditions.

This provides a useful reference for the viscosity behavior of aqueous HPC solutions under the reported test conditions.

Effect of UV Radiation on HPC Aqueous Viscosity

UV exposure was also evaluated using 2% solutions of HPC-L, HPC-M and HPC-H.

The solutions were exposed to UV radiation at a wavelength of 254 nm, at 25–30°C, for 30 days, with viscosity measured at 20°C.

The plotted viscosity profiles remain essentially stable over the reported test period.

Moisture Content Over Time

Moisture uptake was evaluated at 25°C under 50% RH and 80% RH conditions.

The reported curves show greater moisture uptake at 80% RH than at 50% RH, with the moisture content approaching a relatively stable level after the initial increase.

The test includes HPC-L / SL and HPC-M.

These data should be considered together with the product’s stated storage requirements.

Thermal Characteristics

NISSO HPC also has reported softening-temperature and pyrolysis data.

Softening Temperature

For pyrolysis:

• Coloration begins at approximately 195–210°C

• Blackening begins at approximately 260–275°C

Reported burnout temperatures are:

SSL: 497°C

SL: 506°C

L: 508°C

M: 528°C

H: 541°C

These values provide additional physical and thermal characterization of the NISSO HPC grades.

Film Characteristics: Tough and Elastic HPC Films

HPC can be used to create a tough and elastic film when dissolved in appropriate solvents.

Film Property Data

The tensile-strength and elongation measurements were performed using a film of approximately 0.1 mm thickness.

The reported results show that tensile strength, elongation and moisture permeability differ between NISSO HPC grades.

Oxygen-permeability data is also provided for HPC-SL film.

Surface Tension

HPC reduces the surface tension of aqueous solution.

For HPC-L, the following values are reported:

0.01%: 51.0 dyne/cm

0.1%: 49.1 dyne/cm

1%: 46.3 dyne/cm

10%: 45.8 dyne/cm

For HPC-M, reported values include:

0.01%: 54.8 dyne/cm

0.1%: 49.7 dyne/cm

1%: 46.3 dyne/cm

The data therefore shows a reduction in surface tension with increasing HPC-L concentration under the reported test conditions.

Bringing the Technical Variables Together

The NISSO HPC portfolio differs across several measurable properties:

• Viscosity

• Molecular weight

• Particle-size form

• Powder characteristics

• Application range

• Solvent compatibility

• Solution concentration behavior

• Temperature response

• Film properties

For practical grade screening, these properties can be reviewed together with the intended processing method and formulation requirements.

From Application Data to Grade Evaluation

The NISSO HPC portfolio spans a wide range of viscosities, molecular weights and powder forms.

For one project, the relevant starting point may be a low-viscosity grade used within a granulation or coating range. For another, the application matrix may direct attention toward higher-viscosity grades used for controlled-release matrix tablets.

The Application Guide provides a useful starting point for narrowing these options, while final suitability should be confirmed in the intended formulation and process.

At ALKAN Chemical Europe, we can support customers with:

• NISSO HPC grade discussions

• Technical documentation

• Sample coordination

• Commercial quotations

• Commercial supply

• Coordination of further technical discussion through NISSO CTAC, where appropriate

Final Thoughts

The NISSO HPC portfolio should not be viewed as one excipient with several product codes.

From SSL through VH, the grades span a broad range of viscosity and molecular weight. Particle-size options introduce another distinction, while solubility, thermal behavior, powder properties and film characteristics provide additional technical information for grade evaluation.

The practical objective is to connect the appropriate grade and powder form with the intended processing route and formulation requirements.

The NISSO HPC Application Guide provides the technical foundation for that evaluation.

FAQ: NISSO HPC Application Guide

What is NISSO HPC?
NISSO HPC is Hydroxypropyl Cellulose, a modified cellulose available in several viscosity and particle-size grades.

What NISSO HPC grades are available?
The principal viscosity grades are SSL, SL, L, LM, LMM, M, H and VH. Their viscosities range from 2.0–2.9 mPa·s for SSL to 4,001–6,000 mPa·s for VH, measured at 20°C as a 2% aqueous solution.

Which NISSO HPC grades are positioned for high-shear granulation?
The application matrix extends approximately from SSL through L.

Which grades are positioned for fluidized-bed granulation?
The range extends approximately from SSL through LMM.

Can NISSO HPC be used for hot melt processing?
Hot melt processing appears across approximately SSL through VH in the application matrix.

Which NISSO HPC grades are positioned for controlled-release matrix tablets?
The application range is approximately M through VH.

Is NISSO HPC soluble in water?
Yes. NISSO HPC dissolves in water at room temperature and in the majority of polar organic solvents.

Is NISSO HPC soluble in ethanol?
Yes. The 2% HPC-L solubility data reports a transparent, soluble system in ethanol.

What happens when an aqueous HPC solution is heated?
Viscosity decreases as temperature increases. Around the cloud-point region, the solution becomes hazy and viscosity decreases abruptly. The process is completely reversible.

Does NISSO HPC contain silica?
NISSO HPC is listed as containing no additives such as silica.

What is the shelf life of NISSO HPC?
The Application Guide lists a 5-year shelf life.

Which pharmacopeias does NISSO HPC conform to?
NISSO HPC conforms to Japanese Pharmacopeia (JP), United States Pharmacopeia (USP), and European Pharmacopeia (EP).

Can ALKAN support a NISSO HPC project?
Yes. ALKAN Chemical Europe can support product and grade discussions, technical documentation, samples and commercial supply, and coordinate additional technical support through NISSO CTAC where appropriate.

Disclaimer: This article summarizes technical information from the NISSO HPC Application Guide for general informational purposes. Final grade selection and product suitability should be evaluated using the applicable current product specification, SDS, quality documentation and formulation testing.

Technical Source: NISSO HPC Hydroxypropyl Cellulose Application Guide, NIPPON SODA Co., Ltd., Version 2.0 — March 31, 2019.

Author: Dr. Peter Michael, Procurement and Sales Manager, ALKAN Chemical Europe. Pharmacist (B.Pharm). Supporting customers across EMEA with excipient and API sourcing backed by technical documentation.