In the formula, 'R represents a hydrogen atom or a radical (-CH2-CH(CH3)-O)mH, and n represents a common integral number for cellulose derivatives.
 
Nisso HPC consists of hydroxypropyl ethers obtained by the reaction of cellulose with propylene oxide. Manufacturing started in 1967, and the product was mentioned in the pharmacopeia of Japan in 1971.
 
Important Characteristics of Nisso HPC
1. Nisso HPC dissolves in water and organic polar solvents at room temperature.
2. Products of various degrees of polymerization are available, and you can choose one having a suitable viscosity depending on your drug design.
3. Being chemically inert, HPC rarely reacts with other reagents.
 
Use as a Binder for Pharmaceuticals
HPC is a highly effective pharmaceutical binder with a typical use amount of 1 to 5% by weight of the tablet. Generally, grades of lower viscosity such as HPC-L, SL or SSL are used to make control of granulation easy. Higher viscosity grades of HPC-M or H are used when a high degree of bonding strength is required while maintaining a low use amount.
 
Grades (Regular & Fine powder type)
Nisso has 5 grades of HPC depending on your viscosity needs. We are also able to supply special viscosity ranges to suit your specific requirements.
Table 1. Regular type
Grade SSL SL L M H
Viscosity* (mPa-s) 2.0 ~ 2.9 3.0 ~ 5.9 6.0 ~ 10.0 150 ~ 400 1000 ~ 4000
USP N C C C C
EP C C C C C
JP C C C C C
C:conforms   N:conforms on certain condition
*Measured the values of an aqueous solution containing 2% by weight of dry HPC at 20°C (60° F)
Table 2. Fine powder type
Grade SL L M H
Viscosity* (mPa-s) 3.0 ~ 5.9 6.0 ~ 10.0 150 ~ 400 1000 ~ 4000
USP C C C C
EP C C C C
JP C C C C
99% passes through 100mesh sieve (150micron)   C:conforms
*Measured the values of an aqueous solution containing 2% by weight of dry HPC at 20°C (60° F)

Particle Size Distribution
Regular type : 99%passes through 40mesh sieve (350micron)
Fine powder type : 99%passes through 100mesh sieve (150micron)
Figure 1. Particle size distribution

Physical and Chemical Properties
1. Apparent density of the powder : 0.5 ~ 0.6/ml
    Specific gravity of particles : 1.2224
2. Thermal Stability : Coloring temperature : 195 ~ 210°C (380 ~ 410°F)
                                Charring temperature : 260 ~ 275°C (500 ~ 527°F)
 
Nisso HPC complies with the requirements of the National Formulary (USP/NF), the European Pharmacopoeia (EP) and the Japanese Pharmacopoeia (JP).
Table 3. Grades and Specifications
<USP/NF>
Items Specification
Grade SSL SL L M H
Viscosity* (mPa-s) 2.0 ~ 2.9 3.0 ~ 5.9 6.0 ~ 10.0 150 ~ 400 1000 ~ 4000
Appearance of solution Conforms
Identification Conforms
pH 5.0 ~ 8.0
Loss on drying not more than 5.0%
Residue on ignition (N) not more than 0.2%
Hydroxypropoxyl group not more than 80.5%
Heavy metals not more than 20 µg/g
Lead (Pb) not more than 0.001%
Silica not more than 0.6%
*Measured the values of an aqueous solution containing 2% by weight of dry HPC at 20°C (60° F)
*N:Conforms on certain condition

<EP>
Items Specification
Grade SSL SL L M H
Viscosity* (mPa-s) 2.0 ~ 2.9 3.0 ~ 5.9 6.0 ~ 10.0 150 ~ 400 1000 ~ 4000
Appearance of solution Conforms
Identification Conforms
pH 5.0 ~ 8.5
Loss on drying not more than 7.0%
Residue on ignition not more than 1.6%
Hydroxypropoxyl group not more than 80.5%
Heavy metals not more than 20 µg/g
Chloride not more than 0.5%
Silica not more than 0.6%
*Measured the values of an aqueous solution containing 2% by weight of dry HPC at 20°C (60° F)

<JP>
Items Specification
Grade SSL SL L M H
Viscosity* (mPa-s) 2.0 ~ 2.9 3.0 ~ 5.9 6.0 ~ 10.0 150 ~ 400 1000 ~ 4000
Description of solution Conforms
Identification Conforms
pH 5.0 ~ 7.5
Clarity of solution Conforms
Loss on drying not more than 5.0%
Residue on ignition not more than 0.5%
Hydroxypropoxyl group 53.4 ~ 77.5%
Chlorides not more than 0.142%
Sulfate not more than 0.048%
Heavy metals not more than 20 ppm
Arsenic (As) not more than 2 ppm
*Measured the values of an aqueous solution containing 2% by weight of dry HPC at 20°C (60° F)
 
Viscosity of aqueous solution
The relationship between the concentration of HPC and viscosity of the solution, and the relationship between temperature and viscosity of the solution are shown respectively in Figure 2 and Figure 3.
Aqueous solutions are transparent and feel smooth. As shown in Figure 3, viscosity is gradually lowered with elevation of the temperature, and suddenly drops at a temperature above 45°C. Such a process is due to limited solubility. The process is reversible.
Figure 2.
Viscosity vs. concentration of
acqueous solution at 20°C
Figure 3.
Viscosity vs. temperature of
2% acqueous solution
Viscosity of ethanol solution
Figure 4 shows the viscosity change in concentrated ethanol solutions with increased concentration of HPC.
Figure 5 shows the viscosity change in ethanol solutions at various temperatures.
Relationship between the concentration of absolute ethanol solution and it's viscosity is similar to that of aqueous solution.
Viscosity of absolute ethanol solution decreases with elevation of the temperature, but unlike aqueous solution, rapid decrease in viscosity due to gelation is not observed.
Figure 4.
Viscosity vs. concentration of
ethanol solution at 20°C
 Figure 5.
Viscosity vs. temperature of
2% ethanol solution
 
Benefits of Applying Lowest Viscosity Grade, SSL
1. Granulate smaller particle size.
2. Shorten granulation time by increasing concentration as binding solution.
3. Shorten disintegration time while maintaining hardness and low friction loss.
4. Keep particle size small while coating.
Table 4. Making tablets using HPC-SSL, SL, L
HPC Grade SSL SL L
Material Lactose (g) 700 700 700
Corn starch (g) 300 300 300
8% HPC aqueous solution (g) 375 375 375
Property of granule Particle size distribution (%) 1400µ on 0.2 0.2 -
500µ 0.2 0.2 0.4
355µ 0.4 0.6 1.7
250µ 1.3 2.1 8.4
180µ 4.0 6.0 14.4
150µ 8.0 9.6 15.6
106µ 22.1 22.1 24.7
75µ 30.3 26.9 19.6
75µ under 33.6 32.3 15.0
Bulky density (kg/cm3) Loose 90 95 130
packed 0.5 0.47 0.46
Property of tablet Hardness (kg) 14 14 12
Friction loss (%) 0.2 0.2 0.2
Disintegration time (min) 6 8 9
 

Please email us your Nisso HPC sample request: info@nissoamerica.com
Phone: 212.490.0350