Low-Substituted Hydroxypropyl Cellulose

Super Disintegrant

Introduction

L-HPC (Low-Substituted Hydroxypropyl Cellulose) was first approved in 1977 as a disintegrant for pharmaceutical dosage forms in Japan. A recent survey shows that L-HPC is ranked as the first choice of tablet disintegrant by Japanese pharmaceutical companies.

This page briefly describes the properties of L-HPC. If you are interested in its characteristics and application, or have any questions, please contact us for further information.

General Properties

  • Appearance: White to slightly yellow powder
  • True Density: 1.3 g/cm³ (measured with helium pycnometer
  • Solubility: Not soluble in water or practical organic solvents. Swells in water. Soluble in 10% NaOHaq., as a viscous and turbid solution.
  • Thermal degradation temperature: approx 260°
  • Equilibrium moisture content 25°C
  • Water-Soluble substances

Benefits

The key benefits of Hydrocel L-HPC include:

  • Excellent compatibility with active ingredients
  • Disintegration into smaller particles leading to better dissolution
  • Anti-capping effect for tableting process
  • Suitable for pellet extrusion as well as tableting
  • A variety of grades are available depending on application

Hydrocel L-HPC vs. HPC

Hydrocel L-HPC is NOT the same as HPC. Although sharing the same CAS number, Hydrocel L-HPC has different characteristics from Hydroxypropyl-cellulose (HPC), a binding agent widely used for solid dosage forms. Hydrocel L-HPC and HPC have separate monographs in pharmacopeias. While the regular HPC has a large amount of hydroxypropoxy groups in the cellulose backbone, Hydrocel L-HPC has only a small level (See the picture below). Due to this chemical difference, HPC is soluble in water, but Hydrocel L-HPC is insoluble.

Hydrocel L-HPC vs. HPC

HPC is typically used for granulation binder in an aqueous solution, but Hydrocel L-HPC cannot be used in this way. Hydrocel L-HPC is an effective disintegrant due to its swelling action in water, but this is not the case with HPC

Because Hydrocel L-HPC also has good compressibility, dry blending of this material produces hard tablets similar to those made from microcrystalline cellulose. In this application, Hydrocel L-HPC functions as a “dry binder.”

Application Based Properties

Disintegration & Compressibility

Comparing disintegration capability of various disintegrants, the ranking is dependent on active ingredient and formulation. Looking at the data shown below, Hydrocel L-HPC has similar disintegration capability to the other “super-disintegrants.”

Hydrocel L-HPC also has a good compressibility compared to the other disintegrants.


Compatability with Active Ingredients

Because L-HPC is non-ionic, it is less reactive to active ingredients compared with ionic excipients. This excellent compatibility is the main reason for Hydrocel L-HPC being the first choice of Japanese pharma companies.

For example, aspirin tablets with Hydrocel L-HPC were stable under high temperature whereas ionic ingredients showed whiskers of salicylic acid formed by hydrolysis (See picture below). Vitamin C tablets formulated with Hydrocel L-HPC showed no interaction compared with tablets using ionic disintegrants. The color stability was even better than with microcrystalline cellulose which is another non-ionic ingredient under the same moisture level. Our further study suggests that this was due to the low water activity of Hydrocel L-HPC because water molecules are bound to the amorphous region of the polymer. All tablets were made by direct compression.


Anti-Capping

One of the benefits of Hydrocel L-HPC is to resolve “capping,” which is a typical problem in the tableting process. Several reports have pointed out that capping is caused by a high residual die-wall pressure during the tableting process. Hydrocel L-HPC reduces the residual die-wall force and ejection force during the tableting process. LH-11, the highly fibrous grade, is the most effective for anti-capping, as entangling of fibers is important for capping prevention.


Direct Compression

For direct compression, LH-21 is the primary grade to test. If you especially have a problem of capping, consider using of LH-11 . If you need to use a large amount of Hydrocel L-HPC (more than 25 %), consider using LH-11 (high density grade) for better flowability.


Wet Granulation (High Speed Mixer)

In wet granulation, Hydrocel L-HPC gives a “buffer effect” stabilizing the wet- massing process for a wide range of water content. LH- 21 is typically used for this purpose. Especially for active ingredients with poor solubility and low wettability, you can use a higher amount of Hydrocel L-HPC to improve disintegration. Even as much as 20 - 40 % of Hydrocel L-HPC has been used in a tablet for this purpose. In spite of such a high content, stability problems are not significant as seen in other ionic disintegrants. In such applications, tablets disintegrate in very fine individual particles, so the dissolution is rapid and complete.


Wet Granulation (Fluid Bed)

In some cases a larger amount of Hydrocel L-HPC is needed to disintegrate and dissolve a poorly soluble drug. Because Hydrocel L-HPC is originally fibrous, the addition in a large amount may cause larger weight variation of tablets due to low flowability, or blocking of fluidization during the fluid-bed granulation. LH-11, is designed to be effective in such cases. There may be some limitation in compressibility.


Pellet Extrusion

As well as tableting, Hydrocel L-HPC is also applicable for pellet extrusion. Micronized grades (typically LH-21) are best suited for this application because smaller particles can easily pass through the screen. Hydrocel L-HPC provides wet mass with a “buffer effect” in which the wet mass accepts a wider range of water content. Hydrocel L-HPC plasticizes wet mass and shows greater productivity (extrusion speed and yield). The final pellets show quick disintegration and better friability compared with non- Hydrocel L-HPC formulations.

APPLICATION

Primary grade choice

Primary grade choice

Tablets_Application

INTERACTION WITH WATER

SWELLING PROPERTY

Hydrocel L-HPC is not soluble in water. However, it absorbs water and significantly expands in volume. This swelling action causes tablets to quickly disintegrate. The swelling volume is dependent on particle size and hydroxypropoxy content, as shown below. This experiment was carried out using an apparatus shown on the right. For test formulation, disintegrant and alumina were blended 1: 4 to reduce the effect of strong binding between disintegrant particles. Compared to other excipients, Hydrocel L-HPC swells and reaches to its maximum volume quicker.

EFFECT OF TEST FLUID

Water uptake was tested using various test fluids. Hydrocel L-HPC shows pH-independent characteristics. In contrast, the behavior of ionic disintegrants was dependent on test fluids.

Test fluids:

  • Excellent compatibility with active ingredients
  • USP Simulated Gastric Fluid TS (pepsin absent), pH 1.2
  • USP Simulated Intestinal Fluid TS (pancreatin absent), pH 6.8

WATER UPTAKE

This data shows water uptake through a bed of disintegrant powder using an apparatus shown below. Similar to the swelling property, the water uptake level depends on particle size and hydroxypropoxy content. Compared to the other super-disintegrants, Hydrocel L-HPC absorbs a great amount of water and reaches a plateau in a short time.