E463 (Hydroxypropylcellulose) is a water-soluble non-ionic cellulose ether, a semi-crystalline polymer with very low glass transition amorphous polymer domains along with crystalline domains and obtained by chemical reaction of the hydroxyl groups at the 2, 3 and/or 6 positions of the cellulose glucose residues.

Hydroxypropyl Cellulose is a cellulose derivative obtained by replacing some of the hydroxyl groups in natural cellulose with hydroxypropyl groups. This modification gives hydroxypropyl cellulose unique properties, such as solubility in both water and certain organic solvents. It is widely used in the food, pharmaceutical, and cosmetic industries as a thickening agent, stabilizer, binder, and film-former. Its ability to form gels, improve viscosity, and stabilize emulsions makes it a versatile ingredient in various applications.

Chemical Composition and Structure

Hydroxypropyl cellulose is produced through the reaction of cellulose with propylene oxide, which replaces the hydroxyl groups (-OH) in cellulose with hydroxypropyl groups (-CH₂CHOHCH₃). This structure gives hydroxypropyl cellulose good solubility in water and a greater ability to form viscous solutions, making it ideal for enhancing the texture and stability of products.

Physical Properties

It typically appears as a white or granular powder, odorless and tasteless. It is soluble in both hot and cold water, as well as in certain organic solvents. Its ability to absorb water allows it to form viscous solutions and gels, making it useful as a thickening, binding, and stabilizing agent in numerous formulations.

Production Process

Hydroxypropyl cellulose is produced by reacting cellulose with propylene oxide under alkaline conditions. This chemical process replaces the hydroxyl groups in cellulose with hydroxypropyl groups, enhancing its solubility and gel-forming capabilities. The resulting material is purified and dried for use in powder or granular form.

The name defines the structure of the molecule:

• Hydroxypropyl refers to a group derived from propylene, a three-carbon alkene, with an attached hydroxyl (-OH) group.
• Cellulose refers to a type of polysaccharide that is the main component of plant cell walls. Cellulose is a large molecule consisting of many smaller glucose units linked together.

The synthesis process takes place in several stages:

• Cellulose purification. The first step in the synthesis of HPC is the purification of cellulose, derived from plant sources. This involves the removal of impurities such as lignin, hemicellulose and other components.
• Alkaline treatment. Purified cellulose is treated with an alkali, sodium hydroxide. This process, known as mercerization, increases the reactivity of cellulose by breaking down its crystalline structure.
• Reaction to propylene oxide. The alkali-treated cellulose is reacted with propylene oxide. This introduces hydroxypropyl groups (-CH2CHOHCH3) on the cellulose molecule. The degree of substitution, or the average number of hydroxypropyl groups connected to each unit of glucose in cellulose, can be controlled by adjusting the reaction conditions.
• Neutralization and washing. After the reaction, the mixture is neutralized, usually with an acid such as hydrochloric acid. The product is then washed to remove unreacted reagents and by-products.
• Drying and grinding process. The wet mass is then dried and ground into a fine powder to produce the final product, hydroxypropylcellulose.
• Quality control. The final product is then tested to ensure it meets the required specifications. This may involve testing for parameters such as degree of replacement, viscosity, and moisture content.

It appears in the form of a white powder. 

What it is used for and where

Medical

In the pharmaceutical industry, it is used for its biocompatibility as a drug carrier, emulsion stabilizer, binder, thickener. In particular, since hydroxypropylcellulose exhibits organic and water solubility, it is suitable for solvent methods of drug release to produce solid dispersions. At low viscosity, hydroxypropylcellulose is an excellent pharmaceutical excipient. Due to its bioadhesive and hydrophilic properties it can be mainly used in topical and oral pharmaceutical formulations.

It affects the solubility, dissolution and oral bioavailability of drugs (1).

This study reports the behavior of hydroxypropylcellulose and carrageenan used in ophthalmics for use in cataract surgery due to their viscoelastic properties (2).

To reduce intraoperative and postoperative complications after surgery, Hydroxypropylcellulose was added in order to prepare a submucosal injection agent that can gel during endoscopic mucosal dissection and adhere to the wound surface (3).

Hydroxypropylcellulose was used as an artificial ligament coating in a case of anterior cruciate ligament injury and significantly improved the regeneration of ligamentous tissue. hydroxypropylcellulose coating can significantly improve the cytocompatibility and graft-to-bone healing of a polyethylene terephthalate artificial ligament for anterior cruciate ligament reconstruction (4).

Food

Ingredient on the European food additives list as E463, stabiliser, thickener.

Cosmetics

Binder agent. Ingredient that is used in cosmetic, food and pharmaceutical products as an anti-caking agent with the function of making the product in which it is incorporated silky, compact and homogenous. The binder, either natural such as mucilage, gums and starches or chemical, may be in the form of a powder or liquid.

Emulsion stabilizer. Emulsions are thermodynamically unstable. Emulsion stabilisers improve the formation and stability of single and double emulsions. It should be noted that in the structure-function relationship, molar mass plays an important role.

Film-forming agent. It produces a continuous ultra-thin film with an optimal balance of cohesion, adhesion and stickiness on the skin or hair to counteract or limit damage from external phenomena such as chemicals, UV rays and pollution.

Surfactant - Emulsifying agent. Emulsions are thermodynamically unstable and are used to soothe or soften the skin and emulsify, so they need a specific, stabilising ingredient. This ingredient forms a film, lowers the surface tension and makes two immiscible liquids miscible. A very important factor affecting the stability of the emulsion is the amount of the emulsifying agent. Emulsifiers have the property of reducing the oil/water or water/oil interfacial tension, improving the stability of the emulsion and also directly influencing the stability, sensory properties and surface tension of sunscreens by modulating the filmometric performance.

Viscosity control agent. It controls and adapts viscosity to the required level for optimal chemical and physical stability of the product and dosage in gels, suspensions, emulsions, solutions. 

The most relevant studies on this ingredient have been selected with a summary of their contents:

Hydroxypropylcellulose studies

• Molecular Formula: C₁₂H₂₀N₂
• Molecular Weight: 192.30
• CAS: 9004-64-2
• UNII 
• EC Number: 265-995-8
• DSSTox Substance ID: 
• MDL number  MFCD00132688
• PubChem Substance ID 
• NACRES  NA.24

Synonyms :

• Cellulose, hydroxypropyl ether
• Hydroxypropyl cellulose
• HPC

References_______________________________________________________________________

(1) Rashid R, Kim DW, Din FU, Mustapha O, Yousaf AM, Park JH, Kim JO, Yong CS, Choi HG. Effect of hydroxypropylcellulose and Tween 80 on physicochemical properties and bioavailability of ezetimibe-loaded solid dispersion. Carbohydr Polym. 2015 Oct 5;130:26-31. doi: 10.1016/j.carbpol.2015.04.071.

(2) Jones DS, Rafferty GP, Andrews GP. Design of binary polymeric platforms containing ɩ-carrageenan and hydroxypropylcellulose for use in cataract surgery. Carbohydr Polym. 2016 Dec 10;154:296-304. doi: 10.1016/j.carbpol.2016.06.042.

(3) Tang B, Shan J, Yuan T, Xiao Y, Liang J, Fan Y, Zhang X. Hydroxypropylcellulose enhanced high viscosity endoscopic mucosal dissection intraoperative chitosan thermosensitive hydrogel. Carbohydr Polym. 2019 Apr 1;209:198-206. doi: 10.1016/j.carbpol.2018.12.103.

(4) Yang J, Dong Y, Wang J, Chen C, Zhu Y, Wu Y, Zhang P, Chen T, Zhou W, Wu P, Thanh NTK, Ngoc Quyên Trân, Chen J, Chen S. Hydroxypropylcellulose Coating to Improve Graft-to-Bone Healing for Anterior Cruciate Ligament Reconstruction. ACS Biomater Sci Eng. 2019 Apr 8;5(4):1793-1803. doi: 10.1021/acsbiomaterials.8b01145.

Abstract. An anterior cruciate ligament (ACL) injury is one of the most common injuries in sports, and ACL reconstruction with an artificial ligament is a good treatment for quick recovery. However, current artificial ligaments made of polyethylene terephthalate (PET) are still associated with some problems due to the hydrophobic nature and low biological induction activity of PET. Many efforts have been used to improve the biocompatibility of PET in recent years, and our previous work has shown that surface modification is an effective strategy. Here, a hydroxypropylcellulose (HPC) coating was applied on the surface of a PET artificial ligament order to improve its biocompatibility. The effects of the HPC coating on PET artificial ligament graft-bone healing was investigated in vitro using bone marrow stromal cells (BMSCs), fibroblasts, and RSC-364 cells as well as in vivo in a beagle dog model of ACL reconstruction. HPC was coated successfully on the PET and significantly promoted cell growth, adhesion, and capability of osteogenic differentiation compared to the PET graft without HPC coating. In vivo, the HPC coating significantly enhanced ligament tissue regeneration. Moreover, higher expression of some bone-formation- and ligament-tissue-regeneration-contributing proteins and cell factors, such as COL1, BMP-7, COL3, OCN, RUNX2, TGF-β1, and VEGF, was observed on the HPC-coated PET artificial ligament in comparison with the pure PET artificial ligament. In conclusion, HPC coating can significantly improve the cytocompatibility and graft-to-bone healing of a PET artificial ligament for ACL reconstruction.

(5) Sellem L, Srour B, Javaux G, Chazelas E, Chassaing B, Viennois E, Debras C, Salamé C, Druesne-Pecollo N, Esseddik Y, de Edelenyi FS, Agaësse C, De Sa A, Lutchia R, Louveau E, Huybrechts I, Pierre F, Coumoul X, Fezeu LK, Julia C, Kesse-Guyot E, Allès B, Galan P, Hercberg S, Deschasaux-Tanguy M, Touvier M. Food additive emulsifiers and risk of cardiovascular disease in the NutriNet-Santé cohort: prospective cohort study. BMJ. 2023 Sep 6;382:e076058. doi: 10.1136/bmj-2023-076058. PMID: 37673430; PMCID: PMC10480690.