What are the main functions of cellulose as a medicinal excipient? ​

Cellulose substances (such as microcrystalline cellulose, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, etc.) are one of the widely used categories in pharmaceutical excipients. With good biocompatibility, stability, and controllable physical and chemical properties, they play multiple key roles in drug formulations. The core functions can be divided into four categories: formulation molding function, drug release regulation function, stability enhancement function, and other auxiliary functions, as follows:

1、 Formulation molding function: ensuring the stability of the morphology and structure of drug formulations

Cellulose based excipients are the core support for the "molding" of solid preparations such as tablets, capsules, and granules. They provide stable forms to the preparations through physical or chemical interactions, ensuring that they do not disintegrate or deform during production and storage

1. Fillers (diluents): Supplement the volume of the formulation to ensure even dosage

Core function: When the active ingredient (API) content of the drug is low (such as only 1mg API per tablet) or the powder flowability is poor, cellulose excipients can be used as "fillers" to supplement the volume of tablets/capsules (making the tablet weight reach 50-500mg, easy to compress or fill capsules), while improving the flowability and compressibility of the material, ensuring uniform API content per tablet/granule (avoiding dosage deviation).

Common types: Microcrystalline cellulose (MCC, such as PH101, PH102) is a classic filler with good flowability and compressibility, compatible with most APIs, and widely used in ordinary tablets (such as cold pills, antihypertensive pills); Hydroxypropyl methylcellulose (HPMC) can also be used as a filler, especially suitable for APIs that are sensitive to moisture absorption (due to its low hygroscopicity, it can reduce API moisture absorption).

2. Adhesive: Promotes powder bonding to ensure tablet/granule formation

Core function: During the granulation process before tablet compression or powder pretreatment before capsule filling, cellulose based excipients (mostly water-soluble or water swellable) can use "bonding effect" to bond loose API powder with other excipients into uniform particles (or directly bond into tablets), avoiding problems such as "loose tablets" (tablets are prone to breakage) and "fragmentation" (tablet edge cracking) during compression.

Common types:

Hydroxypropyl methylcellulose (HPMC, such as E5, E15): often formulated as a 2% -5% aqueous solution as a "wet granulation adhesive", with moderate bonding strength and good disintegration properties, suitable for most oral tablets;

Carboxymethyl cellulose sodium (CMC Na): With good water solubility and strong adhesion, it is suitable for preparing tablets (such as chewable tablets) or granules with high hardness (to avoid particles scattering during storage).

3. Disinfectant: Promotes rapid disintegration of tablets in the body, releasing drugs

Core function: After oral tablets enter the gastrointestinal tract, they need to be quickly broken into small particles by the action of disintegrants in order for the API to be released and absorbed. Cellulose based disintegrants destroy the internal structure of tablets through "water absorption swelling" or "capillary action", accelerating the disintegration process (to avoid complete discharge of tablets in the gastrointestinal tract, leading to drug efficacy failure).

Common types:

Cross linked carboxymethyl cellulose sodium (CCMC Na): After absorbing water, its volume can expand 300-500 times, its disintegration speed is fast, and it is not affected by the pH of the gastrointestinal tract. It is suitable for ordinary tablets and effervescent tablets;

Carboxymethyl starch sodium (CMS Na, although a starch derivative, functions similarly to cellulose disintegrants and is often used in combination): has high swelling rate and good disintegration effect, and is widely used in drugs that require rapid onset of action.

2、 Drug release regulation function: accurately control the release rate and location of APIs

Some cellulose excipients have "controllable swelling" or "insolubility" and can be used as "sustained-release/controlled release skeleton" or "enteric coating materials" to achieve "slow release" (prolonging drug efficacy) or "specific site release" (avoiding API damage in the stomach) of APIs in the body. This is the key to achieving "long-lasting" and "targeted" formulation:

1. Sustained release/controlled release skeleton material: prolongs drug action time and reduces medication frequency

Core function: In sustained-release tablets or capsules, cellulose excipients form a "three-dimensional skeleton structure", and APIs are uniformly dispersed in the skeleton; After oral administration, gastrointestinal fluids slowly infiltrate the skeleton, and the API is slowly released as the skeleton gradually swells and degrades, maintaining the blood drug concentration within the effective range (12-24 hours), reducing the frequency of medication (such as from 3 times a day to 1 time a day), and improving patient compliance.

Common types:

Hydroxypropyl methylcellulose (HPMC, such as K4M, K15M, K100M): It is a commonly used sustained-release skeleton material. The higher the viscosity (such as K100M), the slower the skeleton swelling rate, and the longer the API release. It is suitable for preparing 12 hour sustained-release tablets (such as antihypertensive drug nifedipine sustained-release tablets) or 24-hour controlled-release tablets;

Ethyl cellulose (EC): insoluble in water but can swell in the gastrointestinal tract, forming a rigid skeleton. API is slowly released through the skeleton pores, making it suitable for sustained release of water-soluble APIs (such as antibiotic sustained-release capsules).

2. Enteric coating material: protects the API from gastric acid damage and achieves intestinal targeted release

Core function: Some APIs (such as pancreatic enzymes, probiotics, and certain antibiotics) are easily destroyed in the stomach acid environment and need to be wrapped in "enteric coating" to allow them to pass smoothly through the stomach (pH 1-3), reach the intestine (pH 5-7), and then dissolve and release. Cellulose based enteric coating materials are insoluble in acidic environments and dissolve in neutral/weakly alkaline environments, which precisely meets this requirement.

Common types:

Cellulose Acetate Phthalate (CAP): A classic enteric coated material that dissolves in the intestinal environment at pH>6.0 and effectively protects the API from being destroyed by gastric acid. It is commonly used in enteric coated tablets;

Hydroxypropyl methylcellulose phthalate (HPMCP): Compared to CAP, HPMCP has stronger acid resistance, better stability, and controllable dissolution rate, making it suitable for formulations that require more accurate intestinal release sites (such as colon targeted formulations).

3、 Stability improvement function: protects the API from external environmental influences

Cellulose based excipients reduce the contact between API and the external environment (moisture, oxygen, light) or inhibit the degradation reaction of API through "physical isolation" or "chemical inertness", thereby extending the shelf life of the formulation

1. Moisture proof/anti adhesive agent: reduces moisture adsorption and prevents the formulation from absorbing moisture and deteriorating

Core function: Some APIs (such as vitamin C and certain alkaloids) are prone to moisture absorption, leading to tablet softening, delayed disintegration, or API degradation; Cellulose based excipients (such as microcrystalline cellulose and ethyl cellulose) have low hygroscopicity and can form a "physical barrier" on the surface of the formulation, reducing the infiltration of moisture into the environment and avoiding adhesion to the die during tablet compression (anti sticking effect).

Application scenario: Adding microcrystalline cellulose to vitamin C tablets and effervescent tablets can effectively reduce their moisture absorption and extend their storage period; Adding a small amount of hydroxypropyl methylcellulose to the capsule shell can enhance its moisture resistance (avoiding softening and deformation in humid environments).

2. Stabilizer: Inhibits API degradation and maintains stable drug efficacy

Core function: Some cellulose based excipients (such as hydroxypropyl methylcellulose and methyl cellulose) have "chemical inertness" and do not react with the API. At the same time, they can isolate the API from excipients that may cause its degradation (such as metal ions and oxidants) through "encapsulation", or inhibit the hydrolysis and oxidation reactions of the API by adjusting the microenvironment of the formulation (such as pH).

Application scenario: Adding a small amount of hydroxypropyl methylcellulose to oral liquid preparations (such as syrup) can encapsulate API molecules, reduce their contact with oxygen, and inhibit oxidative degradation; Adding sodium carboxymethyl cellulose to tablets containing metal ion sensitive APIs can reduce API degradation by chelating a small amount of metal ions.

4、 Other auxiliary functions: Optimize the user experience and production efficiency of the formulation

In addition to the core functions mentioned above, cellulose based excipients can also improve the physical properties of the formulation, enhance the patient experience (such as taste and swallowing), or simplify the production process (such as improving material fluidity):

1. Suspension aid: Improve the stability of liquid formulations and avoid API settling

Core function: In oral suspensions (such as antibiotic suspensions for children), API powder is prone to settling due to density differences, resulting in uneven dosage. Cellulose based suspension aids dissolve or swell to form a viscous liquid, increasing the viscosity of the drug solution and slowing down the settling speed of API particles, keeping the suspension in a uniform state (shake well before taking, no need to worry about dosage deviation).

Common types: Hydroxypropyl methylcellulose (low viscosity model, such as E5) and sodium carboxymethyl cellulose are commonly used as suspension aids, widely used in children's ibuprofen suspension and cough syrup, and can improve the taste of the medicine (reduce particle roughness).

2. Film coating material: improves the appearance and swallowing ability of tablets, and masks unpleasant odors

Core function: Some tablets (such as traditional Chinese medicine tablets) have a bitter odor and rough appearance, making it difficult for patients to swallow or have low compliance. Cellulose film coating materials (such as hydroxypropyl methylcellulose and hydroxypropyl cellulose HPC) can form a transparent and smooth film on the surface of tablets, which can mask the adverse odor of APIs, improve the appearance of tablets (such as coloring and printing), and enhance swallowing ability.

Application scenario: The use of hydroxypropyl methylcellulose film coating in traditional Chinese medicine tablets (such as Danggui Buxue tablets) and bitter western medicine tablets (such as metronidazole tablets) can significantly improve the patient's medication experience and reduce medication resistance caused by odor or taste.

Summary: The "multifunctionality" core value of cellulose based pharmaceutical excipients

The core advantage of cellulose based excipients lies in their "multifunctionality, high compatibility, and easy regulation" - the same excipient (such as hydroxypropyl methylcellulose) can play multiple roles such as filler, adhesive, slow-release skeleton, coating material, etc., depending on the model (viscosity, degree of substitution); And it is compatible with the vast majority of APIs, non-toxic, and meets pharmaceutical grade safety standards. It is precisely these characteristics that make it an "irreplaceable basic excipient" in modern pharmaceutical formulations, from ordinary oral tablets to sustained-release and enteric coated formulations, all of which rely on the support of cellulose excipients, directly affecting the safety, effectiveness, and stability of the formulation.