**2. Classification of cellulose-based polymers**

## **2.1. Cellulose**

Pure cellulose is available in different forms in the market with very different mechanical and pharmaceutical properties. The difference between various forms of cellulose is related

© 2013 Shokri and Adibkia, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 Shokri and Adibkia, licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

to the shape, size and degree of crystallinity of their particles (fibrous or agglomerated). Microcrystalline cellulose (MCC) is the most known cellulose which extensively used in pharmaceutical industries. MCC grades are multifunctional pharmaceutical excipients which can be used as compressibility enhancer, binder in wet and dry granulation processes, thickener and viscosity builder in liquid dosage forms and free-flowing agents in solid dosage forms. Mechanical properties of MCC grades are greatly influenced by their particle size and degree of crystallization. In recent years the new grades of MCC are prepared with improved pharmaceutical characteristics such as silisified MCC (SMCC) and second generation MCC grades or MCC type II (MCC-II). These grades are prepared by coprocessing of cellulose with other substances such as colloidal silicon dioxide or by special chemical procedures. Other types of available pure cellulose are powdered cellulose (PC) and low crystallinity powdered cellulose (LCPC).

Application of Cellulose and Cellulose Derivatives in Pharmaceutical Industries 49

esters have been used in commercial products or in pharmaceutical investigations such as cellulose acetate (CA), cellulose acetate phthalate (CAP), Cellulose acetate butyrate (CAB), Cellulose acetate trimelitate (CAT), hydroxupropylmethyl cellulose phthalate (HPMCP) and so on (Heinämäki et al., 1994). The most available formulations in market which made by these polymers are enteric coated dosage forms which are usually produced applying acid resistant polymeric coats containing phthalate derivatives of cellulose esters especially cellulose acetate phthalate (Lecomte et al., 2003; Liu & Williams III, 2002). Inorganic cellulose esters such as cellulose nitrate and cellulose sulphate are less important than organic cellulose esters in pharmaceutical industries. Cellulose nitrate or pyroxylin is a transparent compound with good film forming ability but rarely applied alone in pharmaceutical formulations due to its very low solubility in currently used pharmaceutical solvents as well as their very high flammability. The use of pure cellulose nitrate in drug formulations only limited to one topical anti-wart solution named collodion that made with 4%w/v concentration in diethyl ether/ethanol mixture as solvent. Cellulose nitrate/cellulose acetate mixture are also exploited to prepare micro-porous membrane filters used in

**3. Applications of cellulose and its derivatives in pharmaceutical** 

**3.1. Application in bioadhesive and mucoadhesive drug delivery systems** 

(Lehr, 2000; Grabovac et al., 2005; Movassaghian et al., 2011).

formulations of sensitive drugs (Lehr, 2000).

Bioadhesives and mucoadhesives are drug containing polymeric films with ability of adhering to biological membranes after combining with moisture or mucus compounds. Bioadhesives were developed in mid 1980s as a new idea in drug delivery and nowadays they have been accepted as a promising strategies to prolong the residence time and to improve specific localization of drug delivery systems on various biological membranes

In compared with tablets, these dosage forms have higher patient compliance due to their small size and thickness. Other advantage of these drug delivery systems is their potential to prolong residence time at the site of drug absorption and thus they can reduce the dosing frequency in controlled release drug formulations. These dosage forms can also intensify the contact of their drug contents with underlying mucosal barrier and improve the epithelial transport of drugs across mucus membranes especially in the case if poorly absorbed drugs (Ludwig, 2005; Lehr, 2000). Some special polymers can be used in these formulations with epithelial permeability modulation ability by loosening the tight intercellular junctions. Some of these polymers also can act as proteolytic enzymes inhibitor in orally used adhesive

Bioadhesives considered as novel drug delivery systems. These dosage forms are formulated to use on the skin and mucus membranes of gastrointestinal, ear, nose, eye, rectum and vagina. The main excipients of these formulations are adhesive and film-former polymer(s). Adhesive polymers are synthetic, semi synthetic or natural macromolecules

pharmaceutical industries.

**industries** 

Regenerated cellulose is one of the other forms of processed cellulose which produced by chemical processing on natural cellulose. In the first step, cellulose dissolves in alkali and carbon disulfide to make a solution called "viscose". Viscose reconverted to cellulose by passing through a bath of dilute sulfuric acid and sodium sulphate. Reconverted cellulose passed through several more baths for sulfur removing, bleaching and adding a plasticizer (glycerin) to form a transparent film called cellophane. Cellophane has several applications in pharmaceutical packaging due to its suitable characteristics such as good compatibility, durability, transparency and elasticity.

## **2.2. Cellulose ether derivatives**

Cellulose ethers are high molecular weight compounds produced by replacing the hydrogen atoms of hydroxyl groups in the anhydroglucose units of cellulose with alkyl or substituted alkyl groups. The commercially important properties of cellulose ethers are determined by their molecular weights, chemical structure and distribution of the substituent groups, degree of substitution and molar substitution (where applicable). These properties generally include solubility, viscosity in solution, surface activity, thermoplastic film characteristics and stability against biodegradation, heat, hydrolysis and oxidation. Viscosity of cellulose ether solutions is directly related with their molecular weights. Examples of mostly used cellulose ethers are: Methyl cellulose (MC), Ethyl cellulose (EC), Hydroxyethyl cellulose (HEC), Hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC), carboxymethyl cellulose (CMC) and sodium carboxymethyl cellulose (NaCMC).

#### **2.3. Cellulose ester derivatives**

Cellulose esters are generally water insoluble polymers with good film forming characteristics. Cellulose esters are widely used in pharmaceutical controlled release preparations such as osmotic and enteric coated drug delivery systems. These polymers are often used with cellulose ethers concurrently for preparation of micro-porous delivery membranes. Cellulose esters categorized in organic and inorganic groups. Organic cellulose esters are more important in pharmaceutical industries. Various types of organic cellulose esters have been used in commercial products or in pharmaceutical investigations such as cellulose acetate (CA), cellulose acetate phthalate (CAP), Cellulose acetate butyrate (CAB), Cellulose acetate trimelitate (CAT), hydroxupropylmethyl cellulose phthalate (HPMCP) and so on (Heinämäki et al., 1994). The most available formulations in market which made by these polymers are enteric coated dosage forms which are usually produced applying acid resistant polymeric coats containing phthalate derivatives of cellulose esters especially cellulose acetate phthalate (Lecomte et al., 2003; Liu & Williams III, 2002). Inorganic cellulose esters such as cellulose nitrate and cellulose sulphate are less important than organic cellulose esters in pharmaceutical industries. Cellulose nitrate or pyroxylin is a transparent compound with good film forming ability but rarely applied alone in pharmaceutical formulations due to its very low solubility in currently used pharmaceutical solvents as well as their very high flammability. The use of pure cellulose nitrate in drug formulations only limited to one topical anti-wart solution named collodion that made with 4%w/v concentration in diethyl ether/ethanol mixture as solvent. Cellulose nitrate/cellulose acetate mixture are also exploited to prepare micro-porous membrane filters used in pharmaceutical industries.

48 Cellulose – Medical, Pharmaceutical and Electronic Applications

and low crystallinity powdered cellulose (LCPC).

durability, transparency and elasticity.

**2.2. Cellulose ether derivatives** 

**2.3. Cellulose ester derivatives** 

to the shape, size and degree of crystallinity of their particles (fibrous or agglomerated). Microcrystalline cellulose (MCC) is the most known cellulose which extensively used in pharmaceutical industries. MCC grades are multifunctional pharmaceutical excipients which can be used as compressibility enhancer, binder in wet and dry granulation processes, thickener and viscosity builder in liquid dosage forms and free-flowing agents in solid dosage forms. Mechanical properties of MCC grades are greatly influenced by their particle size and degree of crystallization. In recent years the new grades of MCC are prepared with improved pharmaceutical characteristics such as silisified MCC (SMCC) and second generation MCC grades or MCC type II (MCC-II). These grades are prepared by coprocessing of cellulose with other substances such as colloidal silicon dioxide or by special chemical procedures. Other types of available pure cellulose are powdered cellulose (PC)

Regenerated cellulose is one of the other forms of processed cellulose which produced by chemical processing on natural cellulose. In the first step, cellulose dissolves in alkali and carbon disulfide to make a solution called "viscose". Viscose reconverted to cellulose by passing through a bath of dilute sulfuric acid and sodium sulphate. Reconverted cellulose passed through several more baths for sulfur removing, bleaching and adding a plasticizer (glycerin) to form a transparent film called cellophane. Cellophane has several applications in pharmaceutical packaging due to its suitable characteristics such as good compatibility,

Cellulose ethers are high molecular weight compounds produced by replacing the hydrogen atoms of hydroxyl groups in the anhydroglucose units of cellulose with alkyl or substituted alkyl groups. The commercially important properties of cellulose ethers are determined by their molecular weights, chemical structure and distribution of the substituent groups, degree of substitution and molar substitution (where applicable). These properties generally include solubility, viscosity in solution, surface activity, thermoplastic film characteristics and stability against biodegradation, heat, hydrolysis and oxidation. Viscosity of cellulose ether solutions is directly related with their molecular weights. Examples of mostly used cellulose ethers are: Methyl cellulose (MC), Ethyl cellulose (EC), Hydroxyethyl cellulose (HEC), Hydroxypropyl cellulose (HPC), hydroxypropylmethyl cellulose (HPMC),

carboxymethyl cellulose (CMC) and sodium carboxymethyl cellulose (NaCMC).

Cellulose esters are generally water insoluble polymers with good film forming characteristics. Cellulose esters are widely used in pharmaceutical controlled release preparations such as osmotic and enteric coated drug delivery systems. These polymers are often used with cellulose ethers concurrently for preparation of micro-porous delivery membranes. Cellulose esters categorized in organic and inorganic groups. Organic cellulose esters are more important in pharmaceutical industries. Various types of organic cellulose
