Archives of Pharmacy Practice Review Article ISSN 2045-080X Vol 3 , Issue 3 , 2012 Basic Concepts Of Cellulose Polymers - A Comprehensive Review Harika K, Sunitha K, Pavan Kumar P, Maheshwar K and Madhusudan Rao Y* Department of Pharmaceutics, National facilities in Engineering and Technology with Industrial Collaboration (NAFETIC) centre, University College of Pharmaceutical Sciences, Kakatiya University, Warangal – 506 009, A.P. India. Citation: Harika K, Sunitha K, Pavan Kumar P, Maheshwar K and Madhusudan Rao Y. Basic Concepts Of Cellulose Polymers- A Comprehensive Review. Archives of Pharmacy Practice. 2012; 3(3)pp202-216. Abstract Man’s pursuance for new and improved materials has been should promote innovation. To assist the exploitation expanding with time and it can be said that it is unending. of novel drug delivery systems the need for polymers Though introduced very late in the chain of materials, continues to increase. polymers occupy a major place and pivotal position in our This review serves as a comprehensive source to improve materials map today. Unfolding of the science of polymers and understanding of cellulose derivative polymers and create polymer – based materials had evoked lot of interest and made new avenues in development of a delivery system. In them as a class of materials for their potential use in the field of addition, this review presents in-depth information on pharmaceuticals and industry based products. In recent years, various aspects of polymer chemistry, nomenclature, an awareness and understanding of these polymers has various polymer grades, physical characteristics of increased based upon the following factors. polymers, solubility, and the utility of polymers for As pharmaceutically active ingredients continue to become various drug delivery systems. more ‘‘potent’’ the effective controlled delivery of doses have become intriguing. As a result, polymers now often Introduction constitute the major portion of many pharmaceutical Cellulose is the most copious naturally occurring dosage forms and as such can have profound impact on the “biopolymer”. The main constituent of various natural reproducibility of drug release and overall performance of fibers such as cotton and higher plants is cellulose. It the dosage forms. consists of long chains of anhydro-D-glucopyranose units The technical complexities associated with drug (AGU) with each cellulose molecule having three hydroxyl development have increased in controlled delivery due to groups per AGU, except at the terminal ends. Cellulose is challenges such as complex drug actives, and in cases of insoluble in water and most common solvents; the poor biotech products, stabilization of the active ingredient. The solubility is accredited primarily to the strong multidisciplinary understanding of polymers is thus intramolecular and intermolecular hydrogen bonding required including technical, safety, quality, and regulatory between the individual chains. Regardless of its poor aspects, which, prior to this effort, has not been available in solubility characteristics, cellulose is used in a wide range a single resource. of applications including composites, netting, upholstery, It also proposes new and innovative ways for regulatory coatings, packing, paper, etc. Cellulose is chemically review of polymers, which, if adopted, modified to improve process ability and to produce cellulose derivatives (cellulosics) which can be tailored Key words for specific industrial applications [1-5]. Cellulosics are in Cellulose Polymers, Premium Product Grades, Viscosities, general strong, reproducible, recyclable and Solubility. biocompatible, being used in various biomedical applications such as blood purification membranes and Manuscript History the like. Thus, through derivatization, cellulosics have Article Received on: 1st Jan, 2012 opened a window of opportunity and have broadened Revised on: 30th April, 2012 their use. Approved for Publication: 10th June, 2012 Cellulose derivatives are a branch of semi-synthetic polymers used in controlled drug delivery. In this review, Corresponding Author we summarize all the critical properties of cellulose ethers Prof. Y. Madhusudan Rao that can be utilized for fulfilling the need of controlling the National facilities in Engineering and Technology with release of active ingredient from a drug delivery system. Industrial Collaboration (NAFETIC) centre, University College of Pharmaceutical Sciences, Kakatiya University Chemically modified derivatives of cellulose: Warangal- 506 009 (A.P), India Tel: +91 870 2438844, Fax: +91 870 2453508 Cellulose (Fig 1) being water insoluble, etherification and esterification at hydroxyl groups bring about drastic Email: [email protected] changes in its original properties making its derivatives Page 202 Archives of Pharmacy Practice Vol 3 , Issue3 , 2012 Archives of Pharmacy Practice soluble in organic and aqueous solvents [6]. The hydroxyl Table 2: Ester derivatives [6] groups (-OH) of cellulose can be partially or fully reacted with Cellulose Reagent Example Reagent various reagents to afford derivatives with useful properties ester like mainly cellulose esters and cellulose ethers (-OR). Organic Organic Cellulose Acetic acid and esters acids acetate acetic anhydride Cellulose Acetic acid and triacetate acetic anhydride Cellulose Propanoic acid propionate Cellulose Acetic acid and acetate propanoic acid Figure 1: Molecular structure of cellulose propionate Etherification: Cellulose ethers can be prepared by treating Cellulose Acetic acid and alkali cellulose with a number of various reagents including acetate butyric acid alkyl or aryl halides (or sulfates), alkene oxides, and butyrate unsaturated compounds activated by electron-attracting Inorganic Inorganic Nitrocellulose Nitric acid or groups (Eq 1). esters acids (cellulose another nitrate) powerful nitrating agent Cellulose Sulfuric acid or Equation 1: Etherification of cellulose. R’= organic radical (CH3- sulfate another , C2H5–, etc) powerful Table 1: Ether derivatives [6,7] sulfuring agent Cellulose Reagent Example Reagent ethers Cellulose acetate phthalate is obtained by partial Alkyl Halogeno Methylcellulose Chloromethane substitution of cellulose acetate (CA) with phthalic alkanes Ethylcellulose Chloroethane anhydride in the presence of an organic solvent and a Ethyl methyl Chloromethane basic catalyst. cellulose and chloroethane METHOD HOW THE INFORMATION WAS Hydroxy Epoxides Hydroxyethyl Ethylene oxide GATHERED/ CRITERIA FOR THE SELECTION OF alkyl cellulose ARTICLES Hydroxypropyl Propylene Information was gathered from product cellulose (HPC) oxide brochures of chemical companies (Dow, Hercules, Hydroxyethyl Chloromethane Aqualon, WeKcelo) which are synthesizing these methyl and ethylene polymers. cellulose oxide Physical description of the materials was Hydroxypropyl Chloromethane obtained from Material safety data sheet (MSDS) methyl and propylene of these particular polymers. cellulose oxide Other information was also considered from (HPMC) monographs of the different pharmacopeias. Ethyl Chloroethane Some basic concepts about the cellulosic hydroxyethyl and ethylene polymers were obtained from articles published cellulose oxide in various journals. Carboxy Halogenated Carboxymethyl Chloroacetic alkyl carboxylic cellulose (CMC) acid PROPERTIES OF CELLULOSE DERIVATIVE acids POLYMERS The sodium carboxymethyl cellulose can be cross-linked to Cellulose ethers: The factors associated with polymers, give the croscarmellose sodium (E468) for use as a such as molecular weight, viscosity, concentration, degree disintegrant in pharmaceutical formulations. of substitution and particle sizes have a significant influence on drug release. Hence, it is necessary to have thorough knowledge of the polymer properties to choose Esterification: The esterification can be considered as a the suitable polymer to control the release from a typical equilibrium reaction in which an alcohol and acid react particular dosage form. Among the known polymers, to form ester and water. Cellulose is esterified with certain cellulose ethers are materials of choice for controlled drug acids such as acetic acid, nitric acid, sulfuric acid and release which are discussed in detail in this review. phosphoric acid. Page 203 Archives of Pharmacy Practice Vol 3 , Issue3 , 2012 Archives of Pharmacy Practice Table 3: A Versatile Range of Polymer Properties [8] METHYL ETHYL HPMC CELLULOSE NITRO PROPERTIES HEC CMC CELLULOSE CELLULOSE &HPC ACETATE CELLULOSE Water soluble Organo soluble Gel forming Film forming Mucoadhesive High swelling Hydrophilic Hydrophobic Viscosifying Thermoplastic Drug solubilizer Table 1 A. Methyl cellulose and hypromellose: Nomenclature: Premium methyl cellulose and hypromellose products are a An example [10]- HPMC E 15 premium LV broad range of water soluble cellulose ethers. They enable Low viscosity pharmaceutical developers to create reliable formulas for tablet coating, granulation, controlled release, extrusion, For pharmaceutical use molding and for controlled viscosity of liquid formulations. Viscosity (15 mPa.s for a 2% solution Chemistry of methyl cellulose ethers: in water at 20°C) These products are available in two basic types: methyl cellulose (Fig 2) and HPMC (Fig 3). Methyl cellulose is made Chemistry type: E and K are using only methyl chloride. These are methocel A brand hypromellose products. For HPMC products (methocel E, F, J and K brand A is methylcellulose