Pharmaceutical Significance of Cellulose: a Review

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Pharmaceutical Significance of Cellulose: a Review eXPRESS Polymer Letters Vol.2, No.11 (2008) 758–778 Available online at www.expresspolymlett.com DOI: 10.3144/expresspolymlett.2008.90 Pharmaceutical significance of cellulose: A review S. Kamel1,3*, N. Ali1, K. Jahangir1, S. M. Shah1, A. A. El-Gendy2 1Pharmacy Department, University of Malakand, Chakdara, N.W.F.P., Pakistan 2Cellulose and Paper Department, National Research Center, Dokki, Cairo, Egypt 3Permanent address: Cellulose and Paper Department, National Research Center, El-Tahrir St., Dokki, Cairo, P.O. 12622, Egypt Received 25 April 2008; accepted in revised form 16 July 2008 Abstract. The amalgamation of polymer and pharmaceutical sciences led to the introduction of polymer in the design and development of drug delivery systems. Polymeric delivery systems are mainly intended to achieve controlled or sustained drug delivery. Polysaccharides fabricated into hydrophilic matrices remain popular biomaterials for controlled-release dosage forms and the most abundant naturally occurring biopolymer is cellulose; so hdroxypropylmethyl cellulose, hydrox- ypropyl cellulose, microcrystalline cellulose and hydroxyethyl cellulose can be used for production of time controlled delivery systems. Additionally microcrystalline cellulose, sodium carboxymethyl cellulose, hydroxypropylmethyl cellu- lose, hydroxyethyl cellulose as well as hydroxypropyl cellulose are used to coat tablets. Cellulose acetate phthalate and hydroxymethyl cellulose phthalate are also used for enteric coating of tablets. Targeting of drugs to the colon following oral administration has also been accomplished by using polysaccharides such as hdroxypropylmethyl cellulose and hydrox- ypropyl cellulose in hydrated form; also they act as binders that swell when hydrated by gastric media and delay absorption. This paper assembles the current knowledge on the structure and chemistry of cellulose, and in the development of innova- tive cellulose esters and ethers for pharmaceuticals. Keywords: biopolymers, cellulose derivatives, drug delivery 1. Introduction 1.1. Drug delivery For many years pharmacists have been employing Drug delivery is highly innovative in terms of polymers in every aspect of their work; polystyrene materials to assist delivery, excipients, and technol- vials, rubber closures, rubber and plastic tubing for ogy which allow fast or slow release of drugs. For injection sets, and polyvinylchloride flexible bags example analgesics, which often involve as much to hold blood and intravenous solutions are all as five or six tablets a day, can be reduced to a sin- examples of such polymers. The initial use was gle dose by using appropriate excipients, based on often restricted to packaging rather than drug deliv- carbohydrate polymers. Polymers are classified in ery. Subsequently, the amalgamation of polymer several ways; the simplest classification used for and pharmaceutical sciences led to the introduction pharmaceutical purposes is into natural and syn- of polymer in the design and development of drug thetic polymers. delivery systems. Polysaccharides, natural polymers, fabricated into hydrophilic matrices remain popular biomaterials for controlled-release dosage forms and uses of a hydrophilic polymer matrix is one of the most pop- *Corresponding author, e-mail: [email protected] © BME-PT and GTE 758 Kamel et al. – eXPRESS Polymer Letters Vol.2, No.11 (2008) 758–778 ular approaches in formulating an extended-release a) Permeation through water-filled pores; in this dosage forms [1–3]. This is due to the fact that mechanistic model, the release of the drug these formulations are relatively flexible and a well involves transfer of the dissolved molecule designed system usually gives reproducible release through water-filled pores. The coating mem- profiles. brane is not homogeneous. The pores can be Since drug release is the process by which a drug created by the incorporation of leachable com- leaves a drug product and is subjected to absorp- ponents, such as sugars or incompatible water- tion, distribution, metabolism, and excretion soluble polymers into the original coating (ADME), eventually becoming available for phar- material [9] or can be produced by an appropri- macologic action, hence drug release is described ate production process. in several ways as follows: b) Permeation through membrane material; in this a) Immediate release refers to the instantaneous mechanism, the release process involves the availability of drug for absorption or pharmaco- consecutive process of drug partition between logic action in which drug products allow drugs the core formulation and the membrane. The to dissolve with no intention of delaying or pro- drug molecules are dissolved in the membrane longing dissolution or absorption of the drug. at the inner face of the coat, representing equi- b) Modified-release dosage forms include both librium between a saturated drug solution and delayed and extended-release drug products. the membrane material. The transport of drug Delayed release is defined as the release of a across the coat is then driven by the concentra- drug at a time other than immediately following tion gradient in the membrane. Outside the administration, while extended release products membrane, the drug is dissolved in an aqueous are formulated to make the drug available over environment. an extended period after administration. c) Osmotic pumping; this release mechanism is c) Controlled release includes extended-release driven by a difference in osmotic pressure and pulsatile-release products. Pulsatile release between the drug solution and the environment involves the release of finite amounts (or pulses) outside the formulation. of drug at distinct intervals that are programmed In addition to the above, controlled release of drug into the drug product. from the matrix is dependent on particle size and One of the most commonly used methods of modu- type of the polymer wetting, polymer hydration, lating tablet drug release is to include it in a matrix polymer dissolution, and drug: polymer ratio [10– system. The classification of matrix systems is 13]. The hydration rate depends on the nature of the based on matrix structure, release kinetics, con- constituents, such as the molecular structure and trolled release properties (diffusion, erosion, the degree of substitution. The viscosity of the swelling), and the chemical nature and properties of aqueous solution can be increased by increasing the employed materials. Matrix systems are usually average molecular weight of the polymer, the con- classified in three main groups: hydrophilic, inert, centration of the polymer or decreasing the temper- and lipidic [4]. In addition, the drug release is a ature of the solution [1, 14]. So, the factors associ- function of many factors, including the chemical ated with polymers, such as molecular weight type nature of the membrane, geometry and its thick- (nominal viscosity), concentration, degree of sub- ness, and the particle surface area of the drug stitution, and particle size [15–22]; have been device, the physico-chemical nature of the active shown to have a significant influence on drug substance and the interaction between the mem- release. For example, in tablet formulations con- brane and the permeating fluids are also important taining hydrophilic polymers like HPMC, the [5–7]. In fact, the mechanism probably varies from release of active drug is controlled by the rate of membrane to membrane, depending on the mem- formation of a partially hydrated gel layer of the brane structure as well as on the nature of the per- tablet surface formed upon contact with aqueous meating solution. It is believed that several differ- gastric media following ingestion and the continu- ent mechanisms are involved in the drug release ous formation of additional gel layers. In addition through a non-disintegrating polymer coat [8]: to this, process variables like method of granula- tion, amount of binder added during granulation, 759 Kamel et al. – eXPRESS Polymer Letters Vol.2, No.11 (2008) 758–778 use of high or low shear mixer, granule size distri- losics have opened a window of opportunity and bution, compression force during tableting, etc., are have broadened the use of cellulosics. also important for extended-release [23–33]. As shown in the molecular structure represented in Figure 1, the hydroxy groups of β-1,4-glucan cellu- lose are placed at positions C2 and C3 (secondary, 1.2. Cellulose and cellulosics equatorial) as well as C6 (primary). The CH2OH Cellulose is the most abundant naturally occurring side group is arranged in a trans-gauche (tg) posi- biopolymer [34, 35]. Various natural fibers such as tion relative to the O5–C5 and C4–C5 bonds. As a cotton and higher plants have cellulose as their result of the supramolecular structure of cellulose, main constituent [36, 37]. It consists of long chains the solid state is represented by areas of both high of anhydro-D-glucopyranose units (AGU) with order (crystalline) and low order (amorphous). The each cellulose molecule having three hydroxyl degree of crystallinity (DP) of cellulose (usually in groups per AGU, with the exception of the terminal the range of 40 to 60%) covers a wide range and ends (Figure 1). Cellulose is insoluble in water and depends on the origin and pretreatment of the sam- most common solvents [35]; the poor solubility is ple (Table 1). The morphology of cellulose has a attributed primarily to the strong intramolecular profound effect on its reactivity, the hydroxyl and intermolecular
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