ETHYLCELLULOSE MICROPARTICLES: A REVIEW

1 Acta Poloniae Pharmaceutica Drug Research, Vol. 69 No. 1 pp. 11 22, 2012 ISSN 0001-6837 Polish Pharmaceutical SocietyMicroparticulate formulationsThroughout the world, continuous efforts are inprogress for developing improved, optimized andadvanced drug delivery systems. Pharmaceuticaltechnologists, biotechnologists, bioengineers andbiophysicists are actively imparting their capabili-ties in the enthusiastic interdisciplinary researchactivities for the formulation of efficacious drugs(1). Recently, exhaustive research has been made onthe microfabrication of polymeric particles, namedas microencapsulation and the resulting formula-tions are expressed as microparticles , microcapsulesor microspheres. The term microparticles representsdrug containing solid, liquid or gaseous cores com-pletely surrounded by continuous porous or non-porous polymeric shells, whereas the microspheresindicate homogeneous solution or dispersion of drugin solid polymeric matrix.

2 Large research is made toevaluate physicochemical characteristics ofmicroparticles particularly release behavior under invitroand in vivoconditions. The microparticles areadministered largely after tabletting or filling intohard gelatin capsules or by injection. The perform-ance of multi-unit coated microparticles is consid-ered better than single unit matrix tablets for con-trolled delivery of high dose and highly solubledrugs (1).Reasons of microencapsulationA substance may be microencapsulated for anumber of reasons, which can be described in detailas given below (2): 1. To develop modified release dosage forms fortargeted or sustained release To mask the taste of bitter or noxious drugs fortheir convenient handling. 3. For converting volatile and oily substances orextracts to tabletted dosage forms to avoid tackygranulations and improve flow To protect drugs from environmental hazardssuch as humidity, light, oxygen or heat and gas-trointestinal biodegradation.

3 5. To enhance compatibility between various drugsand excipients formulated together. 6. For easy handling of hygroscopic and toxic sub-stances such as fumigants, herbicides, insecticidesand pesticides. 7. To prepare immobilized cells or materialsThe physicochemical characteristics of result-ing microparticles depend essentially upon thenature of encapsulating materials. The encapsulatingmaterial should be stable and inert to core and excip-ients, non-hygroscopic and capable of producing aETHYLCELLULOSE microparticles : A REVIEWGHULAM MURTAZAD epartment of Pharmaceutics, COMSATS Institute of Information Technology, Abbottabad, : ETHYLCELLULOSE (EC) based microencapsulated drug delivery systems are being extensively studiedthroughout the world for achieving extended drug release and protecting the core substance from in vitroevaluation of EC microcapsules have elucidated that their particle characteristics are very useful tocontrol drug release behavior, since these enable drugs to be released at a certain controlled release rate basedon the characteristics of drug-EC linkage.

4 This REVIEW encompasses microencapsulation techniques, core sub-stances and other fundamentals involved in the preparation and characterization of EC microcapsules. ECmicrocapsules can be considered as mini-osmotic pumps. The release kinetics for EC microcapsules can befine-tuned by altering osmolality of the dissolution medium or formulations and EC film mechanical charac-teristics by selecting appropriate EC molecular weights (viscosity), EC substitution grades, coating weights, andpore : ETHYLCELLULOSE , microparticles , extended release, in vitrobehavior11* Corresponding author: Mobile: +92-314-2082826; Fax: +92-992-38344112 GHULAM MURTAZA cohesive film with the core substance. It shouldimpart the desired coating properties such asstrength, brittleness, flexibility, impermeability,optical properties and stability. It should be solublein an aqueous media or solvent, or melting and capa-ble of controlling drug release.

5 Various encapsulat-ing materials used in microencapsulation are veg-etable gums, celluloses, condensation polymers,homopolymers, copolymers, proteins and curablepolymers (2). Among these, celluloses are the largest poly-mer family that has most extensively been employedin microencapsulation. On the basis of solubility,cellulose polymers are of two types:1. Hydrophilic cellulose polymers such as hydroxy-propyl methylcellulose (HPMC).2. Hydrophobic cellulose polymers such as ethyl-cellulose (EC).EthylcelluloseEC is a derivative of cellulose in which someof the hydroxyl groups on the repeating anhydroglu-cose units are modified into ethyl ether groups,largely called as non-ionic ethyl ether of cellulose(Fig. 1) (3).EC has extensively been used for microencap-sulation due to its many versatile properties such as(4): 1. white to light tan odorless and tasteless pow-der or granular substance; 2.

6 Melting point range240 255 C; 3. specific density range with135 155 C heat distortion point and 330 360 C firepoint; 4. water insoluble but soluble in many organ-ic solvents such as alcohol, ether, ketone and ester;5. biocompatible and compatible with many cellu-loses, resin and almost all plasticizers; 6. non-biodegradable, thus used in oral formulation only; against light, heat, oxygen and wetness andchemicals; 8. non-toxic; 9. non-irritant; 10. tabletbinder to impart plastic flow properties to particles;11. ability to absorb pressure and hence protect thecoating from fracture during compression. Its thinfilm exhibits good flexibility and mechanicalstrength in a wide range of temperature (5); 12. non-swellable and water insoluble, thus EC compactnessand porosity plays key role in drug release fromsuch hydrophobic materials (6); 13.

7 Although EC iswater insoluble, it can take up water. This is owingto its hydrogen bonding potential with water attrib-utable to the polarity difference between the oxygenatom and the ethyl group of EC (6, 7); 14. EC, likeother hydrophobic polymers used in drug deliverysystems, does not require the addition of releasemodifiers. These additives craft channels in polymermatrix through which drug diffuses out or enhancethe wettness of the hydrophobic polymer matrix (6);15. based on ethoxy contents (%), there are threeclasses of EC such as K, N and T type, which con-tain 44 , 48 and ethoxycontents, respectively. Based on chain length ordegree of polymerization or the number of anhy-droglucose units, EC is available as a number of dif-ferent viscosity grades. The apparent viscosity of thepolymer can be regarded as an indirect measure ofits molecular weight (4).

8 Applications of ECEC is used for microencapsulation of variouspharmaceuticals to stabilize them against activeinteractions, hydrolysis and oxidation. It also isemployed as a matrix and/or coating agent to impartsustained release characteristics. However, theselection of a suitable polymer and development ofmicrocapsules is a time consuming and complexprocess, which requires complete command over thein-depth knowledge of physico-chemical propertiesof various drugs and polymers. This REVIEW narratesthe fundamentals of using EC for the developmentof its microparticles can be considered as mini-osmotic pumps (8). The release kinetics for ECmicroparticles can be fine-tuned by altering osmo-lality of the dissolution medium or formulations andFigure 1. Structural formula of ECEthylcellulose microparticles : a review13EC film mechanical characteristics by selectingappropriate EC molecular weights, EC substitutiongrades, coating weights, and pore formers.

9 Therelease of a highly or sparingly soluble drug from adosage from is considerably reduced when osmolal-ity of the dissolution medium is increased causing areduction in osmotic pressure gradient across therelease controlling membrane (8, 9). Drug releaserates are drastically reduced with the increase in ECmolecular weight. According to a general concept,polymer chain length increases with the increase inits molecular weight, resulting in stronger film withincreased tensile strength and elasticity. It comesinto view that the stronger films may resist hydro-static pressure, ensuring less structural damage tothe film due to stress fractures or channel has been elaborated that formulations coated withlower molecular weight had faster release rates ascompared to the formulations coated with highermolecular weight EC (8).The release of a drug from high ethoxyl T10EC formulation is considerably increased as com-pared to intermediate ethoxyl N10 EC.

10 According toa general concept, EC film tensile strength decreas-es with the increase in ethoxyl contents (%) result-ing in the high release rate. EC molecular weightand ethoxyl contents can thus be utilized to alterfilm permeability characteristics and ultimatelyrelease behavior (8). In addition, selection of suit-able EC grade can be made in accordance with thesolubility of drug. For highly soluble drugs or for-mulations with high osmolality, higher molecularweight intermediate ethoxyl contents (%) EC suchas EC N22 should be preferred. However, coatingweight and addition of a suitable pore former/plasti-cizer should also be considered. For low solubilitydrugs, increased membrane permeability is , low molecular weight intermediateethoxyl grades such as EC N10 or high ethoxyl con-tents (%) such as EC T10 can be used with lowercoating weights , use of low EC concentration.