The Use of Polymers in Liquid Pharmaceutical Formulations - Essay Example

Introduction Polymers are becoming increasingly important in the field of pharmaceuticals. It is necessary to select a nontoxic, biocompatible polymer that causes minimal adverse effect on the activity and stability of drug as well as dosage form. The pharmaceutical polymers are used to produce a wide variety of pharmaceutical dosage forms. Polymers improve the pharmaceutical characteristics of dosage forms. They act as viscosity and flow controlling agents in pharmaceutical liquids, suspensions and emulsions. In tablet formulations polymers are used as binders. Polymers are extensively used to deliver better drug products. They are employed in film coatings to mask the unpleasant taste of the drug, to improve the stability of hydrophilic drugs, to facilitate handling and to alter the drug release properties (Jones 2004). Polymers are increasingly dominating the scene as the drug carrier for controlled-release systems. During the process, drug is released; the polymers get degraded and are sometimes absorbed within the body. Application of polymers in liquid pharmaceuticals formulations The drugs can be administered to the patient in many forms like liquid, solid or semisolid. Oral route of administration consists of liquid solutions, emulsions, or suspensions, or in solid form such as capsules or tablets. It is desirable to provide liquid pharmaceutical formulation to infants, children, older persons, and many other persons are unable to swallow whole tablets and capsules (Yu & Roche 2001). When a medicament is given orally, the palatability of the active ingredient is an extremely important factor in ensuring patient compliance. The contact of the active ingredient with the mouth can not be prevented in liquid dosage forms. Sometimes, the undesirable taste can be masked by adding flavoring ingredients and sweeteners. However, the drugs like antibiotics possess a very strong, bitter, unpleasant taste. To improve taste and palatability of liquid pharmaceuticals, various taste masked coating compositions have been employed in the formulation of liquid suspension dosage forms. These formulations should be stable, palatable in the aqueous environment over prolonged period, relatively insoluble at the non-acidic pHs of the mouth, and exhibit immediate bioavailability after swallowing and ingestion (Danny & Edward 2001). The "reverse enteric coating" provides for rapid release and absorption of the drug in the acidic pH of the stomach, is desirable in the case of liquid dosage forms. The drug particles are spray coated with the taste masking polymer blend either directly or after granulation, and then the coated particles are admixed with an aqueous liquid vehicle for oral administration. The diffusion and solubility of the coating depends on the ratio of the components of the polymer blend and the physicochemical properties of the active ingredient being coated. The examples of the taste masking liquid pharmaceutical formulations are reported. The unpleasant tasting antibiotic drugs, like levofloxacin, ofloxacin and related quinolone antibiotics, macrolide antibiotics, etc are formulated for oral liquid administration by this method. The drug is coated with taste masking effective amount of a polymer blend of (a) dimethylaminoethyl methacrylate and neutral methacrylic acid ester (MM/MAE) and (b) a cellulose ester, in an aqueous vehicle. The polymer weight ratio of the cellulose ester to the MM/MAE is about 40: 60 to about 90: 10. (WO/2001/003698 ) (Yu & Roche 2001). In oral and topical liquid pharmaceutical formulations the polymers like cellulose ethers (methylcellulose and hypromellose products) are used as excellent thickeners and can be used to produce desired viscosity in liquid preparations. The surfactancy properties of cellulose ethers (1 to 2%) enable them to act as suspending agent to stabilize suspension formulations. Thus they can be used to control rheology. Cellulose ethers (5 to 30%) are useful for the liquid formulations of bulk laxatives due to water retention property. Since these polymers gives good viscosity for wide pH range of 4 to 11, they are used with alkaline as well as acidic drugs. The film-forming properties of cellulose ethers (1 to 5%) are useful in topical formulations. Cellulose ethers are used as a protective colloid and can act as emulsifying agent in liquid formulations. They are used as demulcents (0.1 to 0.5%) in ophthalmic solutions (The Dow Chemical Company). Pharmaceutical polymers also provide new strategies to solve pharmacokinetic issues encountered by pharmacologically active compounds. Polymers like polyoxyethylene X-lauryl ether wherein X is from 9 to 20, polyoxyethylene ether, polyoxyethylene sorbitan esters, p-t-octylphenoxypolyoxyethylene, are used as absorption enhancing compounds for oral or nasal delivery liquid pharmaceuticals. The absorption enhancing compounds are present in a concentration of 1.5 to 3.5 wt./wt.% in liquid formulations. The formulation is adapted to oral delivery of proteinic medicament like insulin. The polymers like polyvinyl alcohol, polyethylene glycol and gelatin are used as protective polymer in these formulations for slow release of the pharmaceutical agent. The information is reported in Application No: PCT/CA1996/000305 (Modi & Chandarana 1996). In ophthalmic medications, the polymers are used to improve the ocular bioavailability of drug (hydrophilic and hydrophobic antibiotics), to increase the viscosity of the preparation, to reduce the drainage rate. The polygalactoronic acid, xyloglucan, xanthan gum, and gellan gum, cellulose derivatives like hydroxypropylmethyl cellulose (HPMC) and hydroxypropyl cellulose (HPC) increases the viscosity of liquid formulations and also exhibit surface-active properties influencing the blinking rate and the elimination of the drug instilled. The mucoadhesives polymers like chitosan, poly(acrylic acid) (PAA) and carbomers, sodium hyluronase as tear substitutes are also used in ophthalmic liquid preparations. Cyclic oligosaccharides are useful for formulation of hydrophobic drugs since they solubilize these poorly soluble drugs in their hydrophobic interior and provide a hydrophilic exterior for ophthalmic use (Wagh et al. 2008). For stabilization of sustained-release protein delivery systems the drugs are embedded in biodegradable polymeric microparticles. Microparticles are made from homo- and co-polymers of lactic and glycolic acid (PLGA polymers). These polymer- based drug formulations include luteinizing hormone releasing hormone (LHRH), agonist luprolide etc. But these formulations face administration challenges. The injectability and effective amount of a biologically active agent of these particulate suspensions is improved with the help of an injection vehicle like hyaluronic acid or its derivative. Biologically active agents like growth hormone, a hepatocyte growth factor (HGF), a vascular endothelial growth factor (VEGF), an anti- VEGF Fab, a glucagon-like peptide I (GLP-I), a nerve growth factor, or an insulin-like growth factor are formulated using this strategy. The information is reported in WO/2001/028591 (Cleland 2001). Liquid oral pharmaceuticals having enteric-release properties of delayed and sustained release are very few. These formulations have advantage over expensive tableting or coating processes. Enteric polymers are stimuli responsive polymers having pH-dependent solubility in aqueous media. These smart polymers provide resistance to gastric fluids, allowing the active medicament to be released in intestinal fluid. Examples of enteric polymers include cellulose acetate phthalates (C-A-P), cellulose acetate trimellitates (C-A-T), cellulose acetate succinates (C-A-S), hydroxypropyl methyl cellulose phthalates (HPMCP), carboxymethyl ethylcelluloses (CMEC), hydroxypropyl methyl cellulose acetate succinates (HPMCAS), polyvinyl acetate phthalates (PVAP), copolymers of methacrylic acid and methyl methacrylate or ethyl acrylate, etc. Cellulose derivatives like cellulose acetates, tripalmitates etc. acts as modifiers for enteric coatings. Total weight of the dosage form decides the concentration of the enteric polymers and may vary from 10% to 30% by weight. These liquid formulations are prepared by incorporating drug into the solvent mixtures of the polymer. The resulting liquid dosage forms are ready for oral administration and encapsulation within pharmaceutical capsules. The example is reported for ibuprofen dosage formulation. Ibuprofen is dissolved in PEG 400 and propylene carbonate. Then, C-A-P is dissolved, and triacetin is added. This mixture can be used for encapsulation within a pharmaceutical capsule (WO/2007/050294) (Yuan & Clipse 2007). Polymers are also used to physically stabilize aqueous suspensions of sparingly soluble to insoluble in water, active drug ingredients. These suspension liquid dosage forms are prepared by dispersion of water soluble low viscosity grade cellulose polymer and suspending agent in non-solvent medium such as glycerine, propylene glycol or polyethylene glycol. This fluid slurry is then added to main vehicle water to obtain complete hydration of polymers. Then, other additives along with active ingrdient is dispersed through high shear mixing operation of homogenization or triclover blending operation. At the end flavoring agents are added and volume was made up. One of the examples of physically stable aqueous suspension includes Ibuprofen Suspension Pediatric Liquid Dosage Form (USPTO Application #: 20080260837) (Namburi 2008). Conclusion Polymers have emerged as an important tool in liquid pharmaceutical formulations. The power of the polymers is exploited in stabilizing, handling, altering the drug release properties, providing new strategies to solve pharmacokinetic problems encountered by pharmacologically active compounds and improving palatability of liquid dosage forms. References Jones, David. Pharmaceutical Applications of Polymers for Drug Delivery. ChemTec publishing, 2004. Yu, D., and Roche, E. Taste Masked Pharmaceutical Liquid Formulations. Patent WO/2001/003698. 18 January 2001. Namburi, R. et al. Physically stable aqueous suspensions of active pharmaceuticals. USPTO Applicaton #: 20080260837. Oct 2008. Cleland, J. et al. Injection Vehicle For Polymer-Based Formulations. Patent WO/2001/028591. 26 April 2001. Modi, P., and Chandarana, S. Liquid Formulations For Proteinic Pharmaceuticals Comprising At Least 2 Absorption Enhancers. Patent Application #:PCT/CA1996/000305. Application Date 16 May 1996. Wagh, V., Inamdar, B., and Samanta, M. “Polymers used in ocular dosage form and drug delivery systems”. Asian J Pharm 2 (2008):12-17. Yuan, J., and Clipse N. Liquid Dosage Forms Having Enteric Properties Of Delayed And Then Sustained Release. Patent WO/2007/050294. 3 May 2007. The Dow Chemical Company http://www.dow.com/dowexcipients/applications/liquid.htm. Read More