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Cellulose esters in drug delivery

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Abstract

Cellulose esters have played a vital role in the development of modern drug delivery technology. They possess properties that are not only well-suited to the needs of pharmaceutical applications, but that enable construction of drug delivery systems that address critical patient needs. These properties include very low toxicity, endogenous and/or dietary decomposition products, stability, high water permeability, high T g, film strength, compatibility with a wide range of actives, and ability to form micro- and nanoparticles. This suite of properties has enabled the creation of a wide range of drug delivery systems employing cellulose esters as key ingredients. The following is a review of the most important types of these systems, and of the critical roles played by cellulose esters in making them work, focusing on more recent developments.

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References

  • Appel L.E., Curatolo W.J., Herbig S.M., Nightingale J.A.S., Thombre A.G. (2004). Controlled release by extrusion of solid amorphous dispersions of drugs. US Patent 6:706, 283

    Google Scholar 

  • Bauer C.W., Masucci P.E. (1948). The action of intestinal enzymes upon cellulose acetate phthalate and butyl stearate enteric-coated tablets. J. Am. Pharm. Assoc. 37:124–128

    CAS  Google Scholar 

  • Beyger J.W., Nairn J.G. (1986). Some factors affecting the microencapsulation of pharmaceuticals with cellulose acetate phthalate. J. Pharm. Sci. 75:573–578

    Article  CAS  Google Scholar 

  • Bhardwaj S.B., Shukla A.J., Collins C.C. (1995). Effect of varying drug loading on particle size distribution and drug release kinetics of verapamil hydrochloride microspheres prepared with cellulose esters. J. Microencapsul. 12:71–81

    CAS  Google Scholar 

  • Carino G.P., Jacob J.S., Mathiowitz E. (2000). Nanosphere based oral insulin delivery. J. Contr. Rel. 65:261–269

    Article  CAS  Google Scholar 

  • Catellani P.L., Colombo P., Peppas N.A., Santi P., Bettini R. (1998). Partial permselective coating adds an osmotic contribution to drug release from swellable matrixes. J. Pharm. Sci. 87:726–731

    Article  CAS  Google Scholar 

  • Chang R.-K., Price J. and Whitworth C.W. 1986. Control of drug release rates through the use of mixtures of polycaprolactone and cellulose propionate polymers. Pharm. Tech. October: 24–33

  • Chang R.-K., Price J., Whitworth C.W. (1987). Control of drug release rate by use of mixtures of polycaprolactone and cellulose acetate butyrate polymers. Drug Dev. Ind. Pharm. 13:1119–1135

    CAS  Google Scholar 

  • Cohen J. (2005). Gut assumes sinister new role in HIV pathogenesis. Science 307:1395

    Article  CAS  Google Scholar 

  • Curatolo W.J., Nightingale J.A.S., Shanker R.M. and Sutton S.C. 2003. Basic drug compositions with enhanced bioavailability. US Patent 6,548,555

  • Davis S.S. (2005). Formulation strategies for absorption windows. Drug Del. Tech. 10:249–257

    CAS  Google Scholar 

  • Efentakis M., Koutlis A. and Vlachou M. 2000. Development and evaluation of oral multiple unit and single-unit hydrophilic controlled release systems. AAPS PharmSciTech 1:␣Article 34

    Google Scholar 

  • El-Gibaly I., Safwat S.M., Ahmed M.O. (1996). Microencapsulation of ketoprofen using w/o/w complex emulsion technique. J. Microencapsul. 13:67–97

    CAS  Google Scholar 

  • El-Said Y., Hashem F. (1991). In-vitro evaluation of sustained-release dyphylline tablets. Drug Dev. Ind. Pharm. 17:281–293

    Google Scholar 

  • Evans D.F., Pye G., Bramley R., Clark A.G., Tyson T.J., Hardcastle J.D. (1988). Measurement of gastrointestinal pH profiles in normal ambulant human subjects. Gut 29:1035–1041

    CAS  Google Scholar 

  • Follonier N., Doelker E. (1992). Biopharmaceutical comparison of oral multiple-unit and single-unit sustained-release dosage forms. S.T.P. Pharm. Sci. 2:141–158

    CAS  Google Scholar 

  • Giunchedi P., Conti B., Maggi L., Conte U. (1994). Cellulose acetate butyrate and polycaprolactone for ketoprofen spray-dried microsphere preparation. J. Microencapsul. 11:381–393

    CAS  Google Scholar 

  • Jacobsen O., Højgaard L., Møller E.H., Wielandt T.O., Thale M., Jarnum S., Krag E. (1985). Effect of enterocoated cholestyramine on bowel habit after ileal resection: a double blind crossover study. Brit. Med. J. 290:1315–1318

    Article  CAS  Google Scholar 

  • Kashdan D.S. 1989. Polymer blends having reverse phase morphology for controlled delivery of bioactive agents. US Patent 4,795,641

  • Klausner E.A., Lavy E., Friedman M., Hoffman A. (2003). Expandable gastroretentive dosage forms. J. Contr. Rel. 90:143–162

    Article  CAS  Google Scholar 

  • Kojima M., Nakagami H. (2002). Development of controlled release matrix pellets by annealing with micronized water-insoluble or enteric polymers. J. Contr. Rel. 82:335–343

    Article  CAS  Google Scholar 

  • Kuo C.M., Curtis L.G. and Lucas P.L. 1994. Aqueous dispersion useful in coatings containing hydrolyzed cellulose ester and acrylic resin. US Patent 5,334,638

  • Leuner C., Dressman J. (2000). Improving drug solubility for oral delivery using solid dispersions. Eur. J. Pharm. Biopharm. 50:47–60

    Article  CAS  Google Scholar 

  • Levine D.S., Raisys V.A., Ainardi V. (1987). Coating of oral beclomethasone dipropionate capsules with cellulose acetate phthalate enhances delivery of topically active anti-inflammatory drug to the terminal ileum. Gastroenterology 92:1037–1044

    Google Scholar 

  • Liu J., Chan S.Y., Ho P.C. (2002). Polymer-coated microparticles for the sustained release of nitrofurantoin. J. Pharm. Pharmacol. 54:1205–1212

    Article  CAS  Google Scholar 

  • Lyu S.-P., Sparer R., Hobot C., Dang K. (2005). Adjusting drug diffusivity using miscible polymer blends. J. Contr. Rel. 102:679–687

    Article  CAS  Google Scholar 

  • Makhija S.N., Vavia P.R. (2003). Controlled porosity osmotic pump-based controlled release systems of pseudoephedrine. I. Cellulose acetate as a semipermeable membrane. J. Contr. Rel. 89:5–18

    Article  CAS  Google Scholar 

  • Malm C.J., Emerson J., Hiatt G.D. (1951). Cellulose acetate phthalate as an enteric coating material. J. Am. Pharm. Assoc. 40:520–525

    CAS  Google Scholar 

  • Malm C.J., Fordyce C.R. (1940). Cellulose esters of dibasic organic acids. Ind. Eng. Chem. 32:405–408

    Article  CAS  Google Scholar 

  • Malm C.J., Mench J.W., Fulkerson B., Hiatt G.D. (1957). Preparation of phthalic acid esters of cellulose. Ind. Eng. Chem. 49:84–88

    Article  CAS  Google Scholar 

  • Mathiowitz E., Jacob J.S., Jong Y.S., Carino G.P., Chickering D.E., Chaturvedi P., Santos C.A., Vijayaraghavan K., Montgomery S., Bassett M., Morrell C. (1997). Biologically erodable microspheres as potential oral drug delivery systems. Nature 386:410–414

    Article  CAS  Google Scholar 

  • Moretti M.D.L., Gavini E., Juliano C., Pirisino G., Giunchedi P. (2001). Spray-dried microspheres containing ketoprofen formulated into capsules and tablets. J. Microencapsul. 18: 111–121

    Article  Google Scholar 

  • Nokhodchi A. and Farid D. 2002. Microencapsulation of paracetamol by various emulsion techniques using cellulose acetate phthalate. Pharm. Tech. 54–60

  • Obeidat W.M., Price J.C. (2003). Viscosity of polymer solution phase and other factors controlling the dissolution of theophylline microspheres prepared by the emulsion solvent evaporation method. J. Microencapsul. 20:57–65

    Article  CAS  Google Scholar 

  • Obeidat W.M., Price J.C. (2004). Evaluation of enteric matrix microspheres prepared by emulsion-solvent evaporation using scanning electron microscopy. J. Microencapsul. 21: 47–57

    Article  CAS  Google Scholar 

  • Omidian H., Rocca J.G., Park K. (2005). Advances in superporous hydrogels. J. Contr. Rel. 102:3–12

    Article  CAS  Google Scholar 

  • Palmieri G.F., Bonacucina G., Di Martino P., Martelli S. (2002). Gastro-resistant microspheres containing ketoprofen. J. Microencapsul. 19:111–119

    Article  CAS  Google Scholar 

  • Palmieri G.F., Michelini S., Di Martino P., Martelli S. (2000). Polymers with pH-dependent solubility: possibility of use in the formulation of gastroresistant and controlled-release matrix tablets. Drug Dev. Ind. Pharm. 26: 837–845

    Article  CAS  Google Scholar 

  • Pongpaibul Y., Whitworth C.W. (1986a). Microencapsulation by emulsion non-solvent addition method. Drug Dev. Ind. Pharm. 12: 2387–2402

    CAS  Google Scholar 

  • Pongpaibul Y., Whitworth C.W. (1986b). Preparation and in vitro dissolution characteristics of propranolol microcapsules. Int. J. Pharm. 33: 243–248

    Article  CAS  Google Scholar 

  • Prapaitrakul W., Whitworth C.W. (1989). Microencapsulation of phenylpropanolamine to achieve sustained release. J. Microencapsul. 6: 213–218

    CAS  Google Scholar 

  • Santus G., Baker R.W. (1995). Osmotic drug delivery: a review of the patent literature. J. Contr. Rel. 35: 1–21

    Article  CAS  Google Scholar 

  • Sarisuta N., Kumpugdee M., Müller B.W., Puttipipatkhachorn S. (1999). Physico-chemical characterization of interactions between erythromycin and various film polymers. Int. J. Pharm. 186: 109–118

    Article  CAS  Google Scholar 

  • Schultz P., Kleinebudde P. (1997). A new multiparticulate delayed release system. Part I: Dissolution properties and release mechanism. J. Contr. Rel. 47:181–189

    Article  CAS  Google Scholar 

  • Sertsou G., Butler J., Scott A., Hempenstall J., Rades T. (2002). Factors affecting incorporation of drug into solid solution with HPMCP during solvent change co-precipitation. Int. J. Pharm. 245:99–108

    Article  CAS  Google Scholar 

  • Shukla A.J., Price J.C. (1991). Effect of drug loading and molecular weight of cellulose acetate propionate on the release characteristics of theophylline microspheres. Pharm. Res. 8:1396–1400

    Article  CAS  Google Scholar 

  • Singhal D., Curatolo W. (2004). Drug polymorphism and dosage form design: a practical perspective. Adv. Drug Del. Rev. 56: 335–347

    Article  CAS  Google Scholar 

  • Soppimath K.S., Kulkarni A.R., Aminabhavi T.M. (2001). Development of hollow microspheres as floating controlled-release systems for cardiovascular drugs: preparation and release characteristics. Drug Devel. Ind. Pharm. 27: 507–515

    Article  CAS  Google Scholar 

  • Sprockel O.L., Prapaitrakul W. (1990). A comparison of microencapsulation by various emulsion techniques. Int. J. Pharm. 58: 123–127

    Article  CAS  Google Scholar 

  • Sprockel O.L., Prapaitrakul W., Shivanand P. (1990). Permeability of cellulose polymers: water vapor transmission rates. J. Pharm. Pharmacol. 42: 152–157

    CAS  Google Scholar 

  • Sprockel O.L., Price J.C. (1989). Evaluation of sustained release aqueous suspensions containing microencapsulated drug-resin complexes. Drug Dev. Ind. Pharm. 15: 1275–1287

    CAS  Google Scholar 

  • Stithit S., Chen W., Price J.C. (1998). Development and characterization of buoyant theophylline microspheres with near zero order release kinetics. J. Microencapsul. 15: 725–737

    Article  CAS  Google Scholar 

  • Tanno F., Nishiyama Y., Kokubo H., Obara S. (2004). Evaluation of hypromellose acetate succinate (HPMCAS) as a carrier in solid dispersions. Drug Dev. Ind. Pharm. 30: 9–17

    Article  CAS  Google Scholar 

  • Theeuwes F. (1975). Elementary osmotic pump. J. Pharm. Sci. 64:1987–1991

    Article  CAS  Google Scholar 

  • Theeuwes F. (1983). Oros® osmotic system development. Drug Dev. Ind. Pharm. 9:1331–1357

    CAS  Google Scholar 

  • Thoma K., Bechtold K. (1999). Influence of aqueous coatings on the stability of enteric coated pellets and tablets. Eur. J. Pharm. Biopharm. 47: 39–50

    Article  CAS  Google Scholar 

  • Vaithiyalingam S., Reddy I.K., Khan M.A., Guven N. (2001). Aqueous-based cellulose acetate butyrate dispersion: screening of process and formulation variables to obtain verapamil HCl-controlled release tablets. Part. Sci. Tech. 19: 131–144

    Article  Google Scholar 

  • Vazquez-Torres H., Cruz-Ramos C.A. (1994). Blends of cellulose esters with poly(caprolactone): characterization by DSC, DMA and WAXS. J. Appl. Poly. Sci. 54: 1141–1159

    Article  CAS  Google Scholar 

  • Verma R.K., Mishra B., Garg S. (2000). Osmotically controlled oral drug delivery. Drug Dev. Ind. Pharm. 26:695–708

    Article  CAS  Google Scholar 

  • Watts P.J., Illum L. (1997). Colonic drug delivery. Drug Dev. Ind. Pharm. 23: 893–913

    Article  CAS  Google Scholar 

  • Wilson A.K., Posey-Dowty J. and Kelley S.S. 1996a. Controlled release matrix system using cellulose acetate/poly-2-ethyl-2-oxazoline blends. US Patent 5,536,505

  • Wilson A.K., Posey-Dowty J. and Kelley S.S. 1996b. Controlled release matrix system using cellulose acetate/polyvinylpyrrolidone blends. US Patent 5,523,095

  • Wu C.Y., Benet L.Z. (2005). Predicting drug disposition via application of BCS: transport/absorption/elimination interplay and development of a biopharmaceutics drug disposition classification system. Pharm. Res. 22: 11–23

    Article  CAS  Google Scholar 

  • Wu S.H.W., Wyatt D.M., Adams M.W. (1997). Chemistry and applications of cellulosic polymers for enteric coatings of solid dosage forms. In: McGinity J.W. (ed) Aqueous Coatings for Pharmaceutical Dosage Forms. Marcel Dekker, New York, pp. 385–418

    Google Scholar 

  • Xu X., Lee P.I. (1993). Programmable drug delivery from an erodible association polymer system. Pharm. Res. 10: 1144–1152

    Article  CAS  Google Scholar 

  • Yang M., Cui F., You B., You J., Wang L., Zhang L., Kawashima Y. (2004). A novel pH-dependent gradient release delivery system for nitrendipine I. Manufacturing, evaluation in vitro and bioavailability in healthy dogs. J. Contr. Rel. 98: 219–229

    Google Scholar 

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Acknowledgements

My personal thanks go to Andy Singleton and Jinghua Yuan of Eastman for their help with the table of properties of cellulose esters used in current drug delivery applications.

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Correspondence to Kevin J. Edgar.

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Edgar, K.J. Cellulose esters in drug delivery. Cellulose 14, 49–64 (2007). https://doi.org/10.1007/s10570-006-9087-7

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