Properties and Applications of Polyvinyllactam Polymers

Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 9)


A number of polymers used in melt extrusion have been available to the pharmaceutical scientists for many decades. However, in one case, a vinylcaprolactam structure (Soluplus®) was developed with the intention of using it in particular for melt extrusion. It was designed to address some of the shortcomings of the available polymers. In addition, the properties and applications of many polyvinyllactam polymers, such as the Kollidons®, are outlined, discussing immediate release to sustained release. These “older and newer” polymers, including their structure and applications, are thoroughly discussed within this chapter, including a historical perspective.


Glass Transition Temperature Active Ingredient Sustained Release Polyvinyl Acetate Vinyl Acetate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Agrawal Y, Prakasam K (1988) Effect of binders on sulfamethoxazole tablets. J Pharm Sci 77:885–888PubMedCrossRefGoogle Scholar
  2. Akers M (2002) Excipient—drug interactions in parenteral formulations. J Pharm Sci 91:2283–2300PubMedCrossRefGoogle Scholar
  3. Ali S, Langley N (2010) Dry granulation simplifies tableting process. Pharm Form Quality 12:26–29Google Scholar
  4. Amnuaikit C, Ikeuchi I, Ogawara K, Higaki K, Kimura T (2005) Skin permeation of propranolol from polymeric film containing terpene enhancers for transdermal use. Int J Pharm 289:167–178PubMedCrossRefGoogle Scholar
  5. Breitenbach J (2002) Melt extrusion: From process to drug delivery technology. Eur J Pharm Biopharm 54:107–117PubMedCrossRefGoogle Scholar
  6. Breitkreutz J (1998) Prediction of intestinal drug absorption properties by three-dimensional solubility parameters. Pharm Res 15:1370–1375PubMedCrossRefGoogle Scholar
  7. Brouwers J, Brewster M, Augustijns P (2009) Supersaturating drug delivery systems: the answer to solubility-limited oral bioavailability. J Pharm Sci 98:2549–2572PubMedCrossRefGoogle Scholar
  8. Buera M, Levi G, Karel M (1992) Glass transition in poly(vinylpyrro1idone): Effect of molecular weight and diluents. Biotechnol Prog 8:144–148CrossRefGoogle Scholar
  9. Bühler V (2008a) Pharmaceutical technology of BASF excipients, 9th edn. BASF Pharma Ingredients & Service, LudwigshafenGoogle Scholar
  10. Bühler V (2008b) Kollidon—polyvinylpyrrolidone excipients for the pharmaceutical industry, 9th edn. BASF Pharma Ingredients & Service, LudwigshafenGoogle Scholar
  11. Bühler V, Fussnegger B (2005) Generic Drug Formulations, 5th edn. BASF Pharma Solutions, LudwigshafenGoogle Scholar
  12. Chokshi R, Sandhu H, Iyer R, Shah N, Malick A, Hossein Z (2006) Characterization of physico-mechanical properties of indomethacin and polymers to assess their suitability for hot-melt extrusion process as a means to manufacture solid dispersion/solution. J Pharm Sci 94:2463–2474CrossRefGoogle Scholar
  13. Chowhan Z, Amaro A, Ong JTH (1992) Punch geometry and formulation considerations in reducing tablet friability and their effect on in vitro dissolution. J Pharm Sci 81(3):290–294PubMedCrossRefGoogle Scholar
  14. Crowley M, Zhang F, Repka M, Thumma S, Upadhye S, Battu S, McGinity J, Martin C (2007) Pharmaceutical applications of hot-melt extrusion: part I. Drug Dev Ind Pharm 33:909–929PubMedCrossRefGoogle Scholar
  15. Damian F, Blaton N, Kinget R, Van den Mooter G (2002) Physical stability of solid dispersions of the antiviral agent UC-781 with PEG 6000, gelucire 44/14 and PVP K30. Int J Pharm 244:87–98PubMedCrossRefGoogle Scholar
  16. Djuric D, Maschke A, Kolter K (2010) Modified release of poorly soluble itraconazole by means of polymer combinations for hot-melt extrusion. Poster AAPS Annual Meeting and Exposition, AtlantaGoogle Scholar
  17. Douroumis D (2012) Hot-melt extrusion: pharmaceutical applications. Wiley, HobokenCrossRefGoogle Scholar
  18. Doyle C (1961) Estimating thermal stability of experimental polymers by empirical thermogravimetric analysis. Anal Chem 33:77–79CrossRefGoogle Scholar
  19. Flick D, Fraunhofer W, Rock C, Kolter K (2000) Melt granulation with Kollidon® SR for the manufacture of sustained release tablets. Poster 27th International Symposium on Controlled Release of Bioactive Materials, ParisGoogle Scholar
  20. Forster A, Hempenstall J, Rades T (2001a) Characterization of glass solutions of poorly water-soluble drugs produced by melt extrusion with hydrophilic amorphous polymers. J Pharm Pharmacol 53:303–315CrossRefGoogle Scholar
  21. Forster A, Hempenstall J, Tucker I, Rades T (2001b) Selection of excipients for melt extrusion with two poorly water-soluble drugs by solubility parameter calculation and thermal analysis. Int J Pharm 226:147–161CrossRefGoogle Scholar
  22. Garekani H, Sadeghi F, Ghazi A (2003) Increasing the aqueous solubility of acetaminophen in the presence of polyvinylpyrrolidone and investigation of the mechanisms involved. Drug Dev Ind Pharm 29:173–179PubMedCrossRefGoogle Scholar
  23. Ghebremeskel A, Vemavarapu C, Lodaya M (2007) Use of surfactants as plasticizers in preparing solid dispersions of poorly soluble API. Int J Pharm 328:119–129PubMedCrossRefGoogle Scholar
  24. Ghebre-Sellassie I, Martin C (2007) Pharmaceutical extrusion technology. Drugs and the pharmaceutical sciences 133: 245–260Google Scholar
  25. Gil E, Colarte A, Sampedro J, Bataille B (2008) Subcoating with Kollidon VA 64 as water barrier in a new combined native dextran/HPMC–cetyl alcohol controlled release tablet. Eur J Pharm Biopharm 69:303–311CrossRefGoogle Scholar
  26. Greenhalgh D, William A, Timmins P, York P (1999) Solubility parameters as predictors of miscibility in solid dispersions. J Pharm Sci 88:1182 -1190Google Scholar
  27. He X, Barone M, Marsac P, Sperry D (2008) Development of a rapidly dispersing tablet of a poorly wettable compound-formulation DOE and mechanistic study of effect of formulation excipients on wetting of celecoxib. Int J Pharm 353:176–186PubMedCrossRefGoogle Scholar
  28. Herting M, Klose K, Kleinebudde P (2007) Comparison of different dry binders for roll compaction/dry granulation. Pharm Dev Technol 12:525–532PubMedCrossRefGoogle Scholar
  29. Ishida H, Wu T, Yu L (2007) Sudden rise of crystal growth rate of nifedipine near Tg without and with polyvinylpyrrolidone. J Pharm Sci 96:1131–1138PubMedCrossRefGoogle Scholar
  30. Jain P, Banga AK (2010) Inhibition of crystallization in drug-in-adhesive-type transdermal patches. Int J Pharm 394(1–2):68–74PubMedCrossRefGoogle Scholar
  31. Karl M, Djuric D, Kolter K (2011) Pharmaceutical excipients for hot-melt extrusion. Pharm Tech 35(5):74–82Google Scholar
  32. Karl M, Nalawade S, Maschke A, Djuric D, Kolter K (2010) Suitability of pure and plasticized polymers for hot-melt extrusion. Poster AAPS Annual Meeting and Exposition, AtlantaGoogle Scholar
  33. Klein E, Chiu L, Awni W, Zhu T, Heuser R, Doan T, Breitenbach J, Morris J, Brun S, Hanna G (2007) The tablet formulation of Lopinavir/Ritonavir provides similar bioavailability to the soft-gelatin capsule formulation with less pharmacokinetic variability and diminished food effect. J Acquir Immune Defic Syndr 44:401–410PubMedCrossRefGoogle Scholar
  34. Kolter K, Flick D (2006) Structure and dry binding activity of different polymers, including Kollidon VA 64. Drug Dev Ind 26:1159–1165CrossRefGoogle Scholar
  35. Kolter K, Karl M, Nalawade N, Rottmann N (2010) Hot-melt extrusion with BASF Pharma polymers— extrusion compendium. BASF Pharma Ingredients & Service, LudwigshafenGoogle Scholar
  36. Koltzenburg S (2011) Formulation of problem drugs. In: Reintjes T (ed) Solubility enhancement with BASF Pharma Polymers Solubilizer. BASF Pharma Ingredients & Service, Ludwigshafen.Google Scholar
  37. Kranz H, Wagner T (2006) Effects of formulation and process variables on the release of a weakly basic drug from single unit extended release formulations. Euro J Pharm Biopharm 62(1):70–76CrossRefGoogle Scholar
  38. Kuentz M, Röthlisberger D (2002) Determination of the optimal amount of water in liquid-fill masses for hard gelatin capsules by means of texture analysis and experimental design. Int J Pharm 236:145–152PubMedCrossRefGoogle Scholar
  39. Lee Y, Chien Y (1995) Oral mucosa controlled delivery of LHRH by bilayer mucoadhesive polymer systems. J Control Release 37:251–261CrossRefGoogle Scholar
  40. Leuner C, Dressman J (2000) Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm 50:47–60PubMedCrossRefGoogle Scholar
  41. Lim H, Lan Y, Yao Y, Fahmy R, Hoag S (2011) Enhancing dissolution rate of carbamazepine via solvent casting and hot-melt extrusion with a novel polymeric solubilizer (Soluplus).Google Scholar
  42. Linn M, Collnot E, Djuric D, Hempel K, Fabian E, Kolter K, Lehr C (2012) Soluplus® as an effective absorption enhancer of poorly soluble drugs in vitro and in vivo. Eur J pharm Sci 45:336–343PubMedCrossRefGoogle Scholar
  43. Liu X, Lu M, Guo Z, Huang L, Feng X, Wu C (2012) Improving the chemical stability of amorphous solid dispersion with cocrystal technique by hot-melt extrusion. Pharm Res 29:806–817PubMedCrossRefGoogle Scholar
  44. Ma X, Taw J, Chiang C (1996) Control of drug crystallization in transdermal matrix system. Int J Pharm 142:115–119CrossRefGoogle Scholar
  45. Maniruzzamana M, Boatenga J, Bonnefilleb M, Aranyosb A, Mitchella J, Douroumis D (2012) Taste masking of paracetamol by hot-melt extrusion: an in vitro and in vivo evaluation. Eur J Pharm Biopharm 80:433–442CrossRefGoogle Scholar
  46. Maschke A, Meyer-Böhm K, Kolter K (2007) Application of Kollidon VA64 fine in roller compaction. Poster AAPS Annual Meeting, San DiegoGoogle Scholar
  47. Maschke A, Kumpp U, Güntherberg N, Kolter K (2009) Effect of preparation method on release behavior of Kollidon SR tablets, hot-melt extrusion versus direct compression. 36th Annual Meeting and Exposition of the Control Release Society, CopenhagenGoogle Scholar
  48. Nair R, Gonen S, Hoag S (2002) Influence of polyethylene glycol and povidone on the polymorphic transformation and solubility of carbamazepine. Int J Pharm 240:11–22PubMedCrossRefGoogle Scholar
  49. Özgüney I, Shuwisitkul D, Bodmeier R (2009) Development and characterization of extended release Kollidon SR mini-matrices prepared by hot-melt extrusion. Euro J Pharm Biopharm 73:140–145CrossRefGoogle Scholar
  50. Painter P, Coleman M (2009) Essentials of polymer science and engineering. Destech, LancasterGoogle Scholar
  51. Patterson J, James M, Forster A, Rades T (2008) Melt extrusion and spray drying of carbamazepine and dipyridamole with polyvinylpyrrolidone/vinyl acetate copolymers. Drug Dev Ind Pharm 34:95–106PubMedCrossRefGoogle Scholar
  52. Pielichowski K (2008) Thermal degradation of polymeric materials. Smithers Rapra, ShropshireGoogle Scholar
  53. Plaizier-Vercammen J (1983) Interaction of povidone with aromatic compounds IV: Effects of macromolecule molecular weight, solvent dielectric constant, and ligand solubility on complex formation. J Pharm Sci 72:1042–1044PubMedCrossRefGoogle Scholar
  54. Plaizier-Vercammen J, Neve R (1983) Interaction of povidone with aromatic compounds III: thermodynamics of the binding equilibria and interaction forces in buffer solutions at varying pH values and varying dielectric constant. J Pharm Sci 71:552–556Google Scholar
  55. Qiu L, Bae Y (2003) Polymer architecture and drug delivery. Pharm Res 23:1–30CrossRefGoogle Scholar
  56. Ranzani L, Font J, Galimany F, Santanach A, Gomez-Gomar A, Casadevall G, Gryczke A (2011) Enhanced in vivo absorption of CB-1 antagonist in rats via solid solutions prepared by hot-melt extrusion. Drug Dev Ind Pharm 37:694–701PubMedCrossRefGoogle Scholar
  57. Repka M, Shah S, Lu J, Maddineni S, Morott J, Patwardhan K, Mohammed N (2012) Melt extrusion: process to product. Expert Opin Drug Deliv 9:105–125PubMedCrossRefGoogle Scholar
  58. Ritala M, Jungersen O, Holm P, Schæfer T, Kristensen H (1986) A comparison between binders in the wet phase of granulation in a high shear mixer. Drug Dev Ind Pharm 12:1685–1700CrossRefGoogle Scholar
  59. Schillinga SU, Brucea CD, Shah NH, Malickb AW, McGinity JW (2008) Citric acid monohydrate as a release-modifying agent in melt extruded matrix tablets. Int J Pharm 361:158–168CrossRefGoogle Scholar
  60. Siepmann F, Eckart K, Maschke A, Kolter K, Siepmann J (2010) Modeling drug release from PVAc/PVP matrix tablets. J Control Release 141:216–222PubMedCrossRefGoogle Scholar
  61. Simonelli A, Mehta S, Higuchi W (1970) Inhibition of sulfathiazole crystal growth by polyvinylpyrrolidone. J Pharm Sci 59:633–638PubMedCrossRefGoogle Scholar
  62. Strickley R (2004) Solubilizing excipients in oral and injectable formulations. Pharm Res 21:201–230PubMedCrossRefGoogle Scholar
  63. Strübing S, Metz H, Mäder K (2008) Characterization of poly(vinyl acetate) based floating matrix tablets. J Control Release 126:149–155PubMedCrossRefGoogle Scholar
  64. Tantishaiyakul V, Kaewnopparat N, Ingkatawornwong S (1999) Properties of solid dispersions of piroxicam in polyvinylpyrrolidone. Int J Pharm Sci 181:143–151CrossRefGoogle Scholar
  65. Tantry J, Tank J, Suryanarayana R (2007) Processing-induced phase transitions of theophylline-implications on the dissolution of theophylline tablets. J Pharm Sci 96:1434–1444PubMedCrossRefGoogle Scholar
  66. Van den Mooter G, Wuyts M, Blaton N, Busson R, Grobet P, Augustijns P, Kinget R (2010) Physical stabilisation of amorphous ketoconazole in solid dispersions with polyvinylpyrrolidone K25. Eur J Pharm Sci 12:261–269CrossRefGoogle Scholar
  67. Van Krevelen D, Hoftyzer P (1976) Properties of polymers—their correlation with chemical structures. Elsevier, AmsterdamGoogle Scholar
  68. Wen H, Morris K, Park K (2005) Study on the interactions between polyvinylpyrrolidone (PVP) and acetaminophen crystals: partial dissolution pattern change. J Pharm Sci 94(10):2166–2174PubMedCrossRefGoogle Scholar
  69. Zhang F, McGinity J (2000) Properties of hot-melt extruded theophylline tablets containing poly(vinyl acetate). Drug Dev Ind Pharm 26:931–942PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  1. 1.BASF SELudwigshafenGermany

Personalised recommendations