Abstract
Hydrogels are widely studied materials for the preparation of sustained release drug dosage forms. Their soft, tissue-like consistency and their high biocompatibility in a number of applications make them promising candidates for this purpose. The water and the polymer in the gel form intricate structures and much research has been devoted to the elucidation of these structures, and of the interactions involved in their formation. Simple, drug-loaded hydrogels normally give a matrix-type delivery profile, in which the release rate is proportional to the square root of time; a number of approaches has been used to change this profile to other types of delivery, for instance to zero-order release. A number ofin vivo tests using hydrogel delivery systems has given favourable results.
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References
Kim SW, Petersen RV, Feyen J. Polymeric drug delivery systems. Med Chem (Academic) 1980; 11 (Drug Design V10):193–250.
Ratner BD, Hoffman AS. Synthetic hydrogels for biomedical applications. In: Andrade JD, ed. Hydrogels for medical and related applications. Washington DC: American Chemical Society, 1976:1–37. (ACS Symposium Series. Vol. 31.)
Schacht EH. Hydrogel drug delivery systems. In: Anderson JH, Kim SW, eds. Recent Advances in Drug Delivery Systems. Proceedings of an International Symposium. New York: Plenum Publishing Corporation, 1983:259–78.
Rajasekharan VN, Mutter M. Synthetic hydrophilic polymers. Naturwissenschaften 1981;68:558–66.
Wichterle O, Lim D. Hydrophilic gels for biological use. Nature 1960;185:117–8.
Abrahams RA, Ronel SH. Factors influencing the biocompatibility of hydrogels. Polym Prepr 1975; 16:535–40.
Shichiri M, Kawamori R, Goriya Y, et al. Glycemic control in pancreatectomized dogs with a wearable artificial endocrine pancreas. Diabetologia 1983;24(3):179–84.
Tollar M, Stol M, Kliment K. Surgical structure materials coated with a layer of hydrophilic Hydron gel. J Biomed Mater Res 1969;3:305–13.
Wichterle D, Barth P, Rosenberg M. Water soluble methacrylates as embedding media for preparation of ultra-thin sections. Nature 1970;186:494–5.
Refojo M. Vapor pressure and swelling pressure in hydrogels. In: Andrade JD, ed. Hydrogels for medical and related applications. Washington DC: American Chemical Society, 1976:37–51. (ACS Symposium Series. Vol. 31.)
Spacek P, Kubin M. Poly(ethyleneglycolmethacrylate) as a material for hemodialysis. J Biomed Mater Res 1973;7:201–4.
Pinchuk L, Eckstein E. Pressurized polymerization for reaction casting of poly(2-hydroxyethylmethacrylate). J Biomed Mater Res 1981;15:183–9.
Majkus V, Horakova A, Vymola F, Stol M. Employment of hydron polymer antibiotic vehicle in otolaryngology. J Biomed Mater Res 1969;3:443–54.
Nippon Carbide Industries. Caviar substitute. Jpn Kokai Tokkyo Koho 1980:JP 55/104876 (80/104876).
Kurarai Company. Removal of tattoo from skin by laser radiation and hydrogels. Jpn Kokai Tokkyo Koho 1981:JP 556/116464 A2 (81/116464).
Flory PJ. Principles of polymer chemistry. Ithaca: Cornell University Press, 1957.
Moore WR. An introduction to polymer chemistry. London: University of London Press Ltd., 1963.
Gregonis DE, Russel GA, Andrade JD, De Visser AC. Preparation and properties of stereoregular poly(hydroxyethylmethacrylate) polymers and hydrogels. Polymer 1978;19:1279–84.
Ratner BD. Characterization of graft polymers for biomedical applications. J Biomed Mater. Res 1980; 14:665–87.
Collet JH, Wood JM, Attwood D. The effects of some solutes on the hydration ofp(HEMA) hydrogels, prepared by chemical or radiation procedures. J Pharm Pharmacol 1980;32(suppl):6P.
Chromecek R, Gavrilova I, Satara V. Makroporöse Copolymere des 2-Hydroxyethylmethakrylats mit Äthylenglykol-dimethakrylat. Makromol Chem 1970; 135:35–40.
Shao M, Gregonis DE, Chwen CM, Andrade JD. Rotational viscosimetry studies of the polymerization of hydrophilic methacrylate polymers. In: Andrade JD, ed. Hydrogels for medical and related applications. Washington DC: American Chemical Society, 1976:119–38. (ACS Symposium Series. Vol. 31).
Kopecek J, Lim D. Mechanism of the three dimensional polymerization of glycol methacrylates. 11. The system glycol monomethacrylate-glycol dimethycrylate-solvents. J Polymer Sci [A-1] 1971;9:147–54.
Refojo M. Hydrophobic interaction in poly(2-hydroxyethylmethacrylate) homogeneous hydrogel. J Polym Sci [A-1] 1967;5:3103–13.
Warren TC, Prins W. Polymer-diluent interaction in cross-linked gels of poly(2-hydroxyethylmethacrylate). Macromolecules 1972;3(4):506–12.
Ratner BD, Miller IF. Interaction of urea with poly(2-hydroxyethylmethacrylate) hydrogels. J Polym Sci [A-1] 1972;10:2425–45.
Macret M, Hild G. Hydroxyalkyl methacrylates: Kinetic investigations of radical polymerization of pure 2-hydroxyethylmethacrylate and 2, 3-dihydroxypropyl-methacrylate and the radical copolymerization of their mixtures. Polymer 1982;23:81–90.
Refojo MF, Yasuda H. Hydrogels from 2-hydroxy-ethylmethacrylate and propylene glycol monoacrylate. J Appl Polym Sci 1965;9:2425–35.
Graham NB, McNeil ME. Hydrogels for controlled drug delivery. Biomaterials 1984;5:27–36.
McNeil ME, Graham NB. Vaginal pessaries from crystalline/rubbery hydrogels for the delivery of prostaglandine E2. J Control Rel 1984;1:99–117.
Brandrup J, Immergut EH. Polymer Handbook. New York: Wiley Interscience, 1966.
Gregonis DE, Chen CM, Andrade JD. The chemistry of some selected methacrylate gels. In: Andrade JD, ed. Hydrogels for medical and related applications. Washington DC: American Chemical Society, 1976:88–104. (ACS Symposium Series. Vol. 31).
Macret M, Hild G. Hydroxyalkylmethacrylates: Hydrogel formation based on the radical copolymerization of 2-hydroxyethylmethacrylate and 2, 3-dihydroxypropylmethacrylate. Polymer 1982;23:748–53.
Kolarik J, Migliaresi C. Mechanical properties of hydrophilic copolymers of 2-hydroxyethylmethacrylate with ethylacrylate,n-butylacrylate and dodecylmethacrylate. J Biomed Res 1983;17:757–67.
Kalal J, Drobnik J, Svec F. Herstellung, Eigenschaften und Anwendung hydrophiler und reaktiver Polymeren. Z Chem 1978;18:359–64.
Kolarik J, Janacek J. Effect of low molecular weight compounds on the relaxation behaviour of poly(2-hydroxyethylmethacrylate) in the glassy state and in the transition region from the glassy to the rubberlike state. J Polym Sci [A-2]1972;10:11–22.
Sung YK, Gregonis DE, Russel GA, Andrade JD. Effect of water and tacticity on the glass transition temperature of poly(2-hydroxyethylmethacrylate). Polymer 1978;19:1362–3.
Fox TG, Goode WE, Gratch S, et al. Time dependence of the stereospecificity in the free radical polymerization of Me-methacrylate. J Polym Sci 1958;31:173.
Zagar LA. Determination of residual ethylene oxide in methylmethacrylate powders by GLC. J Pharm Sci 1972;61:1801–2.
Turkova LD, Belen'kii BG, Danilova MYa, Medvedeva LI. GLC analysis of ethylene glycol monomethacrylic ester. Zh Anal Khim 1972;27:410–3.
Brinkman UATh, Van Schaik TAM, De Vries G, De Visser AC, Analysis and purification of 2-hydroxyethylmethacrylate by means of thin layer chromatography. In: Andrade JD, ed. Hydrogels for medical and related applications. Washington DC: American Chemical Society, 1976:105–18. (ACS Symposium Series. Vol. 31).
Costa L, Camino G, Trossarelli L. Combined thermogravimetric-high resolution GC for polymer degradation studies. J Chromatogr 1983;279:125–31.
Fujisawa S, Masuhara E. Determination of partition coefficients of acrylates, methacrylates and vinyl monomers, using HPLC. J Biomed Mater Res 1981;15:787–93.
Adamcova Z. Structure and properties of hydrophilic polymers and their gels 10. Coll Czech Chem Commun 1968;33:336–40.
Lee HB, Andrade JD, Jhon MS. Nature of water in synthetic gels. 11. Proton-pulse NMR of polyhydroxy-ethylmethacrylate. Polym Prepr 1974;15(1):391–4.
Korsmeyer RW, Von Meerwall ED, Peppas NA. Diffusion in swellable drug delivery systems. In: Peppas NA, Haluska RJ, eds. Proceedings of the International Symposium of Controlled Release of Bioactivity Materials. Lincolnshire: The Controlled Release Society, 1985:81–2.
Andrade JD, King RN, Gregonis DE, Coleman DL. Surface characterization of poly(hydroxyethylmethacrylate) and related polymers. Contact angle methods in water. J Polym Sci Polym Symp 1979;66:313–6.
Pines E, Prins W. Structure-property relations of thermoreversible hydrogels. Macromolecules 1973; 6:888–95.
Gouda JH, Povodator K, Warren TC, Prins W. Evidence for a micromesomorphic structure in poly(2-hydroxyethylmethacrylate) hydrogels. J Polym Sci [B]1970;8:225–9.
Andrade JD, Lee HB, Jhon MS, Kim SW, Hibbs JB. Water as a biomaterial. Trans Am Soc Artif Intern Organs 1973;9:1–7.
Holly FJ, Refojo MF. Wettability of hydrogels. J Biomed Mater Res 1975;9:315–26.
Lee HB, Jhon MS, Andrade JD. Nature of water in synthetic hydrogels. J Colloid Interface Sci 1975;51:225–31.
Choi S, Jhon MS, Andrade JD. Nature of water in synthetic hydrogels 3. J Colloid Interface Sci 1977;61:1–8.
Migliaresi C, Nicodemo L, Nicalais L, Passerini P. Physical characterization of microporous poly(2-hydroxyethylmethacrylate) gels. J Biomed Mater Res 1981;15:307–17.
Fort RJ, Polyzoides TM. The unperturbed dimensions of poly(2-hydroxyethylmethacrylate). Makromol Chem 1977;178:3229–35.
Fort RJ, Polyzoides TM. Intrinsic viscosity-molecular weight relationships for poly(2-hydroxyethylmethacrylate). Eur Polym J 1976;12:685–9.
Bohdanecky M, Tuzar Z. Study of unperturbed dimensions of poly(ethyleneglycolmethacrylate). Coll Czech Chem Comm 1969;34:3318–24.
Silberberg A. The hydrogel-water interface. In: Andrade JD, ed. Hydrogels for medical and related applications. Washington DC: American Chemical Society, 1976:198–205. (ACS Symposium Series. Vol. 31.).
Refojo M. Microscopic determination of the penetration of proteins and polysaccharides into poly(hydroxyethylmethacrylate) and similar hydrogels. J Polym Sci Polym Symp 1977;66:227–37.
Korsmeyer RW, Peppas NA. Solute and penetrant diffusion in swellable polymers 3. J Control Rel 1984;1:89–98.
Sato S, Kim SW. Macromolecular diffusion through polymer membranes. Int J Pharm 1984;22:229–55.
Andrade JD, King RN, Gregonis DE. Probing the hydrogel-water interface. In: Andrade JD, ed. Hydrogels for biomedical and related applications. Washington DC: American Chemial Society, 1976:206–24. (ACS Symposium Series. Vol. 31).
Chen RYS. Diffusion coefficients and swelling behaviour of cross-linked poly(2-hydroxyethylmethacrylate). Polym Prepr 1974;15:387–94.
Allen LF. Study of the rate of swelling of poly(2-hydroxyethylmethacrylate) by quantitative metallurgical system. Polym Prepr 1974;15:395–400.
Zierenberg B. Experimental and theoretical studies on the diffusion of drugs in polymer films. Drug Devel Ind Pharm 1983;9:117–37.
Attwood D, Johansen L, Tolley JA, Rassing J. A new ultrasonic method for the measurement of the diffusion coefficient of drugs within hydrogel matrices. Int J Pharm 1981;9:285–94.
Wood JM, Attwood D, Collett JM. Characterization of poly(2-hydroxyethylmethacrylate) gels. Drug Devel Ind Pharm 1983;9(1–2):93–101.
Halden RA, Lee BE. Structure and permeability of porous films of HEMA. Br Polym J 1972;4:491–501.
Ilavsky M, Dusek K, Vacik J, Kopecek J. Deformational, swelling and potentiometric behaviour of ionized gels of 2-hydroxyethylmethacrylate-methacrylic acid copolymers. J Appl Polym Sci 1979;23:2073–82.
Good WR, Mueller KF. A new family of monolithic hydrogels for controlled release application. In: Baker R, ed. Controlled Release on Bioactive Materials. New York: Academic Press, 1980:155–75.
Pouchly J, Benes S, Hasa Z, Biros J. Thermodynamics of mixing water with poly(2-hydroxyethylmethacrylate) and poly(2-hydroxyethoxyethylmethacrylate). Makromol Chem 1982;183:1565–75.
Dusek K, Sedlacek B. Phase separation in poly(2-hydroxyethylmethacrylate) gels in the presence of water. Eur Polym J 1971;7:1275–85.
Yasuda H, Gochin M, Stone W. Hydrogels of poly(hydroxyethylmethacrylate) and hydroxyethylmethacrylate-glycerolmethacrylate copolymers. J Polym Sci [A-1] 1966;4:2913–27.
Ratner BD, Miller IF. Transport through cross-linked poly(2-hydroxyethylmethacrylate) hydrogel membranes. J Biomed Mater Res 1973;7:353–67.
Kopecek J, Jokl J, Lim D. Mechanismus der dreidimensionalen Polymerisation von Glykolmethakrylaten. J Polym Sci [C] 1968;16:3877–89.
Refojo M. Glyceryl methacrylate gels. J Appl Polym Sci 1963;9:3161–70.
Wichterle O, Chromecek R. Polymerization of ethyleneglycol monomethacrylate in the presence of solvents. J Polym Sci [C] 1969;16:4677–86.
Pinchuk L, Eckstein EC, Van der Mark MR. Effects of low levels of methacrylic acid on the swelling behaviour of poly(2-hydroxyethylmethacrylate). J Appl Polym Sci 1984;29:1749–60.
Pinchuk L, Eckstein EC, Van der Mark MR. The interaction of urea with the generic class of poly(2-hydroxyethylmethacrylate) hydrogels. J Biomed Mater Res 1984;18:671–84.
Tanaka T. Gels. Sci Am 1981;244:110.
Jhon MS, Andrade JD. Water and hydrogels. J Biomed Mater Res 1973;7:509–22.
Yasuda H, Lamaze LE, Peterlin A. Diffusive and hydraulic permeabilities of water in water-swollen polymer membranes. J Polym Sci [A-2] 1971;9:1117–31.
Yasuda H, Lamaze CP, Ikenberry LD. Permeability of solutes through hydrated polymer membranes. Makromol Chem 1968;118:19–35.
Yasuda H, Ikenberry LD, Lamaze LE. Permeability of solutes through hydrated polymer membranes. Part III. Permeability of water soluble organic solutes. Makromol Chem 1969;125:108–18.
Wisniewski SJ, Gregonis D, Kim SW, Andrade JD. Diffusion through Hydrogel Membranes. 1. Permeation of water through poly(2-hydroxyethylmethacrylate) and related polymers. In: Andrade JD, ed. Hydrogels for medical and related applications. Washington DC: American Chemical Society, 1976:80–7. (ACS Symposium Series. Vol. 31).
Kim SW, Cardinal JR, Wisniewski S, Zentner GM. Solute permeation through hydrogel membranes. In: Hydrophilic versus hydrophobic solutes. Washington DC: American Chemical Society, 1980:347–59. (ACS Symposium Series. Vol. 127).
Wisniewski S, Kim SW. Permeation of water through poly(2-hydroxyethylmethacrylate) and related polymers: temperature effect. J Membr Sci 1980;6:309–18.
Wisniewski S, Kim SW. Permeation of water-soluble solutes through poly(2-hydroxyethylmethacrylate) cross-linked with ethylene glycoldimethacrylate. J Membr Sci 1980;6:299–308.
Lyman DJ, Kim SW. Aqueous diffusion through partition membranes. J Polym Sci Polym Symp 1973;41:139–44.
Zentner GM, Cardinal JR, Kim SW. Progestin permeation through polymer membranes. J Pharm Sci 1978;67:1352–5.
Zentner GM, Cardinal JR, Feyen J, Song SZ. Progestin permeation through polymer membranes, iv: Mechanism of steroid permeation and functional group contributions to diffusion through hydrogel films. J Pharm Sci 1979;68:970–5.
Zentner GM, Cardinal JR, Gregonis DE. Progestin permeation through polymer membranes. 111: Polymerization solvent effect on progesterone permeation through hydrogel membranes. J Pharm Sci 1979; 68:794–5.
Zentner GM, Cardinal JR, Kim SW. Progestin permeation through polymer membranes. 1: Diffusion studies on plasma-soaked membranes. J Pharm Sci 1978;67:1347–51.
Anderson JM, Koinis K, Nelson T, Horst M, Love DS. The slow release of hydrocortisone sodium succinate from poly(2-hydroxyethylmethacrylate) membranes. In: Andrade JD, ed. Hydrogels for medical and related applications. Washington DC: American Chemical Society, 1976:167–79. (ACS Symposium Series. Vol. 31).
Abrahams RA, Ronel SH. Biocompatible implants for the sustained zero-order release of narcotic antagonists. J Biomed Mater Res 1975;9:355–66.
Gyselinck P, Schacht EH, Van Severen R, Braeckman P. Preparation and characterization of therapeutic hydrogels as oral dosage forms. Acta Pharm Techn 1983;29:9–12.
Sprincl L, Vacik J, Kopecek J. Biological tolerance of ionogenic hydrophilic gels. J Biomed Mater Res 1973;7:123–6.
Sprincl L, Vacik J, Kopecek J, Lim D. Biological tolerance ofp-(N-substituted methacrylamides). J Biomed Mater Res 1971;5:197–205.
Barvic H, Vacik J, Lim D, Zavadil M. Tolerance of modified poly(glycolmethacrylates) by the organism. J Biomed Mater Res 1971;5:225–38.
Imai KY, Masahura E. Long-termin vivo studies of poly(2-hydroxyethyl methacrylate). J Biomed Mater Res 1982;16:609–17.
Ratner BD, Hoffman AS, Hanson SR, Harber LA, Whiffen JD. Blood compatibility-water content relationships for radiation grafted hydrogels. J Polym Sci 1979;66:363–75.
Kim SW, Lee RG, Oster H, et al. Platelet adhesion to polymer surfaces. Trans Am Soc Artif Intern Organs 1974;20:449–54.
Larsson K. Interfacial phenomena, bioadhesion and biocompatibility. Desalination 1980;35:105–14.
Kim SW, Lee GL, Lyman DJ. Interactions of proteins at hydrophobic surfaces. Proc Utah Acad Arts Lett 1971;48(1):56–66.
Kim SW, Lyman DJ. The interfacing of polymers with blood. J Appl Polym Sci Polym Symp 1973;22:289–97.
Kim SW, Lee RG. Adsorption of blood proteins onto polymer surfaces. Adv Chem Ser 1975;145:218–29.
Dillman WJ, Miller IF. On the adsorption of serum proteins on polymer membrane surfaces. J Coll Int Sci 1973;44:221–41.
Drobnik J, Spacek P, Wichterle O. Diffusion of anti-tumor drugs through membranes from hydrophillic methacrylate gels. J Biomed Mater Res 1974;8:45–51.
Vacik J, Czakova M, Exner J, Kalal J, Kopecek J. Permeability of metabolites through hydrophilic membranes. Coll Czech Chem Commun 1977;42(9):2786–90.
Refojo MF. Permeation of water through some hydrogels. Appl Polym Sci 1965;9:3417–26.
Chen RYS. Electrolyte transport through cross-linked poly(2-hydroxyethylmethacrylate). Polym Prepr 1979;20:1005–8.
Collett JH, Wood JM. The release kinetics of somepara-substituted benzoic acids from poly(2-hydroxy-ethylmethacrylate) hydrogels. J Pharm Pharmacol 1982: 1P.
Spacek P, Kubin M. Diffusion in gels. J Polym Sci [C] 1967;16:705–14.
Dittgen M, Stahlkopf W. Investigations of pharmaceuticals containing polyacrylate polymethacrylate films. Pharmazie 1984;39:625–7.
Peppas NA. A model of dissolution-controlled solute release from porous drug delivery polymeric systems. J Biomed Mater Res 1983;17:1079–87.
Paul DR, Ebra-Lima OM. Hydraulic permeation of liquids through swollen polymeric networks. 111. A generalized correlation. J Appl Polym Sci 1975;19:2759–71.
Sung YK. Interactions of water with hydrophilic methacrylate polymers. Utah: University of Utah, 1978. Dissertation.
Korsmeyer RW, Peppas NA. Effect of the morphology of hydrophilic polymer matrices on the diffusion and release of water soluble drugs. J Membr Sci 1981;9:211–27.
Peppas NA, Franson NM. The swelling interface number as a criterion for prediction of diffusional solute release mechanisms in swellable polymers. J Polym Sci Polym Phys 1983;21:983–97.
Wood JM, Attwood D, Collett JH. The influence of gel formulation on the diffusion of salicylic acid inp-HEMA hydrogels. J Pharm Pharmacol 1982;34:1–4.
Alhaique T, Marchetti M, Riccieri FM, Santucci E. A polymeric film responding in diffusion properties to environmental pH stimuli: a model for a self-regulating drug delivery system. J Pharmacol 1981;33:413–8.
Zathurecky LK, Raskova H, Krupa V, Wichterle O, Chromecek R, Gavrilova I. Liberation and resorption of drugs from macromolecular ethylene-glycol monomethacrylate gel. Arnzeim Forsch 1969;19:951–4.
Alfrey T, Gurnee EF, Lloyd WG. Diffusion in glassy polymers. J Polym Sci [C] 1966;12:249–61.
Peppas NA. Release of bio-active agents from swellable polymers: Theory and experiments. In: Anderson JH, Kim SW, eds. Recent Advances in Drug Delivery Systems. Proceedings of an International Symposium. New York: Plenum Publishing Corporation, 1984: 279–89.
Fouli MA, Sayed AA, Badawi AA. Release of drugs from microcapsules of methacrylate polymers. Intern J Pharm 1983;14:95–102.
Lee PI. Dimensional changes during drug release from a glassy hydrogel matrix. Polym Commun 1983;24:45–7.
Lee PI. Effect of non-uniform initial drug concentration distribution on the kinetics of drug release from glassy hydrogel matrices. Polymer 1984;25:973–8.
Bahadir M. Pestizide Polymere Untersuchung pestizider ‘controlled release’ Formulierungen mit LDPE und EVA. Chemosphere 1983;12:1327–36.
Langer RS, Hsieh DST, Brown L. Polymeric delivery systems for macromolecules. Washington DC: American Chemical Society, 1982:95–105. (ACS Symposium Series. Vol. 186.)
Baker RW, Lonsdale HK. Controlled release: mechanisms and rates. In: Tanquary AC, Lacey RE, eds. Advances in Experimental Medicine and Biology. Vol. 47. New York: Plenum Press, 1974:15–71.
Higuchi T. Rate of release of medicaments from ointment bases containing drugs in suspension. J Pharm Sci 1961;50:874–5.
Chien YW, Lau EPK. Controlled drug release from polymeric delivery devices, iv:In vitro-in vivo correlation of subcutaneous release of Norgestomet from hydrophilic implants. J Pharm Sci 1976;65:488–92.
De Leede LGJ. Rate-controlled and site-specific rectal drug delivery. Leiden: State University of Leiden, 1983. Dissertation.
Cardinal JR. Drug release from matrix devices. In: Anderson JH, Kim SW, eds. Recent Advances in Drug Delivery Systems. Proceedings of an International Symposium. New York: Plenum Publishing Corporation, 1984:229–48.
Cardinal JR, Kim SW, Song S, Lee ES, Kim SH. Controlled release drug delivery systems from hydrogels: Progesterone release from monolithic, reservoir, combined reservoir monolithic and monolithic devices with rate controlling barriers. AIChE Symposium Series 1981;77(206):52–61.
Roseman TJ, Higuchi WI. Release of medroxyprogesterone acetate from a silicone polymer J Pharm Sci 1970;59:353–7.
Chien YW, Lambert HJ, Lin TK. Solution-solubility dependency of controlled release of drug from polymer matrix: mathematical analysis. J Pharm Sci 1975:64:1643–7.
Chien YW, Lambert HJ, Grant DE. Controlled drug release from polymeric devices. 1. Technique for rapidin vitro release studies. J Pharm Sci 1974;63:365–9.
Chien YW, Lambert HJ. Controlled drug release from polymeric delivery devices. 11. Differentiation between partition-controlled and matrix-controlled drug release mechanisms. J Pharm Sci 1974;63:515–9.
Chien YW, Mares, S, Berg J, Huber S, Lambert HJ, King KF. Controlled drug release from polymeric devices. 111. J Pharm Sci 1975;64:1776–81.
Haleblian J, Runkel R, Mueller N, Christopherson J, Ng K. Steroid release from silicone elastomer containing excess drug in suspension. J Pharm Sci 1971; 60:541–4.
Chandrasekaran SK, Paul DR. Dissolution controlled transport from dispersed matrixes. J Pharm Sci 1982;71:1399–402.
Brooke D, Washkun J. Zero-order drug delivery systems, theory and preliminary investigation. J Pharm Sci 1977;66:159–62.
Thomas NL, Windle RH. A theory of case 11 diffusion. Polymer 1982;23:529–42.
Thomas N, Windle AH. Discontineous sharp change associated with case 11 transport of methanol in thin sheets of PMMA. Polymer 1977;18:1195.
Peterlin A. Diffusion in a glassy polymer with discontinuous swelling. 11. Concentration distribution of diffusant as function of time. Makromol Chem 1969;124:136–42.
Hopfenberg HB, Hsu KC. Swelling-controlled, constant rate delivery systems. Polym Eng Sci 1978;18:1186–91.
Hopfenberg HB. A mechanistic interpretation of swelling-controlled, constant rate delivery systems. AIChE Symposium Series 1981;77(206):37–41.
Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 1983;15:25–35.
Good WR. Diffusion of water soluble drugs from initially dry hydrogels. Midl Macromol Monogr 1978;5:139–56.
O'Neil WP. Membrane systems. In: Kynodieus AF, ed. Controlled release technologies. Part 1. Boca Raton: CRC Press, 1980:157–60.
Hurkmans JFGM, Boddé HE, Van Driel LMJ, Van Doorne H, Junginger HE. Skin irritation by transdermal drug delivery systems during long term application. Br J Dermatol 1985;112:461–7.
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Roorda, W.E., BoddÉ, H.E., de Boer, A.G. et al. Synthetic hydrogels as drug delivery systems. Pharmaceutisch Weekblad Scientific Edition 8, 165–189 (1986). https://doi.org/10.1007/BF01959775
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DOI: https://doi.org/10.1007/BF01959775