Pharmaceutical Research

, Volume 23, Issue 3, pp 460–474 | Cite as

Methods to Assess in Vitro Drug Release from Injectable Polymeric Particulate Systems

Expert Review


This review provides a compilation of the methods used to study real-time (37°C) drug release from parenteral microparticulate drug delivery systems administered via the subcutaneous or intramuscular route. Current methods fall into three broad categories, viz., sample and separate, flow-through cell, and dialysis techniques. The principle of the specific method employed along with the advantages and disadvantages are described. With the “sample and separate” technique, drug-loaded microparticles are introduced into a vessel, and release is monitored over time by analysis of supernatant or drug remaining in the microspheres. In the “flow-through cell” technique, media is continuously circulated through a column containing drug-loaded microparticles followed by analysis of the eluent. The “dialysis” method achieves a physical separation of the drug-loaded microparticles from the release media by use of a membrane, which allows for sampling without interference of the microspheres. With all these methods, the setup and sampling techniques seem to influence in vitro release; the results are discussed in detail, and criteria to aid in selection of a method are stated. Attempts to establish in vitroin vivo correlation for these injectable dosage forms are also discussed. It would be prudent to have an in vitro test method for microparticles that satisfies compendial and regulatory requirements, is user friendly, robust, and reproducible, and can be used for quality-control purposes at real-time and elevated temperatures.

Key Words

continuous flow dialysis in vitro release methods IVIVC microspheres sample and separate subcutaneous and intramuscular administration 


  1. 1.
    Schrier, J., DeLuca, P. 1999Recombinant human bone morphogenetic protein-2 binding and incorporation in PLGA microsphere delivery systemsPharm. Dev. Technol.4611621PubMedCrossRefGoogle Scholar
  2. 2.
    Hora, M. S., Rana, R. K., Nunberg, J. H., Tice, T. R., Gilley, R. M., Hudson, M. E. 1990Release of human serum albumin from poly(lactide-co-glycolide) microparticlesPharm. Res.711901194PubMedCrossRefGoogle Scholar
  3. 3.
    Capan, Y., Woo, B. H., Gebrekidan, S., Ahmed, S., DeLuca, P. P. 1999Preparation and characterization of poly (d,l-lactide-co-glycolide) microspheres for controlled release of poly (l-lysine) complexed plasmid DNAPharm. Res.16509513PubMedCrossRefGoogle Scholar
  4. 4.
    Cleland, J. L., Johnson, O. L., Putney, S., Jones, A. J. S. 1997Recombinant human growth hormone poly(lactic-co-glycolic acid) microsphere formulation developmentAdv. Drug Deliv. Rev.287184PubMedCrossRefGoogle Scholar
  5. 5.
    Okada, H., Yamamoto, M., Heya, T., Inoue, Y., Kamei, S., Ogawa, Y., Toguchi, H. 1994Drug delivery using biodegradable microspheresJ. Control. Release28121129Google Scholar
  6. 6.
    Mehta, R. C., Jeyanthi, R., Calls, S., Thanoo, B. C., Burton, K. W., DeLuca, P. P. 1994Biodegradable microspheres as depot system for parenteral delivery of peptide drugsJ. Control. Release29375384CrossRefGoogle Scholar
  7. 7.
    Esposito, E., Cortesi, R., Nastruzzi, C. 1996Gelatin microspheres: influence of preparation parameters and thermal treatment on chemico-physical and biopharmaceutical propertiesBiomaterials1720092020PubMedCrossRefGoogle Scholar
  8. 8.
    Morimoto, K., Katsumata, H., Yabuta, T., Iwanaga, K., Kakemi, M., Tabata, Y., Ikada, Y. 2001Evaluation of gelatin microspheres for nasal and intramuscular administrations of salmon calcitoninEur. J. Pharm. Sci.13179185PubMedGoogle Scholar
  9. 9.
    Mladenovska, K., Kumbaradzi, E. F., Dodov, G. M., Makraduli, L., Goracinova, K. 2002Biodegradation and drug release studies of BSA loaded gelatin microspheresInt. J. Pharm.242247249PubMedGoogle Scholar
  10. 10.
    Blanco, M. D., Bernardo, M. V., Gomez, C., Muniz, E., Teijon, J. M. 1999Bupivacaine-loaded comatrix formed by albumin microspheres included in a poly(lactide-co-glycolide) film: invivo biocompatibility and drug release studiesBiomaterials2019191924PubMedCrossRefGoogle Scholar
  11. 11.
    Egbaria, K., Friedman, M. 1990Release profiles of metronidazole and l-phenylalanine from individual albumin microspheresJ. Control. Release14215220Google Scholar
  12. 12.
    Burgess, D. J., Hickey, A. J. 1994Microsphere Technology and ApplicationsMarcel DekkerNew YorkGoogle Scholar
  13. 13.
    Hickey, T., Kreutzer, D., Burgess, D. J., Moussy, F. 2002Dexamethasone/PLGA microspheres for continuous delivery of an anti-inflammatory drug for implantable medical devicesBiomaterials2316491656PubMedCrossRefGoogle Scholar
  14. 14.
    Middleton, J. C., Tipton, A. J. 2000Synthetic biodegradable polymers as orthopedic devicesBiomaterials2123352346PubMedCrossRefGoogle Scholar
  15. 15.
    Wu, L., Ding, J. 2004In vitro degradation of three-dimensional porous poly(d,l-lactide-co-glycolide) scaffolds for tissue engineeringBiomaterials2558215830PubMedGoogle Scholar
  16. 16.
    Chaubal, M. 2002Polylactides/glycolides—excipients for injectable drug delivery and beyondDrug Deliv. Technol.53436Google Scholar
  17. 17.
    Okada, H. 1997One- and three-month release injectable microspheres of the LH–RH superagonist leuprorelin acetateAdv. Drug Deliv. Rev.284370PubMedGoogle Scholar
  18. 18.
    Ertl, B., Platzer, P., Wirth, M., Gabor, F. 1999Poly(d,l-lactic-co-glycolic acid) microspheres for sustained delivery and stabilization of camptothecinJ. Control. Release61305317PubMedCrossRefGoogle Scholar
  19. 19.
    Anderson, J. M., Shive, M. S. 1997Biodegradation and biocompatibility of PLA and PLGA microspheresAdv. Drug Deliv. Rev.28524PubMedCrossRefGoogle Scholar
  20. 20.
    Okada, H., Toguchi, H. 1995Biodegradable microspheres in drug deliveryCrit. Rev. Ther. Drug Carrier Syst.12199PubMedGoogle Scholar
  21. 21.
    In L. Lachman, H. Lieberman, and J. Kanig (eds.), The Theory and Practice of Industrial Pharmacy, Lea & Febiger, PA, 1987.Google Scholar
  22. 22.
    Burgess, D. J., Hussain, A. S., Ingallinera, T. S., Chen, M. L. 2002Assuring quality and performance of sustained and controlled release parenterals: workshop reportAAPS PharmSci4E7PubMedCrossRefGoogle Scholar
  23. 23.
    Washington, C. 1990Drug release from microdisperse systems: a critical reviewInt. J. Pharm.58112Google Scholar
  24. 24.
    U. S. P. 25. Rockville, MD, 2002, pp. 2011–2019.Google Scholar
  25. 25.
    Nastruzzi, C., Esposito, E., Cortesi, R., Gambari, R., Menegatti, E. 1993Kinetics of bromocriptine release from microspheres: comparative analysis between different in vitro modelsJ. Microencapsul.11565574Google Scholar
  26. 26.
    Conti, B., Genta, I., Giunchedi, P., Modena, T. 1995Testing of “invitro” dissolution behaviour of microparticulate drug delivery systemsDrug Dev. Ind. Pharm.2112231233Google Scholar
  27. 27.
    Gido, C., Langguth, P., Kreuter, J., Winter, G., Woog, H., Mutschler, E. 1993Conventional versus novel conditions for the invitro dissolution testing of parenteral slow release formulations: application to doxepin parenteral dosage formsPharmazie48764769PubMedGoogle Scholar
  28. 28.
    Bain, D. F., Munday, D. L., Smith, A. 1999Modulation of rifampicin release from spray-dried microspheres using combinations of poly-(d,l-lactide)J. Microencapsul.16369385PubMedGoogle Scholar
  29. 29.
    Burgess, D. J., Hussain, A. S., Ingallinera, T. S., Chen, M.-L. 2002Assuring quality and performance of sustained and controlled release parenterals: AAPS Workshop Report, co-sponsored by FDA and USPPharm. Res.1917611768PubMedCrossRefGoogle Scholar
  30. 30.
    Burgess, D. J., Crommelin, D. J. A., Hussain, A. S., Chen, M.-L. 2004Assuring quality and performance of sustained and controlled release parenteralsEur. J. Pharm. Sci.21679690PubMedGoogle Scholar
  31. 31.
    D. J. Burgess, A. S. Hussain, T. S. Ingallinera, and M. L. Chen. Assuring quality and performance of sustained and controlled release parenterals: Workshop Report. AAPS PharmSci 4: article 7 (2002).Google Scholar
  32. 32.
    M. Siewert, J. Dressman, C. K. Brown, and V. P. Shah. FIP/AAPS guidelines to dissolution/in vitro release testing of novel/special dosage forms. AAPS PharmSciTech 4: article 7 (2003).Google Scholar
  33. 33.
    M. Shameem, H. Lee, and P. P. DeLuca. A short term (accelerated release) approach to evaluate peptide release fromPLGA depot-formulations. AAPS PharmSci 1: article 7 (1999).Google Scholar
  34. 34.
    S. S. D'Souza, J. A. Faraj, and P. P. DeLuca. A model-dependent approach to correlate accelerated with real-time release from biodegradable. AAPS PharmSciTech 6: article 70 (2005).Google Scholar
  35. 35.
    Schaefer, M. J., Singh, J. 2002Effect of tricaprin on the physical characteristics and in vitro release of etoposide from PLGA microspheresBiomaterials2334653471PubMedCrossRefGoogle Scholar
  36. 36.
    Ruan, G., Feng, S.-S. 2003Preparation and characterization of poly(lactic acid)–poly(ethylene glycol)–poly(lactic acid) (PLA–PEG–PLA) microspheres for controlled release of paclitaxelBiomaterials2450375044PubMedCrossRefGoogle Scholar
  37. 37.
    Diwan, M., Park, T. G. 2003Stabilization of recombinant interferon-[alpha] by pegylation for encapsulation in PLGA microspheresInt. J. Pharm.252111122PubMedCrossRefGoogle Scholar
  38. 38.
    Liu, F.-I., Kuo, J. H., Sung, K. C., Hu, O. Y. P. 2003Biodegradable polymeric microspheres for nalbuphine prodrug controlled delivery: in vitro characterization and in vivo pharmacokinetic studiesInt. J. Pharm.2572331PubMedCrossRefGoogle Scholar
  39. 39.
    Ruan, G., Feng, S.-S., Li, Q.-T. 2002Effects of material hydrophobicity on physical properties of polymeric microspheres formed by double emulsion processJ. Control. Release84151160PubMedCrossRefGoogle Scholar
  40. 40.
    Poulain, N., Dez, I., Perrio, C., Lasne, M.-C., Prud'homme, M.-P., Nakache, E. 2003Microspheres based on inulin for the controlled release of serine protease inhibitors: preparation, characterization and in vitro releaseJ. Control. Release922738PubMedCrossRefGoogle Scholar
  41. 41.
    Blanco-Prieto, M. J., Campanero, M. A., Besseghir, K., Heimgatner, F., Gander, B. 2004Importance of single or blended polymer types for controlled in vitro release and plasma levels of a somatostatin analogue entrapped in PLA/PLGA microspheresJ. Control. Release96437448PubMedGoogle Scholar
  42. 42.
    Sivakumar, M., Panduranga Rao, K. 2002Preparation, characterization and in vitro release of gentamicin from coralline hydroxyapatite–gelatin composite microspheresBiomaterials2331753181PubMedCrossRefGoogle Scholar
  43. 43.
    Dhanaraju, M. D., Vema, K., Jayakumar, R., Vamsadhara, C. 2003Preparation and characterization of injectable microspheres of contraceptive hormonesInt. J. Pharm.2682329Google Scholar
  44. 44.
    S. B. Murty, J. Goodman, B. C. Thanoo, and P. P. DeLuca. Identification of chemically modified peptide from poly(d,l-lactide-co-glycolide) microspheres under in vitro release conditions. AAPS PharmSciTech 4: article 50 (2003).Google Scholar
  45. 45.
    Mi, F.-L., Shyu, S.-S., Lin, Y.-M., Wu, Y.-B., Peng, C.-K., Tsai, Y.-H. 2003Chitin/PLGA blend microspheres as a biodegradable drug delivery system: a new delivery system for proteinBiomaterials2450235036PubMedCrossRefGoogle Scholar
  46. 46.
    Latha, M. S., Lal, A. V., Kumary, T. V., Sreekumar, R., Jayakrishnan, A. 2000Progesterone release from glutaraldehyde cross-linked casein microspheres: in vitro studies and in vivo response in rabbitsContraception61329334PubMedCrossRefGoogle Scholar
  47. 47.
    Yen, S.-Y., Sung, K. C., Wang, J.-J., Yoa-Pu Hu, O. 2001Controlled release of nalbuphine propionate from biodegradable microspheres: in vitro and in vivo studiesInt. J. Pharm.2209199PubMedCrossRefGoogle Scholar
  48. 48.
    Jeong, Y.-I., Song, J.-G., Kang, S.-S., Ryu, H.-H., Lee, Y.-H., Choi, C., Shin, B.-A., Kim, K.-K., Ahn, K.-Y., Jung, S. 2003Preparation of poly(-lactide-co-glycolide) microspheres encapsulating all-trans retinoic acidInt. J. Pharm.2597991PubMedCrossRefGoogle Scholar
  49. 49.
    Volland, C., Wolff, M., Kissel, T. 1994The influence of terminal gamma-sterilization on captopril containing poly(-lactide-co-glycolide) microspheresJ. Control. Release31293305CrossRefGoogle Scholar
  50. 50.
    Rosas, J. E., Hernandez, R. M., Gascon, A. R., Igartua, M., Guzman, F., Patarroyo, M. E., Pedraz, J. L. 2001Biodegradable PLGA microspheres as a delivery system for malaria synthetic peptide SPf66Vaccine1944454451PubMedCrossRefGoogle Scholar
  51. 51.
    Burton, K. W., Shameem, M., Thanoo, B. C., DeLuca, P. P. 2000Extended release peptide delivery systems through the use of PLGA microsphere combinationsJ. Biomater. Sci., Polym. Ed.11715729CrossRefGoogle Scholar
  52. 52.
    Woo, B. H., Na, K.-H., Dani, B. A., Jiang, G., Thanoo, B. C., DeLuca, P. P. 2002In vitro characterization and in vivo testosterone suppression of 6-month release poly(d,l-lactide) leuprolide microspheresPharm. Res.19546550PubMedCrossRefGoogle Scholar
  53. 53.
    Takada, S., Kurokawda, T., Miyazaki, K., Iwasa, S., Ogawa, Y. 1997Utilization of an amorphous form of a water-soluble GPIIb/IIIa antagonist for controlled release from biodegradable microspheresPharm. Res.1411461150PubMedCrossRefGoogle Scholar
  54. 54.
    Bodmeier, R., McGinity, J. W. 1987The preparation and evaluation of drug-containing poly(dl-lactide) microspheres formed by the solvent evaporation methodPharm. Res.4465471PubMedCrossRefGoogle Scholar
  55. 55.
    Ravivarapu, H. B., Lee, H., DeLuca, P. P. 2000Enhancing initial release of peptide from poly(dl-lactide-co-glycolide) (PLGA) microspheres by addition of a porosigen and increasing drug loadPharm. Dev. Technol.5287296PubMedCrossRefGoogle Scholar
  56. 56.
    Castellanos, I. J., Al-Azzam, W., Griebenow, K. 2005Effect of the covalent modification with poly(ethylene glycol) on alpha-chymotrypsin stability upon encapsulation in poly(lactic-co-glycolic) microspheresJ. Pharm. Sci.95327340Google Scholar
  57. 57.
    Thomas, T. T., Kohane, D. S., Wang, A., Langer, R. 2004Microparticulate formulations for the controlled release of interleukin-2J. Pharm. Sci.9311001109PubMedCrossRefGoogle Scholar
  58. 58.
    Özbas-Turan, S., Akbuga, J., Aral, C. 2002Controlled release of interleukin-2 from chitosan microspheresJ. Pharm. Sci.9112451251PubMedGoogle Scholar
  59. 59.
    Naraharisetti, P. K., Ning Lew, M. D., Fu, Y.-C., Lee, D.-J., Wang, C.-H. 2005Gentamicin-loaded discs and microspheres and their modifications: characterization and in vitro releaseJ. Control. Release102345359PubMedCrossRefGoogle Scholar
  60. 60.
    Kim, H. K., Park, T. G. 2004Comparative study on sustained release of human growth hormone from semi-crystalline poly (lactic acid) and amorphous poly(,-lactic-co-glycolic acid) microspheres: morphological effect on protein releaseJ. Control. Release98115125PubMedGoogle Scholar
  61. 61.
    Berkland, C., Kipper, M. J., Narasimhan, B., Kim, K. K., Pack, D. W. 2004Microsphere size, precipitation kinetics and drug distribution control drug release from biodegradable polyanhydride microspheresJ. Control. Release94129141PubMedCrossRefGoogle Scholar
  62. 62.
    Jeong, J.-C., Lee, J., Cho, K. 2003Effects of crystalline microstructure on drug release behavior of poly([epsiv]-caprolactone) microspheresJ. Control. Release92249258PubMedCrossRefGoogle Scholar
  63. 63.
    Montanari, L., Cilurzo, F., Selmin, F., Conti, B., Genta, I., Poletti, G., Orsini, F., Valvo, L. 2003Poly(lactide-co-glycolide) microspheres containing bupivacaine: comparison between gamma and beta irradiation effectsJ. Control. Release90281290PubMedCrossRefGoogle Scholar
  64. 64.
    Berkland, C., King, M., Cox, A., Kim, K. K., Pack, D. W. 2002Precise control of PLG microsphere size provides enhanced control of drug release rateJ. Control. Release82137147PubMedCrossRefGoogle Scholar
  65. 65.
    Yang, Y.-Y., Chia, H.-H., Chung, T.-S. 2000Effect of preparation temperature on the characteristics and release profiles of PLGA microspheres containing protein fabricated by double-emulsion solvent extraction/evaporation methodJ. Control. Release698196PubMedCrossRefGoogle Scholar
  66. 66.
    Sturesson, C., Artursson, P., Ghaderi, R., Johansen, K., Mirazimi, A., Uhnoo, I., Svensson, L., Albertsson, A.-C., Carlfors, J. 1999Encapsulation of rotavirus into poly(lactide-co-glycolide) microspheresJ. Control. Release59377389PubMedCrossRefGoogle Scholar
  67. 67.
    Okumu, F. W., Cleland, J. L., Borchardt, R. T. 1997The effect of size, charge and cyclization of model peptides on their in vitro release from-PLGA microspheresJ. Control. Release49133140CrossRefGoogle Scholar
  68. 68.
    Liggins, R. T., Burt, H. M. 2001Paclitaxel loaded poly(l-lactic acid) microspheres: properties of microspheres made with low molecular weight polymersInt. J. Pharm.2221933PubMedCrossRefGoogle Scholar
  69. 69.
    Wei, G., Pettway, G. J., McCauley, L. K., Ma, P. X. 2004The release profiles and bioactivity of parathyroid hormone from poly(lactic-co-glycolic acid) microspheresBiomaterials25345352PubMedGoogle Scholar
  70. 70.
    Park, T. G., Yong Lee, H., Sung Nam, Y. 1998A new preparation method for protein loaded poly(d,l-lactic-co-glycolic acid) microspheres and protein release mechanism studyJ. Control. Release55181191PubMedCrossRefGoogle Scholar
  71. 71.
    Seo, S.-A., Khang, G., Rhee, J. M., Kim, J., Lee, H. B. 2003Study on in vitro release patterns of fentanyl-loaded PLGA microspheresJ. Microencapsul.20569579PubMedCrossRefGoogle Scholar
  72. 72.
    Kim, H., Burgess, D. J. 2002Effect of drug stability on the analysis of release data from controlled release of microspheresJ. Microencapsul.19631640PubMedGoogle Scholar
  73. 73.
    Eroglu, H., Kas, H. S., Oner, L., Türkoglu, O. F., Akalan, N., Sargon, M. F., Özer, N. 2001The in-vitro and in-vivo characterization of PLGA: l-PLA microspheres containing dexamethasone sodium phosphateJ. Microencapsul.18603612PubMedGoogle Scholar
  74. 74.
    Negrin, C. M., Delgado, A., Llabres, M., Evora, C. 2001In vivo invitro study of biodegradable methadone delivery systemsBiomaterials22563570PubMedGoogle Scholar
  75. 75.
    Jiang, G., Woo, B. H., Kang, F., Singh, J., DeLuca, P. P. 2002Assessment of protein release kinetics, stability and protein polymer interaction of lysozyme encapsulated poly(d,l,-lactide-co-glycolide) microspheresJ. Control. Release79137145PubMedCrossRefGoogle Scholar
  76. 76.
    Lacasse, F.-X., HIldgen, P., Perodin, J., Escher, E., Phillips, N. C., McMullen, J. C. 1997Improved activity of an angiotensin receptor antagonist by spray-dried polymer microsphere preparationPharm. Res.14887891PubMedCrossRefGoogle Scholar
  77. 77.
    Heya, T., Okada, H., Tanigawara, Y., Ogawa, Y., Toguchi, H. 1991Effects of counteranion of TRH and loading amount on control of TRH release from copoly(dl-lactic/glycolic acid) microspheres prepared by an in-water drying methodInt. J. Pharm.696975Google Scholar
  78. 78.
    Burgess, D. J., Davis, S. S., Tomlinson, E. 1987Potential use of albumin microspheres as a drug delivery system. I. Preparation and in vitro release of steroidsInt. J. Pharm.39129136CrossRefGoogle Scholar
  79. 79.
    Washington, C., Koosha, F. 1990Drug release from microparticulates; deconvolution of measurement errorsInt. J. Pharm.597982CrossRefGoogle Scholar
  80. 80.
    Aubert-Pouëssel, A., Bibby, D. C., Venier-Julienne, M.-C., Hindre, F., Benoit, J.-P. 2002A novel in vitro delivery system for assessing the biological integrity of protein upon release from PLGA microspheresPharm. Res.1910461051PubMedGoogle Scholar
  81. 81.
    Kilicarslan, M., Baykara, T. 2003The effect of the drug/polymer ratio on the properties of the verapamil HCl loaded microspheresInt. J. Pharm.25299109PubMedCrossRefGoogle Scholar
  82. 82.
    Aubert-Pouëssel, A., Venier-Julienne, M.-C., Clavreul, A., Sergent, M., Jollivet, C., Montero-Menei, C. N., Garcion, E., Bibby, D. C., Menei, P., Benoit, J.-P. 2004In vitro study of GDNF release from biodegradable PLGA microspheresJ. Control. Release95463475PubMedCrossRefGoogle Scholar
  83. 83.
    Cortesi, R., Esposito, E., Menegatto, E., Gambari, R., Nastruzzi, C. 1994Gelatin microspheres as a new approach for the controlled delivery of synthetic oligonucleotides and PCR-generated DNA fragmentsInt. J. Pharm.105181186CrossRefGoogle Scholar
  84. 84.
    Cheung, R. Y., Kuba, R., Rauth, A. M., Wu, X. Y. 2004A new approach to the in vivo and in vitro investigation of drug release from locoregionally delivered microspheresJ. Control. Release100121133PubMedCrossRefGoogle Scholar
  85. 85.
    Yuksel, N., Dinc, E., Onur, F., Baykara, T. 1998Influence of swelling degree on release of nicardipine hydrochloride from acrylic microspheres prepared by solvent evaporation methodPharm. Dev. Technol.3115121PubMedGoogle Scholar
  86. 86.
    Jollivet, C., Aubert-Pouëssel, A., Clavreul, A., Venier-Julienne, M.-C., Remy, S., Montero-Menei, C. N., Benoit, J.-P., Menei, P. 2004Striatal implantation of GDNF releasing biodegradable microspheres promotes recovery of motor function in a partial model of Parkinson's diseaseBiomaterials25933942PubMedCrossRefGoogle Scholar
  87. 87.
    Longo, W. E., Goldberg, E. P. 1985Hydrophilic albumin microspheresMethods Enzymol.1121826PubMedGoogle Scholar
  88. 88.
    Wagenaar, B. W., Muller, B. W. 1994Piroxicam release from spray-dried biodegradable microspheresBiomaterials154954PubMedCrossRefGoogle Scholar
  89. 89.
    Vandelli, M. A., Rivasi, F., Guerra, P., Forni, F., Arletti, R. 2001Gelatin microspheres crosslinked with d,l-glyceraldehyde asa potential drug delivery system: preparation, characterisation, in vitro and in vivo studiesInt. J. Pharm.215175184PubMedCrossRefGoogle Scholar
  90. 90.
    Woo, B. H., Kostanski, J. W., Gebrekidan, S., Dani, B. A., Thanoo, B. C., DeLuca, P. P. 2001Preparation, characterization and in vivo evaluation of 120-day poly(d,l-lactide) leuprolide microspheresJ. Control. Release75307315PubMedCrossRefGoogle Scholar
  91. 91.
    Schultz, K., Mollgaard, B., Frokjaer, S., Larsen, C. 1997Rotating dialysis cell as in vitro release method for oily parenteral depot solutionsInt. J. Pharm.157163169PubMedCrossRefGoogle Scholar
  92. 92.
    Larsen, D. H., Fredholt, K., Larsen, C. 2000Assessment of rate of drug release from oil vehicle using a rotating dialysis cellEur. J. Pharm. Sci.11223229PubMedGoogle Scholar
  93. 93.
    Larsen, D. B., Joergensen, S., Olsen, N. V., Hansen, S. H., Larsen, C. 2002In vivo release of bupivacaine from subcutaneously administered oily solution. Comparison with in vitro releaseJ. Control. Release81145154PubMedCrossRefGoogle Scholar
  94. 94.
    Lootvoet, G., Beyssac, E., Shiu, G. K., Aiache, J.-M., Ritschel, W. A. 1992Study on the release of indomethacin from suppositories: in vitroin vivo correlationInt. J. Pharm.85113120CrossRefGoogle Scholar
  95. 95.
    Parshad, H., Frydenvang, K., Liljefors, T., Cornett, C., Larsen, C. 2003Assessment of drug salt release from solutions, suspensions and in situ suspensions using a rotating dialysis cellEur. J. Pharm. Sci.19263272PubMedGoogle Scholar
  96. 96.
    Saarinen-Savolainen, P., Jarvinen, T., Taipale, H., Urtti, A. 1997Method for evaluating drug release from liposomes in sink conditionsInt. J. Pharm.1592733CrossRefGoogle Scholar
  97. 97.
    Parsaee, S., Sarbolouki, M. N., Parnianpour, M. 2002In-vitro release of diclofenac diethylammonium from lipid-based formulationsInt. J. Pharm.241185190PubMedCrossRefGoogle Scholar
  98. 98.
    Bodmeier, R., Chen, H., Tyle, P., Jarosz, P. 1991Pseudoephedrine HCl microspheres formulated into an oral suspension dosage formJ. Control. Release156577CrossRefGoogle Scholar
  99. 99.
    Levy, M. Y., Benita, S. 1990Drug release from submicronized o/w emulsion: a new in vitro kinetic evaluation modelInt. J. Pharm.662937CrossRefGoogle Scholar
  100. 100.
    T. M. Martin, N. Bandi, R. Shulz, C. B. Roberts, and U. B. Kompella. Preparation of budesonide and budesonide–PLA microparticles using supercritical fluid precipitation technology. AAPS PharmSciTech 3: article 18 (2002).Google Scholar
  101. 101.
    Leo, E., Cameroni, R., Forni, F. 1999Dynamic dialysis for the drug release evaluation from doxorubicin–gelatin nanoparticle conjugatesInt. J. Pharm.1802330PubMedCrossRefGoogle Scholar
  102. 102.
    Peracchia, M. T., Gref, R., Minamitake, Y., Domb, A., Lotan, N., Langer, R. 1997PEG-coated nanospheres from amphiphilic diblock and multiblock copolymers: investigation of their drug encapsulation and release characteristicsJ. Control. Release46223231CrossRefGoogle Scholar
  103. 103.
    Nah, J.-w., Jeong, Y.-i., Cho, C.-s. 1998Clonazepam release from core-shell type nanoparticles composed of poly(beta-benzyl l-glutamate) as the hydrophobic part and poly(ethylene oxide) as the hydrophilic partJ. Polym. Sci., B, Polym. Phys.36415423CrossRefGoogle Scholar
  104. 104.
    Jeon, H.-J., Jeong, Y.-I., Jang, M.-K., Park, Y.-H., Nah, J.-W. 2000Effect of solvent on the preparation of surfactant-free poly(lactide-co-glycolide) nanoparticles and norfloxacin release characteristicsInt. J. Pharm.20799108PubMedCrossRefGoogle Scholar
  105. 105.
    Heiati, H., Tawashi, R., Shivers, R. R., Phillips, N. C. 1997Solid lipid nanoparticles as drug carriers. I. Incorporation and retention of the lipophilic prodrug 3′-azido-3′-deoxythymidine palmitateInt. J. Pharm.146123131CrossRefGoogle Scholar
  106. 106.
    Dash, A. K., Haney, P. W., Garavalia, M. J. 1999Development of an in vitro dissolution method using microdialysis sampling technique for implantable drug delivery systemsJ. Pharm. Sci.8810361040PubMedCrossRefGoogle Scholar
  107. 107.
    La, S. B., Okano, T., Kataoka, K. 1996Preparation and characterization of the micelle-forming polymeric drug indomethacin-incorporated poly(ethylene oxide)–poly(beta-benzyl l-aspartate) block copolymer micellesJ. Pharm. Sci.858590PubMedCrossRefGoogle Scholar
  108. 108.
    Wang, J., Wang, B. M., Schwendeman, S. P. 2004Mechanistic evaluation of the glucose-induced reduction in initial burst release of octreotide acetate from poly(,-lactide-co-glycolide) microspheresBiomaterials2519191927PubMedGoogle Scholar
  109. 109.
    Lee, W.-k., Park, J.-y., Yang, E. H., Suh, H., Kim, S. H., Chung, D. S., Choi, K., Yang, C. W., Park, J.-s. 2002Investigation of the factors influencing the release rates of cyclosporin A-loaded micro- and nanoparticles prepared by high-pressure homogenizerJ. Control. Release84115123PubMedCrossRefGoogle Scholar
  110. 110.
    Prabhu, S., Sullivan, J. L., Betageri, G. V. 2002Comparative assessment of in vitro release kinetics of calcitonin polypeptide from biodegradable microspheresDrug Deliv.9195198PubMedCrossRefGoogle Scholar
  111. 111.
    Siepmann, J., Faisant, N., Benoit, J.-P. 2002A new mathematical model quantifying drug release from bioerodible microparticles using Monte Carlo simulationsPharm. Res.1918851893PubMedGoogle Scholar
  112. 112.
    Faisant, N., Siepmann, J., Benoit, J. P. 2002PLGA-based microparticles: elucidation of mechanisms and a new, simple mathematical model quantifying drug releaseEur. J. Pharm. Sci.15355366PubMedCrossRefGoogle Scholar
  113. 113.
    Faisant, N., Siepmann, J., Oury, P., Laffineur, V., Bruna, E., Haffner, J., Benoit, J. P. 2002The effect of gamma-irradiation on drug release from bioerodible microparticles: a quantitative treatmentInt. J. Pharm.242281284PubMedCrossRefGoogle Scholar
  114. 114.
    Nastruzzi, C., Pastesini, C., Cortesi, R., Esposito, E., Gambari, R., Menegatti, E. 1994Production and in vitro evaluation of gelatin microspheres containing an antitumor tetra-amidineJ. Microencapsul.11249260PubMedGoogle Scholar
  115. 115.
    Siepmann, J., Faisant, N., Akiki, J., Richard, J., Benoit, J. P. 2004Effect of the size of biodegradable microparticles on drug release: experiment and theoryJ. Control. Release96123134PubMedCrossRefGoogle Scholar
  116. 116.
    J. W. Kostanski and P. P. DeLuca. A novel in vitro release technique for peptide containing biodegradable microspheres. AAPS PharmSciTech 1: article 4 (2000).Google Scholar
  117. 117.
    J. W. Kostanski, B. A. Dani, G.-A. Reynolds, C. Y. Bowers, and P. P. DeLuca. Evaluation of orntide microspheres in a rat animal model and correlation to in vitro release profiles. AAPS PharmSciTech 1: article 27 (2000).Google Scholar
  118. 118.
    Kostanski, J., Thanoo, B. C., DeLuca, P. 2000Preparation, characterization, and in vitro evaluation of 1- and 4-month controlled release orntide PLA and PLGA microspheresPharm. Dev. Technol.5585596PubMedCrossRefGoogle Scholar
  119. 119.
    Park, T. G., Lu, W., Crotts, G. 1995Importance of in vitro experimental conditions on protein release kinetics, stability and polymer degradation in protein encapsulated poly(-lactic acid-co-glycolic acid) microspheresJ. Control. Release33211222CrossRefGoogle Scholar
  120. 120.
    Diaz, R. V., Llabres, M., Evora, C. 1999One-month sustained release microspheres of 125I-bovine calcitonin: in vitroin vivo studiesJ. Control. Release595562PubMedCrossRefGoogle Scholar
  121. 121.
    Kinget, R., Bontinck, A.-M., Herbots, H. 1979Problems of dialysis techniques in the study of macromolecule binding of drugsInt. J. Pharm.36572CrossRefGoogle Scholar
  122. 122.
    S. S. D'Souza and P. P. DeLuca. Development of a dialysis invitro release method for biodegradable microspheres. AAPS PharmSciTech 6: article 42 (2005).Google Scholar
  123. 123.
    Uppoor, V. R. S. 2001Regulatory perspectives on in vitro (dissolution)/in vivo (bioavailability) correlationsJ. Control. Release72127132PubMedCrossRefGoogle Scholar
  124. 124.
    Morita, T., Sakamura, Y., Horikiri, Y., Suzuki, T., Yoshino, H. 2001Evaluation of in vivo release characteristics of protein-loaded biodegradable microspheres in rats and severe combined immunodeficiency disease miceJ. Control. Release73213221PubMedCrossRefGoogle Scholar
  125. 125.
    Heya, T., Mikura, Y., Nagai, A., Miura, Y., Futo, T., Tomida, Y., Shimizu, H., Toguchi, H. 1994Controlled release of thyrotropin releasing hormone from microspheres: evaluation of release profiles and pharmacokinetics after subcutaneous administrationJ. Pharm. Sci.83798801PubMedGoogle Scholar
  126. 126.
    Heya, T., Okada, H., Ogawa, Y., Toguchi, H. 1994In vitro and in vivo evaluation of thyrotropin releasing hormone release from copoly(dl-lactic/glycolic acid) microspheresJ. Pharm. Sci.83 636640PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  1. 1.University of Kentucky College of PharmacyLexingtonUSA
  2. 2.Faculty of Pharmaceutical SciencesUniversity of Kentucky College of PharmacyLexingtonUSA

Personalised recommendations