Thermal stability of vaccines

Journal of Pharmaceutical Sciences

Volumn 92, Issue 2, 2003, Pages 218-231

  Brandau, Duane T ^a   Jones, Latoya S ^a   Wiethoff, Christopher M ^a   Rexroad, Jason ^a   Middaugh, C Russell ^a  

^a UNIVERSITY OF KANSAS   (United States)

Author keywords

Infectious diseases; Thermal instability; Vaccines

Indexed keywords

BCG VACCINE; BIAVAX II; CHICKENPOX VACCINE; CHOLERA VACCINE; DIPHTHERIA PERTUSSIS TETANUS VACCINE; DIPLOID CELL VACCINE; HAEMOPHILUS INFLUENZAE TYPE B VACCINE; HEPATITIS A VACCINE; INFLUENZA VACCINE; IPOL; JAPANESE ENCEPHALITIS VACCINE; LIQUID PEDVAXHIB; LYME DISEASE VACCINE; M R VAX; MEASLES MUMPS RUBELLA VACCINE; MEASLES VACCINE; MENINGOCOCCUS VACCINE; MENOMUNE A; MMR II; MUMPS VACCINE; ORAL POLIOMYELITIS VACCINE; PNEUMOCOCCUS VACCINE; PNU IMMUNE 23; RABIES VACCINE; RECOMBINANT HEPATITIS B VACCINE; RUBELLA VACCINE; TICE BCG VACCINE; TYPHOID VACCINE; VACCINE;

CHEMICAL ANALYSIS; CHEMICAL STRUCTURE; DRUG DEGRADATION; DRUG FORMULATION; DRUG INACTIVATION; DRUG STABILITY; INFECTION; MACROMOLECULE; METHODOLOGY; PHYSICAL CHEMISTRY; PROTEIN FOLDING; SHORT SURVEY; THERMOSTABILITY; VACCINATION;

EID: 0037309755     PISSN: 00223549     EISSN: None     Source Type: Journal    
DOI: 10.1002/jps.10296     Document Type: Short Survey

References (118)

1. Plotkin SA, Orenstein WA, editors. 1999. Vaccines, 3rd ed. Philadelphia: W.B. Saunders Co., p 1.
2. WHO, U., UNAIDS, World Bank, UNESCO, UNFPA. 2000. Health: A key to prosperity. In success stories in developing countries. Geneva: World Health Organization.
3. Zaffran M. 1996. Vaccine transport and storage: environmental challenges. Dev Biol Stand 87: 9-17.
4. Peetermans J. 1996. Factors affecting the stability of viral vaccines. Dev Biol Stand 87:97-101.
5. Galazka A, Milstien J, Zaffran M. 1998. Thermostability of vaccines. Geneva: World Health Organization.
6. Corbel MJ. 1996. Reasons for instability of bacterial vaccines. Dev Biol Stand 87:113-124.
7. Burke CJ, Hsu TA, Volkin DB. 1999. Formulations, stability, and delivery of live attenuated vaccines for human use. Crit Rev Ther Drug Carrier Syst 16:1-83.
8. Newman JF, Tirrell S, Ullman C, Piatti PG, Brown F. 1996. Stabilizing oral polio vaccine at high ambient temperatures. Dev Biol Stand 87:103-111.
9. Lundbeck H, Hakansson B, Lloyd JS, et al. 1978. A cold box for the transport and storage of vaccines. Bull World Health Organ 56:427-432.
10. Expanded Programme on Immunization. 1995. Vaccine vial monitor and open vial policy. Questions and Answers. WHO/EPI/LHIS/95.01.
11. Black FL. 1959. Growth and stability of measles virus. Virology 7:184.
12. Newman JF, Tirrel S, Ullman C, Piatti PG, Brown F. 1995. Stabilizing oral polio vaccine at high ambient temperatures. Vaccine 13:1431-1435.
13. Manning MC, Patel K, Borchardt RT. 1989. Stability of pharmaceutical proteins. Pharm Res 6: 903-918.
14. Li S, Schoneich C, Borchardt RT. 1994. Chemical instability of protein pharmaceuticals: Mechanisms of oxidation and strategies of stabilization. Biotechnol Bioeng 48:490-500.
15. Anchordoquy TJ, Allison SD, Molina MC, Girouard LG, Carson TK. 2001. Physical stabilization of DNA-based therapeutics. Drug Discov Today 6: 463-470.
16. Middaugh CR, Evans RK, Montgomery DL, Casimiro DR. 1998. Analysis of plasmid DNA from a pharmaceutical perspective. J Pharm Sci 87:130-146.
17. Lanz G, Sample J. 1985. Thermal-pH inactivation of herpes simplex virus: Interdependence of the medium composition and the pH on the rate of inactivation. Brief report. Arch Virol 84:141-146.
18. Lauffer MA, Carnelly HL, Macdonald E. 1948. Thermal destruction of influenza A virus infectivity. Arch Biochem 16:321.
19. Salo RJ, Cliver DO. 1976. Effect of pH, salts, and temperature on the infectivity and physical integrity of enteroviruses. Arch Virol 52:269-282.
20. Miller R Jr, Goodner K. 1953. Studies on the stability of lyophilized BCG vaccine. Yale J Biol Med 25:262.
21. Gupta RK, Rost BE, Rellyveld E, Siber GR. 1995. Adjuvant properties of aluminum and calcium compounds. Pharm Biotechnol 6:229-248.
22. Vadas EB. 1995. Stability of pharmaceutical products. In: Gennaro AR, editor. The science and practice of pharmacy. Philadelphia: Philadelphia College of Pharmacy, pp 639-647.
23. Middaugh CR, Volkin DB. 1992. Protein solubility. In: Ahern TJ, Manning MC, editors. Stability of protein pharmaceuticals: Part A. Chemical and physical pathways of protein degradation. New York: Plenum Press, pp 109-134.
24. Colwell WM, Simmons DG, Harris JR, Fulp TG, Carrozza JH, Maag TA. 1975. Influence of some physical factors on survival of Marek's disease vaccine virus. Avian Dis 19:781-790.
25. Arakawa T, Timasheff SN. 1985. Theory of protein solubility. Methods Enzymol 114:49-77.
26. Bam NB, Cleland JL, Yang J, Manning MC, Carpenter JF, Kelley RF, Randolph TW. 1998. Tween protects recombinant human growth hormone against agitation-induced damage via hydrophobic interactions. J Pharm Sci 87:1554-1559.
27. Jones LS, Cipolla D, Liu J, Shire SJ, Randolph TW. 1999. Investigation of protein-surfactant interactions by analytical centrifugation and electron paramagnetic resonance: The use of recombinant human tissue factor as an example. Pharm Res 16:808-812.
28. Kreilgaard L, Frokjaer S, Flink JM, Randolph TW, Carpenter JF. 1998. Effects of additives on the stability of recombinant factor XIII during freeze-drying and storage in a dried solid. Arch Biochem Biophys 360:121-134.
29. Prince AM, Stephan W, Kotitschke R, Brotman B. 1983. Inactivation of hepatitis B and non-A, non-B viruses by combined use of Tween 80, beta-propiolactone, and ultraviolet irradiation. Thromb Haemost 50:534-536.
30. Cherepova N, Veljanov D. 1994. Effect of sorbitan monolaurate polyoxyalkylene (Tween 20) on the ultrastructure of some bacteria. Cytobios 80:179-185.
31. Schwendeman SP, Costantino HR, Gupta RK, Siber GR, Klibanov AM, Langer R. 1995. Stabilization of tetanus and diphtheria toxiods against moisture-induced aggregation. Proc Natl Acad Sci USA 92:11234-11238.
32. Bolgiano B, Fowler S, Turner K, Swsardic D, Xing DK, Crane DT, Corbel MJ. 2000. Monitoring of diphtheria, pertussis and tetanus toxiods by circular dichroism, fluorescence spectroscopy, and size-exclusion chromatography. Dev Biol 103:51-59.
33. Burke CJ, Steadman BL, Volkin DB, Tsai PK, Middaugh CR, et al. 1992. Adsorption of proteins to pharmaceutical container surfaces. Int J Pharml 86:89-93.
34. Goodey AR. 1993. The production of heterologous plasma proteins. Trends Biotechnol 11:430-433.
35. Sakaguchi M, Nakayama T, Fujita H, Toda M, Inouye S. 2000. Minimum estimated incidence in Japan of anaphylaxis to live virus vaccines including gelatin. Vaccine 19:431-436.
36. Sakaguchi M, Inouye S. 2000. Systemic allergic reactions to gelatin included in vaccines as a stabilizer. Jpn J Infect Dis 53:189-195.
37. Kelso JM, Jones RT, Yunginger JW. 1993. Anaphylaxis to measles, mumps, and rubella vaccine mediated by IgE to gelatin. J Allergy Clin Immunol 91:867-872.
38. Burrell LS, White JL, Hem SL. 2000. Stability of aluminum-containing adjuvants during aging at room temperature. Vaccine 18:2188-2192.
39. Shi Y, HogenEsch H, Hem SL. 2001. Change in the degree of adsorption of proteins by aluminum containing adjuvants following exposure to interstitial fluid: freshly prepared and aged model vaccines. Vaccine 20:80-85.
40. WHO. 1977. Manual on the production and control of vaccines-tetanus toxoid. BLG/UNDP/77.2 Rev. 1. Geneva: WHO.
41. Sturgess AW, Rush K, Charbonneau RJ, Lee JI, West DJ, Sitrin RD, Hennessy JP. 1999. Haemophilus influenzae type b conjugate vaccine stability: Catalytic depolymerization of PRP in the presence of aluminum hydroxide. Vaccine 17: 1169-1178.
42. Singh M, O'Hagan D. 1995. Advances in vaccine adjuvants. Nat Biotechnol 17:1075-1081.
43. Vogel FR, Powell MF. 1995. A compendium of vaccine adjuvants and excipients. Pharm Biotechnol 6:141-228.
44. Cleland JL, Kensil CR, Lim A, Jacoobsen NE, Basa L, Spellman M, Wheeler DA, Wu JY, Powell MF. 1996. Isomerization and formulation stability of the vaccine adjuvant QS-21. J Pharm Sci 85: 22-28.
45. Krieg AM, Davis HL. 2001. Enhancing vaccines with immune stimulatory CpG DNA. Curr Opin Mol Ther 3:15-24.
46. Krieg AM, Yi AK, Matson S, Waldschmidt TJ, Bishop GA, Teasdale R, Koretzky GA, Klinman DM. 1995. CpG motifs in bacterial DNA trigger direct B-cell activation. Nature 374:546-549.
47. Gupta RK, Chang AC, Siber GR. 1998. Biodegradable polymer microspheres as vaccine adjuvants and delivery systems. Dev Biol Stand 92: 63-78.
48. Gutierro I, Hernandez RM, Igartua M, Gascon AR, Pedraz JL. 2002. Influence of dose and immunization route on the serum IgG antibody response to BSA loaded PLGA microspheres. Vaccine 20:2181-2190.
49. Pikal MJ. 1994. Freeze drying of proteins. In: Cleland JL, Langer R, editors. Formulation and delivery of proteins and peptides. Washington, DC: American Chemical Society, pp 120-133.
50. Carpenter JF, Pikal MJ, Chang BS, Randolph TW. 1997. Rational design of stable lyophilized protein formulations: some practical advice. Pharm Res 14:967-975.
51. Carpenter JF, Chang BS. 1996. Lyophilization of protein pharmaceuticals. In: Avis KE, Wu VL, editors. Biotechnology and biopharmaceutical manufacturing, processing, and preservation. Buffalo Grove, IL: Interpharm Press, Inc., pp 199-264.
52. Wang W. 2000. Lyophilization and development of solid protein pharmaceuticals. Int J Pharm 203:1-60.
53. Worral EE, Litamoi JK, Seck BM, Ayelet G. 2000. Xerovac: An ultra rapid method for the dehydration and preservation of live attenuated Rinder-past and Peste des Petitis ruminants vaccines. Vaccine 19:834-839.
54. Andya JD, Maa YF, Costantino HR, Nguyen PA, Dasovich N, Sweeney TD, Hsu CC, Shire SJ. 1999. The effect of formulation excipients on protein stability and aerosol performance of spray-dried powders of a recombinant humanized anti-IgE monoclonal antibody. Pharm Res 16:350-358.
55. Costantino HR, Andya JD, Nguyen PA, Dasvich N, Sweeney TD, Shire SJ, Hsu CC, Maa YF. 1998. Effect of mannitol crystallization on the stability and aerosol performance of a spray-dried pharmaceutical protein, recombinant humanized anti-IgE monoclonal antibody. J Pharm Sci 87:1406-1411.
56. Maa YF, Nguyen PA, Hsu SW. 1998. Spray-drying of air-liquid interface sensitive recombinant human growth hormone. J Pharm Sci 87:152-159.
57. Maa YF, Nguyen PA, Sit K, Hsu CC. 1998. Spray-drying performance of a bench-top spray dryer for protein aerosol powder preparation. Biotechnol Bioeng 60:301-319.
58. Maa YF, Nguyen PA, Sweeney T, Shire SJ, Hsu CC. 1999. Protein inhalation powders: Spray drying vs spray freeze drying. Pharm Res 16:249-254.
59. Maa YF, Prestrelski SJ. 2001. Biopharmaceutical powders: Particle formation and formulation considerations. Curr Pharm Biotechnol 1:283-302.
60. Rexroad J, Wiethoff CM, Jones LS, Middaugh CR. 2002. Lyophilization and the thermostability of vaccines. Cell Preservat Technol, to appear.
61. Wang W. 1999. Instability, stabilization, and formulation of liquid protein pharmaceuticals. Int J Pharm 185:129-188.
62. Ravenscroft N, D'Ascenzi S, Proietti D, Norelli F, Costantino P. 2000. Physicochemical characterization of the oligosaccharide component of vaccines. In: Brown F, Corbel M, Griffins E, editors. Physico-chemical procedures for the characterization of vaccines. Basel: Karger, pp 35-47.
63. Volkin DB, Burke CJ, Marfia KE, Oswald CB, Wolanski B, Middaugh CR. 1997. Size and conformational stability of the hepatitis A virus used to prepare VAQTA, a highly purified inactivated vaccine. J Pharm Sci 86:666-673.
64. Burlingame AL. 1998. Mass spectrometry. Anal Chem 70:647R-716R.
65. Griffen TJ, Goodlett DR, Aebersold R. 2001. Advances in proteome analysis by mass spectroscopy. Curr Opin Biotechnol 12:607-612.
66. Kebarle P. 2000. A brief overview of the present status of the mechanisms involved in electrospray mass spectrometry. J Mass Spectrom 35: 804-817.
67. Rostom AA, Fucini P, Benjamin DR, Juenemann R, Nierhaus KH, Hartl FU, Dobson CM, Robinson CV. 2000. Detection and selective dissociation of intact ribosomes in a mass spectrometer. Proc Natl Acad Sci USA 97:5185-5190.
68. Tito MA, Miller J, Griffen KF, Williamson ED, Titball RW, Robinson CV. 2001. Macromolecular organization of the Yersina pestis capsular F1 antigen: Insights from time of flight mass spectrometry. Protein Sci 10:2408-2413.
69. Tito MA, Tars K, Valegard K, Hajdu J, Robinson CV. 2000. Electrospray time-of-flight mass spectrometry of the intact MS2 virus capsid. J Am Chem Soc 122:3550-3551.
70. Fenselau C, Demirev PA. 2001. Characterization of intact microorganisms by MALDI mass spectrometry. Mass Spectrom Rev 20:157-171.
71. Lay JO Jr. 2001. MALDI-TOF mass spectrometry of bacteria. Mass Spectrom Rev 4:172-194.
72. Sela M. 2000. Structural components responsible for peptide antigenicity. Appl Biochem Biotechnol 83:63-70.
73. Karthigesu VD, Allison LM, Ferguson M, Howard CR. 1999. A hepatitis B virus variant found in the sera of immunized children induces a conformational change in the HBsAg"a" determinant. J Med Virol 58:346-352.
74. Oggioni MR, Medaglini D, Romano L, Eruzzi F, Maggi T, Pozzi L, Bracci L, Zazza M, Manca F, Valensin PE, Pozzi G. 1999. Antigenicity and immunogenicity of the V3 domain of HIV type 1 glycoprotein 120 expressed on the surface of Streptococcus gordonii. AIDS Res Hum Retroviruses 15:451-459.
75. McInnes C, Sonnichsen FD, Kay CM, Hodges RS, Sykes BD. 1993. NMR solution structure and flexibility of a peptide antigen representing the receptor binding domain of Pseudomonas aeruginosa. Biochemistry 32:13432-13440.
76. Manivel V, Ramesh R, Panda SK, Rao KV. 1992. A synthetic peptide spontaneously self-assembles to reconstruct a group-specific, conformational determinant of hepatitis B surface antigen. J Immunol 148:4006-4011.
77. Flint M, Dubuisson J, Maidens C, Harrop R, Guile GR, Borrow P, McKeating JA. 2000. Functional characterization of intracellular and secreted forms of a truncated hepatitis C virus E2 glycoprotein. J Virol 74:702-709.
78. Levitsky V, Zhang QJ, Levitskaya J, Kurilla MG, Masucci MG. 1997. Natural variants of the immunodominant HLA All-restricted CTL epitope of the EBV nuclear antigen-4 are nonimmunogenic due to intracellular dissociation from MHC class I: Peptide complexes. J Immunol 159:5383-5390.
79. Niedergang F, Sirand JC, Blanc CT, Kraehenbuhl JP. 2000. Entry and survival of Salmonella typhimurium in dendritic cells and presentation of recombinant antigens do not require macrophage-specific virulence factors. Proc Natl Acad Sci USA 97:14650-14655.
80. Middaugh CR. 1996. Formulation and delivery of biopharmaceuticals. J Pharm Sci 85:1259-1260.
81. Volkin DB, Burke CJ, Sanyal G, Middaugh CR. 1996. Analysis of vaccine stability. Dev Biol Stand 87:135-142.
82. Cleland JL, Powell MF, Shire SJ. 1993. The development of stable protein formulations: A close look at protein aggregation, deamidation, and oxidation. Crit Rev Ther Drug Carrier Syst 10: 307-377.
83. du Plessis M, Cloete M, Aitchison H, Van Dijk AA. 1998. Protein aggregation complicates the development of baculovirus-expressed African horsesickness virus serotype 5 VP2 subunit vaccines. Onderstepoort J Vet Res 65:321-329.
84. Volkin DB, Mach H, Middaugh C. 1995. Degradative covalent reactions important to protein stability. Methods Mol Biol 40:35-63.
85. Middaugh CR. 1994. The analysis of protein pharmaceuticals: Near future advances. Cytotechnology 15:187-194.
86. Stock RS, Ray WH. 1985. Interpretation of photon correlation spectroscopy data: A comparison of analysis methods. Polym Phys Ed 232: 1393-1447.
87. Lawson CL, Hanson RJ. 1974. Solving least squares problems. Englewood Cliffs, NJ: Prentice Hall.
88. Santos NC, Castanho MA. 1996. Teaching light scattering spectroscopy: The dimension and shape of tobacco mosaic virus. Biophys J 71: 1641-1650.
89. Ehrlich LS, Liu T, Scarlatta S, Chu B, Carter CA. 2001. HIV-1 capsid protein forms spherical (immature-like) and tubular (mature-like) particles in vitro: Structure switching by pH-induced conformational changes. Biophys J 81:586-594.
90. Pontes L, Corderio Y, Giongo V, Villas-Boas M, Barreto A, Araujo JR, Silva JL. 2001. Pressure-induced formation of inactive triple-shelled rotavirus particles is associated with changes in the spike protein Vp4. J Mol Biol 307:1171-1179.
91. Wen ZQ, Thomas GJ Jr. 2000. Ultraviolet-resonance Raman spectroscopy of the filamentous virus Pf3: Interactions of Trp 38 specific to the assembled virion subunit. Biochemistry 39:146-152.
92. Yamada T, Iwabuki H, Kanno T, Tanaka H, Kawai T, Fukuda H, Kondo A, Seno M, Tanizawa K, Kuroda S. 2001. Physicochemical and immunological characterization of hepatitis B virus envelope particles exclusively consistent of the entire L (pre-S1 + pre-S2 + S) protein. Vaccine 19: 3154-3163.
93. Jones C, Lemercinier X, Crane DT, Gee CK, Austin S. 2000. Spectroscopic studies of the structure and stability of glycoconjugate vaccines. Dev Biol 103:121-136.
94. Constantino HR, Schwendeman SP, Griebenow K, Kilbanov AM, Langer R. 1996. The secondary structure and aggregation of lyophilized tetanus toxoid. J Pharm Sci 85:1290-1293.
95. Ho MM, Lemercinier X, Bolgiano B, Corbel MJ. 2000. Monitoring stability of meningococcal group C conjugate vaccines; Correlation of physicochemical methods and immunogenicity assays. Dev Biol 103:139-150.
96. Matulis D, Baumann CG, Bloomfield VA, Lovrien RE. 1999. 1-Anilino-8-naphthalene sulfonate as a protein conformational tightening agent. Biopolymers 49:451-458.
97. Ali V, Prakash K, Kulkarni S, Ahmad A, Madhusudan KP, Bhakuni V. 1999. 1-Anilino-8-naphthalene sulfonic acid (ANS) induces folding of acid unfolded cytochrome c to molten globule state as a result of electrostatic interactions. Biochemistry 38:13635-13642.
98. Grimmel M, Zibirre R, Koch G. 1983. Fluorescence spectrophotometric study of structural alterations in the capsid of poliovirus. Arch Virol 78:191-201.
99. Lentz BR. 1993. Use of fluorescent probes to monitor molecular order and motions within liposome bilayers. Chem Phys Lipids 64:99-116.
100. Breeuwer P, Abee T. 2000. Assessment of viability of microorganisms employing fluorescence techniques. Int J Food Microbiol 55:193-200.
101. Venyaminov SY, Yang JT. 1996. Determination of protein secondary structure. In: Fasman GD, editor. Circular dichroism and the conformational analysis of biomolecules. New York: Plenum Press, pp 69-108.
102. Woody RW. 1994. Circular dichroism of peptides and proteins. In: Nakanashi K, Berova N, Woody RW, editors. Circular dichroism. Principles and applications, New York: Wily-VCH, pp 474-498.
103. Braun CS, Kueltzo LA, Middaugh CR. 2001. Ultraviolet absorption and circular dichroism spectroscopy of non-viral gene delivery complexes. Methods Mol Med 65:253-284.
104. Allison SD, Chang B, Randolph TW, Carpenter JF. 1999. Hydrogen bonding between sugar and protein is responsible for inhibition of dehydration-induced protein unfolding. Arch Biochem Biophys 365:289-298.
105. Carpenter JF, Prestrelski SJ, Dong A. 1998. Application of infrared spectroscopy to development of stable lyophilized protein formulation. Eur J Pharm Biopharm 45:231-238.
106. Yang TH, Dong A, Meyer J, Johnson OL, Cleleand JL, Carpenter JF. 1999. Use of infrared spectroscopy to assess secondary structure of human growth hormone within biodegradable microspheres, J Pharm Sci 88:161-165.
107. Thomas GJ Jr. 1999. Raman spectroscopy of protein and nucleic acid assemblies. Annu Rev Biophys Biomol Struct 28:1-27.
108. Villanueva J, Canals F, Villegas V, Querol E, Aviles FX. 2000. Hydrogen exchange monitored by MALDI-TOF mass spectrometry for rapid characterization of stability and conformation of proteins. FEBS Lett 72:27-33.
109. Powell KD, Fitzgerald MC. 2001. Measurements of protein stability by H/D exchange and matrix-assisted laser desorption/ionization mass spectrometry using picomoles of material. Anal Chem 73:3300-3304.
110. Privalov PL, Gill SJ. 1988. Stability of protein structure and hydrophobic interaction. Adv Protein Chem 39:191-234.
111. Lobo BA, Rogers SA, Wieythoff CM, Choosakoonkriang S, Bogdanowich-Knipp S, Middaugh CR. 2001. Characterization of cationic vector-based gene delivery vehicles using isothermal titration and differential scanning calorimetry. Methods Mol Med 65:319-348.
112. Lobo BA, Davis A, Koe G. 2001. Isothermal titration calorimetric analysis of the interaction between cationic. lipids and plasmid DNA. Arch Biochem Biophys 386:95-105.
113. Krishinan KS, Brandts JF. 1978. Scanning calorimetry. Methods Enzynol 49:3-14.
114. Brandts JF, Hull HH, Snyder LM, Fortier NL. 1982. A calorimetric comparison of structural transitions of erythrocytic ghosts from normal individuals and from patients with muscular dystrophy. Arch Biochem Biophys 214:560-562.
115. Brouillette CG, Compans RW, Brandts JF, Segrest JP. 1982. Structural domains of vesicular stomatitis virus. A study by differential scanning calorimetry, thermal gel analysis, and thermal electron microscopy. J Biol Chem 257: 12-15.
116. Yoshioka S, Aso Y, Izutsu K, Kojima S. 1994. Is stability prediction possible for protein drugs? Denaturation kinetics of beta-galactosidase in solution. Pharm Res 11:1721-1725.
117. Bi M, Singh J. 2000. Effect of buffer pH, buffer concentration and skin with or without enzyme inhibitors on the stability of [Arg(8)]-vasopressin. Int J Pharm 197:87-93.
118. Middaugh CR. 1998. Advances in the delivery of pharmaceuticals. J Pharm Sci 87:1265-1266.