Stability of Drugs and Dosage Forms Sumie Yoshioka

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2.2. • Factors Affecting Chemical Stability 105 Figure 87. Effect of oxygen concentration on the apparent first-order rate constants for ascorbic acid oxidation at 25°C. (Reproduced from Ref. 177 with permission.) Oxygen exists in various states. In its ground state, oxygen exists as a diradical or what is called triplet oxygen, but it can be excited by light to singlet oxygen, as shown in Scheme 74. Singlet oxygen is highly oxidizing and capable of attacking olefinic bonds. Oxygen can also form other oxidizing species, as shown in Scheme 75. The superoxide species is a mild reductant whereas hydrogen peroxide is a fairly specific oxidant. The hydroxyl radical is highly reactive but has low selectivity. Therefore, the general term oxidation does not refer just to exposure of oxidatively labile drugs to oxygen but also to conditions that favor oxidation, such as photolysis; the presence of various oxygen species, other radicals, metal ions and pro-oxidants, and high oxygen pressure. Scheme 75. Various oxygen species capable of catalyzing reactions.
106 Chapter 2 • Chemical Stability of Drug Substances Figure 88. Effect of light intensity on the photodegradation of nifedipine at room temperature. Light source: , high-pressure mercury lamp; , sunlight; , fluorescent lamp. (Reproduced from Ref. 403 with permission.) 2.2.10. Light The number and the wavelength of incident photons affect the photodegradation rate of drugs. It is not easy to study the effect of light quantitatively because the wavelength dependence of degradation varies among drug substances and because light sources have different spectral distributions. In many instances, only qualitative data on the photodegradation of drugs have been reported. As shown in Fig. 88, the amount of photodegraded nifedipine was proportional to the number of incident photons. 403 Maximum photodegradation of nifedipine in tablets occurred at 420 nm (Fig. 89). 404 On the other hand, the relationship between the discoloration rate of sulfisomidine in tablets irradiated by a mercury lamp versus ultraviolet light intensity was complex. 405 The values of L, a, and b determined for the discoloration of the tablet depended on the energy of the mercury lamp. 406 Photodegradation of menatetrenon yielded linear plots of log k versus the reciprocal of the illumination intensity, as shown in Fig. 90. 407 Photodegradation of drug substances strongly depends on the spectral properties of the drug substance and the spectral distribution of the light source. Discoloration of sulpyrine is significant in the presence of a mercury lamp, which is a good source of UV energy; however, little discoloration occurs in the presence of a fluorescent lamp, which radiates mainly visible light. 408 Figure 89. Wavelength dependence of photodegradation of nifedipine tablets at 15°C. Light intensity: 1.23 x 10 8 erg/cm 2 . (Reproduced from Ref. 404 with permission.)
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Stability of Drugs and Dosage Forms
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eBook ISBN: 0-306-46829-8 Print ISB
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vi Preface As stated earlier, this
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viii Contents 2.2.4.2. Quantitation
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x Contents 5.1.1.3. Hydrolysis ....
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Chapter 2 Chemical Stability of Dru
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2.1. • Pathways of Chemical Degra
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156 Chapter 4 • Stability of Dosa
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188 Chapter 5 • Stability of Pept
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Chapter 6 Regulations The efficacy
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6.1. • ICH Harmonised Tripartite
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5. • Major Concerns Raised by the
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6.3 • Major Concerns Raised by th
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228 References 21. M. L. Maniar, D.
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230 References 71. A. Tsuji, E. Nak
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232 References 121. D. C. Chatteji,
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234 References 173. M. A. F. Hameli
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236 References 222. P. J. G. Comeli
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238 References 270. K. Okazaki, R.
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240 References 327. H. V. Maulding
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242 References 382. H. Zia, M. Teha
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244 References 433. S. Yoshioka and
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246 References 484. M. E. Moro, J.
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248 References 532. E. Pop, T. Loft
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250 References 578. T. Yokoyama, N.
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252 References 628. M. Angberg, C.
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254 References 679. J. T. Rubino, L
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256 References 727. J. H. Wood and
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258 References 779. I. Matsuura and
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260 References 830. D. J. Kroon, A.
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262 References 879. S. Yoshioka, K.
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264 Index Bromovalerylurea, 146, 14
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266 Index Hydrolysis (cont.) Lacton
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268 Index Shelf life ( cont.) Table
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Stability of Drugs and Dosage Forms Sumie Yoshioka

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