I= PHOTOLYSIS AND INTERACTIONS OF CYANOCOBALAMIN WITH SOME B-VITAMINS AND ASCORBIC ACID IN PARENTERAL SOLUTIONS
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Title of Thesis
PHOTOLYSIS AND INTERACTIONS OF CYANOCOBALAMIN WITH SOME B-VITAMINS AND ASCORBIC ACID IN PARENTERAL SOLUTIONS

Author(s)
Izhar Ahmad Ans
Institute/University/Department Details
University of Karachi/ Department of Pharmaceutical Chemistry
Session
2001
Subject
Pharmacy
Number of Pages
345
Keywords (Extracted from title, table of contents and abstract of thesis)
cyanocobalamin, b-vitamins, ascorbic acid , vitamin b12, thiamine hcl, riboflavin, nicotinamide, pyridoxine hcl

Abstract
The present study is based on an investigation of the photolysis and interaction of cyanocobalamin (vitamin B12) with thiamine HCl (vitamin B1) riboflavin (vitamin B2) nicotinamide (vitamin B3) pyridoxine HCl (vitamin B6) and ascorbid acid (vitamin C) in parenteral solutions (5% dextrose i.v. infusions) at pH 1.0-8.0 using a 125 W visible radiation source with emission at 405,436 545 and 578 nm

Cyanocobalamin undergoes photo degradation in the presence and absence of other vitamins to hydroxocobalamin (vitamin B12b) as the main photoproduct which has been identified by thin-layer chromatography and uv-visible spectrophotometry. Cyanocobalamin and hydroxocobalamin have been assayed in photolysed solutions in the presence of other vitamins by a previously reported two-component spectrophotometric method at 525 and 550 nm (pH 4.0) after proper validation. The precision of the assay method lies with +3%. The photolysis of cyanocobalamin at pH 1.0-8.0 in the presence of other B/C vitamins follows first-order kinetics and the apparent first-order rate constants (kobs) indicate a gradual increase with an increase in the concentration of each vitamin

The kobs values have been used to calculate the second-order rate constants (k2) for the bimolecular interaction of cyanocobalamin with other vitamins. The variation of k2 for the interaction of cyanocobalamin with other vitamins. The variation of k2 for the interaction of cyanocobalamin at pH 1.0-8.0 with thiamine HCI (5.0 to 1.6 M-1 min-1) riboflavin (5.0 to 1.1 m-1 min-1) NOCOTINAMIDE (6.6 TO 2.2 m-1 MIN-1) PYRIDOXINE hci (5.8 to 1.3 M-1 min-1) and ascorbic acide (2.0 to 1.2 m-1 min-1) indicate that the optimum stability to cyanocobalamin occurs around pH7

The log k2-pH profiles for the photolytic interaction of cyanocobalamin and thiamin HCI/riboflavin/ nicotinamide/ pyridoxine HCI are sigmold shaped curves indicating the increase in rate with a decrease in pH due to gradual protonation of cyanocobalamin (pKa 3.3) and the other vitamin species. Thus the protonated form of cyanocobalamin appears to be more susceptible to photolysis compared to that of the neutral form. The log k-pH profile for the interaction of cyanocobalamin and ascorbic acid represents a combination of two bell shaped curves with minima around pH 4 and 7. This may be explained on the basis of the involvement of nonionised and mononionic species of ascorbic acid (pK 4.1) at pH values below and above 4.1 in the photoreaction as well as their redox characteristics

A detailed account of the schemes for the primary (photochemical) and secondary (chemical) reactions involved in the interactions of cyanocobalamin and other vitamins in the pH range studied has been presented and a comparison of cyanocobalamin photo degradation in the presence of individual B/C vitamins has been made

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S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
101.01 KB
2 1 Introduction and literature survey 14
342.75 KB
  1.1 Introduction 14
  1.2 Stability and degradation of cyanocobalamin 20
  1.3 Methods of analysis of cyanocobalamin 30
  1.4 Parenteral solutions 48
3 2 Object of present investigation 50
28.69 KB
4 3 Experimnetal 54
217.51 KB
  3.1 Materials 54
  3.2 Methods 59
5 4 Plan of work 79
14.96 KB
6 5 Results and Discussion, Photolysis of cyanocobalamin solutions-1 qualitative studies and assay method 83
161.63 KB
  5.1 Photochemcial reactions 83
7 6 Photolysis of cyanocobalamin solutions-2 kinetics of reaction and rate-pH profiles 102
1183.47 KB
  6.1 Kinetics of cyanocobalamin photolysis 102
  6.2 Modes of interaction of cyanocobalamin 221
8 7 Conclusions and suggestions 239
44.88 KB
  7.1 Conclusions 239
  7.2 Suggestions 241
9 8 Appendix 244
940.96 KB
  8.1 References 317