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Degradation Kinetics Of A Pharmaceutical Dosage Form

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Degradation Kinetics of a Pharmaceutical Dosage Form

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Degradation Kinetics Of A Pharmaceutical Dosage Form

  1. 1. Citation  First derivative spectrophotometric and high- performance liquid chromatographic determination of cinchocaine hydrochloride in presence of its acid degradation product, Alaa El-Gindy et al, Journal of Pharmaceutical and Biomedical Analysis, Volume 17, Issue 8, 30 September 1998, Pages 1357-1370
  2. 2. Determination of Order of the Reaction  Graphic Method  Substitution Method  Zero order: Ko = (Co- Ct ) / t  First Order: K1 = (2.303/ t) log Co / Ct  Half-Life Method  Zero order: t1/2 = Co / 2 Ko  First order: t1/2 = 0.693 / K1
  3. 3. i) Graphical Analysis (1st order) Kinetic data: 60°C y = -0.0597x + 2.0255 R2 = 0.998 1.84 1.86 1.88 1.9 1.92 1.94 1.96 1.98 0 0.5 1 1.5 2 2.5 3 3.5 hours log%remaining
  4. 4. ii) Graphical Analysis (1st order) Kinetic data: 65°C y = -0.0996x + 1.994 R2 = 0.995 1.74 1.76 1.78 1.8 1.82 1.84 1.86 1.88 1.9 1.92 1.94 0 0.5 1 1.5 2 2.5 3 3.5 hours log%remaining
  5. 5. iii) Graphical Analysis (1st order) Kinetic data: 70°C y = -0.0296x + 1.994 R2 = 0.9969 1.3 1.4 1.5 1.6 1.7 1.8 1.9 2 0 0.5 1 1.5 2 2.5 3 3.5 hours log%remaining
  6. 6. iv) Graphical Analysis (1st order) Kinetic data: 80°C y = -0.0896x + 1.994 R2 = 0.9919 1.6 1.65 1.7 1.75 1.8 1.85 1.9 0 0.5 1 1.5 2 2.5 3 3.5 hours log%remaining
  7. 7. v) Graphical Analysis (1st order) Kinetic data: 90°C y = -0.0796x + 1.994 R2 = 0.9959 1 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 0 0.5 1 1.5 2 2.5 3 3.5 hours log%remaining
  8. 8. i) Comparison of K values at 60°C   Zero Order  (moles/  hour) First Order       (hour –1 )       Graphic  Method 0.221 0.483  Substitution  Method 0.542 0.492 Half-Life  Method 0.061 0.455
  9. 9. ii) Comparison of K values at 65°C   Zero Order  (moles/  hour) First Order       (hour –1 )       Graphic Method 0.435 0.667  Substitution  Method 0.679 0.682 Half-Life  Method 0.773 0.601
  10. 10. iii) Comparison of K values at 70°C   Zero Order  (moles/  hour) First Order       (hour –1 )       Graphic Method 0.008 0.875  Substitution  Method 0.213 0.866 Half-Life  Method 0.501 0.867
  11. 11. iv) Comparison of K values at 80°C   Zero Order  (moles/  hour) First Order       (hour –1 )       Graphic  Method 0.974 0.952  Substitution  Method 0.819 0.961 Half-Life  Method 0.718 0.954
  12. 12. v) Comparison of K values at 90°C   Zero Order  (moles/  hour) First Order       (hour –1 )       Graphic  Method 2.404 1.188  Substitution  Method 1.105 1.186 Half-Life  Method 0.055 1.187
  13. 13. Order followed: 1st Order  Evident from the near constant values of K when treated for the First order kinetics  This is also supported by the linearity of the graphs obtained when treated for First order Kinetic
  14. 14. Shelf-lives at different temperatures Temperature (°C) Shelf-Life ( t10   ) in hours 60 0.217 65 0.190 70 0.157 80 0.133 90 0.088
  15. 15. Construction of Arrhenius Plot Temperature (°C) Temperature (1 / K x 10 3 ) Rate constant (k) (hour –1 )  60 3.003 0.483 65 2.950 0.667 70 2.915 0.875 80 2.832 0.952 90 2.754 1.188
  16. 16. Graphical Representation of Arrhenius Plot Arrhenius Plot y = -0.0779x + 1.994 R2 = 0.9989 0.01 0.1 1 10 2.7 2.75 2.8 2.85 2.9 2.95 3 3.05 1/T X 103 hours logK(hour -1 )
  17. 17. Rate constants at 20, 25 and 30ºC by extrapolation from the Arrhenius plot Temperature (ºC) Rate constant (k) (hour –1 ) 20 0.131 25 0.152 30 0.186
  18. 18. Values of Activation energy and heat of activation from the Arrhenius plot  log k = log A - Ea / 2.303RT  For practical purposes Ea and Ha are considered equal for chemical reactions at constant pressure in which only solids and liquids are involved. Hence, Ea ~ Ha Temperature (ºC) Activation energy (Ea ) Heat of activation (Ha ) 20 12.78 Kcal / mole 12.78 Kcal / mole 25 11.92 Kcal / mole 11.92 Kcal / mole 30 10.75 Kcal / mole 10.75 Kcal / mole
  19. 19. Summary Table for Frequency Factor (A), Entropy of Activation (ΔS* ), Collision Number (Z), Probability Factor (P), Equilibrium Constant (K* ) and Free energy (ΔF* ) Frequency factor (A) 3.6 x 10-4 sec-1 Entropy of activation (ΔS* ) -5.69 Kcal / mole degree Collision number (Z) 6.21×1012 sec-1 Probability factor (P) 5.7 ×10-17 Equilibrium constant (K* ) 2.44×10-14 Free energy (ΔF* ) 3.85 Kcal / mole
  20. 20. Conclusions  Cinchocaine HCl follows 1st order degradation kinetics in 0.1 N HCl media  Shelf-Life ( t10 ) at 25 °C is 41.44 minutes in 0.1N HCl media  Avoid preparations with low pH and refrigerate

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