Formulation Exercise – Replication Of A Marketed Product

1,359 views
1,233 views

Published on

Formulation Exercise – Replication Of A Marketed Product

0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
1,359
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
1
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide

Formulation Exercise – Replication Of A Marketed Product

  1. 1. By : Debanjan Das {DISCLAIMER: Certain details pertaining to proprietorship of the product has been deleted. This exercise is solely for enhancement of knowledge-base and not for any “for-profit” venture} Product Formulation Exercise – Replication of a Marketed Product
  2. 2. Marketed Product chosen: Children’s Pedia Care® Night Rest Cough and Cold Manufactured by Pharmacia Consumer Healthcare (Pfizer)
  3. 3. Drug Facts Ingredients Use Quantity(100ml) Chlorpheniramine maleate Antihistamine 20 mg Dextromethorphan HBr Cough suppressant 150mg Pseudoephedrine HCl Nasal decongestant 300mg Corn Syrup Sweetener - Glycerin Solvent, Preservative Up to 20% Propylene Glycol Solvent, Preservative 10-25% Sorbitol Sweetner, Vehicle 20-35% Sodium Carboxymethylcellulose Viscosity builder 0.1-1% Sodium Benzoate Preservative 0.02-0.5% Citric acid 0.1-2% FD&C Red No 40 Colorant <0.001% Water Vehicle
  4. 4. Measured properties of marketed product Properties of the marketed product pH 3.5 Relative Density 1.2548 Viscosity 50.593 cps Color Pinkish Red Flavor Cherry
  5. 5. Chosen Lab Ingredients Ingredients Suppliers Lot no Chlorphenaramine maleate City Chemical, CT 99D318 Dextromethorphan HBr Sigma-Aldrich Co, MO 013K1428 Pseudoephedrine HCl Sigma-Aldrich Co, MO 11E0090 Light Corn Syrup Englewood Cliffs, NJ 33902 Glycerin, USP; 99.5% Ruger Chemical Co. Inc., NJ 1211-6 Propylene Glycol Ruger Chemical Co. Inc., NJ 782902 Sorbitol Ruger Chemical Co. Inc., NJ 1024-6 Sodium Carboxymethylcellulose, High Viscosity, 2120 cps Ruger Chemical Co. Inc., NJ P34488F11 Sodium Benzoate Amend Drug & Chemical Co. Inc., NJ C65138P28 Citric acid Monohydrate Sigma Chemical Co., MO 126H0140 Cherry Syrup
  6. 6. Solubility Data for drugs: Chlorpheniramine maleate 1g in 4ml water, in 10 ml chloroform/alcohol Dextromethorphan HBr 1g in 65 ml, freely soluble in alcohol/chloroform Pseudoephedrine HCl 1g in 0.5 ml water, 3.6ml alcohol,91ml chloroform
  7. 7. Arbitrary trial batch – first step Ingredients Quantity (50 ml) Chlorphenaramine maleate 10 mg Dextromethorphan HBr -- Pseudoephedrine HCl 150 mg Corn Syrup 8% Glycerin 16% Propylene Glycol 15% Sodium Benzoate 0.3% Sodium Carboxymethylcellulose 0.5% Sorbitol 25% Citric acid 0.5% Water q.s. 50 ml pH 3.2 Density 1.0928 Viscosity 18.468 cps
  8. 8. Initial formulation challenges Inability to achieve desired viscosity pH
  9. 9. Summary of adopted trial batches Ingredients #1 #2 #3 #4 #5 #6 #7 #8 Chlorphenaramine maleate 10mg Dextromethorphan HBr --- Pseudoephedrine HCl 150mg Corn Syrup (%) 8 16 24 20 16 16 16 16 Glycerin (%) 16 10 10 10 10 4 4 4 Propylene Glycol %) 15 10 10 10 10 10 10 10 Sodium Benzoate %) 0.3 12 8 8 8 8 8 25 Sodium CMC (%) 0.5 0.4 1.0 0.5 0.4 0.4 0.4 0.4 Sorbitol(%) 25 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Citric acid(%) 0.5 0.3 0.3 0.3 0.3 0.3 0.3 0.3 Water(q.s) 50ml pH 3.4 3.4 3.4 3.4 3.4 3.4 3.4 3.4 Density 1.0928 Viscosity 18.468 cps 34.95 64.61 48.8 42.62 22.1 21.66 58.21
  10. 10. Ingredients #9 #10 #1 1 #12 #13 # 1 4 #15 #16 #17 #18 #19 Chlorphenarami ne maleate 10mg Dextromethorph an HBr -- 75mg Pseudoephedrine HCl 150mg Corn Syrup (%) 16 18 22 25 25 25 16 16 16 16 16 Glycerin (%) 4 4 4 4 4 4 4 4 4 4 4 Propylene Glycol %) 10 10 10 10 10 10 10 10 10 10 10 Sodium Benzoate %) 16 12 10 8 8 8 20 20 20 20 20 Sodium CMC (%) 0.4 0.4 0.4 0.4 0.4 0.4 0.4 0.3 0.4 0.5 1.0 Sorbitol(%) 0.1 0.1 0.1 0.1 0.3 0.1 0.1 0.1 0.1 0.1 0.1 Citric acid(%) 0.3 0.3 0.3 0.3 0.5 0.3 0.3 0.3 0.3 0.3 0.3 Water(q.s) 50ml pH 3.4 3.4 3.4 3.4 3.4 3.4 3.4 3.4 3.4 3.4 3.4 Density Viscosity 32.01 35.53 44. 8 2 47.7 1 47.71 48.12 47. 6 2 6 13.89 47.626 65.53 135.48
  11. 11. Systematic approach to arrive at the desired viscosity Corn syrup was tried in the first set of trials Increasing concentrations were corn syrup were uses keeping the other ingredients constant A close viscosity was achieved
  12. 12. Corn Syrup (cont.) Ingredients Quantity (50ml) Quantity (50ml) Quantity (50ml) Quantity (50ml) Chlorphenaramine maleate 10 mg 10 mg 10 mg 10 mg Dextromethorphan HBr -- -- -- -- Pseudoephedrine HCl 150 mg 150 mg 150 mg 150 mg Corn Syrup 8% 16% 24% 20% Glycerin 10% 10% 10% 10% Propylene Glycol 10% 10% 10% 10% Sorbitol 25% 12% 8% 8% Na CMC 0.4% 0.4% 0.4% 0.4% Sodium Benzoate 0.3% 0.3% 0.3% 0.3% Citric acid 0.5% 0.5% 0.5% 0.5% Water q.s. 50 ml q.s. 50 ml q.s. 50 ml q.s. 50 ml pH 3.4 3.4 3.4 3.4 Density 1.0928 1. 162 1.3721 1.241 Viscositiy 18.47 34.95 64.61 48.89
  13. 13. Graphical representation Effect of Corn Syrup on Viscosity 0 10 20 30 40 50 60 70 0 5 10 15 20 25 30 Concentration of Corn Syrup Viscosityincps
  14. 14. Problems faced Glycerin was used at a high concentration of about 10% It has a very unpleasant taste which in high quantities makes it unsuitable for pediatric preparations
  15. 15. Trial with glycerin Ingredients Quantity (50 ml) Quantity(50ml) Chlorphenaramine maleate 10 mg 10 mg Dextromethorphan HBr -- -- Pseudoephedrine HCl 150 mg 150 mg Corn Syrup 16% 16% Glycerin 10% 4% Propylene Glycol 10% 10% Sorbitol 8% 8% Sodium Carboxymethylcellulose 0.4% 0.4% Sodium Benzoate 0.3% 0.3% Citric acid 0.5% 0.5% Water q.s. 50 ml q.s. 50 ml pH 3.4 3.4 Density 1.2005 1.0951 Viscosity 42.62 22.12
  16. 16. Problems faced Decreasing the glycerin concentration to 4% lead to reduced viscosity Other viscosity building agents were tried
  17. 17. Trials with Sorbitol Ingredients Quantity (50 ml) Quantity (50 ml) Quantity (50 ml) Chlorphenaramine maleate 10 mg 10 mg 10 mg Dextromethorphan HBr -- -- -- Pseudoephedrine HCl 150 mg 150 mg 150 mg Corn Syrup 16% 16% 16% Glycerin 4% 4% 4% Propylene Glycol 10% 10% 10% Sorbitol 8% 25% 20% Sodium Carboxymethylcellulose 0.4% 0.4% 0.4% Sodium Benzoate 0.3% 0.3% 0.3% Citric acid 0.5% 0.5% 0.5% Water q.s. 50 ml q.s. 50 ml q.s. 50 ml pH 3.4 3.4 3.4 Density 1.093 1.293 1.221 Viscosity 21.66 58.21 47.626
  18. 18. Graphical representation Effect of Sorbitol on Viscosity 0 10 20 30 40 50 60 70 0 5 10 15 20 25 30 Concentration of Sorbitol Viscosityincps
  19. 19. Problems faced Sorbitol is synthetic and used in high proportions ( 20% ) to attain the desired viscosity Attempt was made to lower its concentration and to compensate with Na CMC
  20. 20. Trials with Na CMC Ingredients Quantity (50 ml) Quantity (50 ml) Quantity (50 ml) Quantity (50 ml) Chlorphenaramine maleate 10 mg 10 mg 10 mg 10 mg Dextromethorphan HBr -- -- -- -- Pseudoephedrine HCl 150 mg 150 mg 150 mg 150 mg Corn Syrup 16% 16% 16% 16% Glycerin 4% 4% 4% 4% Propylene Glycol 10% 10% 10% 10% Sorbitol 20% 20% 20% 20% Sodium Carboxymethylcellulose 0.3% 0.4% 0.5% 1.0% Sodium Benzoate 0.3% 0.3% 0.3% 0.3% Citric acid 0.5% 0.5% 0.5% 0.5% Water q.s. 50 ml q.s. 50 ml q.s. 50 ml q.s. 50 ml pH 3.4 3.4 3.4 3.4 Density 1.052 1.221 1.361 1.582 Viscosity (cps) 13.89 47.626 65.53 135.48
  21. 21. Graphical representation Effect of NaCMC on Viscosity 0 20 40 60 80 100 120 140 160 0 0.2 0.4 0.6 0.8 1 1.2 Concentration NaCMC Viscosityincps
  22. 22. Problems faced Concentration of NaCMC must be fine tuned because a small increase ( 0.1%), lead to high increase in viscosity (17.9 cps ) Dissolution of NaCMC is difficult, due to slow hydration Hence, a stock solution ( 200 mL of 0.8% w/v) was prepared and aliquots were used from it Sufficient time was given for its complete hydration Trials with increased corn syrup were tried since it is difficult to control viscosity using Na CMC
  23. 23. Trials with increased corn syrup decreased sorbitol conc.: Ingredients Quantity (50 ml) Quantity (50 ml) Quantity (50 ml) Quantity (50 ml) Chlorphenaramine maleate 10 mg 10 mg 10 mg 10 mg Dextromethorphan HBr -- -- -- -- Pseudoephedrine HCl 150 mg 150 mg 150 mg 150 mg Corn Syrup 16% 18% 22% 25% Glycerin 4% 4% 4% 4% Propylene Glycol 10% 10% 10% 10% Sorbitol 16% 12% 10% 8% Na CMC 0.4% 0.4% 0.4% 0.4% Sodium Benzoate 0.3% 0.3% 0.3% 0.3% Citric acid 0.5% 0.5% 0.5% 0.5% Water q.s. 50 ml q.s. 50 ml q.s. 50 ml q.s. 50 ml pH 3.4 3.4 3.4 3.4 Density 1.102 1.183 1.167 1.211 Viscosities 32.01 35.53 44.82 47.71
  24. 24. Optimizing pH Sodium benzoate and citric acid was so far used in the concentrations of 0.3% and 0.5% respectively Attempt was made to reduce the preservative concentration and still arrive at the desired pH
  25. 25. Effect on pH Ingredients Quantity (50 ml) Quantity (50 ml) Chlorphenaramine maleate 10 mg 10 mg Dextromethorphan HBr 75mg 75mg Pseudoephedrine HCl 150 mg 150 mg Corn Syrup 25% 25% Glycerin 4% 4% Propylene Glycol 10% 10% Sorbitol 8% 8% Sodium Carboxymethylcellulose 0.4% 0.4% Sodium Benzoate 0.3% 0.1% Citric acid 0.5% 0.3% Water q.s. 50 ml q.s. 50 ml pH 3.4 3.4 Density 1.211 1.22 Viscosity (cps) 47.71 48.12
  26. 26. Scale up X 5 Ingredients Quantity (50 ml) Quantity (250 ml) Chlorphenaramine maleate 10 mg 0.05g Dextromethorphan HBr 75mg 0.75g Pseudoephedrine HCl 150 mg 0.375g Corn Syrup 12.5 ml 62.5 ml Glycerin 2ml 10ml Propylene Glycol 5ml 25ml Sorbitol 4ml 20ml Sodium Carboxymethylcellulose 0.4% 0.4% Sodium Benzoate 0.05g 0.25g Citric acid 0.15g 0.75g Water q.s. 50 ml q.s.250 ml pH 3.4 3.4 Density 1.22 1.321 Viscosities 47.12 53.27
  27. 27. Problems faced Minute particulate matters seemed to adhere with the container wall Solubility problems occurred Drug? NaCMC? Viscosity increased by a small extent No problems with pH encountered
  28. 28. Stability studies Studies were done in freezing temperatures at zero degree centigrade for 5 days The marketed formulation did not freeze but the replicated product solidified (?) However, once left at room temperature, it liquefied in less than 15 mins without showing any precipitation problems
  29. 29. Conclusion The desired viscosity and pH could be reasonably achieved by doing the scale up which validated the lab scale formula However, there were some solubility problems seen during the scale up Stability of preparation was plausible

×