M.Pharm Quality Assurance-2-T (2009-2010) Title:- :- Solubility enhancement of paracetamol using cosolvency technique. Exp.No.

:Aim: To enhance the solubility of paracetamol powder using cosolvency technique. Reference: 1. Indian Pharmacopoeia, 1996, 2nd volume , Pg No.554,556. 2. Alfred martins, Physical Pharmacy-Physical chemical principles in the pharmaceutical science, 3rd edition ,Varghese Publishing House, Pg No.225. 3. Leon lechman The Theory and Practice of Industrial Pharmacy, 3rd edition, Varghese Publishing House, Pg.No.461. 4. Aultons pharmaceutics, The design & manufacture of medicines,2nd edition , Churchill Livingstone ,Pg No. 26, 311. Roll No:Date:Page No.:-

Requirements:

A 1) 2) 3) 4) B 1) 2) 3) 4) C 1) 2)

Chemical Paracetamol Cosolvent- Propyleneglycol Cosolvent- Polyethyleneglycol Solvent- Distilled water Apparatus Volumetric cylinder Glass road Beaker Pipette Instrument UV spectrophotometer Digital balance

Theory: Definition: Cosolvent: During chemical processing sometimes second solvent is added to the original solvent, generally in small concentration to form a mixture that greatly enhance the solvent power due to synergism this second solvent is Called cosolvent. Generally water miscible organic solvents are used to increase the solubility of the drug .This technique is based on the mechanism that poor solubility of drug in water results due to great differences in polarity of the two components, water is of very high polarity and the drug(which are lipophilic) has very low ________________________________________________________________________ School of Pharmacy and Technology Management.

M.Pharm Quality Assurance-2-T (2009-2010) Title:- :- Solubility enhancement of paracetamol using cosolvency technique. Exp.No.:Roll No:Date:Page No.:-

polarity.So addition of the cosolvent with the polarity value less than that of water reduces the differences between the polarity of the drug and water and there by improves the solubility . Cosolvent increases the solubility by reducing the interfacial tension. The polarity scale of solvent is defined by a property known as dielectric Constant. Some values of Dielectric Constants are givan as below: Water 80 Ethanol 24 Glycerin 42 Propylene glycol 32 Most poorly soluble drugs have Dielectric Constant values of less than 20. Certain non aqueous solvents used as cosolvents in parenterals are: Glycerol formal, Glycerol dimethyl ketal, Dimethyl acetamide, Ethyl Lactate, Ethyl carbonate.

Procedure: 1. Take 500mg of drug and dissolve in 10 ml. of distilled water which is used as a solvent. 2. Prepare the other cosolvent system in different proportion which are mentioned in the observation table. 3. Keep the all vials on the rotary mixture for mixing purpose around about 12 hours. 4. After mixing keep the all vials for centrifugation. 5. Filter the solution with the help of whatman filter paper. 6. Take the absorbance of the filtrate at 257 maximum wavelength of paracetamol. 7. If dilution is required then dilute the solution with the required proportion of cosolvent. 8. Draw the calibration curve and determine the absorbance and concentration using U.V. spectroscopy and correlate with the solubility..

Observation Table: Table No.: 1 Calibration curve: Concentration (mcg/ml) 8 10 12 14 16 Absorbance 0.2789 0.3456 0.4419 0.4804 0.5731

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M.Pharm Quality Assurance-2-T (2009-2010) Title:- :- Solubility enhancement of paracetamol using cosolvency technique. Exp.No.:Roll No:Date:Page No.:-

Conc
0.7 0.6 concentration 0.5 0.4 0.3 0.2 0.1 0 0 5 10 absorbance 15 20 Conc Linear (Conc) y = 0.0362x - 0.0104 R = 0.988

Table No.: 2 For Propylene glycol: Sr.No. 1 2 3 4 5 6 7 8 9 10 Solvent : Cosolvent Ratio 10:0 9.5:0.5 9:1 8.5:1.5 8:2 7.5:2.5 7:3 6.5:3.5 6:4 5.5:4.5 Absorbance 0.0790 0.1610 0.1862 0.1880 0.1932 0.3000 0.3252 0.3612 0.3885 0.3890 Concentration (mcg/ml) 2472 4750 5450 5500 5644 8611 9311 10311 11069 11083

Calculation: According Graph Y= 0.036x-0.010 Here Y = absorbance X= concentration As per 1st reading 0.0790=0.036x-0.010 X= 0.0890.036 =2.472 mcg/ml ________________________________________________________________________ School of Pharmacy and Technology Management.

M.Pharm Quality Assurance-2-T (2009-2010) Title:- :- Solubility enhancement of paracetamol using cosolvency technique. Exp.No.:Roll No:Date:Page No.:-

Dilution factor: Take 0.1 ml above stock solution & dilute in 100 ml distilled water. Take 1 ml above solution dilute in 10 ml distilled water. So dilution factor 10010 =1000 Now, X= 2.472 1000= 2472mcg/ml
50 45 40 35 30 25 20 15 10 5 0

concentration (mg/ml)

Conc for PEG

Solvent:cosolvent ratio

Table No.: 3 For Polyethylene glycol:

Sr.No. 1 2 3 4 5 6 7 8 9 10

Solvent : Cosolvent Ratio 10:0 9.5:0.5 9:1 8.5:1.5 8:2 7.5:2.5 7:3 6.5:3.5 6:4 5.5:4.5

Absorbance 0.1488 0.2077 0.2698 0.2925 0.3055 0.3794 1.3511 1.4913 1.5232 1.5414

Concentration (mcg/ml) 4411 6047 7772 8402 8763 10816 37808 41702 42588 43094

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M.Pharm Quality Assurance-2-T (2009-2010) Title:- :- Solubility enhancement of paracetamol using cosolvency technique. Exp.No.:Roll No:Date:Page No.:-

12 concentration (mg/ml) 10 8 6 4 2 0 Conc for PG

solvent:cosolvent ratio

Results:

Sr.No. 1 2 3 4 5 6 7 8 9 10

Solvent : Cosolvent Ratio 10:0 9.5:0.5 9:1 8.5:1.5 8:1 7.5:2.5 7:3 6.5:3.5 6:4 5.5:3.5

Concentration (mg/ml) (for PG) 2.472 4.750 5.450 5.500 5.644 8.611 9.311 10.311 11.069 11.083

Concentration (mg/ml) (for PEG) 4.411 6.047 7.772 8.402 8.763 10.816 37.808 41.702 42.588 43.094

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M.Pharm Quality Assurance-2-T (2009-2010) Title:- :- Solubility enhancement of paracetamol using cosolvency technique. Exp.No.:Conclusion:
50 45 40 35 30 25 20 15 10 5 0

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Conc (mg/ml

Conc for PG Conc for PEG

Solvent: cosolvent ratio

1. According to above result it can be concluded that for both PG &PEG, solubility of paracetamol increases as the ratio of cosolvent increases. 2. From the above graph it can be concluded that PEG is the better cosolvent to enhance the solubility of PCM.

DATE: GRADE: SIGN:

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