Cot curve, melting temperature, unique and repetitive DNA
Ppt noopur,anirudh 1-27-02-2018
1. Dr. R K Maheshwari
Prof. (Ex-Head)
Department of Pharmacy
SGSITS, Indore
Contact no:09406621907
Email id: rkrkmaheshwari@yahoo.co.in
Website: www.rkmaheshwari.com
1
ECOFREINDLY PHARMACEUTICAL
APPLICATIONS OF –
1.HYDROTROPIC SOLUBILIZATION
2.MIXED HYDROTROPIC
SOLUBILIZATION
3.MIXED SOLVENCY CONCEPT
2. All substances whether liquids, gases or solids have solubilizing
power.
Liquids are already known as solvents.
In supercritical fluid technology, carbon di oxide gas is liquefied to act
as solvent to produce nanoparticles etc.
There are many proofs to show the solubilizing power of solids.
2
3. Solid substances can act as solvents if they are melted e.g.
If PEG 4000 is melted at about 60°C, this melted liquid dissolves
diclofenac sodium (m.p 283°C).
Melted ibuprofen (m.p. 78°C) dissolves diclofenac sodium (m.p.
283°C), salicylic acid (m. p. 159°C) etc.
Melted urea (132°C) dissolves diclofenac sodium (m.p. 283°C).
Solubility of nalidixic acid in ethanolic solution of Ibuprofen (20% w/v) is
2.689%w/v (Solubility of nalidixic acid in ethanol is 0.1981%w/v)- 13
times enhancement
3
4. Eutectic liquid obtained by triturating equal proportions of menthol (a solid)
and thymol (a solid) dissolves salicylic acid, metronidazole benzoate,
Atenolol, Ornidazole, Benzocaine, Eudragit RSPO, Euragit RLPO,
Resorcinol , Diltiazem HCl, BHA nicely while the same eutectic liquid is bad
solvent for Satranidazole, Frusemide, Nimesulide, Aspartame, Carvedilol,
Gatifloxacin, Piroxicam, Methyl Paraben Sodium.
4
We know that the solvents like ethanol, methanol etc are also
solvents for some solutes and non-solvents for others.
5. Any poor solvent may be made a strong solvent by use of proper
solubilizers.
It may reduce the total concentration of individual solubilizers necessary to
produce modest increase in solubility by employing additives in lower
concentrations from the point of view of safety of solubilizers. This approach
shall be applicable to prepare different dosage forms of the poorly soluble
drugs.
The mixed solvency approach can be utilized to perform titrimetric and
spectrophotometric analysis of poorly soluble drugs precluding the use of
organic solvents.
5
6. The approach shall be useful to develop various novel drug delivery systems using
safer solvents precluding the use of toxic, pollutant organic solvents.
Synergistic action in solvent character can be obtained. For example solubilities of
Ibuprofen in aqueous solutions of 40 % w/v PEG 400 (a solvent), 40 % w/v PEG
4000(solid substance), 40 % w/v Urea, and 40 % w/v sodium citrate (hydrotropic
agent) are 0.593% w/v, 0.440% w/v, 0.599 % w/v and 0.531% w/v respectively.
However, an aqueous solution made by mixing 10% w/v each of PEG 400, PEG
4000, urea and sodium citrate (total dissolved substances 40 % w/v) has solubility of
1.329% w/v for ibuprofen. This shows synergistic solvent action due to application of
mixed solvency.
6
7. Carbon dioxide gas on liquefaction, dissolves solutes to obtain
nanoparticles.
This technology is used for extractions of active constituents from
herbals.
This technology is used for purification of solutes.
Liquefied carbon dioxide gas is solvent for some solutes and non
solvent for others.
Any liquefied gas ( oxygen, hydrogen, nitrogen etc ) shall also be
solvent for some solutes and non solvent for others.
This proves that gases posses solvent character.
7
14. Thymol-camphor
Phenol-aspirin
Phenol-vanillin
Phenol-caffeine
Menthol-camphor
14
All these liquids can act as solvents for some drugs and non-
solvents for others. These all studies also indicate that solids
also possess solvent character.
17. Drug Solvent system Solubility(%w/v)
Nalidixic acid Alcohol 0.198
Nalidixic acid 20% Ibuprofen in alcohol 2.689
Nalidixic acid 20% Ibuprofen+20%
Benzoic acid in alcohol
5.753
Nalidixic acid 20% Oleic acid in alcohol 0.621
Nalidixic acid 15% Niacinamide in
alcohol (pH 3-3.5)
0.347
Nalidixic acid 20% Camphor in alcohol
(pH 4.5)
0.221
Nalidixic acid 7% Atenolol in alcohol (pH
8.5-9.0)
8.545
17
18. Drug Solvent system Solubility(%w/v)
Frusemide Alcohol 1.769
Frusemide 20% Oleic acid in alcohol 2.947
Frusemide 20% Ibuprofen in alcohol 5.009
Frusemide 15% Niacinamide in
alcohol (pH 3-3.5)
5.009
Frusemide 20% Tween20 in alcohol
(pH 4-4.5)
6.777
Frusemide 20% Ibuprofen+20%
Benzoic acid in alcohol
0.630
Frusemide 20% Camphor in alcohol
(pH 4.5)
3.830
Frusemide Alcohol saturated with
niacinamide
8.381
18
19. Drug Solvent system Solubility(%w/v)
Salicylic acid Alcohol 31.746
Salicylic acid 20% Oleic acid in alcohol 24.856
Salicylic acid 20% Ibuprofen in alcohol 27.316
Salicylic acid 20% Tween20 in alcohol
(pH 4-4.5)
33.592
Salicylic acid 20% Camphor in alcohol
(pH 4.5)
36.456
19
20. Phenol, below 8 % w/v concentration and above 70 % w/v
concentration gives clear solutions in water.
5 gm phenol + 95 gm water gives a clear solution (here phenol
is solute and water is solvent).
95 gm phenol + 5 gm water gives a clear solution (here water
is solute and phenol is solvent).
This proves that solid has solvent action.
Soxhelet apparatus can be run by phenol (like solvent).
20
22. S
no.
Blend composition Observed
Solubility
(% w/v)
Contributory
solubility
(% w/v)
1 GL-PG-ST-UR (10% w/v each solubilizer) 0.526 0.427
2 GL-FT-TH-UR (10% w/v each solubilizer) 0.425 0.713
3 FH-FT-UR-SC (10% w/v each solubilizer) 1.329 0.541
4 GL-PG-FH-UR (10% w/v each solubilizer) 0.732 0.448
5 PG-TH-FT-SC (10% w/v each solubilizer) 1.110 0.743
6 TH-FH-FT-ST (10% w/v each solubilizer) 0.877 0.731
7 GL-FH-TH-SC (10% w/v each solubilizer) 0.938 0.734
8 FT-ST-FH-UR (10% w/v each solubilizer) 0.764 0.498
9 FH-TH-UR-SC (10% w/v each solubilizer) 1.146 0.814
10 FT-TH-PG-UR (10% w/v each solubilizer) 0.952 0.460
22
23. 5% (Sodium benzoate + benzoic acid) as buffering agent
5% Lignocain HCl as local anesthetic (to reduce the pain of
injection)
4% Benzyl alcohol as preservative and/or as local anesthetic
2.5% Niacinamide(as stabilizer)
5% Alcohol (upto 10% alcohol can be used)
5% Propylene glycol ( even very large amounts can be safely used)
23
24. 5% PVP (plasma expander)
5% Tween (20/80 etc)
5% HP Beta Cyclodextrin
5% PEG 200/300/400/500/600 etc. (liquids)
5% PEG 4000/6,000/8,000/10,000 etc. (solids)
24
25. Various glycerides of –
1. Stearic acid-3.1%
2. Palmitic acid- 8.3%
3. Oleic acid- 56 %
4. Arachidic acid- 2.4 %
5. Behenic acid- 3.1 %
6. Lignoceric acid- 1.1%
7. Linoleic acid- 26 %
Glyceryl monostearate- a waxy solid of M.P. 63-68 .℃
Glyceryl tripalmitate-a solid having M.P. 66 .℃
Glyceryl monooleate- a solid having M.P. 25 .℃
Glyceryl trioleate-a yellowish oily liquid.
Thus peanut oil consists of several solids and liquids. The present
solid also contributes in the solvent action of peanut oil.
25
39. Naproxen solubility in propylene glycol-0.402% (4.02 mg/ml)
BLEND 1
( M Pharm thesis work of Ms. Lalita Gaur)
S. No. Ingredients Concentration
1 Sodium benzoate 5% w/v
2 Benzoic acid 5% w/v
3 Niacinamide 5% w/v
4 PVP 40000 5% w/v
5 Propylene glycol Up to 100% w/v
Solubility in blend 1 ( 4.81%)
Solubility enhancement- 11.94 Times
40. BLEND 2
( M Pharm thesis work of Ms. Lalita Gaur)
S. No. Solubilizers Concentration
1. Sodium benzoate 2% w/v
2. Benzoic acid 5% w/v
3. Niacinamide 5% w/v
4. PVP 40000 3% w/v
5. Propylene glycol Upto 100% w/v
Solubility in blend-2 (4.53%)
Solubility enhancement- 11.2 times
41. A model dry injection for reconstitution
Model Blend Composition
Sodium benzoate – 5% w/v
Lignocaine HCl – 5% w/v
PVP K 30 – 5% w/v
Niacinamide – 2.5% w/v
PEG 4000 – 7.5% w/v
Water, upto – 100 ml
Solubility of aspirin in this blend at room temperature =
8.811% w/v (pH = 6)
Solubility of aspirin in water at room temperature = 0.331%
w/v
Therefore, solubility enhancement ratio = 8.811/0.331= more
than 25 fold
41
42. NOTE: Sodium benzoate 5% w/v is widely used as
buffering agent in aqueous injections.
Lignocaine hydrochloride 5% w/v is employed as an
additive to reduce the pain (of injections).
PVP K30 5% w/v is safely used additive.
Niacinamide 2.5% w/v is safely used stabilizer in
injections.
PEG 4000 7.5%w/v, safely employed additive.
42
43. 100 mg Aspirin can be easily dissolved by 2 ml of
above blend (Mixed solvent blend).
100 mg Sodium benzoate, fine powder.
100 mg Lignocaine hydrochloride, fine powder.
100 mg PVP K30, fine powder.
50 mg Niacinamide, fine powder.
150 mg PEG4000
+ 100 mg Aspirin, fine powder.
All these are kept in a 5 ml vial. After reconstitution,
using 2 ml water, we get a clear solution.
43
44. Drug Solubility in
distilled water
at room
temperature
(%w/v)
Solubility in
model blend at
room
temperature
(%w/v)
Solubility
enhancement
ratio
Aspirin 0.331 8.811 26.6 fold
Norfloxacin 0.088 0.652 7.4 fold
Tinidazole 0.538 1.206 2.2 fold
Piroxicam 0.040 0.994 24.8 fold
Frusemide 0.064 2.013 31.4 fold
Indomethacin 0.036 3.009 83.6 fold
44
45. Tablet powder equivalent to 50 mg was transfered
to 500 ml volumetric flask.
Then, 10 ml of eutectic liquid of
Phenol: Niacinamide (25:10) was transfered to it
and the flask was shaken for 10 min.
Then, about 400 ml distilled water was added and
flask was shaken for 5 min and volume was made
upto 500 ml with distilled water.
Above solution was filtered through Whatmann
filter paper.
45
46. Then, 10 ml of filtrate was diluted to 50 ml with
distilled water and the absorbance of filtrate was
noted at 318 nm against reagent blank.
The drug content was calculated using the
calibration curve.
46
47. Enhancement in aqueous solubility of a poorly water soluble drug in
the presence of large concentration of a solute (hydrotropic agent).
Concentrated (20 to 50 %) aqueous solution of sodium benzoate,
sodium salicylate, sodium ascorbate, niacinamide and urea etc.
enhances the aqueous solubility of poorly soluble drugs. For
example 30% w/v aqueous solution of sodium benzoate increases
the solubility of ibuprofen, ketoprofen, nalidixic acid, naproxen,
ornidazole, tinidazole, metronidazole, gatifloxacin etc. to a large
extent.
47
48. Same concepts can be utilized for
Extractions of herbal drugs to obtain the active constituents.
In analytical techniques like – TLC, titrimetric analysis and
spectrophotometric analysis of poorly water soluble drugs.
To develop various novel drug delivery systems of herbal origin.
48
The concept shall be very useful in all above mentioned fields. The
common advantage being avoidance of organic solvents (which may
be costlier, hazardous, pollutant).
51. Drug Solvent system Solubility
(% w/v)
Solubility
enhancement
ratio
Ibuprofen DW 0.028 -
Ibuprofen 2 M SB 2.390 85.4
Flurbiprofen DW 0.012 -
Flurbiprofen 2 M SB 1.440 120.0
Naproxen DW 0.009 -
Naproxen 2 M SB 1.081 120.1
Aspirin DW 0.131 -
Aspirin 4 M SA 7.409 56.5
Aspirin 1.25 M SC 4.728 36.1
Aspirin 2 M SB 3.151 24.1
51
52. Drug Solvent system Solubility
(% w/v)
Solubility
enhancement
ratio
Aceclofenac DW 0.011 -
Aceclofenac 2 M SB 11.032 1002.9
Ketoprofen DW 0.007 -
Ketoprofen 4 M SA 0.944 134.9
Ketoprofen 2 M SB 12.321 1760.1
Ketoprofen 2 M SS 2.062 294.6
Metronidazole DW 0.728 -
Metronidazole 2 M SB 3.783 5.2
Metronidazole 2 M NM 7.941 10.9
Metronidazole 10 M UR 3.682 5.1
52
53. Drug Solvent system Solubility
(% w/v)
Solubility
enhancement
ratio
Tinidazole DW 0.538 -
Tinidazole 2 M SB 3.302 6.1
Tinidazole 2 M NM 3.794 7.1
Tinidazole 10 M UR 3.821 7.1
Norfloxacin DW 0.088 -
Norfloxacin 2 M SB 3.822 43.4
Norfloxacin 2 M NM 0.851 9.7
Nalidixic acid DW 0.021 -
Nalidixic acid 2 M SB 2.061 98.1
Nalidixic acid 2 M NM 0.452 21.5
53
54. Drug Solvent
system
Solubility
(% w/v)
Solubility
enhancement
ratio
Hydrochlorothiazide DW 0.039 -
Hydrochlorothiazide 10 M UR 1.784 45.7
Ofloxacin DW 1.452 -
Ofloxacin 2 M SB 8.560 5.9
Gatifloxacin DW 0.131 -
Gatifloxacin 10 M UR 8.183 62.5
Atenolol DW 1.112 -
Atenolol 10 M UR 6.814 6.1
Salicylic acid DW 0.170 -
Salicylic acid 1.25 M SC 15.059 88.6
54
55. SOME CLASS 3 SOLVENTS SOME CLASS 2 SOLVENTS
Ethanol Acetonitrile
Isopropyl acetate Chlorobenzene
Acetone Chloroform
Anisole Cyclohexae
1-Butanol Dichloromethane
2-Butanol Methanol
Dimethyl sulfoxid N,N-Dimethylacetamide
Acetone N,N-Dimethylformamide
Ethyl acetate 1,4-Dioxane
Heptane Formamide
Ethyl formate Ethylene glycol
55
59. Amount of
drug taken
Method of
Analysis
Amount
estimated
%coefficient
of variation
Standard
error
400 mg IP method 398.9±0.63 0.63 0.36
400 mg Proposed
method
398.3±0.70 0.70 0.40
59
62. Involves use of dimethyl formamide (DMF), a
class 2 organic solvent in the titrimetric method.
Analysis of frusemide bulk drug (hydrotropic
method) -organic solvent has been replaced by 2
M sodium benzoate solution.
62
63. Drug Hydrotrope
Aspirin (bulk) 2 M Sodium benzoate
4 M Sodium acetate
1.25 Sodium citrate
2 M Sodium salicylate
2 M Niacinamide
0.5 M Ibuprofen sodium
Sodium citrate
Aspirin (tablet) 2 M Niacinamide
2 M Sodium salicylate
0.5 M Ibuprofen sodium
2 M Sodium benzoate
10 M Urea
1.5 M Metformin HCl
63
64. Drug Hydrotrope
Aceclofenac (bulk) 2.5 M Sodium salicylate
2 M Sodium benzoate
0.5 M Ibuprofen sodium
1.5 M Metformin Hcl
(22.5:22.5) Sodium citrate : urea
NNDU : Sodium citrate(20:20)
Aceclofenac (Tablets) 0.5 M Ibuprofen sodium
2 M Sodium salicylate
(22.5:22.5) Sodium citrate : urea
2 M Sodium benzoate
Chlorpropamaide (bulk) 0.5 M Ibuprofen sodium
2 M Sodium benzoate
64
65. Drug Hydrotrope
Benzoic acid 2 M Sodium benzoate
2 M Sodium salicylate
1 M Calcium disodium edetate
1.5 M Ibuprofen sodium
7.5 M N-N Dimethyl Urea
Flurbiprofen (bulk) 2 M Sodium benzoate
0.5 M Ibuprofen sodium
Flurbiprofen (tablet) 2 M Sodium benzoate
Frusemide (bulk) 0.5 M Ibuprofen sodium
2 M Sodium salicylate
5 M Urea + 1 M Sodium acetate + 0.4 M Sodium citrate
15% NM in ethanol
7.5 M N-N Dimethyl Urea
65
66. Drug Hydrotrope
Frusemide (tablet) 2 M Sodium salicylate
5 M Urea + 1 M Sodium acetate + 0.4 M Sodium
citrate
15% Niacinamide in ethanol
0.5 M Ibuprofen sodium
7.5 M N-N Dimethyl Urea
20% Tween 20 in ethanol
Ibuprofen (bulk) 2 M Sodium benzoate
0.5 M Ibuprofen sodium
Mixed solvency
20 % Chlorpheniramine
7.5 M N-N Dimethyl Urea
66
67. Drug Hydrotrope
Ibuprofen (Tablet) 2 M Sodium benzoate
0.5 M Ibuprofen sodium
20 % Chlorpheniramine
7.5 M N-N Dimethyl Urea
Ketoprofen (bulk) 2 M Sodium benzoate
2 M Sodium salicylate
2 M Sodium acetate
2 M Potassium acetate
0.5 M Ibuprofen sodium
2 M Potassium citrate
1 M Aspirin sodium
30:30 Sodium acetate: Urea
30 Urea, 13.6 Sodium acetate, 11.8 Sodium
citrate
67
68. Drug Hydrotrope
Naproxen (bulk) 2 M Sodium benzoate
2 M Niacinamide
0.5 M Ibuprofen sodium
2 M Sodium Salicylate
7.5 M N-N Dimethyl Urea
Naproxen (Tablet) 2 M Sodium benzoate
2 M Niacinamide
0.5 M Ibuprofen sodium
2M sodium Salicylate
2 M Sodium benzoate
Phenlybutazone 2 M Sodium benzoate
0.5 M Ibuprofen sodium
68
69. Drug Hydrotrope
Salicylic acid 2 M Sodium benzoate
8 M Urea
1.25 M Sodium citrate
0.5 M Ibuprofen sodium
Sodium salicylate
1 M Calcium disodium edetate
Mixed solvency
2 M Sodium saccharin
7.5 M N-N Dimethyl Urea
69
75. Sodium benzoate and niacinamide do not show
absorbence above 290 nm, therefore they do not
interfere in spectrophotometric analysis above 300 nm.
Urea, sodium acetate and sodium citrate do not show
absorbence above 245 nm, therefore they do not
interfere in spectrophotometric analysis above 245 nm.
75
76. Drug Hydrotrope Wavelength
Aceclofenac (tablet) Urea : Sodium citrate (22.5 : 22.5) 274 nm
N-N Dimethyl Urea : Sodium
citrate (20:20)
Amoxycillin 10 M Urea 274 nm
Atenolol 1 M Metformin HCl 275 nm
10 M Urea
Cefixime 8 M Urea 288 nm
4 M Sodium acetate
1.25 Sodium citrate
0.5 M Potassium citrate
2 M Sodium tartrate
2 M Sodium glutamate
7.5 M N-N Dimethyl Urea
76
77. Drug Hydrotrope Wavelength
Cephalexin 8 M Urea 262 nm
Diclofenac Sodium 10 M Urea 276 nm
7.5 M N-N Dimethyl Urea
Famotidine 1.5 M Metformin HCl 286 nm
7.5 M N-N Dimethyl Urea
10 M Urea
Frusemide (bulk) 0.5 M Ibuprofen Sodium 330 nm
5 m Urea + 1 M Sodium acetate + 0.4
M Sodium citrate
277 nm
20 : 20 N-N Dimethyl Urea : Sodium
citrate
330 nm
20 : 20 N-N Dimethyl Urea : Sodium
citrate
277 nm
Frusemide (tablet) 0.5 M Ibuprofen sodium 330 nm
5 m Urea + 1 M Sodium acetate + 0.4
M Sodium citrate
330 nm
77
78. Drug Hydrotrope Wavelength
Gatifloxacin
(Tablet)
1.5 M Metformin HCl 333 nm
2 M Sodium benzoate
0.5 M Ibuprofen Sodium 333 nm
7.5 M N-N Dimethyl Urea
Sodium citrate, Glycine, Sodium
benzoate,4000 (10:10:10:10)
333 nm
4 M Niacinamide 333 nm
N-N Dimethyl Urea : Sodium citrate (20:20) 333 nm
N-N Dimethyl Urea : Sodium citrate (20:20) 288 nm
7.5 M N-N Dimethyl Urea 288 nm
Indomethacin 2 M Sodium benzoate 320 nm
2 M Niacinamide 320 nm
78
79. Drug Hydrotrope Wavelength
Ketoprofen 2M Potassium acetate 260 nm
4 M Sodium acetate
(30:30) Sodium citrate: Urea
1.25 M Sodium citrate
7.5 M N-N Dimethyl Urea
30 Urea, 13.6 Sodium acetate, 11.8 Sodium
citrate
Metronidazole
(tablet)
2 M Sodium benzoate 320 nm
8 M Urea (simultaneous with norfloxacin)
7.5 M N-N Dimethyl Urea
10 M Urea
1.5 M Ibuprofen sodium
79
80. Drug Hydrotrope Wavelength
Naproxen
(Tablet)
2 M Niacinamide 317nm
2 M Sodium benzoate 331, 317nm
0.5 M Ibuprofen sodium 317 nm
7.5 M N-N Dimethyl Urea 317, 272 nm
20:20 N-N Dimethyl Urea Sodium citrate 272, 317 , 332
nm
Ornidazole 0.5M Ibuprofen sodium 320 nm
10 M Urea
2 M Sodium benzoate
Norfloxacin 2 M Sodium benzoate 324 nm
2 M Niacinamide
8 M Urea 272 nm
80
81. Drug Hydrotrope Wavelength
Norfloxacin +
Metronidazole
8 M Urea (Simultaneous
analysis)
Norfloxacin +
Tinidazole
(Simultaneous)
8 M Urea (Simultaneous
analysis)
Nalidixic acid 2 M Sodium benzoate 330 nm
2 M Niacinamide 330 nm
Ofloxacin 2 M Sodium benzoate 332 nm
2.5 M Niacinamide 332 nm
Piroxicam 2 M Sodium benzoate 358 nm
1.5 M Ibuprofen sodium
(20 : 20) N-N Dimethyl Urea:
Sodium citrate
254nm, 287 nm,
360 nm
81
82. Salicylic acid Calcium disodium
edetate
296 nm
Tinidazole 1.25 M Sodium citrate 318 nm
4 M Sodium acetate
8 m Urea
2 M Sodium benzoate
2 M Niacinamide
1 M Lignocaine HCl
7.5 M N-N Dimethyl
Urea
Norfloxacin + Tinidazole 8 M Urea
82
84. Sr.
No.
Drug Method Mobile Phase
Rf
Value
1 Atenolol IPM
A mixture of 99 volumes of methanol and
1 volume of strong ammonia solution
0.67
2 Atenolol PMUR 5.0 M Urea solution 0.77
3. Atenolol PM SB 1.0 M Sodium benzoate solution 0.63
4.
Diclofenac
sodium
IPM
A mixture of 100 volumes of toluene, 10
volumes of hexane and 10 volumes of
anhydrous formic acid
0.87
5.
Diclofenac
sodium
PMUR 5.0 M Urea solution 0.87
6.
Diclofenac
Sodium
PM SB 2.0 M Sodium benzoate solution 0.64
84
85. Sr.
No.
Drug Method Mobile Phase
Rf
Value
7. Paracetamol IPM
A mixture of 65 volumes of chloroform ,
25 volumes of acetone and 10 volumes of
toluene
0.65
8 Paracetamol PM UR 5.0 M Urea solution 0.86
9. Paracetamol PM SB 0.5 M Sodium benzoate solution 0.68
10. Caffeine IPM
A mixture of 40 volumes of isobutanol, 30
volumes of chloroform, 10 volumes of
strong ammonia solution, 3 volumes of
acetone
0.70
11 Caffeine PM UR 5.0 M Urea solution 0.89
12 Caffeine PM SB 2.0 M Sodium benzoate solution 0.87
85
86. Sr. No. Drug Method Mobile Phase Rf
Value
13 Ibuprofen IPM
A mixture of 75 volumes of n-
hexane, 25 volumes of ethyl acetate,
and 5 volumes of glacial acetic acid
0.60
14. Ibuprofen PMUR 5.0 M Urea solution 0.90
15 Ibuprofen PM SB 2.0 M Sodium benzoate solution 0.82
86
88. 88
Hydrotropic agent Concentration 40
% w/v
Solubility
enhancement
ratio
Urea 0.191 23.857
Sodium acetate 0.239 29.857
Sodium benzoate 2.157 296.632
Sodium citrate 0.129 16.125
Solubility of Furosemide in different hydrotropic
agent ( Solubility in distilled water ~ 0.008 % )
( M Pharm thesis work of Mr.Yitesh Jagwani)
89. 89
Solubility of Furosemide in mixture of different hydrotropic
agent ( M Pharm thesis work of Mr.Yitesh Jagwani)
Combination Total
concentratio
n 40 % w/v
Solubility Solubility
enhancement ratio
U + A 40.00 0.651 81.375 (synergistic
solvent action)
U + B 40.00 2.909 363.625
U + C 40.00 0.943 117.875
A + B 40.00 2.148 268.516
A+ C 40.00 0.067 8.375
B + C 40.00 3.005 375.625
U + A + B 40.00 1.918 239.756
U + A + C 40.00 0.243 30.375
A + B + C 40.00 0.926 115.754
U + B + C 40.00 3.958 494.752
90. 90
Solubility of Furosemide in mixture of different hydrotropic
agent ( M Pharm thesis work of Mr.Yitesh Jagwani)
Combination Total
concentratio
n (40 %
w/v)
Ratio Solubility Solubility
enhancement
ratio
U + B + C 40.00 10:20:10 4.782 597.751
U + B + C 40.00 10:10:20 1.934 241.749
U + B + C 40.00 15:20:05 5.285 660.625
U + B + C 40.00 05:20:15 3.405 425.625
U + A + B + C 40.00 10:10:10:10 1.183 147.875
U + A + B + C 40.00 5:5:10:20 1.953 244.125
U + A + B + C 40.00 5:20:10:5 1.132 141.575
U + A + B + C 40.00 20:5:10:5 3.085 385.625
U + A + B + C 40.00 10:5:20:5 4.524 565.529
U + A + B + C 40.00 15:5:15:5 4.247 530.875
91. 91
Suggestions
Since all compounds posses solubilising power, we
should try to use nutraceuticals, proteins, amino acids,
herbal harmless constituents, fruit and vegetable juices
etc to enhance the solubility of poorly soluble drugs to
develop different pharmaceutical dosage forms.
Since there are no mathematical formulae for solubility
enhancement, hence we have to try them by trial and
error methods.
92. Dr. R K Maheshwari
Prof. (Ex-Head)
Department of Pharmacy
SGSITS, 23 Park road Indore
E mail id:
rkrkmaheshwari@yahoo.co.in
Website: www.rkmaheshwari.com
Contact No. - 0731- 2542213
09406621907
92
