This document describes a study comparing different solubility enhancement techniques for rosuvastatin calcium. The objectives were to enhance solubility using solid dispersion techniques and develop an analytical profile. Various formulations were prepared using rosuvastatin and polymers PEG4000 and PEG6000. Formulation F1 with a 1:0.25 drug to PEG4000 ratio showed the highest release of 94.95% within 50 minutes, indicating PEG4000 most effectively improved the solubility and dissolution of rosuvastatin. The results demonstrated that solid dispersion with PEG4000 is a promising approach for enhancing the solubility and dissolution properties of rosuvastatin calcium.

1. COMPARATIVE EVALUATION OF VARIOUS
SOLUBILITY IMPROVEMENT TECHNIQUES
TO ENHANCE THE DISSOLUTION
PROPERTIES OF ROSUVASTATIN CALCIUM

2. INTRODUCTION
• THE ORAL ROUTE IS MOST COMMON AND
PREFFERED ROUTE FOR DRUG DELIVERY SYSTEM
• PATIENT COMPLIANCE AND DRUG TREATMENTIS
MORE EFFECTIVE WITH ORAL ADMINISTRATION
THAN OTHER ROUTES OF ADMINISTRATION
• ORAL DRUG ABSORPTION FROM SOLID DOSAGE
FORMS DEPENDS ON THE RELEASE OF DRUG
SUBSTANCE FROM THE DELIVERY SYSTEM

3. PURPOSE OF STUDY
• OBJECTIVES:
• TO ENHANCE THE AQUEOUS SOLUBILITY OF
ROSUVASTATIN BY SUITABLE SOLID
DISPERSION TECHNIQUE
• TO DEVELOP ANALYTICAL PROFILE OF
ROSUVASTATIN
• TO CARRY OUT FOLLOWING EVALUATION
PARAMETERS

4. A)ANGLE OF REPOSE
B)BULK DENSITY
C)TAPPED DENSITY
D)COMPRESSIBILITY INDEX

5. DRUG PROFILE
• CHEMICAL STRUCTURE:
ROSUVASTATIN

6. • CHEMICAL NAME:
• (3R,5S,6E)-7-(4-(4-FIUOROPHENYL)-2-(N-
METHYLMETHANESULFONAMIDO)-6-(PROPAN-2-
YL)PYRIMIDIN-5-YL)-3,5-DIHYDROXYHEPT-6-ENOIC ACID
• MOLECULAR FORMULA: C22H28FN3O6S
• MOLECULAR WEIGHT: 481.539gm/mol
• CATEGORY:THE PRIMARY USES OF ROSUVASTATIN
IS FOR THE TREATMENT OF DYSLIPIDEMIA,HMG-CoA
REDUCTSE INHIBITORS
• APPEARANCE: WHITE POWDER
• MELTING POINT:208-209c

7. SOLUBILITY: IT IS INSOLUBLE IN WATER AND
ALCOHOLS,BUT SOLUBLE IN 0.1NNaOH.IT IS FREELY
SOLUBLE IN DIMETHYLFORMAMIDE
Pka:5.9
HALF LIFE:2 to 5 hours
Protein binding: 98-99% primarily to albumin
METABOLISM:Hepatic hydroxylation
ELIMINATION:Renal and fecal
MECHANISM OF ACTION:Rosuvastatin is acompetitive
inhibitor of the enzyme HMG-CoA reductase having a
mechanism of action similar to that of other statins.
SIDEEFFECTS:Nausea,vomiting,constipation,erythema,urtica
ria,leucopenia,etc….

8. METHODOLOGY
• PRE FORMULATION STUDIES:Pre formulations
involves the applications of bio pharmaceutical
principles to the physiochemical parameters of
drug substance are characterized with the goal of
designing optimum drug delivery system
• FORMULATION DEVELOPMENT:Solid dispersions
were prerared by solvent evoporation
method.methonol was used as
solvent.Rosuvastatin dose was taken as
80mg.water soluble polymers such as PEG 4000
and PEG6000

9. FORMULATION TABLE
F1 F2 F3 F4 F5 F6 F7 F8 F9
DRUG 80 80 80 80 80 80 80 80 80
PEG400
0
50 100 150 200 100
PEG600
0
50 100 150 200 100
MCC 290 240 190 140 290 240 190 140 140
AEROSI
L
5 5 5 5 5 5 5 5 5
MG
STEARA
TE
5 5 5 5 5 5 5 5 5

10. Total weight of tablets=550mg
The tablets were prepared by using 8mm flat
surfaced punch.the hardness of the tablets was
maintained as 4.5kg/cm

11. EVALUTION OF TABLETS
1.ANGLE OF REPOSE
2.BULK DENSITY
3.TAPPED DENSITY
4.COMPRESSIBILITY INDEX
5.HAUSNERS RATIO

12. FLOW PROPERTIES&CORRESPONDING
ANGLE OF REPOSE
FLOW PROPERTY ANGLE OF REPOSE
EXCELLENT 25-30
GOOD 31-35
FAIR-AID NOT NEEDED 36-40
PASSABLE-MAY HANG UP 41-45
POOR-MUST AGITATE,VIBRATE 46-55
VERY POOR 56-65
VERY,VERY POOR >66

13. RESULTS&DISCUSSION
• IN VITRO RELEASE STUDIES (USING PEG4000)
TIME(MIN) %DRUG
RELEASE
F1 F2 F3 F4
0 0 0 0 0
5 26.73 16.73 12.56 7.73
10 31.06 20.4 16.57 11.56
20 44.9 25.9 18.9 16.56
30 57.06 35.56 27.73 18.9
40 75.56 44.9 42.4 22.73

14. 50 94.9 54.4 47.9 36.06
60 79.9 66.56 48.4

15. FORMULATIONS F5-F8 by using
PEG6000 POLYMER
TIME(MIN) %DRUG
RELEASE
F5 F6 F7 F8
0 0 0 0 0
5 11.86 8.18 9.21 7.51
10 19.01 11.86 12.60 10.90
20 26.16 16.06 16.43 15.55
30 28.22 21.44 24.83 23.80
40 36.99 29.62 31.32 30.98
50 58.81 59.77 37.95 31.98
60 73.55 65.59 40.90 37.58

16. FORMULATIONS F9 by using PEG4000&PEG6000
polymers
TIME(MIN) %DRUG RELEASE
F9
0 0
5 7.51
10 10.90
20 15.55
30 23.80
40 28.29
50 34.98
60 39.58

17. RESULTS&CONCLUSION
• A mong the all the formulations F1 formulation containing drug and
PEG4000 in the ratio of 1:0.25 showed good results that is 94.95%in 50
minutes
• As the concentration of polymer increase the drug release was decreased.
• While the formulations containing PEG6000 showed less release
• Data it was evident that F1 formulation is the better formulation.
• The combination of PEG 4000 & PEG6000 was also not producing desired
percentage drug release.
• The formation is following zero order release kinetics