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Rosuvastatin orodispersible tablet
1. DESIGNING ROSUVASTATIN ORODISPERSIBLE
TABLET WITH MODIFIED STARCH-5-PHOSPHATE
SOLID DISPERSION TARGETING IMPROVEMENT
OF SOLUBILITY AND BIOEQUIVALENCE
MODULATION
UNDER GUIDANCE OF
PROF. DR. TAPAS KUMAR PAL
DEBADITYA SAHA M.PHARM (PHARMACEUTICS)
ROLL NO: 27720313003; REGD NO: 132772310015 of 2013-2014
NSHM COLLEGE OF PHARMACEUTICAL TECHNOLOGY
2. Objective of the Study
The work plan has been proposed as per following steps
• Comparison of Rosuvastatin commercial branded and generic
tablets of their bio-equivalence and interchangeability by
comparative dissolution profile.
• Formulation Development of Orodispersible sublingual
immediate release tablet utilizing solid dispersion with modified
starch phosphate.
• Comparison of in vitro cumulative release, dissolution
efficiency of formulated sublingual immediate release tablets of
Rosuvastatin with commercial brands & generics
• Comparative in-vivo evaluation of cholesterol reducing activity
of formulated sublingual immediate release tablets with
reference to marketed tablets.
3. ROSUVASTATIN CALCIUM
• Anti-hyperlipidemic, HMG-CoA reductase inhibitor.
• belongs to BCS class II.
• reduces low density lipoprotein (LDL) cholesterol and triglycerides.
• increases high density lipoprotein (HDL) in patients with hypercholesterolemia and
dyslipidemia.
• Chemical IUPAC name: bis[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2-
[methyl(methyl sulfonyl)amino]pyrimidin-5-yl](3R,5S)-3,5-dihydrohexyhept-6-
enoic acid]calcium salt.
• Empirical formula: (C22H27FN3O6S)2Ca
• Molecular weight: 1001.14
• Appearance: White amorphous powder.
• Melting point: 122C.
• Solubility: Sparingly soluble in water and methanol,
and slightly soluble in ethanol.
4. Pharmacokinetic properties of Rosuvastatin Calcium
• Absorption: In clinical pharmacology studies in man, peak plasma
concentrations of rosuvastatin were reached 3-5 hours following oral dosing.
The absolute bioavailability of rosuvastatin is approximately 20%.
• Distribution: Mean volume of distribution at steady-state of rosuvastatin is
approximately 134 liters.
Rosuvastatin is 88% bound to plasma proteins, mostly albumin.
• Metabolism: Rosuvastatin is not extensively metabolized; approximately 10%
of a radio labeled dose is recovered as metabolite. The major metabolite is N-
desmethyl rosuvastatin.
• Excretion: Following oral administration, rosuvastatin and its metabolites are
primarily excreted in the feces (90%) of which 28% was via the renal route and
72% via the hepatic route.
The elimination half-life (t1/2) of rosuvastatin is approximately 19 hours.
5. What is Solid Dispersion
Involves a dispersion of one or more active ingredients in an inert carrier
or matrix in solid state prepared by:
Fusion (melt)
Solvent evaporation
Spray drying
Lyophilization
Hot melt extrusion
Electrostatic spinning method
Supercritical fluid technology
Coating on sugar beads using fluidized bed-coating system.
Used to improve
o solubility
o dissolution rates
o Bioavailability of poorly water soluble drug.
6. Starch 5-Phosphate
Starch phosphate is one of the modified starches that have been evaluated
as effective disintegrant as well as solid dispersions to increase solubility
and to optimize bioavailability.
Preparation: by reacting starch IP (100g) with di-sodium hydrogen
orthophosphate anhydrous (30g) at elevated temperatures (130°C for 3
hrs).
Appearance: white, crystalline, non-hygroscopic powder.
Solubility: insoluble in water and aqueous fluids of acidic and alkaline
pHs.
Swelling property: 400 times more swelling in water.
7. Property Result
Solubility Insoluble in all aqueous and organic solvents tested
pH (1% w/v aqueous dispersion) 7.27
Melting point Charred at 210C
Viscosity (1% w/v aqueous dispersion) 2.15cps
Swelling index 400
Gelling property No gelling and swollen particles of Starch-5-
phosphate separated from water.
Density 1.567 gm/cc
Bulk density 0.534 gm/cc
Angle of Repose 23.05
Compressibility Index 15%
Physical properties of Starch-5-phosphate prepared
21. TREATMENT GROUP TOTAL CHOLESTEROL (mg/dl)
24 HRS 48 HRS
NORMAL CONTROL 150.34±0.25 151.43±0.25
POSITIVE CONTROL 198.83±0.65 209.57±1.17
F4 FORMULATION 144.95±0.35 78.14±0.10
CRESTOR 146.05±0.10 111.25±0.92
0.00
50.00
100.00
150.00
200.00
250.00
normal control positive control F4 crestor
24hrs 48hrs
Group
TotalCholesterol
(mg/dl)
Comparative effect of F4 formulation and Crestor in Total Cholesterol levels
22. Histopathology studies of liver
Normal control
Triton induced positive
control
F4 (5mg/kg) + Triton
(200mg/kg) treated group
Crestor (5mg/kg) + Triton
(200mg/kg) treated group
Normal control liver sections illustrates
portal vein surrounded by cords of
hepatocytes extended radialy from central
portal vein and branches of hepatic artery
around the lobular periphery .Among the
nonparanchymal cells, the following
types have been identified bile duct,
endothelial, kupffer cells, kupffer cells
are located preferentially in the per portal
region figure. There were flat endothelial
cells around the central vein and
sinusoids with normal architecture of
their liver sections.
In treated rats with mild changes these
changes includes, moderate congestion,
necrosis, hepatocytes degeneration with
enlargement of some hepatocytes
(ballooning shape), and some of which
have two nuclei and some of hepatocytes
undergo hepatocytomegally with
pyknotic nuclei.
23. Histopathology studies of heart
Normal control Triton induced positive
control
F4 (5mg/kg) + Triton
(200mg/kg) treated group
Crestor (5mg/kg) + Triton
(200mg/kg) treated group
Light microscopy of the cardiac tissue
sections of normal control group
showing normal myofibrillar structure
with striations, branched appearance
and continuity with adjacent myofibrils.
Light microscopy of the cardiac tissue
sections of positive control group
showing loss of normal architecture of
cardiac muscle fibers, loss of cross
striations and fragmentation of
sarcoplasm, infiltration of mononuclear
cells in between the muscle fibers and
connective tissue proliferation in the area
of necrosis.
Light microscopy of the cardiac tissue
sections of F4 formulation (5mg/kg)
treated group showing almost normal
appearance of cardiac muscle fibers. It
shows the area of congestion &
hemorrhage with fragmentation and loss
of cross striation of muscle fibers in
occasional areas.
24. Starch-5-phosphate prepared by reacting starch IP with di-sodium hydrogen
orthophosphate anhydrous at elevated temperatures was insoluble in water and has good
swelling (400%) property without pasting or gelling when heated in water. Rosuvastatin
Calcium tablets formulated employing starch-5-phosphate disintegrated within 3mins.
Dissolution followed first order kinetics and increase in the dissolution rate of
Rosuvastatin calcium was observed with solid dispersions prepared at 1:2:5 and 1:1:9
ratios of drug: PEG 6000: starch-5-phosphate. The dissolution was also increased when
the drug: carrier ratio was increased.
FTIR study showed there was no interaction between Rosuvastatin calcium and
excipients .
Thus starch-5-phosphate, a new modified starch was found to be a promising disintegrant
in tablet formulations and can be used in the concentration of 5-10% as an effective
disintegrant.
Based on the study it may be concluded that rosuvastatin calcium tablets (F1, F4, F5)
prepared with 20% cross-carmellose sodium as superdisintegrant showed rapid drug
release when compared to marketed tablet formulations.
CONCLUSION
25. REFERENCES
• A.RAMU, S. VIDYADHARA, N. DEVANNA, CH. ANUSHA and J. KEERTHI
“Formulation and Evaluation of Rosuvastatin Fast Dissolving Tablets”, Asian journal of
chemistry; vol. 25; No. 10(2013); 5340-5346.
• BHEEMESWARA RAO K, PRASANNA KUMAR DESU, SUDHAKAR BABU AMS,
VENKATESWAR RAO P “Formulation and evaluation of rosuvastatin immediate
release tablets 20mg”, Singapore journal of pharmaceutical research; 2014; 1(1); 12-18.
• K.P.R. CHOWDARY, VEERAIAH ENTURI AND A. SANDHYA RANI “Formulation
Development of Aceclofenac Tablets Employing Starch Phosphate -A New Modified
Starch”, International Journal of Pharma Sciences and Research (IJPSR); vol. 2(3); 2011;
124-129.
• M.KIRAN BABU, N.TARUN, MD. REHANA SULTHANA, SRINIVAS.M,
CH.VIJAY “Formulation and evaluation of rosuvastatin immediate release tablets”, An
International Journal of Advances in Pharmaceutical Sciences; vol. 5; issue 2; march-
April 2014; 1924-1928.
• K. VEERREDDY, TEJA KUMAR. P, BOLLI SANDEEP AND SUNIL KUMAR
DANGETI “Comparative evaluation of modified starches in different tablet formulations
as disintegrants”; Scholar Research Library, Der Pharmacia Lettre; 2012; 4(6); 1680-
1684.
26. • K.P.R. CHOWDARY AND VEERAIAH ENTURI “Preparation, characterization and
evaluation of starch phosphate: A new modified starch as directly compressible vehicle in
tablet formulations”, Journal of Pharmacy Research; 2011; 4(9); 3241-3243.
• I. JUBRIL, J. MUAZU AND G. T. “Mohammed Effects of Phosphate Modified and
Pregelatinized Sweet Potato Starches on Disintegrant Property of Paracetamol Tablet
Formulations”, Journal of Applied Pharmaceutical Sciences; 2012; 2(2); 32-36.
• SANJOY KUMAR DAS, SUDIPTA ROY, YUVARAJA KALIMUTHU, JASMINA
KHANAM, ARUNABHA NANDA “Solid Dispersions: An Approach to Enhance the
Bioavailability of Poorly Water-Soluble Drugs”, International Journal of Pharmacology
and Pharmaceutical Technology (IJPPT); volume 1; issue 1; 2277-3436.
• MOGAL S. A, GURJAR P. N, YAMGAR D. S AND KAMOD A.C. “Solid dispersion
technique for improving solubility of some poorly soluble drugs”, Scholar Research
Library, Der Pharmacia Lettre; 2012; 4(5); 1574-1586.