FORMULATION AND EVALUATION OF IMMEDIATE RELEASE TABLET OF SIMVASTATIN

Simvastatin belongs to a class of medications called HMG-CoA Reductase Inhibitors. The goal is to develop and test immediate-release Simvastatin tablets using the wet granulation process. The super disintegrants that were utilised were sodium starch glycolate and sodium croscarmellose. Formulations were developed by Simvastatin with varying quantities of cross-carmel sodium and sodium starch glycolate, (1%,2% and 3% )respectively. The formulations were assessed using a variety of pre-and post-compression characteristics, and an in vitro release study investigation. FTIR studies evaluated the interaction between the drug and polymer. The findings of batch 11 to 16 pre-compression parameters were compared to the prescribed limits. It was discovered that the batch 11 to 16 powder blend has good flow and compressibility properties. In formulation I1-I6, disintegration time was observed to be 3-8 min and 100% of the drug was released within a 10-60m time interval. After looking at several criteria, it was decided that the way Simvastatin release tablets were made worked well, as 12 of them showed that almost the entire drug was released within 10 minutes.

a hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (statin) and an anti-lipidemic agent.Simvastatin lowers the lipid level in the blood and thereby protects you from cardiovascular disease.Simvastatin is a drug that is used to treat primary hypercholesterolemia.It works by lowering total and LDL cholesterol, and also plasma triglycerides levels.Patients with T2DM who are at high risk for a CHD occurrence because they have an existing CHD, peripheral vascular disease, or a history of stroke or other cerebrovascular disease, an initial dose of 10 mg orally is preferred for once-a-day delivery.Based on its pharmacological properties, simvastatin is used as a right-away launch layer3.

Materials
Simvastatin was a present sample from aquatic remedies', Sodium Starch Glycolate, Croscarmellose sodium, lactose monohydrate, Magnesium stearate, Aerosil was produced by modern industry Nashik.

Method
Simvastatin, croscarmellose sodium, and sodium starch glycolate, respectively, were passed through a 40 mesh sieve.They were mixed thoroughly for 5 minutes.Granulated with binding solution (starch in purified water).Granules were dried in a hot air oven at 600C.

Method of preparation (Batch I1 to I6):
The Simvastatin IR blend was prepared by wet granulation.Simvastatin, croscarmellose sodium, and sodium starch glycolate, respectively, were passed through a 40 mesh sieve.They were mixed thoroughly for 5 minutes.Granulated with binding solution (starch in purified water).Granules were dried in a hot air oven at 600C.After drying, they passed through a 20 mesh sieve.These granules were blend with croscarmellose and sodium starch glycolate, respectively, talc, and magnesium stearate.This blend is compressed into tablets in a rotary machine.The composition of different formulations of immediate release tablets is mentioned in table 1.
Pre compression parameters [4,5] The pre compression parameters were the primary requirements to determine whether the specific material was suitable for the targeted formulation or not.The various officially required pre compression parameters to be identified were bulk density, tapped density, Carr's be identified were bulk density, tapped density, Carr's index, Hausner's ratio and angle of repose for dosage form formulation.

Post compression parameter: 1) Thickness
Vernier callipers were used to measure the thickness of the tablets.The average values were derived using five tablets.

2) Hardness
The Pfizer hardness tester was used to determine the hardness of tablets, The average values were derived using five tablets.

3) Friability
The tablets' friability was determined using the Roche friabilator.Tablets of a known mass (W0) or a sample of 20 tablets are placed in a drum for a predetermined period of time and reweighed (W).The following calculation was used to get the percentage of friability from the weight loss.The weight reduction should not exceed 1 percent.

4) Disintegration time
Fill each tube with one tablet.Suspend the assembly in a beaker filled with filtered water and kept at 37.020.0°C.Run the machine for the chosen amount of time.Note down the disintegration time when all six have disintegrated.The disintegration time should not be more than 15 minutes.

5) Weight variation test
To determine weight variance test, 20 tablets were weighed using a Mettler Toledo balance, and the test was conducted according to the established protocol.

6) In vitro dissolution test:
A dissolution study was performed using USP paddle apparatus.The experiment was carried out at 37oC and 50 rpm.At various time intervals, a 5 ml sample is withdrawn and replaced with the same amount of 0.1N Hcl

RESULT AND DISCUSSIONS FT-IR of Simvastatin
The peak of Simvastatin as shown in Figure 1 and Table 3 matches with the peak mentioned in the literature, which confirms the identification of the drug with its functional group.It can be seen from the results of the calibration curve of Simvastatin in 0.1 N Hcl that the relationship between concentration and absorbance was linear (R2 = 0.999).Simvastatin, cross-carmellose sodium, sodium starch, and physical combinations all have large peaks in the FTIR spectrum attributable to ester 1300-1100, with observed peaks at 1266.04 and 1269.04,respectively.Ketone stretching peaked at 1750-1600, while the functional group C-H peaked at 3000-2850.All of the above peaks were also present in the physical mixture, indicating that the medication was present without any interaction.

Differential scanning colorimetry
Any possible drug excipient interaction can be detected by thermal analysis.The DSC study was performed on pure drugs, drug+CCS, and drug+SSG.The study was carried out using a DSC.The 1mg samples were heated in hermetically sealed aluminium pans at a temp of 25-3000c at a heating rate of 100c/min under nitrogen flow of 30ml/min.The results of the DSC analysis are presented.

Pre compression parameter
Table 4 summarises the results of the pre-compression parameters.The angle of repose and Carr's index of batches I1 to I6 were compared to pre-determined limits.
It was discovered that the batch I1 to I6 powder blend has good flow and compressibility properties.

Post compression parameter
Table 4 summarises the results of the pre-compression parameters.The angle of repose and Carr's index of batches I1 to I6 were compared to pre-determined limits.
It was discovered that the batch I1 to I6 powder blend has good flow and compressibility properties.

V Mean Standard Deviation (n = 3)
Figure 3: Drug dissolution study of simvastatin.