Formulation and Evaluation of Immediate Release Tablet of Simvastatin

Mr. Dhruv Patel*, Dr. Upendra Patel, Maitri Shukla, Mr. Bhavin Bhimani, Mr. Ghanshyam Patel

Arihant School of Pharmacy and Bioresearch Institute, Adalaj, Gandhinagar-382421

*Corresponding Author E-mail: maitrishukla1234@gmail.com

ABSTRACT:

Simvastatin is an Antilipidemic agent. The aim is to formulate and evaluate immediate release Simvastatin tablets prepared by wet granulation method. Sodium starch glycolate and crosscarmellose sodium were used as superdisintegrants. Formulations were prepared by Simvastatin with different concentration (1%, 2% and 3%) of crosscarmellose sodium and sodium starch glycolate. Formulations were evaluated for different pre and post compression parameter and in vitro drug release studies. The FTIR studies showed that there is no interaction between the drug and polymer. The results of pre compression parameters of batch I1 to I6 were compared with prescribed limits. It showed that batch I1 to I6 powder blend exhibit good flow property and compressibility property. In formulation I1-I6, disintegration time was observed 3-8 min and 100% drug released within 10-60 min time interval. Thus, based on evaluation of different parameters it was concluded that formulation of immediate release tablets of Simvastatin was successfully done and I2 showed almost 100% drug release at 10 min.

KEYWORDS: simvastatin, antilipidemic agent, wet granulation method, sodium starch glycolate, croscarmellose sodium, immediate release tablet.

INTRODUCTION:

The term of “immediate release” pharmaceutical formulation includes any formulation in which the rate of release of drug from the formulation and/or the absorption of drug, is neither intentionally, nor appreciably, retarded by galenic manipulation”. IR might be provided for an appropriate pharmaceutically acceptable carrier or diluents in which carrier or diluents does not prolong, to an appreciable extent, the rate of drug release and/or absorption. Thereby, the term of formulations adapted to provide are “modified”, “controlled”, “sustained”, “prolonged”, “extended” release of drug¹.

Release phase includes the provision of drug from the formulation to body into systemic circulation or body tissue tissues of the gastrointestinal tract. For GI tract, the release is under pH=1 to 3 or specially such as pH=1.

The design of formulation is such that when an acid or salt is added, it’s crystalline form releases drug under pH conditions. The unique invention of design of released drug will release drug under a range of pH=1 to 3 or especially such as pH=1. Some formulations of design may release at least 70% of drugs within 240 minutes, such as within 180 minutes, preferably 120 minutes, more ideally within 90 minutes, and finally within an hour (such as within 30 minutes) for oral or parenteral.²

Simvastatin is a BCS class II drug with a half-life of 2-3 hours. Simvastatin, a hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor (statin) is an Antilipidemic agent. Simvastatin lowers the lipid level in blood and thereby prevent cardiovascular disease. Simvastatin is used in the treatment of primary hypercholesterolemia and is effective in reducing total and LDL-cholesterol as well as plasma triglycerides. Patients with T2DM, high risk for a CHD event due to existing CHD, peripheral vascular disease, history of stroke or other cerebrovascular disease, an Initial dose of 10 mg orally is preferred for once a day delivery. Based on their pharmacological properties, simvastatin is used as an immediate release layer³.

MATERIALS AND METHODS:

Materials used in this study were obtained from the different sources. Simvastatin was a gift sample from Emcure Pharmaceuticals Ltd., Ahmedabad, India. Sodium Starch Glycolate was produced from Gujarat Microwax Pvt Ltd. Crosscarmellose sodium was produced from S D FINE, Mumbai. Other Excipients such as Starch was produced from Central Drug House Pvt Ltd., New Delhi, and Lactose monohydrate was produced from Emcure Pharmaceuticals Ltd. Magnesium stearate was obtained from ACME Chemicals, Mumbai. Talc was produced from chemdyes corporation, Ahmedabad.

Method of preparation (Batch I1 to I6):

Simvastatin IR blend were prepared by wet granulation method. Simvastatin and croscarmellose sodium and Sodium starch Glycolate respectively were passed through 40 mesh sieve. They were mixed thoroughly for 5min. Granulated with binding solution (starch in purified water). Granules were dried in hot air oven at 60°C after drying pass it to 20 mesh sieve. These granules were mixed with crosscarmelose and Sodium starch glycolate respectively, talc and magnesium stearate. This blend is compressed into tablet in rotary machine. The composition of different formulations of immediate release tablet are mentioned in table 1.

Table 1: Formulation of single layer Simvastatin immediate release tablet

Ingredients (mg)	I1	I2	I3	I4	I5	I6
Simvastatin	10	10	10	10	10	10
Cross Carmellose Sodium	1(1%)	2(2%)	3(3%)	-	-	-
Sodium Starch Glycolate	-	-	-	1(1%)	2(2%)	3(3%)
Starch	4	4	4	4	4	4
Lactose	82	81	80	82	81	80
Talc	2	2	2	2	2	2
Mg. Stearate	1	1	1	1	1	1
Total	100	100	100	100	100	100

Pre Compression Parameters^4,5:

The Precompression 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 index, Hausner’s ratio and angle of repose for dosage form formulation.

Post compression parameter:

1) Thickness:

The thickness of the tablets were determined by using vernier calipers. Five tablets were used, and average values were calculated.

2) Hardness:

The hardness of five tablets was determined using the Pfizer hardness tester and the average values were calculated.

3) Friability:

The friability of the tablets was measured in Roche friabilator. Tablets of a know weight (W₀) or a sample of 20 tablets are abraded in a drum for a fixed time and weighted (W) again. Percentage friability was calculated from the loss in weight as given in equation as below. The weight loss should not be more than 1%.

W_{0 –}W

% friability = –––––––– 100

W₀

4) Disintegration time:

Introduce one tablet in to each tube. Suspend the assembly in the beaker containing the purified water maintained at 37.0±2°C. Operate the apparatus for specified time. Note down the disintegration time when all six have disintegrated. The disintegration time should not more than 15 min.

5) Weight variation test:

To study weight variation 20 tablets of the formulation were weighed using a mettler Toledo balance and the test was performed according to the official method.

Table 2: Weight variation specification as per IP

Average Weight of Tablet	% Deviation
80 mg or less	±10
More than 80 mg but less than 250 mg	±7.5
More than 250	±5

6) In vitro Dissolution test:

Dissolution study is performed using USP paddle apparatus. Study is carried out at 37^oC temperature and 50 rpm. At various time intervals, 5 ml sample is withdrawn and is replaced with 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 match with the peak mentioned in the literature, which confirms identification of drug with its functional group.

Figure1: peak of simvastatin

Interpretation of FTIR spectra of Simvastatin:

Table 3: Interpretation of FTIR spectra of simvastatin

Functional group	Frequency (cm^-1)
Functional group	Stretching	Observed Peak	Reported Peak
Functional group of ester C-O	Stretching	1266.04	1300-1000
Functional group of C-O-C	Stretching	1063.55	1250-1050
Functional group Lactone C=O	Stretching	1699.94	1690-1630

It can be seen from the results of calibration curve of Simvastatin in 0.1 N HCl that the relationship between concentration and absorbance was linear. (R²=0.999)

Simvastatin with other physical mixtures:

Figure 2: FTIR spectra of physical mixture, Croscarmellose sodium with simvastatin

Figure 3: FTIR spectra of physical mixture, Sodium starch glycolate with simvastatin

Evaluation of Simvastatin single layer tablet:

Pre compression parameters:

Table 4: Result of pre compression parameter of batch I1 to I6

Batch	*Angle of repose (θ)**	*Bulk density (gm/ml)**	*Tapped bulk density (gm/ml)**	*Carr’s index (%)**	Hausner’s ratio*
I1	33.16±1.09	0.625±0.01	0.735±0.08	14.96±0.06	1.17±0.02
I2	30±0.06	0.622±0.03	0.748±0.05	16.84±0.09	1.20±0.18
I3	32.10±1.02	0.628±0.02	0.767±0.02	18.12±0.11	1.22±0.02
I4	30.12±1.20	0.625±0.01	0.759±0.02	17.65±0.02	1.21±0.04
I5	36±0.02	0.632±0.02	0.768±0.02	17.70±0.01	1.21±0.02
I6	34.19±1.01	0.621±0.01	0.770±0.06	19.35±0.16	1.23±0.08

*Values are means ± SD, (n=3)

Post compression parameter:

Table 5: Result of post compression parameter of batch I1 to I6

Batch	*Thickness (mm)**	*Hardness (kg/cm2)**	*Friability(%)**	Disintegration Time*	Content uniformity*	Weight variation*
I1	2.54±0.02	2.96±0.10	0.45±0.01	8 min 25 sec	95.88±2.74	0.104±0.67
I2	2.59±0.08	2.99±0.10	0.30±0.04	4 min 38 sec	99.90±1.23	0.103±0.42
I3	2.58±0.08	3.01±0.14	0.36±0.08	3 min 47 sec	98.55±1.98	0.102±0.57
I4	2.54±0.04	3.09±0.10	0.59±0.04	7 min 12 sec	102.02±2.5	0.101±0.99
I5	2.51±0.02	2.92±0.16	0.47±0.01	6 min 20 sec	98.63±1.85	0.103±1.02
I6	2.55±0.09	2.98±0.12	0.42±0.03	6 min 52 sec	101.11±2.9	0.103±0.69

*Values are means ± SD, (n=3)

1. In vitro drug release study of Simvastatin single layer tablet:

Figure 4: In vitro drug release of Simvastatin formulation I1 to I6

The result of pre compression parameters was summarized in Table 11. Angle of repose and Carr’s index of batch I1 to I6 compared with prescribed limits. It showed that batch I1 to I6 powder blend exhibit good flow property and compressibility property.

The result of post compression parameters was summarized in Table 6.12. All the formulation showed uniform thickness. All the formulation got uniform hardness which was in the acceptable range. The normal acceptable criterion for friability is not more than 1.0%. The formulation I1 to I6 has got fribility within the acceptable range. Hence, all the formulations passed the uniformity of weight. In formulation I1, disintegration time was 8 min 25 sec and 99.30% drug released within 30 min. In formulation I2, disintegration time was 4 min 38 sec and 99.81% drug released within 10 min. In formulation I3, disintegration time was 3 min 47 sec and 99.27% drug released within 10 min. In formulation I4, disintegration time was 7 min 12 sec and 99.51% drug released within 45 min. In formulation I5, disintegration time was 6 min 20 sec and 99.81% drug released within 20 min. In formulation I6, disintegration time was 6 min 52 sec and 99.09% drug released within 10 min. From above result, the batch I2 was found to be optimized batch for further work.

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