Formulation and in Vitro Evaluation of oral Dispersible tablets of Sildenafil Citrate

G. Srikanth*, Ramya Sri S

Department of Pharmaceutics, Sura Labs, Dilsukhnagar, Hyderabad, Telangana.

*Corresponding Author E-mail: rajinisuralabs1@gmail.com

ABSTRACT:

The aim of the present work is to develop the disintegrating tablets of sildenafil citrate. All the formulations are prepared by the direct compression method. The blend of all the formulations showed good flow properties such as angle of repose, bulk density and tapped density. All the prepared tablets were showed good post compression parameters like, weight variation, Friability, Hardness and Thickness are in the IP limits. Among all then Formulations F14 is consider as optimized. It shows good drug release i.e., 99.3%.

KEYWORDS: Sidenafil Citrate, Vivasole, Polyplasdone XL

INTRODUCTION:

Drug delivery systems (DDS) are a strategic tool for expanding markets/indications, extending product life cycles and generating opportunities. DDS make a significant contribution to global pharmaceutical sales through market segmentation, and are moving rapidly. Drug delivery systems are becoming increasingly sophisticated as pharmaceutical scientists acquire a better understanding of the physicochemical and biochemical parameters pertinent to their performance.¹

Despite of tremendous advancements in drug delivery, the oral route remains the perfect route for the administration of therapeutic agents because the low cost of therapy, ease of administration lead to high levels of patient compliance.²

It is always the aim of a scientist or a dosage form designer to enhance the safety of a drug molecule while maintaining its therapeutic efficacy. Recent advances in NDDS aim for the same by formulating a dosage form, convenient to be administered so as to achieve better patient compliance. Mouth Dissolving Tablet (MDT) is one among such approaches³

Improved patient compliance has achieved enormous demand. Consequently demand for their technologies is also increasing many folds. To develop a chemical entity, a lot of money, hard work and time are required. So focus is rather being laid on the development of new drug delivery systems for already existing drugs, with enhanced efficacy and bioavailability, thus reducing the dose and dosing frequency to minimize the side effects.⁴

The oral route of administration is the most preferred route due to its many advantages like ease of administration, accurate dosage, self-medication, pain avoidance, versatility and patient compliance. Tablets and capsules are the most popular dosage forms.⁵

But one important drawback of such dosage forms is Dysphasia or difficulty in swallowing. This is seen to afflict nearly 35% of the general population. This disorder is also associated with a number of pathological conditions including stroke, Parkinson’s disease, neurological disorders, AIDS etc.⁶

1. Parkinsonism

2. Motion sickness

3. Unconsciousness

4. Elderly patients

5. Children

6. Mentally disabled persons

7. Unavailability of water

To solve the above-mentioned problems, pharmaceutical technologists have put in their best efforts to develop a Fast dissolving drug delivery, i.e. Mouth Dissolving Tablet that disintegrates and dissolves rapidly in the saliva, within a few sec without the need of drinking water or chewing. A mouth dissolving tablet usually dissolves in the oral cavity within 10 sec to 3 min. Most of the MDTs include certain super disintegrants and taste masking agents.^7,8,9,10

AIM AND OBJECTIVE

1. To formulate oro dispersible tablets of Sildenafil citrate for the improvement of solubility, dissolution rate & oral bioavailability.

2. To optimize optimum concentration of co processed super disintegrating agent.

3. To perform various quality control evaluation parameters for the prepared tablets.

MATERIALS AND METHOD MATERIALS:

Sildenafil citrate was Provided by SURA LABS, Dilsukhnagar, Hyderabad. Microcrystalline cellulose, Vivasole, Polyplasdone XL, Magnesium stearate, Talcwas gift ample from Merck Specialities Pvt Ltd, Mumbai, India.

METHODOLOGY:

Formulation of Oro dispersible tablets of Sildenafil citrate:

Preparation of co processed super disintegrates:

Co processed super disintegrates were prepared by using sodium Vivasole and polyplasdone XL. The super disintegrates were mixed in different concentrations and labeled as CP1, CP2, CP3. The blend of super disintegrates was mixed thoroughly for a period of 15 min, collected and used for preparing formulations in different concentrations.

CP = Coprocessed super disintegrate

Table: Composition of co processed super disintegrates

Ingredients	CP1	CP2	CP3	CP4	CP5
Vivasole (mg)	500	500	500	1500	1000
Polyplasdone XL (mg)	500	1000	1500	500	500

Preparation of tablets:

Composition of Sildenafil citrate Dispersible Tablet by direct compression is shown in table 6.4. All the ingredients were weighed. Required quantity of drug and excipient mixed thoroughly in a polybag. The blend is compressed using rotary tablet machine-10 station with 9mm flat punch, B tooling. Each tablet contains 50 mg Sildenafil citrate and other pharmaceutical ingredients.

Table no 1: Composition of various tablet formulations

Ingredients	F1	F2	F3	F4	F5	F6	F7	F8	F9	F10	F11	F12	F13	F14	F15
Sildenafil citrate (mg)	50	50	50	50	50	50	50	50	50	50	50	50	50	50	50
CP 1(mg)	15	30	45	-	-	-	-	-	-	-	-	-	-	-	-
CP 2(mg)	-	-	-	15	30	45	-	-	-	-	-	-	-	-	-
CP 3(mg)	-	-	-	-	-	-	15	30	45	-	-	-	-	-	-
CP 4 (mg)	-	-	-	-	-	-	-	-	-	15	30	45	-	-	-
CP 5(mg)	-	-	-	-	-	-	-	-	-	-	-	-	15	30	45
Mg St(mg)	6	6	6	6	6	6	6	6	6	6	6	6	6	6	6
Talc(mg)	6	6	6	6	6	6	6	6	6	6	6	6	6	6	6
MCC(mg)	Qs	Qs	Qs	Qs	Qs	Qs	Qs	Qs	Qs	Qs	Qs	Qs	Qs	Qs	Qs
Total wt(mg)	300	300	300	300	300	300	300	300	300	300	300	300	300	300	300

RESULTS AND DISCUSSION:

Standard Calibration curve of Sildenafil citrate:

Table 2: Concentration and absorbance obtained for calibration curve of Sildenafil citrate in 0.1N HCL

S. No.	Concentration (µg/ml)	*Absorbance (at 278 nm)**
1	0	0
2	5	0.106
3	10	0.177
4	15	0.265
5	20	0.344
6	25	0.431

It was found that the estimation of Sildenafil citrate by UV spectrophotometric method at λ_max290.0 nm in 0.1N HCL had good reproducibility and this method was used in the study. The correlation coefficient for the standard curve was found to be closer to 1.

Fig1: Standard graph of Sildenafil citratein0.1N HCl

Evaluation Parameters for Fast Dissolving Tablets of Sildenafil citrate:

Pre-compression parameters:

The data’s were shown in Table 7.2. The values for angle of repose were found in the range of 25°-30°. Bulk densities and tapped densities of various formulations were found to be in the range of 0.41 to 0.50 (gm/cc) and 0.50 to 0.58 (gm/cc) respectively. Carr’s index of the prepared blends was fall in the range of 13.06% to 18.18%. The Hausner ration was fall in range of 1.14 to 1.22. From the result it was concluded that the powder blends had good flow properties and these can be used for tablet manufacture.

Table 3: Pre-compression parameters

Formulations	Bulk Density(gm/cm²)	Tap Density(gm/cm²)	Carr’s Index (%)	Hausnerratio	Angle of Repose(Ɵ)
F1	0.45	0.55	18.18	1.22	27.91
F2	0.47	0.55	14.54	1.17	28.23
F3	0.50	0.58	13.79	1.16	29.34
F4	0.46	0.55	16.36	1.19	26.71
F5	0.50	0.58	13.79	1.16	29.34
F6	0.47	0.55	14.54	1.17	28.23
F7	0.50	0.58	13.79	1.16	29.34
F8	0.41	0.50	18.34	1.21	26.78
F9	0.41	0.50	18.02	1.21	26.78
F10	0.45	0.55	18.18	1.22	25.85
F11	0.48	0.57	15.78	1.18	27.45
F12	0.46	0.54	14.81	1.17	28.12
F13	0.49	0.58	15.51	1.18	27.02
F14	0.51	0.59	13.55	1.15	26.36
F15	0.41	0.49	16.32	1.19	28.75

Table no 4: Post-Compression parameters:

Formulation code	Average Weight (mg)	Hardness (kg/cm²)	Thickness (mm)	Disintegration Time (sec)	Friability (%)	Assay (%)
F1	305.9	2.5	4.59	20.33	0.43	97.23
F2	304.4	2.3	4.64	23.66	0.34	98.55
F3	310.7	2.5	4.59	25.33	0.49	98.16
F4	309.2	2.4	4.58	19.00	0.47	99.34
F5	299.4	2.3	4.59	20.33	0.49	98.16
F6	302.4	2.6	4.64	22.66	0.34	98.55
F7	301.3	2.5	4.59	20.33	0.49	98.16
F8	307.3	2.3	4.56	17.00	0.34	99.25
F9	302.32	2.3	4.56	19.45	0.34	100.26
F10	298.36	2.5	4.98	24.36	0.43	98.45
F11	295.34	2.4	4.73	23.72	0.52	99.36
F12	300.2	2.4	4.82	20.63	0.35	100.02
F13	301.3	2.2	5.03	18.34	0.64	97.34
F14	297.6	2.3	5.13	17.47	0.53	99.36
F15	299.4	2.5	5.32	19.35	0.48	98.63

Invitro Dissolution studies:

Table no 5: In vitroDrug release

Time (Min)	F1	F2	F3	F4	F5	F6	F7	F8	F9	F10	F11	F12	F13	F14	F15
0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
2	25.4	31.7	40.8	24.3	39.5	44.9	35.2	44.2	53.2	43.7	54.2	75.2	53.2	79.3	83.1
4	39.6	40.5	56.72	31.6	56.3	58.4	50.2	52.1	66.2	55.2	70.3	85.3	60.2	99.3	96.3
6	48.6	51.9	76.16	49.3	76.2	63.1	62.1	64.9	79.3	74.2	86.3	99.3	75.3
8	54.3	62.4	87.4	58.3	89.7	79.7	73.5	75.3	85.2	89.3	97.3		94.3
10	66.4	79.1	98.5	74.3	97.8	89.3	80.4	87.3	98.2	95.3
15	73.1	85.5		88.1		98.9	89.3	96.2
20	80.6	95.2		97.6			94.2
25	91.5						100.2
30	98.23

Fig no 2: Percentage Drug release

From the tabular column 7.4 it was evident that the formulations prepared with super disintegrate CP5 showed maximum % drug release in 4 min i.e.99.3%, 96.3% (F13, F14) formulations and the concentration of super disintegrate is 30mg,45 mg). So the principle of coproceesed super disintegrates was found to be useful to produce oro dispersible tablets.F13 formulation was considered as optimized formulation as it contains less concentration of super disintegrate.

Fourier Transform-Infrared Spectroscopy:

Fig no 3: FT-TR Spectrum of Sildenafil citratepure drug.

Fig no 4: FT-IR Spectrum of Optimized Formulation

CONCLUSION:

In the present work, an attempt has been made to develop fast disintegrating tablets of sildenafil citrate. Novel method of co processed super disintegrates technology was employed to formulate the tablets. All the formulations were prepared by direct compression method. The blend of all the formulations showed god flow properties such as angle of repose, bulk density, tapped density. The prepared tablets were shown good post compression parameters and they passed all the quality control evaluation parameters as per I.P limits. Among all the formulations F14 formulation showed maximum drug release i.e., 99.3% in 4 min hence it is considered as optimized formulation. The F14 formulation contains CP5 as super disintegrate in the concentration of 30 mg. (CP 5 contains Vivasole and polyplasdone XL in 3:1 ratio).

АCKNOWLEDGEMENT:

Thе authors arе thankful to Sura Labs, Dilshukhnagar, Hydеrabad for providing thе nеcеssary

facilitiеs, Materials for thе rеsеarch work.

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Received on 11.01.2020 Modified on 10.02.2020

Asian J. Pharm. Tech. 2020; 10(1):15-19.

DOI: 10.5958/2231-5713.2020.00004.5