An Immediate Release tablet of Carvedilol with Natural Superdisintegrants Fenugreek seed Mucilage and synthetic Superdisintegrants

Neha Kumari*, Ruchika Sharma

Sri Sai College of Pharmacy, Badhani, Pathankot-145001.

*Corresponding Author E-mail: neha91sn@gmail.com

ABSTRACT:

In many formulations, we start moving towards the Ayurvedic powders and other excipients, although it is good because the chances of adulteration can be decrease and patient compliance can be increased. And Immediate Release Tablets are those tablets which are designed to disintegrate and release their medication with no special rate controlling features, such as special coatings and other techniques. Recently immediate release tablets have started gaining popularity and acceptance as a drug delivery system, mainly because they are easy to administer, has quick onset of action is economical and lead to better patient compliance. In this research work on immediate release tablet Carvedilol and natural superdisintegrants (fenugreek seed mucilage) were prepared by wet granulation method. When work is started, Preformulation studies show us that powder blend is not having floating nature. Formulation was optimized and prepare under minimum possible disintegrating time. Tablets then further evaluated for FT-IR, solubility, hardness, weight variation, friability, wetting time, In vitro process, and for this we design nine formulations. In first three there is a Crospovidone, another three contain natural superdisintegrant (fenugreek seed mucilage), and for last three contain SSG. All were gone through pre and post compression method. All the prepared formulations show significant result obtained by Pharmacopoeia quality control test. On the basis of disintegration test observations F3 and F6 formulation were found to be best among all batches.

KEYWORDS: Immediate release tablet, superdisintegrant, Carvedilol, Pharmacopoeia, fenugreek seed mucilage.

INTRODUCTION:¹

An Oral Dosage Form is the physical form of a dose of a chemical compound used as a drug or medication intended for administration or consumption by oral route. Common oral dosage forms are tablets or capsules. Tablets are solid preparations each containing a single dose of one or more active substances with or without excipients usually obtained by compressing uniform volumes of particles. Tablets are intended for oral administration. Some are swallowed whole, some after being chewed, some are dissolved or dispersed in water before being administered and some are retained in the mouth where the active substance is liberated. The excipients can include binders, glidants and lubricants to ensure efficient tabletting, disintegrants to promote tablet break-up in the digestive tract, sweeteners or flavors to enhance taste, and pigments to make the tablets visually attractive.

Tablets:^[2]

In 1843, the first patent for a hand operated device used to form a tablet was granted.” Tablets are defined as solid preparations each containing a single dose of one or more active ingredients and obtained by compressing uniform volumes of particles. They are intended for oral administration, some are swallowed whole, some after being chewed. Some are dissolved or dispersed in water before being administered and some are retained in the mouth, where the active ingredient “liberated”. Tablets are used mainly for systemic drug delivery but also for local drug action. For systemic use drug must be released from tablet that is dissolved in the fluids of mouth, stomach and intestine and then absorbed into systemic circulation by which it reaches its site of action.^[3] Tablets remain popular as a dosage form because of the advantages, afforded both to the manufacturer [e.g. simplicity and economy of preparation, stability and convenience in packing, shipping and dispensing] and the patient [e.g. accuracy of dosage, compactness, portability, blandness of taste and ease of administration].^[4]

Advantages of tablets: ^{[4, 5]}

· Lightest and most compact of all oral dosage forms.

· A unit dosage form.

· Simplest and cheapest.

Disadvantages of tablets:^[4,5]

Some drugs resist compression into dense compacts, owing to their amorphous nature or flocculent, low-density character.

Immediate release tablet^[7,8]:

An immediate release tablet is a dosage form which is designed to disintegrate and release their medication with no special rate controlling feature, like any specific coating or any other techniques.

Advantages of Immediate Release:

· Economical and cost effective.

· Quick onset of action.

· Suitable for industrial production.

· Improved stability and bioavailability.

· Provides some advantages of liquid dosage forms.

· Adaptable and amendable to existing processing and packaging machinery.

Disadvantages of Immediate Release Tablets:

· Rapid drug therapy intervention is not possible.

· Sometimes may require more frequency of administration.

· Dose dumping may occur.

· Reduced potential for accurate dose adjustment.

CARVEDILOL:^[8]

With the increasing number of heart patients the demand of advance and improve medicine. Carvedilol is a drug which acts on β blockers, α blocker and as an antioxidant.

Figure1.1: Structure of Carvedilol ^[10]

Fenugreek seed mucilage:

Trigonella Foenum-graceum commonly known as Fenugreek is an herbaceous plant of the leguminous family. Fenugreek seeds contain a high percentage of mucilage (a natural gummy substance present in the coatings of many seeds). Although it does not dissolve in water, mucilage forms a viscous tacky mass when exposed to fluids. Like other mucilage- containing substances, fenugreek seeds swell up and become slick when they are exposed to fluids

IDEAL REQUIREMENT OF MOUTH DISSOLVING TABLET^[11]

1. Does not require water to swallow and should dissolve or disintegrate in the mouth within few seconds.

2. Allow high drug loading.

3. Have a pleasing mouth feel.

4. Leave minimal or no residue in the mouth after oral administration.

5. Exhibit low sensitivity to environmental conditions such as humidity and temperature.

Material:

Carvedilol, MCC102, Talc, Crospovidone, SSG, Aerosol, Magnesium stearate (All gifted sample by Acme Company) fenugreek seed mucilage (Local market of Shahpur).

Methods:

Nine different formulations prepared by wet granulation method.

Wet Granulation Method:

Procedure:

Carvedilol + Crospovidone

Carvedilol and Crospovidone were weighed and mixed properly.

A wet granulate was prepared by adding the MCC (binder) to the powder blend and mixing thoroughly.

The wet mass was granulated using sieve no. 12 and granules formed were dried in the dryer at 40°C for 30 min. The granules were further blended with the remaining quantity of superdisintegrants (extra granular disintegrate), purified talc and magnesium stearate were added and compressed into tablets.

Then subjected the blend for tablet compression by using Round and flat faced punches in CADMACH 16 punches tablet punching machine.

Punches of 8 mm diameter were used for compression. Tablet of 150 mg was prepared by adjusting hardness and volume screw of compression machine properly.

Carvedilol + Fenugreek seed powder

Preparation of Fenugreek seeds powder

· The dried fenugreek seeds were collected and size reduction was done in the grinder then sieved through mesh no. 80 and stored in desiccators.

Procedure:

Carvedilol and Fenugreek seed powder were weighed and mixed properly.

A wet granulate was prepared by adding the MCC (binder) to the powder blend and mixing thoroughly.

The wet mass was granulated using sieve no. 12 and granules formed were dried in the dryer at 40°C for 30 min. The granules were further blended with the remaining quantity of superdisintegrants (extra granular disintegrate), purified talc and magnesium stearate were added and compressed into tablets.

Then subjected the blend for tablet compression by using Round and flat faced punches in CADMACH 16 punches tablet punching machine.

Punches of 8mm diameter were used for compression. Tablet of 150mg was prepared by adjusting hardness and volume screw of compression machine properly.

Carvedilol + SSG

Carvedilol and SSG were weighed and mixed properly.

A wet granulate was prepared by adding the MCC (binder) to the powder blend and mixing thoroughly.

The wet mass was granulated using sieve no. 12 and granules formed were dried in the dryer at 40°C for 30 min. The granules were further blended with the remaining quantity of superdisintegrants (extra granular disintegrate), purified talc and magnesium stearate were added and compressed into tablets.

Then subjected the blend for tablet compression by using Round and flat faced punches in CADMACH 16 punches tablet punching machine.

Punches of 8 mm diameter were used for compression. Tablet of 150 mg was prepared by adjusting hardness and volume screw of compression machine properly.

EVALUATION OF TABLETS^[40-43]

I. Post compression tests

1. Organoleptic properties of tablets

2. Uniformity of thickness.

3. Hardness.

4. Friability test.

5. Weight variation test.

6. Disintegration time.

7. Drug content uniformity.

8. In-vitro Dissolution studies.

DISCUSSION:

Analytical evaluation (Determination of λ_max)

The absorption wavelength maximum was found to be at 243 nm. (Table: 1.1) and (Figure: 1.2)

Table1.1: Calibration Curve of Carvedilol with 0.1N HCl

Sr. No.	Concentration	Absorbance at 243nm	Beer’s Lambert range(mg/ml)	Coefficient of regression
1.	0	0	5-35	0.996
2.	1	0.084	5-35	0.996
3.	2	0.165	5-35	0.996
4.	3	0.249	5-35	0.996
5.	4	0.330	5-35	0.996
6.	5	0.445	5-35	0.996

Figure 1.2: Calibration Curve of Carvedilol with 0.1NHCl

DISCUSSION:

The above results shown that Carvedilol’s r²value is 0.996.

Spectroscopic technique:

FT-IR spectral data:

The FT-IR represents the peaks of the Carvedilol functional groups. These peaks were not affected, they were prominently observed in IR-spectra of Carvedilol along with natural super disintegrant and other excipients. The spectral details of the drug and the excipients are shown in (Figure: 1.3, 1.4). There was no difference in the position of the absorption bands, hence providing evidence for the absence of any chemical incompatibility between pure drugs with the excipients. And C103- E076D IR Affinity- 1 is used.

Figure 1.3: FT-IR spectra of Carvedilol: a). Crospovidone, b). SSG

Figure 1.4: FT-IR spectra of Carvedilol with Fenugreek seed mucilage

Interpretation of IR spectra:

Sr. No	Group frequency (cm^-1)	Functional group/assignment
1.	2950-2850(m or s)	Alkyl C-H stretch
2.	3100-3010(m) 1680-1620(v)	Alkenyl C-H stretch Alkenyl C=H stretch
3.	3300(s) 2260-2100(v)	Alkenyl C-H stretch Alkenyl CC stretch
4.	3030 (v) 860-680(s) 1700-1500(m)	Aromatic C-H stretch Aromatic C-H bending Aromatic C=C bending
5.	3550-3300(broad, s)	Alcohol/Phenol O-H stretch
6.	3000-2500(broad, v)	Carboxylic acid O-H stretch
7.	2260-2220(m)	Nitrile Cstretch
8.	1740-1690(s) 1750-1680(s) 1750-1735(s) 1780-1710(s) 1690-1630(s) 1630-1575	Aldehyde C=O stretch Ketone C=O stretch Ester C=O stretch Carboxylic acid C=O stretch Amide C=O stretch Open chain azo (-N=N-)
9.	3700-35009(m)	Amide N-H stretch
10.	500-470	Polysulphides S-S stretch
11.	880-860 840-815	Carbonate ion Nitrate ion
12.	1100-1000	Phosphate ion
13.	1100-900 1190-1080	Silicate ion Cyanate (-OCN and C-OCN stretch)

PRE- COMPRESSION PARAMETERS:

1. Angle of repose:

All the formulations prepared by wet granulation method showed the angle of repose less than 25, which reveals excellent flow property. And F6 showing angle of repose24.64 (Table: 8.3)

Table 1.2: Angle of repose of formulations (F1-F9)

Sr. No.	Formulation	Angle of repose (±SD)
1.	F1	26.09±0.02
2.	F2	27.16±0.04
3.	F3	25.57±0.06
4.	F4	26.38±0.05
5.	F5	28.94±0.07
6.	F6	24.64±0.03
7.	F7	29.10±0.02
8.	F8	27.69±0.04
9.	F9	25.18±0.05

DISCUSSION:

F3 and F6 showing excellent flow properties

2. Bulk density, Tapped density, Hausner ratio, Compressibility index

The bulk density and tapped density for all formulation (F1 – F9) varied from 0.35 - 0.46gm/cm³ and 0.41 - 0.52 gm/cm³ respectively. The results of car's consolidate index or % compressibility index and Hauser's ratio for the entire formulation (F1 – F9) blend range from 11.11- 14.63 and 1.12-1.17 respectively, shows fair flow properties. The results are shown in the (Table no.1.3).

Table 1.3: Bulk density, Tapped density, Hausner ratio, Compressibility index of formulations (F1 – F9)

Sr. N o.	Formulation	Bulk Density (g/cc) (±SD)	Tapped Density (g/cc) (±SD)	Hausner ratio (±SD)	Compressibility index (%) (±SD)
1.	F1	0.42±0.03	0.48±0.04	1.14±0.03	12.50±0.05
2.	F2	0.39±0.07	0.45±0.05	1.15±0.04	13.33±0.07
3.	F3	0.35±0.02	0.41±0.03	1.17±0.06	14.63±0.03
4.	F4	0.39±0.04	0.50±0.04	1.13±0.02	12.00±0.04
5.	F5	0.41±0.05	0.47±0.06	1.12±0.03	10.64±0.05
6.	F6	0.36±0.03	0.44±0.04	1.13±0.04	11.23±0.06
7.	F7	0.38±0.06	0.43±0.02	1.13±0.04	11.63±0.04
8.	F8	0.40±0.04	0.45±0.05	1.13±0.03	11.11±0.07
9.	F9	0.46±0.05	0.52±0.03	1.13±0.02	11.54±0.05

DISCUSSION:

F3 and F6 showing all the values in range that indicates that they have excellent properties.

POST COMPRESSION PARAMETERS:

1. Organoleptic properties:

All the tablets show similar colour, odour, taste and physical appearance. There is no impact of natural superdisintegrants in their Organoleptic properties.

2. Hardness test:

By using the natural superdisintegrants, the hardness values ranged from 3.0-3.5 kg/cm²for formulations (F1-F9) and were given in (Table no. 1.4) and (Figure:1.5)

Table1.4: Hardness test of formulation (F1-F9)

Sr. No.	Formulations	Hardness(kg/cm^2) (Mean ±SD)
1.	F1	3.2±0.2
2.	F2	3.3±0.3
3.	F3	3.4±0.2
4.	F4	3.6±0.3
5.	F5	3.2±0.2
6.	F6	3.1±0.4
7.	F7	3.2±0.3
8.	F8	3.3±0.2
9.	F9	3.4±0.3

Figure 1.5: Bar graph comparison hardness for formulations (F1-F9)

DISCUSSION:

All formulation was in range.

3. Weight variation test

The entire tablet passes weight variation test, as the average % weight variation was within the Pharmacopeia limit - 7.5%. It was found to be 148mg -152 mg. The weight of all the tablets was found to be uniform with less deviation (Table no. 1.5).and (Figure: 1.6)

Table 1.5: Weight variation test of formulations (F1-F9)

Sr. no.	Formulations	Weight (mg)
1.	F1	151
2.	F2	149
3.	F3	150
4.	F4	151
5.	F5	150
6.	F6	148
7.	F7	152
8.	F8	151
9.	F9	149

Figure 1.6: Bar graph comparison weight for formulations (F1-F9)

DISCUSSION:

F3 and F6 showing values in range.

4. Friability test

The friability values were found to be within the limit 0.32-0.41 (0.5 - 1%). The above evaluation parameter showed no significant difference between F1-F9 formulations (Table: 1.6) and (Figure: 1.7)

Table 1.6: Friability of formulations (F1 – F9)

Sr. No.	Formulation	Friability (%)
1.	F1	0.35
2.	F2	0.34
3.	F3	0.36
4.	F4	0.34
5.	F5	0.37
6.	F6	0.33
7.	F7	0.37
8.	F8	0.38
9.	F9	0.40

Figure 1.7: Bar graph comparison friability for formulations (F1- F9)

DISCUSSION:

All formulations showing results in friability range.

5. Thickness

By using natural superdisintegrants, the thickness values ranged from2.11-2.20(mm) for formulations (F1-F9) and shown in (Table: 1.7) and (Figure: 1.8)

Table 1.7: Thickness of formulations (F1-F9)

Sr. no.	Formulations	Thickness(mm)
1.	F1	2.20
2.	F2	2.21
3.	F3	2.16
4.	F4	2.11
5.	F5	2.19
6.	F6	2.11
7.	F7	2.20
8.	F8	2.18
9.	F9	2.14

Figure 1.8: Bar graph comparison weight for formulations (F1-F9)

DISCUSSION:

F3, F4 and F6 showing good result.

6. In-vitro Disintegration test:

Disintegration test carried out in modified dissolution apparatus, Results shows the formulations with 3%, 5%, 7.5% of SSG having high disintegrating time as 32, 24, 20 sec. The disintegration time of F1, F2, F3 with 3%, 5%, 7.5% CP formulations is 17, 14, 10 sec respectively and is almost better than F4, F5, F6, F7, F8, F9 formulations (Table no: 1.8), and comparative profile (Figure: 1.9).

Table 1.8: Disintegration Time of formulations (F1 – F9)

Formulation	Disintegration time(sec)	Drug content (%)
F1	17	97.80
F2	14	99.05
F3	10	98.12
F4	25	99.10
F5	20	98.18
F6	15	98.16
F7	32	97.45
F8	24	98.16
F9	20	98.19

Figure 1.9: Bar graph comparison between Disintegration times for formulations (F1- F9)

DISCUSSION:

F3 and F6 showing minimum time in disintegration.

7. Drug content uniformity:

The concentration of the drug in all the formulations with natural super-disintegrant was found to be 99.18%. It was within the IP limits. The concentration of drug with Crospovidone was found to be 98.66%. And the concentration of drug with SSG was found to be 97.12%.

8. in-vitro Dissolution studies:

Dissolution is carried out in USP Apparatus Type-II apparatus at 50rpm in 900ml dissolution media (0.1N HCL) for 60 minutes. At the end of 30 minutes almost total amount of the drug is released (i.e. 98%), from the formulation prepared by the wet granulation method with fenugreek seed mucilage. (Table: 1.9andFigure: 1.10, 11 and 12) Showing cumulative % drug release for formulations

Table 1.9: Cumulative % drug release for formulations (F1 – F9)

Time in min	F1 (Mean ±SD)	F2 (Mean ±SD)	F3 (Mean ±SD)	F4 (Mean ±SD)	F5 (Mean ±SD)	F6 (Mean ±SD)	F7 (Mean ±SD)	F8 (Mean ±SD)	F9 (Mean ±SD)
0	0	0	0	0	0	0	0	0	0
5	19±0.81	21±0.89	13±0.78	21±0.89	33±0.80	39±0.56	28±0.78	29±0.76	28±0.67
10	32±0.64	34±0.81	22±0.57	45±0.67	54±0.60	56±0.67	40±0.87	43±0.87	45±0.78
15	40±0.73	45±0.56	52±0.67	52±0.61	63±0.70	75±0.78	62±0.66	67±0.57	60±0.76
30	51±0.67	53±0.89	76±0.80	63±0.56	70±0.56	98±0.67	74±0.67	81±0.87	78±0.89
45	67±0.76	70±0.78	89±0.78	75±0.67	92±0.76	-	83±0.76	89±0.65	82±0.80
60	80±0.78	94±0.80	-	88±0.78	98±0.75	-	89±0.87	98±0.87	99±0.56

Figure 1.10: Linear graph comparison between cumulative % drug release for formulations (F1- F3)

Figure 1.11: Linear graph comparison between cumulative % drug release for formulations (F4 - F6)

Figure1.12: Linear graph comparison between cumulative % drug release for formulations (F7- F9)

DISCUSSION:

F3 and F6 showing excellent results.

CONCLUSION:

The above results suggest that the formulated immediate release tablets of Carvedilol with Fenugreek seed mucilage exhibited good physical parameters. The overall results indicated that formulation F6 and F3with (Fenugreek seed mucilage and Crospovidone) (7.5%) had a higher edge compared to other formulations containing superdisintegrants. They satisfy all the criteria for immediate release tablets. With the progress in the formulation of Rapid disintegrating tablets, now it is possible to formulate these tablets with reduced quantity of superdisintegrants. Rapidly disintegrating dosage forms have been effectively commercialized by using numerous types of super disintegrating agents. By the use of many and different types of super disintegrating agent’s patient compliance, commercial and therapeutic benefits have enhanced. At a time when researchers are faced with increasing amounts of poorly soluble drugs, it is very important to select super disintegrating agents that maximize drug dissolution. Due to fast acceptance of RDTs by patients and pharmaceutical companies, the market of this dosage form is growing and the product pipeline quickly, but without the field of super disintegrating agents it would not have been possible

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Received on 13.04.2020 Modified on 18.05.2020

Accepted on 21.06.2020      ©Asian Pharma Press All Right Reserved

Asian J. Pharm. Tech.  2020; 10(3):156-164.

DOI: 10.5958/2231-5713.2020.00027.6