Optimizing Badam gum towards tableting excipients

 

Gayathri M1, Mithra Chandrasekaran1, Arun Radhakrishnan1, Gowthamarajan Kuppusamy1* Sachin Kumar Singh2

1Department of Pharmaceutics, JSS College of Pharmacy,

JSS Academy of Higher Education & Research, Ooty. Nilgiris, Tamil Nadu, India

2School of Pharmaceutical Sciences, Lovely Professional University, Punjab.

*Corresponding Author E-mail: gowthamsang@jssuni.edu.in

 

ABSTRACT:

Background: Badam gum (BG), a plant exudate is obtained from Terminalia catappa. As BG is a novel polysaccharide, physico-chemical characterization was performed in order to establish its suitability as pharmaceutical excipient. Natural Polymers are economical, abundant, non-toxic and potentially Bio-degradable. Objective: To Characterize the Badam gum and to prepare and evaluate paracetamol tablet with different ratios of Badam gum. Method: Badam gum was prepared and subjected to biochemical tests (Molisch’s, Benedicts and fehling’s test) and preformulation studies. Direct Compression of paracetamol tablets using different ratios of Badam gum (0.06g, 0.12g, 0.24g, 0.36g, 0.48g, 0.6g, 0.72g, 0.84g) as disintegrant and MCC (5.94, 5.88, 5.76, 5.64, 5.52, 5.4, 5.28, 5.16) was carried out. Tablets were evaluated for Physicomechanical Properties, disintegration and dissolution. Results: Positive results obtained in the preliminary tests in the identification of Badam gum. Swelling Index was found to be 220%. DSC and FTIR Studies revealed that Badam gum is compatible with the drug. Hardness of formulation F5 was found to be 6 and other formulations was found to be 4. Disintegration time of F2 was found to be 90 Sec, whereas F6 disintegrated at 5 min 25 Sec. In in vitro dissolution studies, on comparing to all formulation, increasing the concentration of badam gum retards the faster release of Paracetamol. Conclusion: In this study, paracetamol tablets were prepared with different ratios of Badam gum. From the study it can be concluded that 2.5% of Badam gum can be used as disintegrant.

 

KEYWORDS: Badam gum, Disintegrant, Direct compression, Swelling index, Dissolution.

 

 


1.    INTRODUCTION:

Substances other than pharmacologically active drugs/ pro-drugs included in the manufacturing process/ are contained in a finished Pharmaceutical dosage form are called Pharmaceutical excipients[1]. Excipients has different functions such as Disintegrants, Binders, Lubricants, Glidants (flow enhancers), Fillers, Compression aids, Colors, Sweeteners, Suspending/ dispersing agents, Preservatives, Printing inks, Film formers / coatings, Flavours[2]. Excipients helps in the targeted delivery of drugs, whereas others releases the drug slowly in a sustained/ controlled manner (GI Irritant drugs).

 

Some excipients helps in the disintegration process, so that the drug reaches the blood stream at a faster rate. Other excipients helps in maintaining the product stability, so that the drug remain effective until it is used. Further, some excipients helps in finding the drug product[3]. Incompatibility between drug and excipients exists in some cases. So there is a need for quicker manufacturing of formulations. Today, excipients having high compressibility with very high compression speed are needed in tablet dosage form. Three main interrelated factors that affect the development of new excipients are – Safety, Patent life after approval and Economic return of investment.

 

Polysaccharides are widely distributed in nature and can be used in food products, cosmetics and Pharmaceutical industry[4]. Polysaccharides are used broadly as excipients in pharmaceutical dosage forms. Polysaccharide complexes (Gums and mucilages) obtained from sugar and uronic acid units are insoluble in alcohol but it will either dissolve or swell in water[5]. In Pharmacy, Gums and mucilages has wide applications such as they are used as ingredients in Dental and Other adhesives. It can also be used as Bulk Laxatives. Polysaccharides are hydrophilic polymers. They are used as disintegrants, tablet binders, gelling agents, emulsifiers, suspending agents, sustaining agents and stabilizing agents[6]. Almond gum is a water soluble gum extrudes obtained from the tree Prunus communis. It contains aldobionic acid, L-arabinose, L-galactose, Dmannose etc. It can be used as emulsifier, suspending pharmaceutical, glazing agent, adhesive and stabilizer[7]. Physicochemical properties of drugs and the polymers,, morphology and size of the particles biodegradation rate of polymers, shape of the delivery devices and the thermodynamic compatibility that exist between the polymers and the drugs influences release rate of drugs[8]. Almond gum is a colourless pale yellow or amber brown and is only 10% soluble in water[9]. Almond gum is washed. It is dried for 24 hr, further dried at 30-40ºC and grinded. Grinded Powder mixed with distilled water. It is heated at 60°C for approximately 4h. Using muslin cloth, Concentrated solution is filtered. It is cooled at 4°C-6°C[10]. Obtained almond gum is evaluated for chemical analysis, SEM, DSC, IR, Florescence analysis, X-ray Diffractometry[11]. Natural gums has wide variety of uses such as tablets binder, disintegrating agent, emulsifier, suspending agent, gelling agent, protective colloids in suspension and sustaining agent in tablets, stabilizing agent and also acts as adjuvant in some pharmaceutical formulation[12]. In this research article, feasibility of natural polymer (Badam Gum) as a disintegrant and sustained release polymer in paracetamol tablet formulation was carried out and evaluated.

 

2. MATERIALS AND METHODS:

2.1 Materials:

Paracetamol, Lactose, Microcrystalline Cellulose, Sodium Starch Glycolate, HPMC, Potassium Hydroxide, Sodium Hydroxide, Alcoholic α Naphthol, Conc. Sulphuric acid, Benedict’s reagent, Fehling’s reagent A and B were procured from SD fine chemicals, Badam Gum was procured from local market.

 

2.2 Method:

2.2.1 Extraction of Badam Gum:

Badam gum in dried form was collected and it was crushed in order to obtain fine particles using the motor and pestle. Fine particles sieved through the sieve number 80. It was kept under storage in a self sealing cover for further studies.[13]

 

3. Preliminary Phyto-Chemical Test:

The badam gum was tested for the presence of polymer. The tests chosen were Molisch’s test, Benedict’s and Fehling’s test. Prior to the test, the gum was mixed with suitable quantity of distilled water (10ml). It was filtered to obtain the filtrate, which is taken for further studies.[14]

 

3.1 Molisch’s Test:

Add 2-3 drops of 1% alcoholic α-naphthol + 2ml of conc H2SO4 along the sides of test tube containing the filtrate. Presence of carbohydrate was confirmed by the development of brown colour precipitate.

 

3.2 Benedict’s Test:

Benedict’s reagent was added to the filtrate. It is heated gently. Precipitate was formed, which again confirmed the presence of reducing sugar.

 

3.3 Fehling’s Test:

Dil. HCL + neutralized with alkali solution was added to the filtrate. It is heated gently heated. Then, Fehling’s A and B reagent were added. Blue colour indicated the presence of carbohydrates.

 

4. Pre-Formulation Studies:[15]

4.1. Angle of Repose:

5 g of powder was permitted to flow right through the tip of the funnel. The height (h) and radius(r) of the powder was measured. Angle of repose was determined:

                      h

      θ = ----------------

                      r

Where, θ = angle of repose, h = height (cm), r = radius (cm)

 

4.2. Bulk Density:

20gram of fine mixture was weighed and transferred into 100ml measuring cylinder. Volume of the powder mixture was measured. Bulk density calculated by the given equation:

                                   m

Bulk density = -----------------

                               v0

 

where, m = mass (g), v0 = apparent volume (cm)

 

4.3. Tapped Density:

20gram of fine mixture was weighed. It was transferred into 100ml measuring cylinder. It was subjected for tapping 100 times using tapped density tester. The tapped density volume was recorded using the equation given below:

                                   m

Tapped density = -----------------

                               vf

where, m = mass (g), vf = final tapped volume (cm3)

 

4.4. Compressibility Index:

Based on the bulk and tapped volume, Compressibility index of the powder was calculated. Both bulk and tapped volume determined using above procedure. After measuring both the volume, compressibility index was determined.

                                                v0 -vf

Compressibility Index = -------------------------- x 100

                                                     v0

 

Where, v0 = unsettled apparent volume (cm3), Vf = final tapped volume (cm3)

 

4.5. Hausner Ratio:

Hausner ratio was calculated by using the following equation:

                               v0

Hausner Ratio =------------------

                               vf

 

where, v0 = unsettled apparent volume (cm3), vf = final tapped volume (cm3)

 

4.6. Swelling Index:

The swelling index test procedure is used to determine the general swelling characteristics. The swelling index test has not been demonstrated to have a proportional co-relation, to have a good gum quality, a high swell is considered by most. This test factor can be used as a simple qualitative indicator.

                               Initial volume – final volume

Swelling Index = ------------------------------------ x 100

                                        Initial volume

To determine the compatibility between the drug and the excipients, pre-formulation studies are carried out. It was necessary to convert the active pharmaceutical ingredient into a suitable dosage form. In other words, Preformulation is the study of physico-chemical properties of drugs and excipients.

 

4.7 Development of Calibration Curve:[16]

Paracetamol Stock solution was prepared by dissolving 10mg of drug in 10ml of PBS solution 6.8, to obtain conc of 100μg/ml. From this solution, 2, 4, 6, 8, and 10μg/ml dilution were prepared. The λmax of the drug was determined by scanning one of the dilution between 247nm using UV. The standard curve between the conc and absorbance was plotted.

 

4.8. Fourier Transform Spectroscopy (FTIR):

The compatibility studies were performed in order to find out the possible interaction between the polymer (Badam Gum) and drug (Paracetamol). The IR spectra of the drug, polymer, and physical mixture were studied. The solid sample was grounded into the fine powder by using the mortar and pestle in 1:1 ratio (drug and polymer). The spectra obtained were compared and interpreted for major functional groups and functional peaks of drug and polymer.

 

4.9. Differential Scanning Calorimeter (DSC):

The thermograms of drug, drug and polymer were recorded on model differential scanning calorimeter. An empty pan was used as a standard. About 1 gram of sample including pure drug (paracetamol), physical mixture (drug, polymer) and excipient (badam gum) were separately weighed and sealed in a small aluminium pan and it was heated up to 20-400oC at the heating rate of 10oC/min with constant purging of dry nitrogen 50ml/min. For reference, a blank pan was sealed and used. Using automatic thermal analyzer system, DSC thermogram was obtained. The DSC thermo gram obtained from this study was used for determining the compatibility between the drug and the excipients.

 

5. Tablet Compression:[17]

Direct compression was employed in preparation of tablet. For tablet compression, different ratios of Badam Gum, Sodium Starch Glycolate and HPMC were taken and each were triturated separately with other excipients using mortar and pestle. Suitable quantity of the dose was weighed and filled into the die cavity and it was compressed using tablet punching machine.

 

6. Evaluation:[18]

6.1. Weight Variation:

This test was carried out 20 tablets from each formulation. Weight of the each tablet was measured. Weight variation was calculated and results were reported.

                                   Total Weight

Average weight (mg) =---------------- 

                                          20                   

6.2. Thickness:

It was determined by placing the tablet vertically in the Vernier Caliper. Thickness of 8 tablets were measured and their average values were calculated.


 

 

Table. No. 1: Different ratio of Badam Gum and MCC.

S. No

Formulation

Badam Gum (g)

Starch (g)

MgS (g)

Talc (g)

MCC (g)

Paracetamol (g)

1.

F1

0.16 (1.25%)

0.65 (5%)

0.13 (1%)

0.13 (1%)

5.43

6.5

2.

F2

0.325 (2.5%)

0.65

0.13

0.13

5.265

6.5

3.

F3

0.65 (5%)

0.65

0.13

0.13

4.94

6.5

4

F4

1.3 (10%)

0.65

0.13

0.13

3.79

6.5

5.

F5

1.95 (15%)

0.65

0.13

0.13

3.14

6.5

6.

F6

2.6 (20%)

0.65

0.13

0.13

2.49

6.5

7.

F7

3.25 (25%)

0.65

0.13

0.13

2.34

6.5

8.

F8

3.9 (30%)

0.65

0.13

0.13

1.69

6.5


6.3. Hardness:

It is an important parameter to know whether the drug undergoes any capping, lamination etc during shifting of the products. Monsanto hardness tester was employed for this test. The main aim of determining hardness is to know how much force is required to break the tablet. The tablet was placed between two pieces. The strength necessary to break the tablet was considered. The crushing strength test was executed on 8 tablets from the formulation.

 

6.4. Friability:

                          Initial weight – Final weight

Friability (%) = ------------------------------- X 100

                                     Initial weight

 

6.5. Disintegration:

 

6.6. In Vitro Dissolution Studies:

In-vitro drug release was done for 6 tablets. USP dissolution apparatus II (paddle) was used. The study was performed with 900ml of PBS 6.8 at 37°C. Since, F1-F8 formulations have passed all the previous studies; they were subjected to this study. The first F1 formulation was added to the dissolution medium and paddle was fixed. The shaft was fixed and rotated at 75rpm. At different time interval (5, 10, 15, 20, 25 and 30 min), 10ml equivalent sample was with drawn from the basket. After withdrawing the sample, the same quantity was replaced with the fresh PBS. The UV absorbance was measured at 246nm. The cumulative percentage drug release was calculated using the below formula.

 

Conc (μg/ml) =  Absorbance ± Intercept X slope

 

                       Conc. X Batch Volume X Dilution factor

Amount release (mg) =--------------------------------------

                                                      1000

Percentage drug release = Amount released label claim

 

Cumulative release (%) = volume withdraw X PDR (t-1) +  PDR Bath volume.

 

Whereas,

PDR = percentage drug release at time t

PDR (T-1) = previous percentage drug release at time t

 

7. RESULTS AND DISCUSSION:

7.1 Preliminary phytochemical test:

1.     Molisch’s test:

Appearance of brown colour indicates the positive result.

 

2.     Benedict’s test:

Emergence of blue colour indicates the positive result.

 

3.     Fehling’s test:

Appearance of blue colour indicates the positive result.

 

Image. No. 1: Figure representing the results of Molisch’s, benedict’s and Fehling’s test

 

7.2 Preformulation studies:

7.2.1. Bulk density, tapped density, hausner ratio, compressibility indexand angle of repose for different formulations:

 

7.2.2. Swelling index:

Swelling index for the gum was found to be = 220%

So, it can be said that the Badam gum was having a good swelling property as a natural polymer.

 

7.2.3. Development of calibration curve:

It was developed by using PBS at 6.8 and perfect correlation was observed. From the regression value (R2= 0.9995) it was found that perfect linearity existed between the conc and absorbance


 

Table. No. 2: Outcomes of different parameters

 

Batch

Various parameters in different formulations

Bulk density (g/cc)

Tapped density (g/cc)

Hausner Ratio

Compressibility index (%)

Angle of repose

F1

0.574 ±0.00

0.586±0.01

1.09±0.01

14.01±0.01

30.5±0.32

F2

0.582±0.01

0.593±0.00

1.12±0.00

14.2±0.02

32.9±0.12

F3

0.599±0.01

0.632±0.02

1.09±0.02

15.3±0.03

35.6±0.65

F4

0.562±0.00

0.585±0.00

1.12±0.00

12.6±0.00

30.9±0.35

F5

0.488±0.01

0.523±0.00

1.15±0.00

14.2±0.02

33.7±0.24

F6

0.462±0.00

0.562±0.01

1.14±0.01

11.9±0.01

32.6±0.30

F7

0.501±0.00

0.545±0.02

1.18±0.01

12.5±0.01

30.4±0.65

F8

0.493±0.01

0.537±0.00

1.17±0.00

15.2±0.02

31.9±0.12


Table. no. 3 Calibration curve of paracetamol

Conc

Absorbance

0

0

2

0.146

4

0.291

6

0.445

8

0.609

10

0.743

 

 

Figure.No.1: Calibration Curve of Paracetamol.

 

7.2.4. Compatibility studies:

7.2.4.1. In order to detect any possible chemical reaction between drug and polymer, FTIR spectral matching approach was employed

 

 

Figure. No.2: IR Spectra of Badam Gum, Paracetamol, Physical mixture.

 

7.3. Evaluation tests for tablets:

·       Functional groups present in badam gum are C-H (2800 cm-1), COOH (1653-1431 cm-1), COOH [Symmetric Stretch] (1431 cm-1), C-H Bending (818 cm-1)

·       Functional group present in paracetamol are N-H [Stretching] and O-H (3160cm-1),C=C [Stretching] and C=O[Amide] (1653 cm-1) ,N-H (1433 cm-1), C-H bending and (C-N) Aryl (1327-1170 cm-!)

·       Functional groups present in physical mixture are O-H and N-H (3322cm-1), C=C (1653 cm-1), COOH ( 1432 cm-1), CH and C-N (809 cm-1)

·       The polymeric peak of CC, COOH, CH are found in the physical mixture spectrum and paracetamol function group peak also found without any chemical shift and so found to be stable.

 

7.2.4.2. Differential scanning calorimeter:

The DSC studies have been done to know the compatability between paracetamol, Badam gum and physical mixture. Consequently, the assignment of the thermogram clearly showed that there was no physical interaction among the Badam gum and the paracetamol in the physical mixture.

 

 

Figure. No.3: DSC Thermogram of Badam Gum, Paracetamol and Physical mixture

 

7.3.1 Weight Variation: Weight Variation is within ±5%

7.3.2 Friability: Friability is within 1%

7.3.3 Thickness: 4mm

7.3.4 Hardness: Hardness is between 5-8 kg/cm2

7.3.5 Disintegration Time: Fast Disintegration (F2- 30 sec)

 

7.3.5.1 Comparison of Badam gum and Sodium Starch Glycolate as Disintegrant:

Disintegration time of Badam Gum (2.5%) is 30 sec, whereas disintegration time of sodium starch glycolate is 34 sec[19]. By comparing badam gum with sodium starch glycolate, it is proved that has better disintegrant property than Sodium Starch Glycolate. From disintegration test, it is confirmed that Badam Gum disintegrates faster than Sodium starch glycolate.

 


Table.no.4 - Post-Compression Parameters:

Formulation

Weight Variation (mg)

N=20

Friability (%)

N=8

Thickness (mm)

N=8

Hardness (Kg/cm2)

N=8

Disintegration Time

 (sec)

F1

649

0.35%

4

4

65

F2

649

0.23%

4

4

30

F3

647

0.18%

4

4

90

F4

650

0.45%

4

4

150

F5

646

0.14%

4

6

210

F6

649

0.25%

4

4

325

F7

648

0.36%

4

4

500

F8

651

0.40%

4

4

480

 


 

7.3.6 Invitro dissolution:

In vitro dissolution studies was done with the help of USP-II paddle type apparatus. Dissolution test was carried out for F1 to F8 formulations, obtained from direct compression method.

 

Table.no.5: Represents the cumulative percentage release of different formulations

Time

F1

F2

F3

F4

F5

F6

F7

F8

15

47

41

38

34

22

18

19

22

30

59

59

49

45

36

30

27

40

60

72

70

64

60

53

48

39

54

120

83

84

76

74

69

64

54

65

240

90

91

83

80

78

76

68

78

480

99

99

95

91

90

89

85

88

 

 

Figure. No. 4: Invitro drug release (F1-F8)

 

7.3.6.1 Comparison of Almond gum and HPMC as sustained Release Polymer:

The cumulative percentage drug release for Almond gum is 85%, whereas for HPMC is 74%.[20] By comparing Almond gum with HPMC, it was found that Almond gum is not an effective sustained release polymer, as it releases 85% of drug in 8hrs.From the dissolution study, it is confirmed that Sustain release capacity of almond gum is lesser than HPMC.

 

8. CONCLUSION:

In this Study, Paracetamol tablets were prepared with different ratios of badam gum and the prepared tablets were evaluated. From the study, it can be concluded that 2.5 % Badam Gum can be used as disintegrant. From the study, it is confirmed that Badam gum is not an effective sustain release polymer.

 

9. ACKNOWLEDGEMENT:

The authors are thankful for Department of science and technology – Fund for Improvement of Science and Technology Infrastructure in Higher Educational institutions (DST-FIST) for providing the laboratory facility to carry out the research work.

 

10. CONFLICT OF INTEREST:

The authors have no conflict of interest.

 

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Received on 25.11.2019           Modified on 26.02.2020

Accepted on 29.04.2020         © RJPT All right reserved

Research J. Pharm. and Tech. 2020; 13(12):6176-6181.

DOI: 10.5958/0974-360X.2020.01077.X