Development and Evaluation of Kukkutandatvak bhasma tablet by using Dry Granulation Techniques
Khalapurkar Priya, Baheti Akshay1*, Wani Manish, Polshettiwar Satish, Gawade Ashwini,
Tagalpallewar Amol, Pande Varun, Sabale Mrunal, Joshi Ameya
School of Pharmacy, Dr. Vishwanath Karad MIT World Peace University, Pune, Maharashtra, India.
*Corresponding Author E-mail: akshay.baheti@mitwpu.edu.in
ABSTRACT:
Aims: This study aimed to formulate and evaluate Kukkutandatvak (Hen Eggshell) bhasma tablet intended for optimum disintegration and release in the gastrointestinal tract. Methods and Material: Calcium content in Kukkutandatvak bhasma was determined using the titrimetric method. 9 formulations (F1 to F9) were prepared with Polyvinylpyrrolidone and SGS as super disintegrants. The granules were then evaluated for angle of repose, bulk density, tapped density, Hausner's ratio and Carr's index. The granules were then converted into caplet shaped tablets and were evaluated for uniformity of weight, drug content, friability, Hardness, Disintegration (in a sec) and % drug release. Results and Discussions: Calcium content in Kukkutandatvak bhasma was found to be 98%. The granules were found to be free-flowing and compressible. The Kukkutandatvak bhasma tablet had good strength and lower disintegration time (less than 135 sec), indicating a better balance between the binding and disintegration properties. The antacid activity of the tablet was evaluated by preliminary antacid test, i.e. acid-neutralizing capacity test and Rosset-Rice test. Conclusions: It was observed that Kukkutandatvak bhasma tablet (500 mg) prepared by both methods comply with Preliminary Antacid Test U.S.P. The tablet prepared neutralized 15.15 mEq of respectively in just 9.25min.
KEYWORDS: Kukkutandatvak bhasma, Tablets, Calcium carbonate, Acid Neutralizing Capacity Test, Rosset-Rice Test.
INTRODUCTION:
Rasa-Shastra (Vedic-chemistry) is one of the parts of Ayurveda, which deals with herbs-mineral/metals/non-metals preparations called Bhasmas. Bhasma is metallic or mineral preparation, in which metal or mineral is treated with herbal juices or decoctions and exposed to several calcination steps (Puta); these preparations are potent as the minimal dosage is sufficient and are claimed to be fast-acting.1 The various steps involved in the preparation of bhasma are shodhana (purification), Marana (burning or calcinations) and Bhavana (processing). Bhasma is claimed to be biologically produced nanoparticles, which are prescribed with several other medicines of Ayurveda2.
Kukkutandatvak bhasma (Hen Eggshell bhasma), known as calcinated Hen eggshell, is used to treat leucorrhea in the form of bhasma since ancient times in the Ayurveda system of medicines3,4. As per Ayurveda, Kukkutanda Tvak bhasma is helpful in the treatment of leucorrhea, leukaemia and arthritis5. Ayurvedic practitioners prescribe it in oligospermia, amenorrhea, leucorrhoea, polyuria, osteoporosis, arthritis etc.6,7. The eggshell contains 94% calcium carbonate, 1% calcium phosphate, 4% organic compounds and 1% magnesium carbonate8. The eggshell contains a high percentage of calcium and very low phosphorous. Eggshell calcium is more effective in increasing bone mineral density9.
Kukkutandatvak Bhasma is in powder form; the present aim of the study was to convert it into tablet dosage form to obtain a unit, accurate, stable dose with great precision and most minor variability. Moreover, tablets are easy to handle, use and carry with an attractive and elegant appearance compared to powders. Caplet shape tablets are easy to swallow as against large dose round-shaped tablets. The scored tablet can be easily divided into halves whenever a fraction dose is required, and tablets do not need more space for storage.
The objective of this study was to convert Kukkutandatvak bhasma into dry granules having good flow property using suitable excipient and compress it into caplet shaped scored tablet with required appearance, friability, hardness and disintegration. The Kukkutandatvak tablet should contain and release the optimum dose of calcium carbonate.
MATERIALS AND METHODS:
Materials:
The present work was carried out in Dr Vishwanath Karad MIT World Peace University School of Pharmacy. Kukkutandatvak bhasma was prepared in the laboratory. Excipients such as Lactose, Polyvinylpyrrolidone, Starch, Magnesium Stearate and Talc has been obtained from McW Health care Indore.
Methods:
Determination of % calcium content10
Weighed amounts of bhasma (500mg) were taken in the conical flask, in which several drops of ethanol were added (Ethanol acts as a wetting agent and helps HCl to dissolve calcium carbonate). 10 ml of 1M HCl were added to the flask. This solution was heated on the hotplate. It was removed from the plate as it began to boil. After cooling, it was titrated with 0.1M sodium hydroxide using a phenolphthalein indicator. The persistent pink colour was the endpoint, and the final volume of NaOH was recorded.
Formulation and preparation of Bhasma granules11
Kukkutandatvak bhasma was sifted through 100# sieve on a sifter, and fine particles were collected in a suitable container. Excipients were added, and the mixture was blended correctly using a double cone blender. Granules of Kukkutandatvak bhasma were prepared by dry granulation technique using Polyvinylpyrrolidone (PVP) as a binder and starch as a disintegrating agent. Lactose was used as filler. Slugs were designed on an automatic rotary tablet compression machine and were milled using Kalweka Rimek tablet miller. Milled material was sifted through 40# sieve, and granules were collected. These dry granules were further mixed with lubricant magnesium stearate and glidant talc. The formulation table is as per Table 1.
EVALUATION OF GRANULES12,13
1. Determination of Flow property and Compressibility
The angle of repose was determined using the funnel method. Maximum cone height (h) and Radius of the heap (r) was measured. The angle of repose (Ø) was calculated using the formula. Ø = tan-1 h/r. Bulk Volume (v) was noted by pouring pre-weighed 50mg granules (w) into a graduated cylinder. The bulk density was calculated using the formula
ρv = w/v
while
Tap volume (vt) was noted by tapping the above-graduated cylinder till granule volume reached its minimum using Biotech labs bulk density apparatus. Tap density was calculated using the formula ρvt = w/vt. Hausner ratio was calculated to determine the flow property of granules. Hausner ratio lower than 1.11 indicates excellent flow properties. It was calculated using the following formula. Hausner ratio = tapped density / bulk density. Carr’s index is an indication of the flowability and compressibility of a powder. A free-flowing compressible powder has bulk density and tapped density in comparable value; therefore, Carr’s index is small. On the other hand, for poor-flowing non-compressible powder, the difference between the bulk and tapped density observed would be greater; therefore, Carr’s index is more extensive. Carr’s index below 10 indicates good flowable compressible material. Carr's index of the dry granules was calculated based on the formula.
Carr's index (%) = (Tapped density - Pored density) / Tapped density x 100.
Preparation of Kukkutandatvak Bhasma Tablets:
The die fill cavity and pressure of the tablet compression machine were adjusted such that it can occupy 570 mg of granules. Tablets were compressed on Rimek Mini press II, 8 station, rotary tablet compression machine using caplet shape punch BB type tooling.
Table 1: Bhasma Tablet Formulation
Sr. No. |
Name of Ingredients |
Qty (per tablet) in mg |
|||||||||
F1 |
F2 |
F3 |
F4 |
F5 |
F6 |
F7 |
F8 |
F9 |
|
||
1. |
Bhasma |
500 |
500 |
500 |
500 |
500 |
500 |
500 |
500 |
500 |
|
2. |
Lactose |
23 |
24 |
25 |
24 |
25 |
26 |
25 |
26 |
27 |
|
3. |
Polyvinylpyrrolidone |
10 |
10 |
10 |
9 |
9 |
9 |
8 |
8 |
8 |
|
4. |
Starch |
27 |
26 |
25 |
27 |
26 |
25 |
27 |
26 |
25 |
|
5. |
Magnesium Stearate |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
6. |
Talc |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
5 |
|
Total Weight of Tablet |
570 |
570 |
570 |
570 |
570 |
570 |
570 |
570 |
570 |
|
Evaluation of Kukkutandatvak Bhasma Tablets:
1. General Test:14
Appearance: The tablet were randomly selected and checked for shape, colour and texture.
Dimensions:
Five tablets were randomly selected from the batch, length and thickness were measured by using Vernier Caliper.
2. Weight Variation:13
Twenty tablets were randomly selected from each batch and individually weighed. The average weight was calculated. % deviation of each tablet was noted. The batch passes the test for weight variation test if not more than two of the individual tablet weight deviates by 5% from the average weight.
3. Hardness:14
Hardness or diametric crushing strength, i.e. the force required to break a tablet by applying pressure diametrically on the tablet, was measured using Monsanto hardness tester. Though the test is not official in IP, it is helpful to determine whether the tablet can maintain its structural integrity during storage, transportation, and handling.
4. Friability13,17
The friability of the tablets was determined using Roche Friabilator. During this test, the tablets are subjected to the combined effect of abrasions and shock in a plastic chamber that was revolving at 25 pm. The tablets are dropped from a height of 6 inches every 100 revolutions. 12 tablets have a cumulative weight of more than 6.5g, which were taken. The exact weight (W1) of the tablets were determined, and tablets were placed in the Roche Friabilator. After100 revolutions, tablets were removed, dedusted using a soft brush and reweighed (W2).
Friability (F) is given by the formula: [(W1-W2)/W1] x 100
Where W1 is the weight of the tablets before the test and W2 is the weight of the tablet after the test.
5. Disintegration time13
The Disintegration test was carried out using a tablet Disintegration Test machine. 6 tablets were sampled, and 1 tablet was placed in each tube of the apparatus. Distilled water was used as the disintegration medium. The time requires for each tablet to disintegrate was noted.
6. Dissolution Study13
The dissolution rate of Kukkutandatvak bhasma from the tablets was studied using Lab India 05 8000 dissolution apparatus. Experimental conditions maintained were as follows, USP apparatus 2 (paddle type), Medium 900ml of 0.1N HCl, the temperature was 37oC±2oC, Paddle speed of 50rpm. A sample of 1 ml was withdrawn every 10 min. Intervals filtered it absorbance of the resulting solution was noted till 60 min. Sink condition was maintained by replacing the same amount of the fresh medium each time; the number of dissolved drugs was calculated using the standard calibration curve.
Table 2: Evaluation of Dry Granules
Parameters |
Formulation (Average of 5 readings) |
||||||||
F1 |
F2 |
F3 |
F4 |
F5 |
F6 |
F7 |
F8 |
F9 |
|
Bulk Volume |
59 |
57 |
58 |
56 |
57 |
57 |
57 |
58 |
56 |
Tap Volume |
55 |
55 |
57 |
54 |
53 |
54 |
56 |
57 |
54 |
Total weight of powder in mg |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
50 |
Bulk density* |
0.85 |
0.88 |
0.86 |
0.89 |
0.88 |
0.88 |
0.88 |
0.86 |
0.89 |
Tap Density* |
0.91 |
0.91 |
0.81 |
0.93 |
0.94 |
0.93 |
0.89 |
0.88 |
0.93 |
% Compressibility* |
6.78 |
3.58 |
1.73 |
3.57 |
7.02 |
5.26 |
1.75 |
1.72 |
3.57 |
Hausner's Ratio* |
1.07 |
1.04 |
1.02 |
1.04 |
1.08 |
1.06 |
1.02 |
1.02 |
1.04 |
The angle of repose* |
36.18 |
29.43 |
25.33 |
30.17 |
40.11 |
33.22 |
26.53 |
25.32 |
28.84 |
*Figures rounded off to two digits
Acid Neutralizing Capacity Test (ANC):14,15
Test preparation:
20 tablets were weighed, and the average tablet weight was determined. The tablets were grinded to a fine powder and mixed to obtain a uniform mixture. Accurately weighed quantity of mixture, equivalent to the minimum labelled, was then transferred to a 250mL beaker. Add 70mL of water, and mix on the Magnetic Stirrer at 300±30rpm for about 1 minute.
ANC: 30.0mL, 1.0 N hydrochloric acid was Pipetted into the Test Preparation while continuing to stir with Magnetic Stirrer. Stirring was further continued for 15 minutes. In the next 5 min, the excess hydrochloric acid was titrated with 0.5 N sodium hydroxide to attain a stable pH of 3.5.
Calculate the number of mEq of acid consumed by the formula:
Total mEq = (30 × NHCl) – (VNaOH × NNaOH),
NHCl and NNaOH are the normalities of the hydrochloric acid and sodium hydroxide, respectively, and VNaOH is the volume of sodium hydroxide used for titration.
The results were expressed in terms of mEq of acid consumed per g of the substance tested.
Rosset-Rice Test (RRT):16
Weighed quantity of calcinated sample was transferred to 100 ml beaker containing 70ml of water, to it 30ml 0.1 N HCl was added at a rate of 4ml/min under continuous stirring (300±30rpm) at 370C. Changes in pH values were recorded as a function of time. The procedure was continued until the pH value falls below 3.0. The antacid dose is considered adequate when the pH of the mixture rises above 3.0 within 10 min, and the pH value remains above the level for more than 1hr. The area under pH versus time profile was considered as a parameter to reflect the overall efficiency of an antacid.
Table 3: Results of preliminary Batches of Bhasma tabklets
Independent Variable |
Formulation |
||||||||||
F1 |
F2 |
F3 |
F4 |
F5 |
F6 |
F7 |
F8 |
F9 |
|
||
Coded Values |
Polyvinylpyrrolidone |
|
1 |
1 |
0 |
0 |
0 |
-1 |
-1- |
1- |
|
SGS |
1 |
0 |
-1 |
1 |
0 |
-1 |
1 |
0 |
-1 |
|
|
Actual Values |
Polyvinylpyrrolidone |
10 |
10 |
10 |
9 |
9 |
9 |
8 |
8 |
8 |
|
SGS |
27 |
26 |
25 |
27 |
26 |
25 |
27 |
26 |
25 |
|
|
Dependent Variable |
A. Hardness in kg |
9.6±0.4 |
10.1±0.5 |
10.4±0.3 |
8.5±0.5 |
8.9±0.4 |
9.2±0.4 |
8.1±0.2 |
8.2±0.2 |
8.3±0.2 |
|
B. Disintegration in sec |
25 |
31 |
35 |
23 |
30 |
37 |
22 |
30 |
40 |
|
|
C. % drug release after 60min |
95.38 |
92.93 |
91.53 |
96.54 |
93.33 |
90.11 |
98.82 |
93.13 |
87.26 |
|
|
Other Ebaluation |
Length (cm) |
1.8175 |
1.8175 |
1.8175 |
1.8175 |
1.8175 |
1.8175 |
1.8175 |
1.8175 |
1.8175 |
|
Thickness (cm) |
0.9675 |
0.9675 |
0.9675 |
0.9675 |
0.9675 |
0.9675 |
0.9675 |
0.9675 |
0.9675 |
|
|
Weight Variation (% deviation) |
NMT 2.3 |
NMT 3.3 |
NMT 1.4 |
NMT 1.5 |
NMT 2.0 |
NMT 1.6 |
NMT 1.7 |
NMT 1.6 |
NMT 2.0 |
|
Fig. 1a: Pareto Chart of the effect of PVP and SCG on drug release
Fig. 1b: Pareto Chart of the effect of PVP and SCG on Drug Release
Fig. 1c: Pareto Chart of the effect of PVP and SCG on Drug Release
Fig. No: 2a: Response surface model Contour Plot Drug Release:
Fig. No: 2b: Contour Plot of Disintegration time:
Fig. No: 2c: Contour Plot of Hardness:
RESULTS AND DISCUSSION:
The calcium content of the Bhasma was determined by titrimetric analysis and was found to be 98% w/ w. Kukkutandatvak tablet formulated were having caplet shape, buff-coloured with a smooth finish. The average size of tablets for all formulations was found to be 1.8175cm x 0.9675cm. The angle of repose, Carr's index and Hausner ratio showed that the granules prepared by dry granulation technique for all batches had good flow and compressible properties Table 2. Table 3 showed that the hardness of the tablets was in the range of 8 to 11 kg/cm2. The percentage weight loss for all batches during the friability test was less than 1%. As the pressure was maintained constant and due to uniform die fill thickness was uniform in almost all the batches. Though batch no. F-5 showed relatively high disintegration time, but it was definitely an intolerable limit; this may be attributed to the presence of the high amount of binder and low amount of disintegrant. Not a single tablet out of the 5 batches failed the weight variations test. Dissolution studies showed the release of calcium carbonate ranges from 89.24 (Formulation F5) to 97.28 (Formulation F3) Table 3 Fig 1. Thus the prepared tablet batches were of good quality with respect to hardness, friability, weight variation, thickness, disintegration time and dissolution parameter. Total mEq was found to be 15.15, indicating that the tablet has a good acid-neutralizing capacity test (ANC). Rosset-rice test (RRT), i.e. test time required to reach pH above 3 is 9.25 min. All the tablets showed similar results for ANC and RRT.
CONCLUSION:
Literature review indicates eggshell contains a high percentage of calcium. Kukkutandatvak bhasma (Hen Eggshell bhasma) is already prescribed in oligospermia, amenorrhea, leucorrhoea, polyuria, osteoporosis and arthritis. Bhasma is a powder dosage form and needs to be converted in Tablet dosage form for patient compliance and its other obvious advantages. Caplet shape tablets were hence formulated using the dry granulation technique. Granules were found to be free-flowing, and the tablets prepared from them showed good quality parameters in terms of weight variations, hardness, friability, disintegration and dissolution. Kukkutandatvak bhasma tablet had a good acid-neutralizing capacity test (ANC) with a Total mEq of 15.15, and the time required to reach pH above 3 is just 9.25 min. Thus, in conclusion, we can say that a good ayurvedic formulation was developed, which is market/ patient ready and a good substitute to synthetic drugs to take care of a common problem like hyperacidity.
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Received on 17.01.2021 Modified on 10.08.2021
Accepted on 30.11.2021 © RJPT All right reserved
Research J. Pharm. and Tech. 2022; 15(8):3764-3768.
DOI: 10.52711/0974-360X.2022.00632