INTRODUCTION:

Herbal medicines have been known to improve world well-being due to their rich sources of various therapeutic agents. Plants contain a much greater diversity of bioactive compounds than any known manmade chemical library. The plant kingdom represents a rich source of organic components, many of which have been used for medicinal and other purposes¹.

Herbal medicines remain the major source of health care for the world’s population². Inspite of advances in modern system of medicine, there are various areas which still remain a challenge to present day drug therapy. Currently, there is a growing interest in plant based or herbal medicines even in the western world. In many respects, the mechanism of action of the herbal drugs differs from that of the synthetic drugs or pure compounds. In one of the study of the World Health Organization it is estimated that 80% of the population of developing countries relies on traditional plant based medicines for their health requirements³. Because of its many benefits and high patient compliance when compared to many other routes, the oral route continues to be the recommended method of administration for the majority of therapeutic drugs used to elicit systemic effects. The majority of currently available medication delivery devices are tablets and hard gelatin capsules⁴. However, ingesting these dosage forms is challenging for many patient groups, including the elderly, children, intellectually challenged patients, patients who are recalcitrant, nauseous, or on decreased liquid intake or diets⁵. The same is true for people who are on the road or have limited access to water. The leaf's ability to function as a natural antioxidant is very strong. The antioxidant activity is connected to a range of biological activities, such as hepatoprotective, antidiabetic, antarthritic, anti-stroke, and anticancer properties, because free radicals are associated in many of these disorders^7,8.

MATERIALS AND METHODS:

Collection and authentication of drug: Collection and authentication of herbal drug (Piper betel Linn.). The plant Piper betel Linn in powdered form was purchased from R. Chemicals, Navi- Mumbai and raw material was authenticated by Dr. H.M. Pandit, Department of Botany, Gurunanak Khalsa College, Matunga, Mumbai.

PREPARATION OF FORMULATION:

It is evident from the results of characterization of powder flow characteristics of Piper betel⁹, that as it has good flow, ODT of Piper betel can be made by direct compression. Thus trials were taken for screening the diluents and superdisintegrants to formulate the ODT^10,11. All excipients were first sieved through mesh #100. 100mg Piper betel powder and other ingredients like Microcrystalline Cellulose (MCC) is used as diluent, Sodium Starch Glycolate is used as superdisintegrants and Saccharin is used as sweetener were mixed together and finally Magnesium stearate is used as lubricant was added. Powder was compressed on single punch machine using flat bevelled 8 mm punch.

EVALUATION PARAMETERS:

PRE-COMPRESSION PARAMETERS:

The flowability of the powder blend is very important. Consequently, two techniques were employed to measure the flowability of powder¹¹. To compute the Hausner ratio and Carr's index, the powder mixes' bulk and tapped densities were ascertained. The second method for flowability characterization was to determine the angle of repose¹².

POST COMPRESSION PARAMETERS:

Post compression parameter such as tablet disintegration time, weight variation test, hardness, thickness and friability were carried out as per procedure.¹²

1. Uniformity of thickness and diameter

To determine uniformity of the diameter and thickness 10 tablets were selected and diameter as well as thickness, was measured using Vernier callipers. The average diameter and thickness of the tablet was determined.¹³ The test requirements were met if none of the individual diameter and thickness value deviated by ± 5% of the average.

2. Hardness:

The hardness of the tablet was measured using Monsanto hardness tester. This test was conducted by sandwiching the tablet between two hardness tester anvils, applying force to the anvils, and recording the crushing strength that only resulted in the tablet breaking. Total 6 tablets were subjected to this test.¹⁴

3. Weight variation:

Twenty randomly chosen pills were weighed for this test, and the average weight was determined. No two individual weights should deviate from the average weight by more than 5%, and none should deviate by more than twice the amount.

4. In vitro disintegration time:

Disintegration testing (6 tablets) was performed using modified method. After placing the tablet in 5 cm diameter petri plate, the test was carried out in 5 ml of distilled water at temperature of 37ºC and agitation speed of 40 shakes per/min, using a mechanical shaker (Neolab reciprocating mechanical shaker).¹⁵

5. In vitro drug release:¹⁶

USP2 paddle apparatus was used, 900ml buffer pH 5.8 was prepared by dissolving 1.19g dihydrogen phosphate dehydrate and 8.25g of potassium dihydrogen phosphate in water. 5 ml aliquots were withdrawn at each 5 min interval for 30 min with fresh dissolution medium replenished each time. The samples were filtered and analysed spectrophotometrically at 280 nm.

6. Wetting Time:

Each of the five petri dishes had five circular filter papers with a diameter of five centimeters. The petri dish was then filled with five milliliters of eosin solution, a dye that dissolves in water. On the filter paper, a tablet was carefully positioned. The wetting time was defined as the amount of time needed for water to reach the tablets' upper surface.¹⁷

RESULT AND DISCUSSION:

Formulation of orally Disintegrating Tablets:

It is evident from the results of characterization of powder flow characteristics of Piper betel that it has good flow; ODTs of Piper betel can be made by direct compression. Thus the screening of various diluents and superdisintegrants was carried out to formulate the ODTs¹⁷. By using 8 mm concave punch tablets were formed. Formulation composition is summarised in table 1.

Table 1: Formulation batches of ODTs of Piper betel to evaluate superdisintegrants and diluents.

Ingredient	Quantity per tablets (mg)
Ingredient	B1	B2	B3	B4	B5	B6	B7	B8	B9
Drug	100	100	100	100	100	100	100	100	100
MCC	98	98	--	--	--	--	118	118	118
Dicalcium phosphate	--	--	98	98	118	118	--	--	--
CCS	40	40	--	--	20	20	--	--	--
SSG	--	--	40	40	--	--	20	20	20
Aerosil	5	5	5	5	5	5	5	5	5
Saccharine	5	5	5	5	5	5	5	5	5
Magnesium stearate	2	2	2	2	2	2	2	2	2
Total	250	250	250	250	250	250	250	250	250

Screening of the diluents in preparation of ODTs: For the formulation of ODTs, the effect of two diluents i.e., microcrystalline cellulose and dicalcium phosphate were studied on in-vitro disintegration time at the end of 6 minutes. Thus, Microcrystalline cellulose gave the optimum result and was chosen as the diluent.¹⁸ Table 2 shows the result of the same.

Table 2: Screening of diluents

S. No	Diluent	*In vitro* disintegration time
1	Microcrystalline cellulose	25 sec
2	Dicalcium phosphate	94 sec

Fig 1: Effect of different diluents on in vitro disintegration time at the end of 6 minutes.

Screening of the superdisintegrants in preparation of ODTs: The impact of two superdisintegrants, namely Croscarmellose and Primojel (Sodium Starch Glycolate), on the in-vitro disintegration time at the end of six minutes was investigated for the development of ODTs. Primojel (Sodium Starch Glycolate) was selected as the superdisintegrants because it produced the best results. Table 3. shows the result of the same.

Table 3: Screening of superdisintegrants

S. No

Diluent

In-vitro disintegration time

Croscarmellose

60 sec

Primojel (Sodium Starch Glycolate)

25 sec

Fig 2: Effect of different superdisintegrants on in vitro disintegration time at the end of 6 minutes.

PRE-COMPRESSION PARAMETERS:¹⁸

The flowability of powder blend is measured using Hausner ratio, Carr’s index and Angle of repose which is summarized in table 4 and table 5.

Table 4: Flow properties of the powder blends: angle of repose value and flowability, mean ± standard deviation (n=3).

Formulation	Flow properties
Formulation	Angle of repose (⁰)	According to USP
F1	26.96±0.3	Excellent
F2	26.49±0.8	Excellent
F3	26.58±0.4	Excellent
F4	25.82±1.8	Excellent
F5	25.79±1.8	Excellent
F6	25.82±1.1	Excellent
F7	29.95±0.1	Excellent
F8	29.86±0.8	Excellent
F9	30.43±0.4	Excellent

Table provides the data obtained for the angle of repose for all the batches prepared. The values were found to be in the range of 26.96⁰to 30.43⁰, which indicates excellent flow property for the powder blend according to the USP. ^19,20(Table 5)

Table 5: Flow properties of the powder blends: bulk and tapped density, Carr’s index, and Hausner ratio, mean ± standard deviation (n=3).

Formulation	Density (g/cm³)		Flow Properties
Formulation	Bulk	Tapped	Carr’s index	According to USP	Hausner ratio
F1	0.51±0.00	0.57±0.00	10.30±0.16	Excellent	1.11±0.003
F2	0.48±0.00	0.52±0.00	10.86±0.216	Excellent	1.08±0.004
F3	0.49±0.00	0.54±0.00	10.25±0.346	Excellent	1.06±0.006
F4	0.48±0.01	0.55±0.00	10.64±0.506	Excellent	1.14±0.009
F5	0.50±0.00	0.54±0.00	10.67±0.890	Excellent	1.08±0.016
F6	0.50±0.00	0.52±0.00	10.77±0.304	Excellent	1.04±0.006
F7	0.51±0.00	0.56±0.00	10.30±0.16	Excellent	1.09±0.003
F8	0.50±0.02	0.57±0.00	10.86±0.216	Excellent	1.04± 0.004

Table provides the data obtained for the Carr’s index and Hausner ratio for all the formulation batches. The range of 10.30 to 10.86 for Carr's index values was determined to be satisfactory for the powders and suggests that the blends had good compressibility. Excellent flow characteristics for the powder blend based on the USP are demonstrated by the Hausner ratio values that were obtained, which ranged from 1.04 to 1.11¹⁹.

POST COMPRESSION PARAMETERS:

The evaluation criteria for orally disintegrating tablets, including appearance, weight variation, thickness, height, hardness, friability, disintegration time, and drug content, are shown in the table. ODTs were made and visually inspected for color and shape. 20 After compressing the compositions, a concave, circular surface with a light green hue was seen. Every tablet was confirmed to be within the USP-recommended permissible limit (±10%) after passing the weight variation test. All batches' tablet thickness and height findings were between 3.33 and 3.35 mm and 3.66 and 3.98 mm, respectively.^15,20Hardness or breaking force of tablets for all batches was found to range from 34 to 37 N. For tablet formulations to withstand shipping and transit, they must have enough hardness and strong mechanical strength. All of the formulations' friability values were found to be between 0.24 and 0.40 percent. According to the USP, the results showed adequate mechanical integrity and strength for the produced tablets, falling below the permitted range (<1%). Based on the USP, the disintegration time test was employed. By measuring the absorbance at 280 nm, the percent drug content for each formulation was determined to be between 83% and 95.54%, which is within the USP-acceptable limits.²⁰.

Table 6: Evaluation parameters for orally disintegrating tablet

Formulation	Weight variationα (mg)	Thickness α(mm)	Height α (mm)	Hardnessα Test (N )	Friability test (%)	*Disintegration time (sec)**	% Drug contentβ
F1	251.9±4.09	3.35±0.05	3.98±0.0	36±4.57	0.40	14.3±1.0	89.85±6
F2	254.7±1.16	3.35±0.03	3.91±0.0	37±6.02	0.24	14.7±2.5	87.83±1
F3	251.5±2.46	3.34±0.04	3.89±0.0	38±2.90	0.29	14.7±3.5	87.84±1
F4	254.4±1.17	3.33±0.04	3.77±0.0	36±2.95	0.40	13.3±4.7	88.87±2
F5	253.3±1.42	3.33±0.03	3.80±0.0	35±2.78	0.37	14.7±2.5	83±1.9
F6	252.7±1.73	3.33±0.02	3.66±0.0	35±9.03	0.24	13.7±2.5	93.72±1
F7	253.9±3.19	3.33±0.04	3.88±0.0	34±4.27	0.27	13.0±1.1	94.75±5
F8	252.7±1.26	3.33±0.03	3.81±0.0	36±5.34	0.26	13.7±2.2	94.58±5
F9	254.3±2.16	3.33±0.04	3.82±0.0	36±3.92	0.26	13.7±1.4	95.54±3

α: each value represents the mean ± standard deviation (n=10). β: each value represents the mean ± standard deviation (n=3).

*: Disintegration time must be less than 1 minute according to the USP monograph

Table 7 : Percent drug release in formulation at Refrigeration (5°C) condition

Time (min)	0 days (%)	1 week (%)	2 week (%)	4 week (%)	6 week (%)	8 week (%)
0	82.76	82.54	82.42	82.37	82.25	82.624
5	88.62	88.42	88.41	88.32	88.15	88.05
10	90.55	90.54	90.55	90.55	90.55	90.55
15	91.98	91.88	91.67	91.53	91.44	91.24
20	92.83	92.74	92.54	92.41	92.26	92.15
25	93.85	93.65	93.51	93.31	93.21	93.1
30	94.75	94.54	94.33	94.31	94.25	94.16

In vitro drug release study was performed at three stability conditions where ODTs were kept at refrigerator condition(5⁰C), at room temperature (27⁰C) and at Oven (40⁰C) condition .The release was studied for 8 weeks and found to be 82.25 % at 0 min to 94.75% in 30 min for refrigerator condition (5⁰C).

Figure 3: Dissolution Testing for the 250 mg Tablets under Refrigeration (5°C) Conditions

Drug release at room temperature (27⁰C) was found to be 82.25% at 0 min for 6^th week which is lowest in studied period and 94.85% as maximum at 30 min on the first day.

Table 8: Percent drug release in formulation at Room temperature(27⁰C) condition

Time (min)	0 days (%)	1 week (%)	2 week (%)	4 week (%)	6 week (%)	8 week (%)
0	82.76	82.54	82.42	82.37	82.25	82.624
5	86.62	86.42	86.41	86.32	86.15	86.05
10	89.55	89.54	89.5	89.45	89.25	89.6
15	90.98	90.88	90.67	90.53	90.44	90.24
20	91.83	91.74	91.54	91.41	91.26	91.15
25	92.85	92.65	92.51	92.31	92.21	92.1
30	94.85	94.64	94.43	94.39	94.35	94.26

Figure 4: Dissolution Testing for the 250 mg ODTs under Room temperature Condition

Storing ODTs at Oven (40⁰C) condition decreased drug release to 82.25% in 0 min to 93.75% in 30 min, which is not significantly less as compared to other conditions.

Table 9: Percent drug present in formulation at Oven (40°C) condition

Time (min)	0 days (%)	1 week (%)	2 week (%)	4 week (%)	6 week (%)	8 week (%)
0	82.76	82.54	82.42	82.37	82.25	82.624
5	84.62	84.42	84.41	84.32	84.15	84.05
10	85.85	85.74	85.65	85.45	85.25	85.6
15	89.98	89.88	89.67	89.53	89.44	89.24
20	90.83	90.74	90.64	90.54	90.36	90.3
25	91.85	91.69	91.6	91.58	91.21	91.13
30	93.75	93.54	93.33	93.3	93.25	93.16

Figure 5: Dissolution Testing for the 250 mg ODTs under Oven (40°C) Conditions

CONCLUSION:

The most crucial factors in creating any formulation are patient compliance and ease of administration. Oral candidiasis is a condition in which fungal growth is observed on the mucous membrane of the oral cavity. It is mostly caused due to weakened immune system. Since, the infection is in oral cavity, an intraoral drug delivery system is needed so that the drug is retained at the site of the infection.

Various synthetic drugs are currently in use for the treatment of local antimicrobial activity, but they exhibit several side effects. Thereby, an attempt is made to formulate a herbal based medication to minimize the side effects.

Literature survey was done and it is found that, there are numerous herbal drugs that show this activity. Traditional use of piper betel after consuming food which enhances the metabolic activity and helps in digestion. Piper betel the herbal drug which was used for the formulation in this project. This is widely grown in the India, irrespective climate constrains and hence cheap, that would further help in reducing the medication cost to minimum.

The ODTs were evaluated using various parameters and the following conclusion were drawn from them:

Comparison was carried out with two different diluents based on their disintegration time, for the selection of the diluent in the formulation of herbal ODT. Comparison was carried out with two different superdisintegrants based on their disintegration time, for the selection of the superdisintegrant in the formulation of herbal ODT.

The ODT's in vitro evaluation showed that it decomposed in just one minute, demonstrating its effectiveness as an oral formulation that doesn't require water to be eaten. Although orally disintegrating tablets are faster disintegrating tablets but typically are not meant to have faster therapeutic onset.

The release profile from the ODT remained unchanged even after change in the storage condition b u t tablets stored under less thermal stress would be viable for longer period of time.

ACKNOWLEDGEMENT:

We are grateful to Principal Bharati Vidyapeeth’s College of Pharmacy, C.B.D Belapur, Navi Mumbai, India-400 614, for providing facilities to complete this work.

CONFLICTS OF INTEREST:

The authors declare that there are no conflicts of interest regarding the publication of this paper.

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Received on 30.03.2024 Revised on 13.12.2024

Accepted on 17.06.2025 Published on 01.12.2025

Available online from December 06, 2025

Research J. Pharmacy and Technology. 2025;18(12):5827-5832.

DOI: 10.52711/0974-360X.2025.00840

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