INTRODUCTION:

The objective of this work is the conversion of trikutachurna into stable, palatable and patient acceptable granules to swallow conveniently by wet granulation method, using suitable binding agents. In Trikuta as essential ingredients of numerous prescription and formulations used for wide range of disorders. Ayurvedic system of medicine prescribes Trikatu for the management of tastelessness (Arocaka) disturbed digestion (Agnimandya and Amadosa), diseases of nose (Pinasa) and upper respiratory tract (Gala and swasaroga, Kasa), excess and frequent urination (Meha), edema (Gulma), obesity (Sthaulya), Filariasis (Slipada), and skin diseases (Tvakroga).

Trikatu acts primarily by its effect on stomach, liver, and pancreas. In stomach, it increases production of digestive juices thereby stimulating digestion. In liver, it acts as Cholagogue and increases production of bile salts by stimulating gallbladder functioning. Trikatu also has its influence on pancreatic functioning.

In a nutshell, Trikatu affects overall digestive system along with its curative effects on respiratory, urinary, immunity, skin, and metabolic systems of our bod Trikatu churna is an Ayurvedic polyherbal formulation of Maricha (Piper nigrum L., fruit), Pippali (Piper longum L., fruit) and Sunthi (Zingiber officinale Rosc, rhizome). All of the required functionality of a compression mix – good flow, good compactability, uniform distribution of drug and controllable drug release – can be built in using wet granulation without relying on the intrinsic properties of the drug or the excipients. Additionally using wet granulation it is possible to get stabilising agents such as pH modifiers into close contact with the drug and so potentially maximize tablet stability.

For high dose drugs, poor flow and compaction of the active mean that wet granulation may be the only feasible means of producing tablets, and for low dose drugs the granulation process is seen as being capable of “locking” drug into granules and thereby minimising the potential for segregation and poor content uniformity. There are therefore a number of advantages inherent to wet granulation, but there also a number of disadvantages. Water used in granulation processes can bring about unwanted changes in drugs or in excipients; the benefits of content uniformity of low dose drugs are not necessarily realised; and the complexity of the process compared to, say, direct compression greatly increases the number of quality critical factors that need to studied and controlled in a QbD development programme. Thus despite the broad applicability of wet granulation it may be simpler and ultimately more production efficient to first look at direct compression or dry granulation. During the granulation process, small fine or coarse particles are converted into large agglomerates called granules. Generally, granulation commences after initial dry mixing of the necessary powder ingredients along with the active pharmaceutical ingredient (API), so that a uniform distribution of each ingredient throughout the powder mixture is achieved. Although granules used in the pharmaceutical industry have particle size in the range of 0.2-4.0mm, they are primarily produced as an intermediary with a size range of 0.2-0.5mm. Granules are produced to enhance the uniformity of the API in the final product, to increase the density of the blend so that it occupies less volume per unit weight for better storage and shipment, to facilitate metering or volumetric dispensing, to reduce dust during granulation process to reduce toxic exposure and process-related hazards, and to improve the appearance of the product.¹

MATERIAL AND METHOD:

A] Collection of powder drug:

Trikatu Churna consist of three main ingredients in powder form, it consist of powder fruits of Piper nigrum, fruits of Piper longum and rhizomes of Zingiber officinale. All ingredients procured from local market, Pune. Ingredients were identified on the basis of morphological and microscopically chracters.

B] Method of preparation of Trikatu Churna:

Trikatu churna was prepared in laboratory using method described in Ayurvedic Formulary. All the ingredient passed through 80# sieve and then mixed together in equal proportion to get uniform blended churna by using spatula.

Pharmacognostic Study:

1] Organoleptic Characteristics:

Organoleptic evaluation refers to evaluation of formulation by appearance, colour, odour, taste, etc. The organoleptic characters of the preparations were carried out. However, these characteristic are judge subjectively and substitutes or adulterants may closely resemble the genuine material, it is often necessary to substantiate the findings by microscopy and physicochemical analysis.

Color: Churna was taken into watch glasses and placed against white background in white tube light. It was observed for their color by naked eye.

Odour: Two gram Churna was smelled.

Taste: A pinch of Churna was taken and examined for its taste on taste buds of the tongue.

2] Physico-chemical properties:

pH 5.9 -6.2

Total ash 3.8- 3.5

Acid insoluble ash 1.9 -1.5

Water soluble ash 2.1- 2.2

Water soluble extractive 0.15 gm 0.80 gm

Alcohol soluble extractive 0.56 gm 1.30 gm

Physio-chemical study:

1. Physio-chemical parameters of the Trikatu churna and its ingredients are tabulated.

2. The pH value of Trikatu churna was acidic. Deterioration time of the churna depends upon the amount of water present in plant material/ churna.

3. If the water content is high, the plant material can be easily deteriorated due to fungus. The loss on drying at 105°C in Trikatu churna was found to be 17.61%. Total ash involves an oxidation of the components of the products.

4. A high ash value is indicative of contamination, substitution, adulteration or carelessness in preparing the formulations for marketing.

5. Total ash value of plant material/ churna also indicated the amount of minerals and earthy materials attached to the plant material/ churna.

6. Analytical results showed total ash value content was 1.76%.

7. The negligible amount of acid-insoluble ash is siliceous matter present in the Trikatu churna sample was 0.29%.

8. The water-soluble extractive value was indicating the presence of sugar, acids and inorganic compounds, the water soluble extractive value in the Trikatu churna sample was 6.58%.

9. The alcohol soluble extractive value in Trikatu churna was 3.95%, it is indicated the presence of polar constituents like phenols, alkaloids, steroids, glycosides, flavonoids in churna.²

4.Drug Profile:

a. Active Ingredients:

i. Piper longum:

Fig2:-Piper longum

Kingdom	Plantae
Division	Manoliophyta
Class	Magnoliopsida
Order	Piperales
Family	Piperaceae
Genus	Piper
Species	nigrum

Long pepper, sometimes called long pepper or pipli, is a flowering vine in the family-Piperaceae, cultivated for its fruit, which is usually dried and used as a spice and seasoning. Long pepper has a taste similar to, but hotter than, that of its close relative Piper nigrum – from which black, green and white pepper are obtained.

Chemical constituents:

The essential oil obtained from the fresh parts of root, stem, fruit, and leaf of Piper longum growing wild in Western Ghats, Kerala was analyzed by GC-MS. The study led to the identification and quantification of 38 (root), 36(stem), 29(fruit) and 37(leaf) chemical constituents belonging to different classes of compounds accounting for 96.9%, 97.2%, 97.1% and 76.7% of the total oil composition respectively. The essential oil production, yield of total volatile oil content in fruit and leaf was higher than that of root and stem. The principal components in root, stem, and fruit were comparable.

Uses:

Parts used: Immature spikes, roots and seeds .Dried unripe fruits are used as an alternative to tonic.

Decoction of immature fruits and roots is used in chronic bronchitis, cough and cold. Roots and fruits are also used as anti-dote in snake biting and scorpion sting11. An equal part of powdered seeds of Embeliaribes, fruit of P.longumL.and borax powder has been used as an ayurvedic contraceptive.

ii.Black Pepper:

Fig3:-Black Pepper

Kingdom	Plantae
Clade	Angiosperms
Order	Piperales
Family	Piperaceae
Genus	Piper
Species	P.nigrum

Regarded as the “king of spices, ” black pepper is an incredibly popular among spices since ancient times. Peppercorn is native to the tropical evergreen rain forest of South Indian Kerala state, from where it spread to rest of the world through Indian and Arab traders. Pepper fruit, also known as the peppercorn, is actually a berry obtained from the pepper plant.³

Chemical constituents:

Black pepper contains Piperine. Molecular formula for Piperine is C17H19NO3.

The most important candidate of p. nigrum is piperine, its concentration varies in different species of p. nigrum. For example the amount of piperine in long pepper varies upto 1-2% and in white and black pepper, it varies upto 5-10%.

The reason behind its very essential therapeutic use is that due to presence of piperine, it increases the bioavaibility of many nuitrients and drugs by inhibiting various metabolizing enzymes .thus it play an essential role in regulating obesity induced dyslipidemia.

Piperine can be extracted from the unripe fruit of black pepper. It is present in the concentration of 6-9% in the black pepper. In addition to Piperine, it also contains betacarotene, lauric-acid, palmitic acid, and pepper phellandrene.

Piperine is such a dominant constituent of p. nigrum that it is responsible for its pungency i.e. its strong odor and taste property. Also with addition of chavicine, which is an alkaloid with diastereomeric geometric isomers of piperine, have a synergistic effect on its pungency.

Essential compounds such as steroid, alkaloid, flavonoid, phenolics, chalcones and various lignans derivatives, in addition with terpenes isolated from black pepper.

Uses:

It is also used as a preservative.

It has application in cosmetic industries and also in the preparation of insecticides.

It improves appetite, increases digestive power and also has antimicrobial activities.

It is used in the treatment of fever, colic, dysentery, piles and infections of worms.

In reduces inflammatory responses by inhibiting lipopolysaccharides.

Also used as a cure of cold, cough and dysponea and other diseases of the throat

It works as an analgesic, antipyretic and antioxidant.⁴

Fig 4: Ginger

Kingdom	Plantae
Clade	Angiosperms
Order	Zingiberales
Family	Zingiberaceae
Genus	Zingiber
Species	Z.officinale

Chemical Constituents:-

It contains over 450 compounds. The major composition of ginger rhizomes is carbohydrates (50–70%), lipids (3–8%), terpenes, phenolic compounds, amino acids, raw fiber, ash, protein, phytosterols, vitamins, and minerals. Volatile terpenoidal constituents of Z. officinale include zingiberene, β-bisabolene, α-farnesene, α-curcumene, and βsesquiphellandrene. Phenolic compounds include gingerol, paradols, and shogaol. Gingerols and shagols are responsible for pungency of Ginger.

These gingerols and shogaol are found in higher quantities of up to 20–25%. Other gingerol- or shogaol-related compounds (1–10%), which have been reported in ginger rhizome, include 6-paradol, 1-dehydrogingerdione, 6- gingerdione and 10-gingerdione 4- gingerdiol, 6-gingerdiol, 8-gingerdiol, and 10-gingerdiol, and diarylheptanoids. The characteristic odor and flavor of ginger are due to a mixture of volatile oils such as shogaols and gingerols

Uses:

Ginger is commonly used for many types of nausea and vomiting. It's also used for menstrual cramps, osteoarthritis, diabetes, migraine headaches, and other conditions, but there is no good scientific evidence to support many of these uses.

In foods and beverages, ginger is used as a flavoring agent.

In manufacturing, ginger is used as for fragrance in soaps and cosmetics.

One of the chemicals in ginger is also used as an ingredient in laxative, anti-gas, and antacid medications.

b. Excipients:

Typically a wet granulated formulation will contain one or more diluents for bulk or to aid processing, a binder to facilitate granule growth and to aid compaction into hard tablets, a disintegrant and a lubricant.Additionally wetting agents, stabilising agents and colourants are used as required. Table 1 shows commonly used key excipients.

Fnction	Excipients	Typical Level (approximate)
Diluent	Mannitol	Up to 90%
Binder	Pregelatinisedstarch	2-5%
Lubricant	Talc	3-5%
Glidant	Colloidal sillicon dioxide	0.1- 0.3%

Diluent:

For low to medium dose drugs the diluents are likely to make up the majority of the tablet. But diluents domore than provide bulk and some properties of commonly used diluents are discussed below.

Mannitol:

Mannitol is used in wet granulation in milled form. The most stable form for wet granulation is the βform, and it has been reported that δmannitol undergoes moisture activated transition back to the βform on t wet granulation, with an increase in surface area and improvement in compactability.

Binder:

Binder are usually natural or synthetic water soluble polymers that may be used as solutions, but in high or low shear granulation they may also be added to the dry powder mix and granulation effected using water only. Studies on various cellulosic binders showed that their use in solution increased the proportion of coarse granules compared to dry addition by both high shear and fluid bed granulation.

Starch:

Starch is the most traditional binder, but in native form it has to be gelatinised (cooked) in hot water to form a paste. However nowadays pregelatinised starch is available and a fully pregelatinised form is preferred. Starches are typically used in relatively high concentrations of about 5% of the tablet weight, or higher for partly pregelatinised starch. Various botanical sources are found in pharmacopoeia, but maize and potato based starches are the most common.

Lubricant:

As with all tablet formulations, magnesium stearate is the commonest lubricant. Sodiumstearyl fumarate is an effective lubricant that is not hydrophobic. Mixtures of talc and stearic acid can also be effective.

Glidant:

Since one purpose of wet granulation is to prepare a free flowing compression mix, the need for a glidantshould in principle be unnecessary. However in practise colloidal silica at 0.1% to 0.3% is sometimes used.

Others:

Stabilisers can be brought into close intimate contact with the drug during wet granulation. For example, stabilisation of an unnamed drug sensitive to acid catalysed hydrolysis by sodium carbonate was found to be enhanced by wet granulation compared to dry processing.⁵

EVALUATION OF PHYSICAL PARAMETER:

Evaluation is carried out in order to know the quality of the finished product. General tests include determination of contents in the formulation along with the stability test. This is carried out to know whether the product remains stable for prolonged period of time (i.e.1 shelf life).

1] Determination of pH:

Placed accurately weighed 1 gm of churna in a 100 ml volumetric flask and made up the volume up to 100 ml with distilled water. The solution was sonicated for about 10 minutes. pH was measured with the help of digital pH meter.

2] Determination of loss on drying:

Loss on drying was determined by weighing about 2 gm of the powdered material in previously weighed dried petridish (tarred evaporating dish) and dried in an oven at 105-110 ºC, till two consecutive weights, which do not differ by more than 5mg. The weight after drying was noted and loss on drying was calculated. The percentage was expressed as % w/w with reference to air dried Sample.

3] Determination of Ash Value:

a) Water Soluble Ash Value:

5gms of each Trikatu churna was accurately weighed and placed inside a glass stoppered conical flask. It is then macerated with 100ml of chloroform water for 18 hours. It was then filtered and about 25ml of filtrate was transferred into a china dish and was evaporated to dryness on a water bath. It was then dried to 105°C for 6 hours, cooled and finally weighed and water soluble extractive value was calculated.

Determination of Extractive Value:

b) Water Soluble Extractive Value:

5gm of churna was accurately weighed and placed inside a glass stoppered conical flask. It is then macerated with 100ml of chloroform water for 18 hours. It was then filtered and about 25ml of filtrate was transferred into a china dish and was evaporated to dryness on a water bath. It was then dried to 105° C for 6 hours, cooled and finally weighed.

a. Bulk Density:

a) Bulk density:

Bulk or fluff density is the ratio of given mass of powder and its bulk volume. It is determined by transferring an accurately weighed amount of powder sample to the graduated cylinder with the aid of a funnel. The initial volume was noted as untapped or poured volume. The ratio of weight of the volume it occupied was calculated.

Bulk Density = (W/V0) gm/ml

Where,

W = mass of the powder,

V0 = untapped volume

b) Tapped density:

It is measured by transferring a known quantity (25 gm) of powder into a graduated cylinder and tapping it for a specific number of times. The initial volume was noted. The graduated cylinder was tapped continuously for a period of 10-15 min. The density can be determined as the ratio of mass of the powder to the tapped volume.

Tapped Volume = (w/vf) gm/ml,

Where,

W = mass of the powder

Vf = tapped volume

C) Angle of Repose:

Angle of Repose has been used as indirect methods of quantifying powder flowability because of its relationship with inter particle cohesion 16. The internal angle between the surface of the pile of powder and the horizontal surface is known as the angle of repose. The powder is passed through funnel fixed to a burette at a height of 4cm. A graph paper is placed below the funnel on the table. The height and the radius of the pile were measured. Angle of repose of the powder was calculated using the formula.⁶

Angle of Repose= tan-1(h/r)

Where

h=heightof the pile

r =radius of the pile

FORMULATION OF GRANULES:

Wet Granulation Method:-

In wet granulation method, powders mixed with excipents and compressed into tablets using 10 mm punch with single punch machine. The average weight of tablets 700 ± 8mg All three ingredients cleaned manually, dried at 40ºC for 8 hrs, pulverized into powder form and sieved through British standard (BSS) 85 No. sieve.

Three ingredients mixed together for 20 min using a double cone blender. Weighed Quantity of lactose (30gm), 30microcrystalline cellulose (63.75gm), sucrose (15gm) were passed through BSS # 40 sieve and mixed with Trikatu powder (187.5gm) for 15 min using a double cone blender for complete mixing.

In wet granulation method, powders were mixed with excipients and compressed into tablets using 10 mm punch with single punch machine.

All three ingredients cleaned manually, dried sucrose (15gm) were passed through BSS # 40 sieve and mixed with Trikatu powder (187.5gm) for 15 min using a double cone blender for complete mixing.

Binder solution is prepared by dissolving PVP in demineralized water by stirring to obtain a clear solution. This binder solution was added into the dry mix blend to generate a wet dougmass. Wet dough was passed through BSS # 18 sieve, to obtain granules.

The latter is dried in a fluidized bed dryer (RETSCH, Germany) at inlet air temperature of 50-60ºC. Remaining ingredients “talc, Magnesium stearate, Aerosil 200, Stevia and Flavour Vanilla ”were mixed with dry granules in double cone blender.

The mixture is converted into tablets using Mini Press (RIMEK, Minipress 2MT, Karnavati, Gujarat). The prepared Trikatu was evaluated for hardness, friability, weight variation, disintegration and in vitro dissolution studies.

The hardness of tablets is determined using Electrolab hardness tester and the friability of tablets was determined using (Friabilator EF-2W, Electrolab). The disintegration test was carried out using Disintegration Tester (USP) ED-2AL, Electrolab and their mean disintegration time is calculated. In vitro dissolution studies were carried out on Dissolution Tester (USP) TDT-06L, Electrolab and Temperature Controller ETC-11L, Electrlab) USP II (paddle type). Percentage of piperine and 6-gingerol release in 0.1 N HCl (900 mL) media at 100 rpm is calculated. Dissolution studies were carried out up to 40 min. Samples (5 ml) were withdrawn at specified time intervals and percent drug release was calculated. Validation of HPTLC method.^7,8

CONCLUSION:

According to the parameters of the applied mathematical models, the mechanical strength of granules made with K30 was lower than that of the granules made with PGS and GEL which have similar values of model parameters. However, regarding consolidation and compressibility behaviors, FR forms of K30 and also PGS presented more affirmative properties beyond protecting initial properties of their UFR forms, while the initial properties of the granules of GEL changed negatively in its FR form. This emphasizes the importance of binder type. Different binders have different binding properties. In this study, same concentrations and amounts of binders were used for the granulation under the same process conditions. Therefore, we have thought that the concentration of individual binder and the amount of it to be added to the formulation may have to be optimized to obtain similar binding of the primary particles. Such an optimization can be performed advantageously by the mathematical modeling for the evaluation of binders through the friability rates of the granules produced.⁹

REFERENCES:

1. International Educational Applied Research Journal (Iearj) Volume 03, Issue 06, June 2019 E-ISSN: 2456-6713

2. Journal of Ayurveda Medical Sciences Peer Reviewed Journal of Ayurveda and other Traditional Medicines Standardisation and Quality Control – Formulation Pharmacognostical and Phytochemical Evaluation of a PolyherbalAyurvedic Formulation Trikatu churna

3. Indian Journal of Traditional Knowledge Vol. 16(2), April 2017, pp. 256-262 Development of chewable tablet of Trikatu churna and standardization by densitometry Shailendra Mani Tripathia, Ram JeeSharmaa

4. Trikatu - A combination of three bioavailability enhancers Rahul Kaushik, Jainendra Jain, Azhar Danish Khan, Pallavi Rai1 Department of Pharmacy, Ram-Eesh Institute of Vocational and Technical Education, Greater Noida, Uttar Pradesh, India

5. ShailajanSunita et al / IJRAP 2011, 2 (6) 1676-1678 International Bioanalytical Tools Shailajan Sunita, Sayed Neelam, Joshi Harshvardhan, Tiwari Bhavesh F-13, Herbal Research Lab, RamnarainRuia College, Matunga (E), Mumabai – 400 019 India.

6. Granulation techniques and technologies: recent progresses Srinivasan Shanmugam, Pharm. R and D Institute, Hanmi Pharm. Co., Ltd., Hwasung, Gyeonggi, Korea.

7. Introduction To Trikatu churna: Comparative Study Of PolyherbalAyurvedic FormulationsDivya N1., Pramod V. Pattar1† and Ramalingappa2 1Department of Botany, Davangere University, Shivagangothri, Davangere. Karnataka, India. 577 002.2Department of Microbiology, Davangere University, Shivagangothri, Davangere. Karnataka, India. 577 002.

8. International research journal of pharmacy www.irjponline.com

9. Comparative study of herbal formulation and marketed formulation of trikutachurna.Vikassharma, Rahulkaushik, Pallavi rai.

Received on 24.06.2022 Modified on 14.09.2022

Res. J. Pharmacognosy and Phytochem. 2023; 15(1):39-45.

DOI: 10.52711/0975-4385.2023.00007