Formulation and Evaluation of Polyherbal Tablet for Digestive Disorder

Abstract

Enzymes are dissolution large complex molecules like proteins, carbohydrates, and fats into smaller ones. They are secreted by the salivary glands and gastric mucosa of the stomach,pancreas, and small intestine, also present in many fruits and vegetables in significant amounts. The objective of this study was to review the available literature on the naturally available enzyme on food like fruits and vegetables and the impact of heat on their activity. Foods that contain natural digestive enzymes include Amla , papayas, and fennel seeds indicating that enzyme disintegration is influenced by temperature.A polyherbal tablet was formulated using a combination of herbs and evaluated for its physical characteristics, phytochemical content, and in vitro antioxidant activity. The tablet showed satisfactory physical characteristics, presence of various bioactive compounds, and significant antioxidant activity. This study suggests that the tablet has potential as a natural remedy for digestive disorders, warranting further in vivo studies to confirm its efficacy and safety.

Keywords

Digestive enzymes, Natural enzymes , Digestion, Dissolution.

Introduction

The digestive system is a system of body which breakdown food into forms that can be Absorbed and used by body cells. It also absorbs water, vitamins, and minerals, and eliminates Wastes from the body. It breakdowns the larger molecules present in food into molecules that are Small enough to enter body cells by a process known as digestion. The organs which are Involved in the breakdown of food are collectively called the digestive system. The digestive System is a tubular system which extends from the mouth to the anus.  digestive disorders are diseases that affect the digestive tract (also called the gastrointestinal system). The gastrointestinal system includes the digestive system, which is made up of the following organs The esophagus, liver, stomach ,Small and large intestines, gallbladder, pancreas. Digestive disorders can range from mild to severe, depending on the severity of the disorder.

Common gastrointestinal disorders include:

• Gastric reflux disease.
• Cancer
• Irritable bowel syndrome.
• Lactose intolerance

The most common gastrointestinal disorders are:

• Bleeding Bloating
• Constant constipation Diarrhoea
• Heartburn
• Pain,
• Nausea
• vomiting

Gastric cancer is that the third commonest reason for cancer-related death within the world, and it remains troublesome to cure in Western countries, primarily as a result of most patients gift with advanced sickness. Within the USA abdomen malignancy is presently the fifteenth commonest cancer. The abdomen begins at the internal organ junction and ends at the small intestine. Almost all viscus cancers .Gastric cancer is that the third commonest reason for cancer-related death within the world, and it remains troublesome to cure in Western countries, primarily as a result of most patients gift with advanced sickness. Within the USA abdomen malignancy is presently the fifteenth commonest cancer. The abdomen begins at the internal organ junction and ends at the small intestine. Almost all viscus cancers are adenocarcinomas (cancers that begin in cells that create and unharness mucous secretion and alternative fluids). Alternative kinds of viscus cancer ar duct neoplasm tumors, duct stromal tumors, and lymphomas. Infection with microorganism known as H. pylori may be a common reason for viscus cancer

GI hormones are chemical messengers that are involved in several aspects of physiological functions of the canal, as well as the regulation of secretion, absorption and digestion, and gut motility. GI hormones are an oversized family of peptides and are secreted by endocrine cells that are cosmopolitan throughout the GI tissue layer and exocrine gland. Gastrin, secretin, and cholecystokinin (CCK) were the primary discovered gut hormones, and as of nowadays, there are over fifty gut internal secretion genes and a large number of bioactive peptides

Papaya,amla and fennel seeds processed products have been found to have a positive effect on digestive disorders or diseases. Also use to improve the immunity power. This combination has been used as a traditional treatment for gastrointestinal functional dys-order in countries where papaya plants are grown and fennel seeds and amlais used. Clinical studies have shown that the ingredients of this processed product can help to treat mild digestive dysfunctions in both young and adults. Patients with GI tract disorder constipation and loose stools and heartburn have been found to benefit from this combination. This study looked at the treatment effectiveness of this combination in patients with irritable bowel symptoms. The goal of this clinical study was to evaluate the treatment effectiveness in patients with a functional digestive tract disorder under randomised controlled conditions. Digestive disease is any health problem that occurs in the digestive tract. Conditions may range from mild to serious. Some common problems include heartburn, cancer, irritable bowel syndrome, and lactose intolerance.

Drug Profile:-

PAPAYA:-

Papaya, scientifically known as Carica papaya, is a widely cultivated fruit crop in tropical and subtropical regions. It belongs to the Caricaceae family and is available throughout the year. This fruit is highly nutritious, packed with essential vitamins such as vitamin C, vitamin E, and vitamin A. Additionally, it contains minerals like potassium and magnesium, as well as pantothenic acid, folic acid, and fiber. Papaya also contains papain, a digestive enzyme that effectively addresses allergies, sports injuries, and trauma. It is a powerhouse of enzymes, with unripe fruits containing papain and chymopapain, while ripe fruits contain B carotene, carotenoids, crytoxanthin, monoterpenoids, and seeds containing distinct enzymes. The leaves of the papaya plant are rich in zinc, manganese, iron, potassium, and other minerals. Numerous studies have demonstrated the plant’s medicinal properties, including antioxidant, antihypertensive, wound healing, hepato protective, anti- inflammatory, antimicrobial, anthelmintic, tumor-fighting, malaria prevention, blood sugar-lowering, anti-ulcer, and immune modulatory properties. Papaya is known for its effectiveness in treating various digestive and abdominal disorders. It is a remedy for dyspepsia, hyperacidity, dysentery, and constipation. Papaya aids in protein digestion due to its rich source of proteolytic enzymes. The digestive enzyme papain, extracted from papaya, is dried into a powder and used to aid in digestion.

Toxonomical classification:-

• Kingdom :- Plantae
• Family :- caricaceae
• Subfamily :- Dilleniidae
• Genus :- carica L. Papaya
• Species :- carica papaya L
• Synonyms :- Pawpaw
• Biological sources :- ripe fruits of carica papaya

Chemical composition:-

• Carbohyatrate
• Protein
• Alkaloids (carpain and pseudocarpaine)
• Protolytic enzymes (papain and quimiopapain
• Uses:-
• Inflammation
• Digestion
• Anticancer Properties
• Boost Immunity
• Diabetis
• For skin
• Powerful antioxidanrt

AMLA:-

Emblemium officinalis, also known as Phyllanthus Emblica, is a plant species in the Euphorbiaceae family. It is native to India, where it grows in both wild and cultivated conditions. The fruits of this plant are globose, depressed, and bright yellow green when ripe. They have distinct ridges and a sour, astringent taste, followed by a slightly sweet taste. The main components of this plant are vitamin C (2%) and tannins (gallic acid, ellagic acid, and embricol) as well as two alkaloids (phyllantidine, and phyllantine) and pectin (pectin) and minerals. It can be used to treat a variety of ailments, such as Asthma, Bronchitis, Diabetes, Cephalalgia, Hyperacidity, Peptic ulcer, Eye Diseases, Inflammation, Cardiac Disorders, Anemia, Colic, Flatulence, Diarrhea and Dysentery. It can also be used to treat intermittent fevers.

Toxonomical classification:-

• • • Kingdom :- Plantae
    • Family :- Phyllanthaceae
    • Subfamily:- Euphorbiaceae
    • Genus :- Phyllanthus emblica
    • Species:- Phyllanthus emblic
    • Synonyms:-Indian gooseberry
    • Biological sources :- consists of dried ripe fruit as well as fresh fruit.

Chemical composition:-

• • • Polyphenols like gallic acid
    • ellagic acid
    • different tannins
    • minerals
    • vitamins
    • amino acids
    • fixed oils
    • flavonoids like rutin

Uses:-

1. Helps in controlling diabetes.
2. Improves digestion.
3. It keeps the hair amazing.
4. Keeps the eyes healthy.
5. It helps in losing weight.
6. Keeps the skin healthy.

FENNEL SEEDS:-

F. vulgare is an Apiaceae plant from the genus “Foeniculum” with aromatic and medicinal properties. This resilient perennial herb has yellow flowers, feathery leaves and is native to Asia and Southern Europe. There are many types and races of F. vulgare, ranging from wild to domesticated, with varying This resilient perennial herb has yellow flowers, feathery leaves and is native to Asia and Southern Europe. There are many types and races of F. vulgare, ranging from wild to domesticated, with varying sizes, aromas and flavours of fruits. Most of the varieties are grown in Russia and Romania, Hungary and Germany, France, USA and Japan, and India. Seeds are used for alcoholic beverages and baked goods, as well as for ments, fish mealsand herbal blends. The major phytochemicals found in this plant are phenols (a glycosaminoglycant), phenolic (a glycoside), volatile fragrance (a volatile fragrance compound) and fenone (a flavouring compound). Many infectious diseases, including those caused by bacteria, fungi, viruses and mycobacterials, are treated with this plant due to its anti- inflammatory and anti-inflammatory properties, as well as anti-cancer, anti-hepatitis, anti- hypoglycemic and anti-epileptic. It also has hypoglycemic and estrogenic properties.

Toxonomical classification:-

• Kingdom :- Plantae
• Family :- Apiaceae
• Subfamily :- Piperitum and vulgare
• Genus :- Foeniculum
• Species :- valgare var. Vulgare
• Synonyms :- saunf
• Biological sources :- ripe fruits of Foeniculum vulgare

Chemical  composition:-

• Trans-anethole (31.49%)
• 2-pentanone (25.01%)
• fenchone (11.68%)
• benzaldehyde-4-methoxy (8.01
• Uses:-
• Stimulate GI motility
• Support digestion
• Promote menstruation
• Dispels flatulence
• Claim the nerves
• Support milk flow during breastfeedin

 Objective:-

1. To return the body to a state of natural balance so that it can heal itself.
2. To achieve greater therapeutic efficacy.
3. The goal of combining these three herbs into a single polyherbal tablet is to address a wide range of digestive problems, such as indigestion and bloating, as well as gas and irregular bowel movement.The synergy of these herbs may improve their individual benefits, improving digestive health and comfort.
4. Reduce the side effects. 

Experimental work :-

Collection and Drying of the plant material:-

The plant part of the fennel seeds Amla and papaya procured to the market .The plant part Of fennel seeds, Amla and papaya were collected As a whole and dried in shade. In fresh condition, it is then Oven-dried at reduced temperature (40°C) to make suitable for grinding purpose. The ginger crushed in the mixed grinder To a coarse powder. The coarse powder is then stored in an airtight container or polybags and kept in a cool, dark, and dry Place for further. All other ingredients used to college.

 Preparation of Amla powder :-

• Fresh Amla
• Drying
• Washing Until clean with running water
• Sizes cut using knife with thickness
• Using the mortar pestle or blender to reduce the size • Use a 60 no mesh sieve • Powder of Amla.

Preparation of papaya powder:-

• Unripe papaya
• Drying
• Wash until clean with running water
• Sizes cut using knife with thickness
• Using the mortar pestle or blender to reduce the size
• Use a 60 no mesh sieve
• Powder of Unripe papaya

Preparation of fennel seeds powder:-

• Fresh fennel seeds
• Drying
• Using the mortar pestle or blender to reduce the size
• Use a 60 no mesh sieve
• Powder of fennel seeds.

Granulation method :-

Ingredients:-

Tablet no 1. Ingredients and role.

Serial no	Excipients	Role
1	Unripe papaya (extract)	API
2	Amla (extract)	API
3	Fennel seeds powder	API
4	Lactose	Filler
5	Gelatin	Binder
6	Starch soluble	Disintegrant
7	Magnesium sterate	Lubricants
8	Methyl paraben	Preservative

Wet Granulation Method:-Preparation of granules:-

• Wet granulation is extensively employed in the pharmaceutical industry as the primary method of granulation.
• This technique entails introducing a liquid solution, either with or without a binder, to powders. The result is the formation of a wet mass or granules through the combination of the powder and an adhesive, rather than through compaction.
• Afterwards, the wet mass is dried and sized to obtain granules. The liquid that is added binds the moist powder particles through a combination of capillary and viscous forces while in the wet state.
• During the subsequent drying process, more durable bonds are formed, leading to the creation of agglomerates.

Step 1: weighing and mixing of formulation ingredients (Excluding the lubricant).

This step involves weighing, sifting, and introducing the drug substance(s) and bulking agent(s), filler(s) or diluent(s), and disintegrant into the powder mixer. The ingredients are mixed using a planetary bowl mixer (or ribbon/ trough mixer), rotating drum mixer (or high-speed mixer), until a homogeneous powder mix is obtained. Mixing efficiency can be improved by using powders with similar average particle size. However, this is not usually the case in most mixing operations.

Diluents

There are many different diluents available commercially, but those used in the wet granulation method are:

• Lactose
• Microcrystalline Cellulose
• Starch
• Powdered Sucrose
• Mannitol
• Fructose
• Sorbitol
• Calcium Phosphate

The most commonly used diluents are lactose, due to its low cost, its solubility and its compatibility with most drugs and excipients, and the fact that it readily compacts.

Step 2: preparing the damp mass:-

Mixing the binder solution with the powder mixture creates an adhesive mass that can be granulated here. The number of binding agent and the amount of fluid needed to form a wet and cohesive mass depends on the operator’s skill; but the resulting binder and powder mixture should be compact when squeezed in your hand. If you use too little binder, you will have poor adhesion, a capping, and soft tablets; if you use too much, you will have hard tablets with slow dissolving properties. Granulating agents include povidone solutions, which are aqueous solutions of cornstarch, molasses, methylcellulose, carboxymethyl Cellulose, glucose solution & microcrystalline cellulose. For drug substances adversely affected by an aqueous solution, you can use a dry binder or a nonaqueous solution. To prepare a granulation, you can add colourants or flavour to the binding agent.

Step 3 : wet screening/ screening the dampened powder into pellets or granules:-

The powder mixture is pre-screened with 6 to 12 mesh screens to prepare the wet Granules; this can be done manually or with equipment that pre-prepares the granules through perforation in the machine. The pre-screened granules are evenly distributed on tray and dried in the oven.

Step 4: drying of moist granules:-

Screened moist granules are then dried in a controlled oven at a temperature no higher than 55°C to maintain a consistent weight or moisture content. The temperature and drying time depend on the active ingredient and moisture content needed to produce satisfactory tablets. A shelf or tray dryer and a fluidized-bed dryer can be used.

Step 5: Sizing the granulation by dried:-

Dried granules pass through a smaller screen than the one used for wet granules. The final size of the granules is determined by the size of the punches Screen size is 14-to-20- mesh size.

Step 6 : lubrication of granules:-

After dry screening, granules are divided into coarse and fine by shaking them on 250 mesh sieves. The appropriate amount of lubricant is then passed through a 200 mesh sieve. The lubricant is mixed with the coarse granules prior to incorporation into the coarse granules. Common lubricants used in wet granulation are magnesium stearate, calcium stearate, stearic acid, talc, starch.

Pre formulation study:

1] Angle of repose:-

The angle of repose, was determined by the funnel method. The accurately weighed (10gm) granules were taken in a funnel. The height of the funnel was adjusted in such a way that the tip of the funnel just touched the apex of the heap of granules the granules were allowed to flow through the funnel freely on to a clean surface. The diameter of the cone was measured and angle of repose was calculated using the equation:

tan 0º = h/ r

Where,

H is the height of the granules cone,

R is the radius of the granules cone.

Table no. 2: Angle of repose

Sr. No	Flowability	Angle of repose
1	Excellent	<25
2	Good	25-30
3	Moderate flow	30-40
4	Poor flow	>40

2] Loose bulk density and Tapped bulk density:-

An accurate weighed granule from each formula was lightly shaken to break any agglomerate formed and it was introduced into a measuring cylinder. The volume occupied by the granules was measured which give bulk volume. The measuring cylinder was tapped until no further changes in volume was noted which gave the tapped volume. Both loose bulk density (LBD) and Tapped bulk density (TBD) of granules were determined using the following formulae.

LBD= Weight of the granules/ Volume of the granules TBD = Weight of the granules/ Tapped volume of the granules.

Carr’s compressibility:-

The compressibility index of granules was determined using following equation

Carr’s Compressibility Index (%) = [(TBD-LBD)/TBD]×100

Table no. 3: Carr’s compressibility

Compressibility	Index properties
<10	Excellent
11-15	Good
16- 20	Fair
21-25	Passable
26- 31	Poor
32-37	Very poor
>38	Very very poor

3] Hausner’s ratio:-

Hausner’s ratio is the ratio between tapped density and bulk density.

Hausner’s ratio = Tapped bulk density/ loose bulk density

Table no.4: Hausner Ratio

Flow properties	Hausner ratio
Excellent	1.00-1.11
Good	1.12-1.18
Fair	1.19-1.25
Passable	1.25-1.34
Poor	1.35-1.45
Very poor	1.46-1.59
Very very poor	>1.60

Formulation of tablet:

Table no: 5 formulation

Sr. No	Excipients	Role	Quality in mg
1	Unripe papaya	API	15.26 mg
2	Amla	API	18.8 mg
3	Fennel seeds powder	API	17.3mg
4	Lactose	Filter	3mg
5	Gelatin	Binder	3.5 mg
6	Starch soluble	Disintegrate	2.5mg
7	Magnesium sterate	Lubricants	2mg
8	Methyl paraben	Preservative	2mg

Preparation of tablet (compression method):-

Before use, all the solid fractions and the excipients were passed through sieve No 80. The individual materials doses were precisely measured in electronic balance. Then, the diluents, binder, lactose, and dry powder were combined and passed through the sieve No 44. To the above mixture, the required amounts of starch were added. The necessary amount of methyl paraben was added.  The wet coherent mass was formed and then sieved using sieve No 14. The dry granules were dried in hot air ovens at 40 degrees Celsius for 30 minutes. The dried granules were again sieve No 22. The granules were lubricated with pure tale, magnesium stearate.

Fig no : 11 formulation of tablet

Evaluation of tablets:- Apperance:

The general apperance and colour of tablets were found by visual and sensual basis. 

• Colour :- Brownish Colour.
• Thikness:- 1.5 mm2

Hardness test:-

The tablet crushing strength, also referred to as the hardness test, was conducted utilizing the Monsanto hardness tester. The lower plunger of the tester was placed in contact with the tablet, and an initial reading was recorded. Subsequently, the tablets were fractured by applying force, and the resulting measurement was expressed in kg/cm 

Weight variation test:-

The process of assessing weight consistency is commonly referred to as uniformity in weight. To conduct the weight variation test, each of the 20 tablets was individually weighed, and the average weight was   consistency is commonly referred to as uniformity in weight. To conduct the weight variation test, each of the 20 tablets was individually weighed, and the average weight was calculated. Subsequently, a comparison was made between the weight of each tablet and the average weight.

Calculation:-

1. Average weight per tablet

Average weight per tablet= collective weight of 20 tablets/20

2. Percent deviation= 5× average weight of tablet/100
3. Upper limit = average weight per tablet+ 5% deviation from average
4. Lower limit= Average weight per tablet -5% deviation from average 

Friabilty Test:-

The purpose of this examination is to assess the cumulative impact of abrasion and stock. The Roche Friabilator was employed as the testing apparatus. Tablets that were pre-weighed were inserted into the friabilator and spun at a rate of 25 rpm for a duration of 4 minutes. Each revolution involved dropping the tablets from a height of 6 inches. Subsequent to the elimination of fines, the tablets were reweighed, and the weight loss percentage was determined .

Percentage friability = Initial wt – final wt/ Initial wt×100

Disintegration test:-

Three tablets are utilized to assess the disintegration time. These tablets are inserted into the disintegration apparatus, and the duration is monitored until complete disintegration of the tablet occurs. The temperature within the apparatus is controlled at 37º C.

RESULT AND DISCUSSION:

Characterization of drugs

Colour:- the drug colour is brownish same as the reported reference.

Thickness of tablet:- the thickness of tablet is same as this reported reference 1.5±0.001mm2

Table no.6: Result and Discussion

Sr. No	Evaluation parameters	Result
1	Angle of repose	28.30
2	Hardness of tablet	5.1 kg/cm2
3	Weight variation	500±5mg
4	Friability test	0.41

CONCLUSION:-

The herbal tablets were prepared by combining various herbs, either individually or in combination, to enhance their synergistic effects. The formulation included unripe Carica papaya fruits, Amla fruits, and Fennel seeds. Several parameters such as hardness, thickness, pH determination, weight variation, loss on drying, and friability were evaluated to assess the quality of the tablets. The results of these tests indicated that the herbal tablets performed well. It is worth noting that the herbs used in the tablet formulation primarily possess digestive properties.

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