Development Of Syzygium Cumini Seed Tablets And Their Pharmaceutical Evaluation

Diabetes mellitus is a long-term metabolic condition marked by high blood glucose levels, arising from either inadequate insulin production or reduced responsiveness of the body to insulin. It is among the most common non-communicable diseases worldwide and contributes significantly to health complications and economic strain. Although modern antidiabetic medications are effective, their prolonged use may lead to undesirable side effects, increasing the demand for safer and more sustainable plant-based therapeutic options. Jamun (Syzygium cumini), also referred to as black plum or Indian blackberry, is a medicinal plant extensively utilized in Ayurvedic and Unani medicine. The seeds of this plant are rich in bioactive constituents such as jamboline, gallic acid, and ellagic acid, which possess notable antidiabetic properties. These compounds aid in controlling blood glucose levels by improving insulin function, limiting glucose absorption, and supporting the activity of pancreatic β-cells..[1] The present study focuses on utilizing the therapeutic benefits of Jamun seeds by developing them into a tablet dosage form for easier administration. This approach enhances patient compliance, ensures uniform dosing, and improves the stability and shelf life of the product. The formulation of Jamun seed tablets represents a promising natural strategy for diabetes management and may help reduce reliance on synthetic medications. Diabetes mellitus is a multifactorial and chronic endocrine disorder that affects a large population worldwide. It is broadly classified into two main types: Type 1 diabetes, caused by autoimmune destruction of pancreatic β-cells, and Type 2 diabetes, which involves insulin resistance along with a relative deficiency of insulin. Among these, Type 2 diabetes is the most prevalent and is commonly linked to factors such as a sedentary lifestyle, obesity, unhealthy dietary patterns, and genetic susceptibility. [2] The plant possesses various phytoconstituents and has high antioxidant potential, which is very much beneficial for our bodies. It possesses phytoconstituents that include glucoside, anthocyanin, steroids, phenols, flavonoids, and terpenoids. [3]

Its purple-to-blackish color is the result of the anthocyanins present within the plant [3]. Other than the fruits, leaves and bark also have medicinal properties.[4] Scientific studies have supported the traditional use of Jamun seeds, showing that their extracts can effectively reduce fasting blood glucose levels, enhance lipid profiles, and protect pancreatic β-cells from oxidative stress. Considering these therapeutic benefits, formulating Jamun seeds into a tablet dosage form provides advantages such as precise dosing, better bioavailability, improved patient compliance, and convenient administration.[5]

Figure 1: Jamun Syzygium cumini fruits in natural form on the tree (top) and ripened fruits (bottom).

MAJOR BIOACTIVE CONSTITUENTS

Jamun fruit is nutritionally rich, containing appreciable levels of carbohydrates such as glucose, sucrose, fructose, and galactose. It also provides proteins in the form of free amino acids including asparagine, alanine, glutamine, tyrosine, and cysteine. In addition, it is a source of essential vitamins like ascorbic acid, thiamine, and niacin, along with important minerals such as potassium, calcium, sodium, phosphorus, and iron. [6] The nutritional composition of Jamun seed may differ slightly from its fruit. Raza et al. [6] analyzed the Jamun seeds’ and Jamun fruits’ nutritional composition and found the seeds to have the following approximate composition (%): moisture level of 16.34 ± 0.49, ash level of 2.18 ± 0.06, crude protein level of 1.97 ± 0.59, crude fat level of 0.65 ± 0.01, and crude fiber level of 4.19 ± 0.12; and calculated the composition of Jamun fruit as 82.19 ± 2.46, 2.04 ± 0.06, 2.15 ± 0.06, 0.83 ± 0.02, and 1.76 ± 0.05, respectively [7] Anthocyanins are water-soluble pigments belonging to the flavonoid group, known for their strong antioxidant and anticancer properties. They consist of a diverse range of glycosylated compounds derived from the flavylium cation, characterized by polyhydroxy and polymethoxy substitutions. Common sugars attached to anthocyanidins include glucose, arabinose, and galactose. The color of anthocyanins varies depending on their chemical structure and pH conditions, appearing red, blue, or purple. In highly acidic environments (pH 1–3), the red flavylium cation form is most stable. As the pH increases, deprotonation leads to the formation of blue quinonoid structures, while at pH 4–5, they convert into colorless hemiketal forms. [8], and the color change in Acn with variation in pH condition could be utilized in intelligent packaging of food products or could be used as a biocolorant. Further, based on structural variation in methoxylation and hydroxylation around benzene rings, Acns exist in six different glycoside forms, namely, cyanidin, peonidin, pelargonidin, delphinidin, petunidin, and malvidin [9,10]. Recent studies have investigated the fatty acid profile of Jamun seed using various extraction solvents. In one such analysis employing hexane, the major fatty acids identified (%) included oleic acid (26.8%), linoleic acid (25.2%), and palmitic acid (19.9%), followed by stearic acid (6.4%). Minor components comprised linolenic acid (2.6%), arachidic acid (1.2%), eicosapentaenoic acid (0.6%), erucic acid (0.5%), myristic acid (0.4%), docosahexaenoic acid (0.3%), and lauric acid (0.3%).[ 11] Carotenoids are naturally occurring pigments formed from eight isoprene units and are classified as either cyclic or linear hydrocarbons. Their characteristic yellow coloration is due to the presence of conjugated double bonds within their polyene structure. Jamun fruit is a notable source of carotenoids, containing approximately 48–55 mg per 100 g. Key carotenoids present include β-carotene, zeaxanthin, β-cryptoxanthin, and lycopene. Among these, all-trans-lutein (43.7%) and all-trans-β-carotene (25.4%) have been identified as the major carotenoids in the pulp. [12] Known for their antioxidant properties, carotenoids like phenol contribute to eye health and possess antiaging effects [13]

Figure 2 : Jamun seed powder

NUTRACEUTICAL PROPERTIES OF JAMUN

Jamun is widely recognized for its therapeutic and nutraceutical benefits, demonstrating effectiveness in managing oxidative stress, hyperglycemia, inflammation, and cancer, along with notable antimicrobial properties. Flavonoids contribute significantly to these effects through their antioxidant activity, primarily by donating hydrogen atoms or electrons to neutralize free radicals. This activity is largely attributed to the presence of hydroxyl groups in their structure. As a result, flavonoids can efficiently scavenge reactive oxygen species (ROS), singlet oxygen, and other free radicals, thereby helping to prevent diseases linked to oxidative stress, including cancer, neurological disorders, and immune-related dysfunctions. [14] Antidiabetic Potential. Diabetes, a chronic disease caused by increased hyperglycemic levels in the blood, might be due to the unavailability or inefficiency of the human body to utilize insulin effectively [15] α-Amylase, a digestive enzyme that hydrolyzes starch to glucose, is responsible for the increase in postprandial hyperglycemia levels in the human body. Bioactive compounds present in jamun seeds, such as glycosides, jambosine, alkaloids, and polyphenolic compounds like quercetin, catechins, and tannins present in fruit parts, help to inhibit α-amylase activity [16] Among the various bioactive constituents of Jamun, triterpenoids are particularly significant due to their multiple health benefits, including enhancement of insulin secretion, inhibition of α-glucosidase, support of pancreatic β-cell regeneration, and notable antioxidant activity. The process of insulin release is complex and essential for maintaining glucose balance in the body, involving a series of coordinated cellular events. Insulin secretion from pancreatic β-cells is primarily regulated by blood glucose levels and can also be influenced by bioactive compounds such as triterpenoids present in Jamun extracts. Under low-energy conditions, when ATP levels are reduced, potassium ions (K⁺) flow through ATP-sensitive potassium channels, keeping the cell membrane in a polarized state and limiting insulin release. When glucose levels rise, ATP production increases, causing these potassium channels to close, which leads to depolarization of the cell membrane. This change triggers the opening of voltage-gated calcium (Ca²⁺) channels, allowing calcium ions to enter the cells. The resulting increase in intracellular calcium concentration stimulates the release of insulin, a key hormone responsible for regulating blood glucose levels. [17,18]

NEED FOR HERBAL ALTERNATIVES:[19]

• Growing interest in herbal remedies due to:
• Fewer side effects
• Cost-effectiveness
• Cultural and traditional acceptance
• Availability in rural areas
• WHO recommends integrating traditional medicine into national health systems.

MATERIALS USED

1. Jamun Seed Powder (Syzygium cumini)

• Source & Preparation: Seeds are obtained from fully ripe Jamun fruits, thoroughly washed, shade-dried, and finely powdered.
• Key Phytoconstituents: Jamboline, gallic acid, ellagic acid, flavonoids, alkaloids, and tannins.
• Function in Formulation:

o Serves as the active pharmaceutical ingredient (API).

o Exhibits hypoglycemic effects by:

• Slowing down carbohydrate absorption.
• Promoting insulin secretion.
• Supporting regeneration of pancreatic β-cells.

o Additionally provides antioxidant and anti-inflammatory effects, aiding overall metabolic health.

2. Microcrystalline Cellulose (MCC)

• Chemical Nature: A purified, partially depolymerized form of cellulose.
• Function in Formulation:

o Acts as a diluent/filler, increasing tablet bulk when the active ingredient is present in smaller amounts.

o Enhances flow characteristics of the powder blend.

o Improves compressibility, enabling formation of tablets with adequate hardness.

o Chemically stable and non-reactive with herbal components.

3. Starch (Maize or Potato Starch)

• Nature: A naturally occurring polysaccharide derived from plant sources such as maize or potato.
• Dual Functionality:

o Binder: Assists in particle aggregation during wet granulation, providing mechanical strength.

o Disintegrant: Swells in contact with water, facilitating tablet breakdown and dissolution.

• Biodegradable and natural, making it appropriate for herbal formulations.

4. Magnesium Stearate

• Nature: A magnesium salt of stearic acid, appearing as a fine white powder.
• Function in Formulation:

o Functions as a lubricant, minimizing friction during tablet compression.

o Prevents adhesion of powder to punches and dies.

o Facilitates smooth ejection of tablets from the machinery.

• Note: Excessive use may negatively affect tablet disintegration.

5. Talc

• Nature: Hydrated magnesium silicate.
• Function in Formulation:

o Acts as a glidant, improving the flowability of the powder mixture.
o Reduces inter-particle friction during processing.
o Contributes to a smoother tablet surface finish.

6. Purified Water

• Role: Utilized as a granulating agent in the wet granulation process.
• Function in Formulation:

o Aids in binding powders during granule formation.
o Evaporates upon drying without leaving residue.
o Must be of high purity to prevent microbial contamination, particularly in herbal preparations.

6. Formulation Process

The preparation of Jamun seed tablets can be done using direct compression or wet granulation methods. Here, we describe the wet granulation method, which is more suitable for herbal powders with poor flow and compressibility. Step-by-Step Formulation Process (Wet Granulation Method)

1. Step 1: Preparation of Jamun Seed Powder

• Collect seeds from fresh Jamun fruits.
• Clean thoroughly to remove any adhering pulp.
• Dry the seeds under shade for about 7–10 days to preserve active phytoconstituents.
• Pulverize the dried seeds into a fine powder using a grinder or pulverizer.
• Pass the powder through a 60# mesh sieve to achieve uniform particle size.

2. Step 2: Weighing of Ingredients

• Accurately measure all required ingredients:
  • Jamun seed powder (Active ingredient)
  • Starch (Binder/Disintegrant)
  • Microcrystalline Cellulose (Diluent)
  • Talc (Glidant)
  • Magnesium Stearate (Lubricant)
  • Lactose (optional, for taste and bulk)
• The quantities should be determined based on batch size and tablet formulation.

3. Step 3: Dry Mixing

• Blend Jamun seed powder, MCC, and starch uniformly using a mortar or mechanical blender.
• Ensure proper and homogeneous distribution of all components.

4. Step 4: Preparation of Binder Solution

• Prepare a 5% w/v starch paste by first dispersing starch in a small quantity of cold water.
• Heat the mixture until a clear, viscous gel is formed.
• Allow the binder solution to cool before use.

5. Step 5: Wet Granulation

• Gradually incorporate the starch paste into the dry powder blend with continuous mixing.
• Knead the mixture to obtain a cohesive damp mass.
• Avoid excessive addition of liquid to prevent poor granule formation.

6. Step 6: Sieving of Wet Mass

• Pass the moist mass through a 12# or 16# sieve to produce wet granules.

7. Step 7: Drying of Granules

• Dry the granules in a tray dryer or hot air oven at 40–50°C for about 30–60 minutes or until the moisture content falls below 2%.
• Maintain moderate temperature to prevent degradation of herbal constituents.

8. Step 8: Sizing of Dry Granules

• Pass the dried granules through a 20# sieve to obtain uniformly sized granules and remove lumps.

9. Step 9: Addition of External Excipients

• Blend the dried granules with magnesium stearate and talc.
• Add these excipients after drying to avoid interference with the binding process.

10. Step 10: Compression into Tablets

• Compress the prepared granules into tablets using a tablet compression machine.
• Choose a suitable punch size (e.g., 8 mm or 10 mm, flat or round).
• Adjust compression parameters to achieve the desired tablet hardness and weight.

7. Formulation Table: Jamun Seed Tablet (500 mg) [26]