Antidiabetic Efficacy of Cynodon Dactylon: Formulation and Evaluation of Herbal Tablets

Diabetes mellitus, a chronic metabolic disorder characterized by hyperglycaemia and insulin resistance, poses significant global health challenges. Conventional treatments often involve synthetic medications, which, despite their efficacy, may lead to adverse effects and long-term complications. ^[24] Diabetes mellitus is the common endocrine disorder that affects more than 100 million People worldwide (6% of the population) and in the next 10 years it may affect about five times more people than it does now. ^{[11, 13]} In India, the prevalence rate of diabetes is estimated to be 1-15%.^[11] The disease was well known to the ancient Indian medical experts. All the renowned classic texts of Ayurveda like Charaka Samhita (1000 B.C.), Sushruta Samhita (600 B.C.) and subsequent works refer to this disease under the term Madhumeha or Ikshumeha.^[10,15] Consequently, there has been an increasing focus on exploring natural remedies for diabetes management due to their potential efficacy, safety, and affordability. ^[13,24] The main objective of the present study is to focus on the formulation and evaluation of herbal anti diabetic tablet. Cynodon dactylon (commonly known as Durva grass or Bermuda grass) has garnered attention for its antidiabetic properties. ^[16,17] Rich in bioactive compounds such as flavonoids, alkaloids, and glycosides, Durva Grass has demonstrated promising effects in reducing blood glucose levels and improving insulin sensitivity in preliminary studies. ^[19,26] To enhance its therapeutic potential, a synergistic combination with other medicinal herbs has been proposed. Tinospora cordifolia (Gulvel or Guduchi), known for its immunomodulatory and antihyperglycemic effects, ^[14,23] and Cinnamomum verum (cinnamon), recognized for its role in enhancing insulin activity and reducing blood sugar levels, ^[13,23] are ideal candidates for such formulations.  This research focuses on developing and evaluating a tablet formulation containing Durva Grass as the primary ingredient, complemented by gulvel powder and cinnamon powder. The aim is to create an effective, natural antidiabetic formulation that harnesses the synergistic effects of these ingredients. This study investigates the phytochemical profile, formulation process, and antidiabetic potential of the developed tablet to provide a scientifically validated alternative for diabetes Management.

MATERIALS:

1) Durva Grass (Cynodon dactylon):

Durva grass, also known as Cynodon dactylon or Bermuda grass, has a long history of use in traditional medicine, particularly in Ayurveda, for managing diabetes and related metabolic disorders.

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Hypoglycemic and Anti-Diabetic Effects:

Blood Sugar Regulation: Multiple studies and traditional practices suggest that durva grass exhibits significant hypoglycemic (blood sugar-lowering) effects. Both animal studies and anecdotal human reports indicate that extracts of durva grass can reduce elevated blood glucose levels.

Mechanism: The hypoglycemic action is attributed to the presence of flavonoids and sterols in the grass, which may help regenerate pancreatic beta cells (responsible for insulin production) and enhance insulin secretion. ^{[3, 13]}

Experimental Evidence:

In animal studies, oral administration of durva grass extract at doses of 250–1000 mg/kg led to significant reductions in blood glucose, with 500 mg/kg being particularly effective. In diabetic rats, this dose lowered fasting blood glucose by up to 59% over 14 days, and also improved lipid profiles by reducing cholesterol and triglycerides. The non-polysaccharide fraction of the aqueous extract was found to be especially effective in lowering blood sugar in diabetic rats.

Human Use: While most scientific studies are on animals, traditional and folk medicine recommend durva grass juice (often combined with neem leaves) taken on an empty stomach for controlling blood sugar, even in chronic diabetes cases.

Additional Benefits for Diabetics

Reduces Diabetes-Related Complications: Regular consumption of durva grass may help lower the risk of complications associated with diabetes, such as high cholesterol and cardiovascular issues, by improving lipid profiles and acting as a blood purifier.

Immunomodulatory Effects: Durva grass contains protein fractions that may help optimize immune system function, which is beneficial for diabetics who are at higher risk of infections.

Other Health Benefits: Besides its anti-diabetic action, durva grass is noted for its anti-inflammatory, antioxidant, and detoxifying properties, which can support overall health in diabetic patients.

Traditional Usage and Recommendations

Preparation: Durva grass is commonly consumed as fresh juice, sometimes mixed with neem leaves, and taken in the morning on an empty stomach.

Safety: While durva grass is widely used in traditional medicine and is generally considered safe, scientific studies on its long-term safety and efficacy in humans are limited. Always consult with a healthcare provider before starting any herbal remedy, especially for chronic conditions like diabetes.

2) Gulvel Leaves (Tinospora cordifolia):

Tinospora cordifolia, commonly known as Gulvel, Giloy, or Guduchi, is a widely recognized herb in Ayurveda with significant antidiabetic properties supported by scientific research.

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Antidiabetic Effects:

Blood Sugar Reduction: Giloy has demonstrated hypoglycemic effects by lowering blood glucose levels in adults with type-2 diabetes and in animal studies. It helps increase insulin production and improves insulin sensitivity, facilitating better glucose utilization by cells.

Pancreatic Beta Cell Protection: Studies indicate that Tinospora cordifolia preserves pancreatic beta cells, which produce insulin, enhancing their function and reducing insulin resistance. This contributes to better blood sugar regulation and may prevent diabetes progression.^[8]

Mechanism of Action: The antidiabetic activity is attributed to bioactive phytochemicals such as alkaloids (including berberine), tannins, flavonoids, saponins, and steroids. Berberine, in particular, has a blood sugar-lowering effect comparable to the diabetes drug metformin.

Additional Benefits Related to Diabetes:

Antioxidant and Anti-Inflammatory Properties: Giloy combats oxidative stress and chronic inflammation, both of which are linked to insulin resistance and diabetic complications. This helps reduce damage caused by free radicals and inflammation in diabetic patients.

Hepatoprotective Effects: It supports liver health, which is crucial for glucose metabolism, thereby aiding in better blood sugar control. ^[5]

Immune Modulation: Diabetes often weakens the immune system; Giloy's immunomodulatory effects help strengthen immunity, reducing susceptibility to infections common in diabetics.

Prevention of Diabetic Complications: Giloy may help prevent complications such as kidney damage (nephropathy) and diabetic foot ulcers through its antioxidant and anti-inflammatory actions.

Traditional and Practical Use:

Preparation: Fresh Giloy juice made by blending stems and leaves with water, often consumed in the morning on an empty stomach, is a common traditional remedy for diabetes management.

Dosage: Ayurvedic practice suggests taking Giloy powder about ½ teaspoon twice daily after meals, but it is essential to consult a healthcare provider for personalized advice.

3) Dalchini (Cinnamon) powder:

Dalchini has been studied for its potential benefits in managing diabetes, particularly type-2 diabetes.

Effects on Blood Sugar and Lipids:

Several studies have found that cinnamon intake can significantly reduce fasting blood glucose levels in people with type 2 diabetes. For example, consuming 1 to 6 grams of cinnamon daily for 40 days reduced fasting serum glucose by 18–29% compared to placebo groups. Cinnamon also lowers triglycerides (by 23–30%), LDL cholesterol (7–27%), and total cholesterol (12–26%) levels, which are important factors in reducing cardiovascular risk associated with diabetes. The beneficial effects on glucose and lipid levels persisted even after stopping cinnamon for 20 days, indicating sustained action.

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Mechanism of Action:

Cinnamon improves insulin sensitivity by activating insulin receptor kinase and inhibiting dephosphorylation of the insulin receptor, leading to enhanced insulin signaling. It activates glycogen synthase and inhibits glycogen synthase kinase-3β, promoting glucose uptake and storage. Cinnamon contains potent antioxidants that help reduce oxidative stress, which is linked to insulin resistance and diabetes complications

Additional Insights:

Cinnamon’s bioactive compounds include cinnamaldehyde, proanthocyanidins, catechins, coumarin, trans-cinnamic acid, and flavonoids, which contribute to its antidiabetic and anti-inflammatory effects. It may also positively influence the gut microbiome, promoting beneficial bacteria that aid glucose metabolism. Some studies suggest cinnamon supplements can help reduce blood glucose in prediabetic and overweight individuals, potentially preventing progression to diabetes.

4) Lactose:

Lactose is widely used as an *excipient* in tablet manufacturing, including antidiabetic medications, due to its *compressibility, stability, and compatibility* with active pharmaceutical ingredients (APIs). While specific antidiabetic formulations are not explicitly mentioned in the provided sources, the general pharmaceutical applications of lactose can be directly applied to this context:

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Key Roles of Lactose in Tablet Manufacturing:  

1. Compressibility and Binding: 

Lactose monohydrate is favoured for its ability to form sturdy tablets under compression, ensuring structural integrity during production and handling.^[7][8] This property is critical for maintaining consistent dosage forms, including antidiabetic tablets. 

2. Chemical Stability: 

Lactose exhibits low reactivity with APIs, reducing the risk of degradation or unwanted interactions ^[5][8]. This is particularly important for antidiabetic drugs, which often require precise dosing and stability over time. 

3. Low Hygroscopicity: 

Its minimal moisture absorption helps prevent tablet degradation in humid environments, ensuring shelf-life stability ^[5][8]. 

4. Solubility and Dissolution: 

Lactose dissolves readily in water, aiding rapid disintegration and bioavailability of the active ingredient—a critical factor for immediate-release antidiabetic formulations. ^[8] 

Considerations for Antidiabetic Tablets: 

Excipient Compatibility: Lactose is chemically inert, making it suitable for combination therapies common in diabetes treatment (e.g., metformin-based formulations, though specific compatibility would require formulation-specific testing). 

Patient Tolerance: While most antidiabetic tablets containing lactose pose minimal risk for lactose-intolerant patients (due to low lactose content), ^[3] severe intolerance or allergy may necessitate lactose-free alternatives. 

Limitations and Alternatives: 

Lactose Crystallization: While rare in solid dosages, excessive lactose in formulations can lead to texture issues (as seen in ice cream production), ^[1] though this is less relevant for tablets.   Alternative Excipients: For patients with lactose allergies, manufacturers might use cellulose derivatives (e.g., microcrystalline cellulose) or starch-based fillers. ^[3]

5) Starch:

Starch paste is a traditional yet effective binder in antidiabetic tablet manufacturing, particularly in wet granulation processes. Below is a structured breakdown of its roles, preparation, and formulation considerations:

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Key Functions in Antidiabetic:

1. Binding Agent: Starch paste (typically 5-10% concentration) binds powder particles into granules during wet granulation, preventing tablet defects like capping or lamination.^[8]

Mechanism: Forms a gel-like matrix when heated, creating cohesive granules under compression. ^[7]

Compatibility: Works with common antidiabetic APIs (e.g., metformin, glimepiride) without significant interactions

2. Disintegration Influence: While primarily a binder, native starch also contributes to tablet disintegration due to its swelling properties upon contact with water ^[3].

Balancing Act: Excessive starch paste can delay disintegration; formulators often pair it with super-disintegrants (e.g., croscarmellose sodium) for rapid-release antidiabetic tablets.^[6]

Preparation:

1. Slurry Formation: Mix starch (e.g., maize) in cold water to avoid lumping.^[5]

2. Gelatinization: Heat to 95°C to form a viscous paste ^[3].

3. Granulation: Blend paste with API-excipient mix, then dry at 45-50°^C

Fresh Use: Susceptibility to microbial growth necessitates immediate use post-preparation ^[3].

Formulation Considerations for Antidiabetic Tablets:

Low Binder (e.g., 5%): Risk of friability (as seen in glimepiride sublingual tablets). ^[5] High Binder (e.g., >10%): Hard tablets with delayed disintegration. ^[4]

Combination with Modified Starches:

Pregelatinized starch (partially pregelatinized) enhances compressibility in direct compression or hybrid processes ^{[5, 8]}.

Moisture Control:

Drying granules to 2-3% moisture prevents capping and ensures tablet hardness. ^[6]

ADVANTAGES:

Cost-Effectiveness: Cheaper than synthetic binders like povidone. ^{[3, 8]}

Versatility: Compatible with both herbal and synthetic antidiabetic formulations. ^{[4, 5]}

Drawbacks:

Requires precise temperature control during paste preparation.^[3]

Less efficient than modern binders (e.g., HPMC) for moisture-sensitive API’s.^[41]

6) Magnesium stearate:

Magnesium stearate plays a critical role in the manufacturing of antidiabetic tablets, primarily as a lubricant and flow aid. Its inclusion ensures efficient production, consistency, and stability of solid dosage forms. Below are its key functions and considerations specific to antidiabetic tablet formulations.

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Core Functions in Antidiabetic Tablet Manufacturing:

1. Lubrication and Anti-Adhesion:

Magnesium stearate reduces friction during tablet compression, preventing ingredients from sticking to machinery.^[1] This ensures smooth ejection of tablets and minimizes equipment wear, critical for high-volume production of antidiabetic medications like metformin or sulfonylureas.

2. Improved Powder Flowability:

By preventing clumping, it ensures uniform powder flow during blending and compression, leading to consistent tablet weight and dosage accuracy.^[2] This is vital for antidiabetic drugs requiring precise dosing for efficacy and safety.

3. Stability Enhancement:

Acts as a moisture barrier, reducing hygroscopicity and protecting active ingredients from degradation.^[5] This is particularly important for antidiabetic APIs sensitive to humidity or oxidation.

4. Compression Aid:

Facilitates uniform compaction, reducing tablet defects (e.g., capping or chipping) during manufacturing.^[4] However, excessive use (>5% concentration) can weaken tablet hardness and delay disintegration.^[5]

Key Considerations for Antidiabetic Formulations

Dissolution Impact: 

Over-lubrication can create a hydrophobic film, slowing drug dissolution.^[5] For antidiabetic tablets requiring rapid release (e.g., immediate-acting formulations), optimizing magnesium stearate concentration (typically 0.25–5%) is critical.^[3]

Compatibility with APIs: 

While generally inert, magnesium stearate may interact with specific antidiabetic compounds under certain conditions (e.g., moisture-sensitive drugs). Pre-formulation studies are essential to rule out incompatibilities.^[6]

Regulatory Compliance: 

Widely approved by global agencies (FDA, EMA) for use in solid dosages, ensuring safety and quality standards.^[2]

Advantages Over Alternatives:

Cost-Effectiveness: More affordable than specialty lubricants like sodium stearyl fumarate.^[3]

Versatility: Functions as a lubricant, anti-adherent, and flow agent, reducing the need for multiple excipients.^[6] 

Limitations:

Over-Lubrication Risks: Excessive use can compromise tablet hardness and dissolution rates, necessitating careful formulation balancing.^[7] Patient-Specific Concerns: Rare reports of hypersensitivity (unlikely at typical concentrations).^[6]

7) Silicon dioxide:

Silicon dioxide (SiO?) serves as a *multifunctional excipient* in antidiabetic tablet manufacturing, with critical roles in production efficiency and drug delivery enhancement. Below are its key applications and emerging advancements.

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Primary Functions in Tablet Manufacturing:

1. Glidant and Flow Aid:

Reduces interparticle friction, ensuring uniform powder flow during compression. This improves content uniformity and tablet weight consistency, critical for precise antidiabetic dosing (e.g., metformin or sulfonylureas). Typical usage: 0.5–2% of the total blend.^[7]

2. Anti-Caking Agent:

 Prevents clumping in hygroscopic formulations, particularly beneficial for moisture-sensitive APIs in antidiabetic tablets.^[5]

3. Moisture Control:

 Adsorbs trace moisture, protecting APIs from degradation and extending shelf life. This is vital for drugs prone to hydrolysis in humid environments.^[5]

4. Disintegrant Support:

While not a primary disintegrant, its inclusion can indirectly aid disintegration by improving porosity when combined with other excipients.^[1]

Emerging Applications in Antidiabetic Therapy:

Nano-Enabled Drug Delivery:  Silica nanoparticles (especially mesoporous types) enhance oral bioavailability of poorly soluble antidiabetic drugs (e.g., repaglinide) by improving dissolution rates and cellular uptake. They also enable glucose-responsive insulin delivery systems.^[6]

Stabilization of Sensitive APIs: Protects peptide-based antidiabetic drugs (e.g., GLP-1 analogs) from enzymatic degradation in the gastrointestinal tract.^[6] Advantages Over Conventional Excipients: Biocompatibility: Recognized as GRAS (Generally Recognized as Safe) by the FDA, with minimal toxicity concerns at standard concentrations.^[1] Versatility: Functions as a glidant, moisture scavenger, and nano-carrier, reducing the need for multiple excipients.^[5] Thermal/Chemical Stability: Maintains performance under high compression forces and diverse pH conditions.^[8]

METHODS:

The Powder form of herbal materials used are Durva, Gulvel, and Cinnamon, to formulate the tablet. ^{[4, 5]}

Excipients used to formulate tablets:

In this Formulation; Lactose, Starch, Magnesium stearate, and Silicon dioxide were used to compose the tablet. ^{[9, 10]} Now here is the table representing the Formula for composing the Tablets [weigh is for 100 tablets (where 1Tablet = 500 mg)].

Evaluation:

Angle of repose:

Angle of repose is defined as the angle that an inclined plane makes with the horizontal when a body placed on it just starts sliding, and is determined by the formula given below;

Tan θ = h/r

Where; h = height of powder cone formed

  r = radius of the powder cone formed. ^{[9, 10]}

Table: Relationship Between Angle of Repose (Θ) And Powder Flow.

Bulk Density:

Bulk density refers to the mass of a substance per unit volume, including the voids between its particles.

                    Bulk Density = MassBulk Volume  

Tapped Density:

Tapped density is a measure of how much a powder compacts when mechanically tapped, revealing its ability to fill spaces and achieve a higher density than its bulk density.

Tapped Density = MassTapped Bulk Volume

Compressibility Index [C.I.]:

The Compressibility Index, also known as Carr's Index, is a measure of how much a powder's volume decreases under pressure, indicating its ability to consolidate.

C.I. = Tapped Density - Bulk DensityTapped Density  × 100

In the pharmaceutical industry, the Carr's Index is used to predict powder behavior during processes like blending, granulation, and tableting, ensuring efficient and consistent manufacturing. ^[9,10] 

Table: Showing the C.I. with its flowability accordingly USP standard.

RESULTS:

The formulations developed via the wet granulation technique underwent comprehensive pre-formulation studies to assess their physicochemical properties and determine their suitability for subsequent tablet compression. All evaluated pre-formulation parameters are summarized in the table below:

Following the evaluation of pre-formulation parameters, the process was continued with tablet compression using the wet granulation method. After compression, the tablets were assessed for various physical parameters, the results of which are presented in the table below:

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Fig.: Label of the Herbal Tablet Formulated, with its Brand Name “DIABETA”