Formulation And Evaluation of Giloy Lozenges for Antidiabetic Activity

Diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose levels resulting from impaired insulin secretion, action, or both. It is a major global health concern, affecting millions of people worldwide and contributing to severe complications such as cardiovascular diseases, neuropathy, nephropathy and retinopathy. Conventional treatment methods rely on oral hypoglycemic agents and insulin therapy, which often come with adverse effects and limitations in long-term efficacy. As a result, there is a growing interest in natural remedies, particularly medicinal plants, for their potential role in diabetes management. Among various herbal remedies, Tinospora cordifolia (Giloy) has been extensively studied for its antidiabetic activity. Traditionally used in Ayurveda, this plant possesses a range of pharmacological properties, including antioxidant, immunomodulatory and hypoglycemic effects. The bioactive compounds present in T. cordifolia, such as alkaloids, flavonoids and glycosides, contribute to its ability to enhance insulin secretion, improve glucose uptake and regulate carbohydrate metabolism. Several studies have demonstrated the efficacy of T. cordifolia in lowering blood glucose levels in diabetic models, making it a promising candidate for herbal-based antidiabetic formulations.

Herbal lozenges represent an innovative and convenient dosage form for drug delivery. Lozenges offer several advantages, including prolonged contact time with the oral mucosa, improved bioavailability and ease of administration, making them suitable for long-term use in chronic conditions such as diabetes. The formulation of polyherbal lozenges containing T. cordifolia and other synergistic herbal extracts, such as Gymnema sylvestre, Pterocarpus marsupium and Acacia arabica, can potentially enhance therapeutic efficacy through multiple mechanisms of action. These herbs have been recognized for their ability to modulate glucose metabolism, stimulate insulin production and inhibit glucose absorption in the intestine. This study aims to develop and evaluate herbal lozenges incorporating T. cordifolia as a natural antidiabetic agent. The formulation will undergo various physicochemical tests, including hardness, friability, disintegration time and phytochemical characterization, to ensure stability and efficacy. Additionally, the pharmacological activity of these lozenges will be assessed to validate their potential role in diabetes management. The findings from this research could contribute to the development of an effective, safe and patient-friendly herbal formulation for controlling diabetes, offering an alternative to conventional synthetic drugs with minimal side effects.

1. 1. Medicinal Importance of Giloy (Tinospora Cordifolia)

Tinospora cordifolia, commonly known as Giloy or Guduchi, is a widely used medicinal plant in Ayurveda with a long history of therapeutic applications. Among its many pharmacological properties, Giloy is especially recognized for its potential in managing type 2 diabetes mellitus (T2DM), a chronic metabolic disorder characterized by insulin resistance, impaired insulin secretion and elevated blood glucose levels. Giloy contains a diverse array of bioactive constituents, including alkaloids (such as magnoflorine and berberine), diterpenoid lactones (like tinosporaside and cordifolide), flavonoids, steroids (β-sitosterol), glycosides, lignans and polysaccharides. These compounds are largely responsible for its antidiabetic, antioxidant, anti-inflammatory and immunomodulatory effects. Giloy’s antidiabetic action is mediated through multiple mechanisms. It has been shown to stimulate pancreatic β-cells, thereby enhancing insulin secretion, which is beneficial in early-stage T2DM. It also improves insulin sensitivity in peripheral tissues by increasing glucose uptake through the upregulation of glucose transporter type 4 (GLUT4). Furthermore, Giloy inhibits the digestive enzymes α-amylase and α-glucosidase, slowing down carbohydrate digestion and reducing postprandial blood glucose spikes. Its antioxidant properties, driven by the presence of flavonoids and polyphenols, help to neutralize free radicals and protect pancreatic β-cells from oxidative damage, thereby supporting insulin production and function. Additionally, its anti-inflammatory action reduces pro-inflammatory cytokines such as TNF-α and IL-6, which are implicated in insulin resistance. Another important mechanism involves the regulation of hepatic gluconeogenesis. Giloy downregulates enzymes like glucose-6-phosphatase and phosphoenolpyruvate carboxykinase (PEPCK), reducing glucose production in the liver. It also improves lipid profiles by lowering total cholesterol, triglycerides and LDL cholesterol while increasing HDL levels, thereby reducing cardiovascular risks associated with diabetes. Preclinical studies on diabetic animal models have consistently demonstrated a significant reduction in fasting blood glucose and improvements in insulin levels and oxidative stress markers. Clinical studies, though limited, also suggest that Giloy supplementation can reduce fasting blood sugar, postprandial glucose and HbA1c levels, with some studies showing improved overall metabolic function and patient well-being. In terms of safety, Giloy is generally considered non-toxic when used at recommended doses. However, prolonged or excessive use should be approached with caution, particularly in individuals with autoimmune conditions due to its immune-stimulating effects.Giloy acts—enhancing insulin secretion, improving insulin sensitivity, inhibiting carbohydrate digestion, reducing oxidative stress and inflammation and improving lipid metabolism—makes it a highly promising natural therapeutic agent for the management of type 2 diabetes. Further clinical trials and standardization of extracts are necessary to fully validate its therapeutic efficacy and integrate it into mainstream diabetic care.

1. DRUG PROFILE

Tinospora cordifolia, commonly known as Giloy or Guduchi, is a well-known medicinal plant in Ayurveda, revered for its broad-spectrum therapeutic properties. It is a large, deciduous climbing shrub belonging to the family Menispermaceae. The stem is the most widely used part of the plant and contains a variety of bioactive compounds, including alkaloids, diterpenoid lactones, glycosides, steroids and polysaccharides. Giloy is traditionally used as an adaptogen and immunomodulator, helping the body resist stress and infections. It possesses potent antidiabetic, antioxidant, anti-inflammatory and hepatoprotective properties. In the context of type 2 diabetes, Giloy has demonstrated the ability to enhance insulin sensitivity, modulate glucose metabolism and reduce oxidative stress. Due to its natural origin and broad pharmacological profile, Giloy is considered safe and effective when used appropriately and is commonly formulated into extracts, tablets, syrups and lozenges for therapeutic use.

1. 1. Botanical Description of Giloy (Tinospora cordifolia)

Fig. no. 1. Giloy (Tinospora Cordifolia)

• Scientific Name: Tinospora cordifolia
• Common Names: Giloy, Guduchi, Amrita
• Family: Menispermaceae
• Synonyms: Tinospora malabarica, Menispermum cordifolium
• Plant Type: Perennial deciduous climbing shrub
  2. Active Constituents

Tinospora cordifolia is rich in diverse phytochemicals that contribute to its wide range of therapeutic effects. Key constituents and their associated medicinal uses include:

1. Alkaloids (e.g., tinosporine, magnoflorine, palmatine): These compounds exhibit antimicrobial, antipyretic, anti-inflammatory and anxiolytic properties. Palmatine, in particular, has been noted for its hepatoprotective effects.
2. Diterpenoid Lactones (e.g., tinosporide, cordifolide): These constituents have demonstrated antidiabetic effects by enhancing insulin secretion and glucose utilization. They also possess anti-inflammatory and immunomodulatory activities.
3. Glycosides (e.g., giloin, tinocordiside): These compounds contribute to the plant's antioxidant and immunostimulatory properties, enhancing phagocytic activity and supporting immune modulation.
4. Steroids (e.g., β-sitosterol): Known for their anti-inflammatory and cholesterol-lowering effects, β-sitosterol also supports joint health and cardiovascular function.
5. Polysaccharides (e.g., arabinogalactan-type polysaccharides): These are responsible for Giloy’s strong immunomodulatory and anti-stress activities, stimulating macrophages and natural killer (NK) cell functions.
6. Flavonoids (e.g., quercetin, rutin): These potent antioxidants reduce oxidative stress, improve capillary strength, reduce inflammation and offer cardioprotective benefits.
   3. Pharmacological Properties

Tinospora cordifolia has been extensively studied for its wide range of pharmacological activities, many of which support its traditional use in Ayurveda:

5. Antidiabetic Activity: The plant enhances insulin secretion and sensitivity, modulates glucose metabolism and reduces oxidative stress in pancreatic beta cells.
5. Immunomodulatory Effects: It stimulates macrophage function, enhances natural killer (NK) cell activity and increases the production of cytokines like IL-1, IL-6 and TNF-α, supporting recovery from immune deficiencies and infections.
5. Antioxidant Properties: Giloy scavenges free radicals, protects cellular components from oxidative damage and enhances levels of endogenous antioxidants like superoxide dismutase (SOD), catalase and glutathione.
5. Anti-inflammatory Effects: It inhibits pro-inflammatory mediators such as COX-2 and prostaglandins, making it useful in chronic inflammatory conditions like arthritis.
5. Hepatoprotective Activity: The plant protects liver tissue from toxic injury (e.g., due to carbon tetrachloride or alcohol) and stimulates liver enzymes involved in detoxification.
5. Antipyretic and Antimicrobial Actions: Giloy reduces fever by acting on hypothalamic centers and is effective against gram-positive and gram-negative bacteria, as well as some fungi.
5. Adaptogenic and Anti-stress Benefits: It enhances physical endurance, modulates cortisol and stress response pathways and increases resistance to stress.
5. Anticancer Potential: Investigational studies suggest that Giloy induces apoptosis in cancer cell lines and modulates immune surveillance in experimental models.

3.  MATERIALS AND EQUIPMENTS

3.1Materials

The ingredients used for the formulation of giloy lozenges (balanced formulation) are listed below:

3.2 Equipment

• Weighing Balance
• Hot Plate
• Beaker
• Stirrer
• Soxhlet Apparatus
• Mold

4.  METHODOLOGY

4.1 Extraction of Giloy

The extraction of Tinospora cordifolia (giloy) was performed using the Soxhlet extraction method, which is suitable for obtaining concentrated plant extracts.

1. Preparation of Giloy Powder:

Dried stems of giloy were cleaned, coarsely powdered using a grinder and sieved to obtain uniform particle size.

2. Soxhlet Assembly Setup:

A standard Soxhlet apparatus was assembled, consisting of a round-bottom flask, Soxhlet extractor and a condenser.

3. Loading the Sample:

10 g of giloy powder was placed in a thimble and inserted into the main chamber of the Soxhlet extractor.

4. Solvent Selection and Extraction:

Ethanol was chosen as the extraction solvent due to its polarity and efficiency in extracting bioactive constituents. A 1:10 ratio of powder to ethanol was used (i.e., 100 mL ethanol for 10 g powder). The solvent was heated and its vapors condensed and repeatedly passed through the plant material for continuous extraction.

5. Completion of Extraction:

The process continued for several cycles until the solvent in the siphon tube appeared colorless, indicating complete extraction.

6. Concentration of Extract:

The ethanolic extract was collected and evaporated under reduced pressure to remove the solvent, yielding a semi-solid concentrated extract. The extract was then stored in an airtight container for formulation.

Fig. no. 2. Giloy Extraction by Soxhlet Apparatus

4.2 Formulation of Giloy Lozenges

The lozenges were prepared by the fusion method, which involves melting and molding the ingredients into the desired shape.

1. Weighing of Ingredients:

All required ingredients—sorbitol (7.2 g), acacia gum (1.92 g), citric acid (0.16 g), magnesium stearate (0.04 g) and giloy extract (1.12 mL)—were accurately weighed using a digital weighing balance.

2. Melting Base Material:

Sorbitol was used as the base and melted on a hot plate using a clean, dry beaker. The temperature was maintained to avoid overheating and degradation.

3. Incorporation of Excipients:

After complete melting of sorbitol, acacia gum was added slowly with constant stirring to ensure uniform mixing. Citric acid and magnesium stearate were then incorporated sequentially, ensuring even distribution in the molten mass.

4. Addition of Giloy Extract:

Once the base and excipients were homogeneously mixed, the giloy extract was added to the mixture with thorough stirring to ensure uniform distribution of the active ingredient.

5. Molding the Lozenges:

The molten mixture was poured into pre-lubricated molds to form lozenges of uniform size and shape.

6. Cooling and Solidification:

The molds were kept undisturbed at room temperature for approximately 4 hours to allow the lozenges to cool and solidify.

7. Demolding and Storage:

After solidification, the lozenges were carefully removed from the molds and stored in airtight containers to protect them from moisture and environmental degradation.

Fig. no. 3. Giloy Lozenges Formulation

0. 5. EVALUATION
1. Organoleptic Evaluation

Organoleptic properties include the sensory characteristics of the lozenge such as color, taste, odor, shape and texture. These attributes play a significant role in consumer acceptance and compliance, especially for long-term use in chronic conditions like diabetes. The color should be uniform and aesthetically acceptable, the taste should be palatable (often masked with sweeteners or flavors) and the odor should be pleasant or neutral. Texture and mouthfeel also influence user experience, with a preference for smooth, non-gritty formulations. For herbal lozenges containing bitter ingredients like Giloy, organoleptic optimization through flavoring agents and sweeteners is essential to ensure continued patient use and adherence.

2. Hardness

Hardness is a critical quality control parameter that assesses the mechanical strength of Giloy lozenges. It determines the force required to break the lozenge and ensures it is robust enough to withstand manufacturing, handling and packaging processes. The test is typically carried out using Monsanto or Pfizer hardness testers, where the lozenge is placed between two anvils and pressure is applied until it breaks. An optimal hardness for lozenges lies between 4 to 10 kg/cm², providing a balance between structural integrity and sufficient dissolution time in the oral cavity. For diabetic patients, a firm lozenge allows a gradual release of the active herbal compounds, such as tinosporaside, which supports sustained glycemic control.

3. Friability

Friability measures the ability of the lozenges to resist crumbling under mechanical stress. This test evaluates the physical stability of the dosage form and is vital for ensuring that lozenges maintain their integrity during handling and transportation. The test is performed using a Roche friabilator, where a set number of lozenges are rotated at 25 rpm for 4 minutes. The weight loss after tumbling is recorded and a maximum acceptable limit is usually less than 1%. A friable lozenge can result in dosing inconsistencies and reduced consumer confidence. In diabetic care, where precision in active ingredient delivery is essential, low friability is a must.

4. Disintegration Test

Although Giloy lozenges are intended to dissolve slowly in the mouth, disintegration testing provides insights into how they break down under simulated physiological conditions. The test is conducted using a USP disintegration apparatus in a medium such as phosphate buffer (pH 6.8) or simulated saliva, maintained at 37 ± 0.5°C. The time taken for the lozenge to disintegrate into smaller particles is recorded. An acceptable disintegration time ranges from 10 to 30 minutes, depending on the hardness and formulation. This controlled disintegration ensures the lozenge remains effective over time and provides a steady release of active ingredients, which is especially valuable for diabetic individuals.

5. Dissolution Test

The dissolution test determines the rate and extent of drug release from the lozenge into a dissolution medium, which mimics the oral environment. It is carried out using USP Type I (basket) or Type II (paddle) apparatus at 100 rpm and 37°C, with media such as phosphate buffer or simulated saliva. Samples are collected at various intervals—5, 10, 15, 30, 45 and 60 minutes—and analyzed using UV-Visible spectrophotometry. A satisfactory formulation should release at least 80% of the active constituents within 30 to 45 minutes. This predictable release is essential for maintaining therapeutic consistency, particularly for managing blood glucose levels in diabetic patients.

6. pH Determination

The pH test as s esses the acidity or alkalinity of the lozenge when dissolved in water. A suitable pH is essential for the comfort and safety of the user, especially considering the sensitive mucosal tissues in the oral cavity. The test involves dissolving one lozenge in 10 mL of distilled water and measuring the pH with a digital pH meter. The ideal range for oral lozenges is between 5.5 and 7.5, which closely resembles the natural pH of saliva. Maintaining a near-neutral pH ensures user comfort and protects oral tissues, especially important for diabetics who are more prone to oral sensitivity and infections.

7. Weight Variation Test

Weight variation is conducted to ensure each lozenge contains a uniform amount of the active ingredient and excipients. It is a basic but essential quality control parameter for solid dosage forms. The test involves weighing 20 individual lozenges and comparing the individual weights to the average. According to pharmacopeial standards, the acceptable deviation depends on the total weight of the lozenge. Typically, for lozenges weighing more than 250 mg, the permissible deviation is ±5%. Uniformity in weight is particularly critical in diabetic lozenges, where precise dosing of herbal constituents like Giloy extract is needed for effective glycemic management.

1. 6. RESULT AND DISCUSSION

The evaluation of the Giloy lozenges revealed that all three formulations showed acceptable organoleptic and physical characteristics, making them suitable for oral administration. Each batch displayed good consistency in appearance, taste, and shape, indicating uniform formulation. Mechanical strength and friability tests confirmed that the lozenges could withstand handling and packaging without breaking. Disintegration and dissolution assessments showed effective breakdown and release of the active herbal components, essential for therapeutic efficacy. The pH levels were within the acceptable range for oral use, and the weight variation test demonstrated consistency across batches. Overall, the results indicated that the lozenges were pharmaceutically acceptable and potentially effective for antidiabetic application.

Table no. 3. Evaluation Parameters-Results