Development and Evaluation of Ficus carica and Annona reticulata Fruit-Enriched Polyherbal Nutraceutical Jelly for Immune Support

1. Drug: Lemon ,Dry Ginger, Black Pepper, Tulsi, Turmeric, Cinnamon, Ashwagandha, Beetroot , Fig Fruit Powder, Annona reticulata Fruit Powder.⁽³⁾
2. Gelling agent: Hydrocolloids are widely used in the preparation of gel-like matrices because of their ability to form stable and flexible gel structures. When these gelling agents are dispersed in a liquid medium, they hydrate and create a three-dimensional network that imparts the formulation its characteristic gel consistency. Owing to their excellent gelling, thickening, and stabilising properties, hydrocolloids are commonly employed in pharmaceutical, food, and cosmetic products.

1. Sodium Alginate: Sodium alginate is a natural polysaccharide widely used as a gelling, thickening, and suspending agent in various pharmaceutical formulations, including gels, lotions, and pastes. It is also widely used in food and cosmetic products for its biocompatibility and ability to enhance product texture and stability.
2. Pectin: Pectin is a naturally occurring polysaccharide that serves as an effective gelling agent and is valued for its low cost and biodegradability. In pharmaceutical applications, it is used in colon-targeted, mucoadhesive, gastroprotective, and controlled-release drug delivery systems. Additionally, pectin is employed as a stabiliser and thickening agent in cosmetic and food formulations.
3. Gelatin: Gelatin is one of the most commonly used gelling agents in pharmaceutical preparations. It is extensively utilized in the manufacture of capsules, medicated jellies, cosmetic products, and photographic emulsions. Due to its biocompatibility and biodegradability, gelatin is also employed in controlled and implantable drug delivery systems, where it serves as a matrix for the sustained release of active ingredients.
4. Carrageenan: Carrageenan is a natural polysaccharide derived from red seaweed and is widely used as a vegetarian alternative to gelatin in food and pharmaceutical formulations. It possesses excellent gelling, thickening, and stabilising properties. which contains three sulfate groups and functions primarily as a thickening agent rather than a gelling agent.

3. Sweeteners: Sweetening agents are added to formulations to improve palatability and patient acceptance. This is especially important in pediatric dosage forms. Sucrose is commonly used, often combined with saccharin to enhance sweetness and limit crystallisation. Dextrose, about 70% as sweet as sucrose, is used similarly. Sorbitol, at about 60% of sucrose's sweetness, has various functions. It is a sweetener, humectant, thickening agent, and excipient for soft gelatin capsules. Sorbitol also serves as a laxative and may help manage hyperkalemia.
4. Colouring agent: Coloring agents are added to pharmaceutical formulations to improve visual appeal and patient acceptance. They help keep a uniform appearance when different colored raw materials are used. Coloring agents complement flavor and overall product looks. They also aid product identification and differentiation, reducing medication errors. Common colorant categories include FD&C (Food, Drug, and Cosmetic) colors, D&C (Drug and Cosmetic) colors, and other approved coloring agents.
5. Preservatives: Preservatives holds an essential role in maintaining the stability and shelf life of pharmaceutical formulations by preventing microbial growth and minimizing potential incompatibilities among formulation components. They are particularly important in aqueous and gel-based preparations, where microbial contamination can occur during storage. Preservatives are widely used in formulations containing cellulose derivatives and other hydrocolloids to ensure product safety and quality. Frequently used preservatives include benzoic acid, benzalkonium chloride, methyl paraben, propyl paraben, and chlorhexidine acetate.
6. Flavouring Agents: Flavouring agents are added to improve the taste and overall acceptability of pharmaceutical formulations, especially those intended for pediatric and geriatric patients. The selection of an appropriate flavour is based on the inherent taste of the active ingredients and the impact of the flavour on the formulation’s organoleptic and therapeutic properties. Different flavours are used to mask specific tastes and enhance palatability. For example, lemon, orange, grapefruit, and cherry flavours are commonly used to complement acidic-tasting formulations, while orange, anise, and lemon flavours are effective in masking bitter tastes. The careful selection of flavouring agents contributes significantly to patient compliance and product acceptance.
7. Stabilising Agents: Stabilisers are incorporated into pharmaceutical formulations to maintain their physical, chemical, and organoleptic properties throughout the product's shelf life. In jelly formulations, stabilisers help retain moisture, prevent drying or shrinkage, and preserve the desired texture and consistency. Commonly used stabilisers include sorbitol and propylene glycol, which also function as humectants by reducing moisture loss and improving product stability.
8. Chelating Agents: Chelating agents are added to formulations to prevent undesirable interactions between formulation components and trace metal ions that may be present in raw materials or during manufacturing. These metal ions can catalyse degradation reactions, affecting the stability and efficacy of the product. Ethylenediaminetetraacetic acid (EDTA) is a widely used chelating agent that binds to heavy metal ions, thereby enhancing the stability and shelf life of the formulation.

Procedure:

1. Accurately weigh all the required ingredients, namely dry ginger (1.5 g), black pepper (500 mg), tulsi (2.5 g), turmeric (0.4 g), cinnamon (2 g), ashwagandha (1.5 g), fig fruit powder (2 g), and Annona reticulata fruit powder (2 g).
2. Add dry ginger, black pepper, tulsi, turmeric, cinnamon, and ashwagandha to 50 ml of distilled water and heat gently, continuously, to prepare a herbal decoction.
3. Continue heating till the volume level is lowered to approximately 25 mL (50% of the original volume) to obtain a concentrated decoction.
4. Filter the decoction and allow it to cool slightly. Add fig fruit powder (2 g), Annona reticulata fruit powder (2 g), lemon juice (2.5 mL), and beetroot juice (2.5 mL) to the concentrated decoction and mix thoroughly.
5. Prepare a simple sugar syrup by dissolving the required quantity of sugar in distilled water with gentle heating.
6. Add gelatin (4 g) to the warm sugar syrup and stir continuously until completely dissolved, forming a clear gel base.
7. Add suitable stabilisers (e.g., sorbitol or propylene glycol) to the gelatin-sugar mixture and mix uniformly.
8. Slowly add the concentrated polyherbal decoction to the gelatin base with continuous stirring to ensure uniform distribution of all ingredients.
9. Add a suitable preservative (e.g., methyl paraben) and mix thoroughly until a homogeneous solution is obtained.
10. Pour the prepared jelly mixture into clean and dry moulds.
11. Allow the moulds to cool at ambient temperature and then refrigerate until complete gelation occurs.
12. Remove the jellies from the moulds and store them in airtight containers for further evaluation.

Evaluation parameters:

1. Appearance: The appearance of the medicated jelly was evaluated visually for its color, texture, thickness and overall aesthetic acceptability.⁽⁴⁾

2. pH Determination: The pH of the formulated jellies was measuredusing  digital pH meter at room temperature (25 ± 5°C). A 1% jelly solution was prepared in 25 mL of distilled water, and the pH was recorded.⁽⁵⁾

3. Stickiness and grittiness: The texture of the medicated jelly was evaluated by gently rubbing it between two fingers to assess its smoothness and stickiness.⁽⁶⁾

4. Viscosity: The viscosity  is measured using a Brookfield viscometer (LV type). Since the mechanism is non-Newtonian, spindle number 63 is employed. The viscosity was measured at room temperature (25°C ± 5°C ) during a period of two minutes at 50 rpm.⁽⁷⁾

5. Spreadability: The concentration of  gelling agent significantly influences the spreadability of oral jellies. It was measured by placing a known quantity of jelly between two glass plates and recording the time taken for the plates to separate under a fixed weight.⁽⁸⁾

S=W×L/T

Where, S = spreadability,

W = weight tide to upper side

L= Length of glass slide

T= time required to separate 2 slides.

6. Syneresis: Syneresis is the contraction of the gel during storage that results in the separation of water from the gel. It is more pronounced in gels with low concentrations of gelling agents. All jellies are tested for syneresis at 25 °C ± 5 °C and 8 °C ± 1 °C.⁽⁷⁾

7. Drug Content / Content Uniformity: One medicated jelly of formulation is dissolved in 50 ml phosphate buffer pH 6.8 to make a solution of 100 µg /ml and spectrophotometric analysis is done.⁽⁷⁾

1. In vitro drug release / Dissolution Study : In vitro dissolution profile of the drug was studied using USP paddle type II apparatus. The dissolving medium consisted of 900 mL of distilled water. Then, release study was carried out at 50 rpm and temperature 37°C ± 5°C. Samples (1 ml) were taken every 5 minutes. phosphate buffer pH 6.8 in equal volume was used instead of the sample. The drug content of the samples was measured by UV visible spectrophotometer. The absorbance was measured and the percentage of the drug release was calculated.⁽⁹⁾