Formulation And Evaluation Of Soft Medicated Jellies For Treatment Of Vitamin B12 Deficiency

Oral medicated jelly may be more advantageous than other traditional dose forms due to its quick start of action, ease of use, and better patient compliance. This type of formulation is a great substitute for traditional methods of administering medication to younger patients. Elderly patients benefit greatly from both solid and liquid dosage forms because the former stay solid in storage, contributing to the stability of the dosage form, and the latter change into a liquid state in a matter of seconds to minutes after administration. Thus, oral jellies have a huge potential for becoming the primary delivery route for most medications in the near future. The advantages of these prepared jellies include enhanced bioavailability by skipping the first pass metabolism.  Jellies were prepared by dispersing the gelling agent in water. Many medicinal drugs are absorbed through the mouth mucosa. For medications that have a high buccal absorption rate, dosage forms such as Medicated Jelly and Chewing Gums provide for faster therapeutic effect than oral dose forms. Parents have responded positively to the use of medicated jelly in children with full dentitions. The use of medicated jelly is possible for both the local treatment of systemic disorders and oral cavity ailments. Jellies can be made from natural ingredients or synthesized versions of natural substances

Classification Of Jellies: [2]

1. Medicated Jelly:

These are mostly utilized on the mucous membranes and skin, and they have spermicidal, local anaesthetic, and antibacterial characteristics. These jellybeans are sufficiently filled with water to evaporatively provide a localized cooling effect and residual film protection.  Example: Ephedrine sulphate jelly is used to seize the bleeding of nose since it is vasoconstrictor. 

2. Lubricating Jelly:

These jellies are meant to lubricate diagnostic equipment such as surgical gloves, catheters, and cystoscope. 

3. Miscellaneous Jelly:

These are meant for various uses, such as electrocardiography and patch testing.

Ideal Characteristics of Jelly: [3]

• It should melt or disintegrate within seconds of being administered in the mouth.
• There should be no aftertaste in the mouth following administration.
• It should be suitable for flavour masking.
• High drug loading should be feasible.
• It shouldn't be breakable or delicate when being transported.
• When exposed to varying external circumstances, such as variations in temperature and humidity, it should remain stable. Production and packaging costs should be economical. 
• Excipients utilized should be inert, safe, and compatible with the other ingredients. 

Advantages: [3]

• All the medicated jellies have a good mouth feel property. 
• Easy to administer and handle.
• Quick distribution of the medication and a quick start to its effects. 
• It has improved the medication's bioavailability and speed of absorption from the pre-gastric area, which includes the pharynx, oesophagus, and mouth. 
• There is no chance of asphyxia or suffocating, enhancing safety.
• Permits substantial drug loading.
• When compared to other traditional dosage forms, manufacturing time is reduced.
• Jelly for oral use has strong chemical stability.  
• Terminating therapy is easy and may be done at any moment.

Introduction to oral cavity:

• The arch produced by teeth and gums easily divides the mouth cavity into the following parts:
• Oral vestibule - Lies between gums and teeth.
• Oral cavity proper - Lies behind and within the arch of teeth.

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Saliva:

• Saliva is a biological fluid that circulates in the mouth cavity.
• It is a complicated fluid generated by a number of specialized glands and discharged into the mouth cavity.
• Salivary glands generate 90%–95% of the saliva, whereas 100 smaller salivary glands on the oral mucosa create the remaining 5%–10%.
• Saliva includes proteins as well as electrolytes.
• Saliva has a pH of 6.5–7.5.
• In adults, 500–1500 ml of saliva is generated every day on average. 

MATERIALS AND METHODS:[4]

Excipients used in jellies:

1. Sugar:

The white substance we know as sugar is sucrose; like other compounds composed of these three components, sugar is a carbohydrate. It occurs naturally in most plants, including sugarcane and sugar beets.

2. Gelling agents:

Gelling agents are chemicals that create a weakly cohesive internal structure when dissolved in a liquid phase as part of a colloidal mixture. They are organic hydrocolloids or hydrophilic inorganic compounds like gelatin, pectin, and agar.

3. Glucose Syrup:

Glucose syrup, often known as confectioner's glucose, is a liquid sweetener that is well tolerated and highly flexible. Glucose is sugar. It produces elongated chains of carbohydrates that tangle and prevent the other sugars from crystallizing, giving jelly sweets its transparent look.

4. Purified Water:

The universal and primary solvent that you will use in combining all the components for manufacturing jellies. The proportions of water that you add to the mixture for a perfect mixture. It is also the key lubricating element that helps to make the jellies softer.

5. Flavours:

To give Jelly Candy a diverse mouthfeel of flavours. You may also manufacture several flavours of jelly candy, such as orange, raspberry, cherry, grape, pineapple, strawberry, and lemon, among others.

6. Flavours:

To give Jelly Candy a diverse mouth feel of flavours. You may also manufacture several flavours of jelly candy, such as orange, raspberry, cherry, grape, pineapple, strawberry, and lemon, among others.

7. Citric Acid:

Citric acid is a key element in jelly candies that helps to awaken the flavour. It comes from citrus fruits and juices. It also acts as a preservative, extending the shelf life of jelly sweets.

Method of Preparation:[1]

Preparation Of Sugar Syrup: [According to I.P. 2007, sugar syrup (33.4% w/w)]

1. 33.4 grams of sugar was accurately weighed on a digital electronic balance and transferred to a 250 mL beaker.
2. 16.6 g of water were gradually added to it while stirring continually, and it was then heated over a heating mantle to produce a supersaturated sugar syrup solution.

Preparation Method of Jelly:

1. All the components were precisely weighed using a computerized weighing scale.
2. Sugar syrup was made in one beaker by combining 67.7 grams of sugar and 100ml of water.
3. To get the appropriate firmness, a gelling agent was added to that mixture, stirred continuously, and heated until it dissolved.
4. Once the gelling ingredient has completely dissolved, add the stabilizer and citric acid and stir again to improve the jelly's softness and preserve pH, respectively. Boil for a few minutes.
5. After boiling the aforesaid solution, the preservative will be added to it, completely and consistently combined.
6. Now, the medication is precisely weighed, dissolved in an appropriate medium, added before the jelly sets, and well mixed.
7. The entire mixture was then poured into the moulds, and the moulds were properly covered to keep the outside environment out while the solution cooled and settled.

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Batch Optimization:

Table 1: Batch Optimization

Organoleptic Properties/Sensory Evaluation:

1. The scientific field of sensory assessment of jellies is based on the principles of experimental design and statistical analysis.
2. It makes use of taste, smell, sight, and touch senses. When participants evaluate a product, their answers are recorded to facilitate sensory assessment.
3. The answers from the volunteers would provide further information and conclusions about the tested product following a comprehensive investigation.
4. The texture of jelly was distinguished from other parameters such as colour, appearance, smell, and texture using a sensory test based on the 5-point rating system.
5. All participants were given complete instructions about the formulation, including the fact that it included no hazardous chemicals. Following that, all participants were ready to sample the product with their own consent.
6. Participants were told to provide a rating of excellent (more intense) to bad (least intense) in each of the attributes depending on their opinion.
7. A survey was conducted among volunteers using the Google form link to assess the organoleptic qualities of Vitamin B12-medicated jellies.

Weight Uniformity:

The goal is to keep the fill weight of jellies within a specific range. The main goal of this test is to assure proper dosage delivery. Mass uniformity was implemented to guarantee that each jelly had the appropriate amount of medication. Following steps were conducted for performing weight uniformity:

1. Select 10 jellies.
2. Weighing each of 10 jellies separately with an analytical balance. 
3. Then calculating the average weight of jellies.
4. Calculate standard deviation (SD).

Drug and ingredients compatibility studies:[13]

Jelly was made by combining the medication with polymers. There is a possibility of chemical interaction, which might lead to Mecobalamin breakdown. Hence The FTIR method was used to test medication compatibility with polymers. FTIR was performed using a KBr disk in the region of 4000-400 cm-1.

Moisture Content Test: [14]

1. The moisture content of jelly formulations is determined using the loss on drying technique.
2. Turn on the hot air oven to preheat, then adjust the temperature to 30 ºC.
3. Weight the initial weight of jellies at 0 hr.
4. Place the jelly samples in a hot air oven.
5. After a while, weigh the jellies and record the final weight.
6. Calculate the % loss of moisture using the mathematical formula:

 %Loss On Drying = [W1-W2] * 100

W1

Measurement Of pH:[15]

The stability and taste of oral jellies are influenced by the formulation's pH. The pH of the produced jellies was determined using a digital pH meter at room temperature (25°C ± 5°C). For this purpose, 0.5 g of jelly was dissolved in 50 mL of distilled water to create a 1% solution, and the pH was recorded. Following are the steps involved in the process:

1. Rinse the pH electrode thoroughly with distilled water before beginning of any pH measurements.
2. Avoid rubbing the lightbulb since this may lead to a build-up of static charge. To avoid contamination, the rinse procedure needs to be carried out in between each sample.
3. While swirling, dip the pH electrode into the sample. It is necessary to maintain the same stirring speed as during calibration. 
4. Wait for the measurement to stabilize, which should take less than 60 seconds for most samples, and then record the pH.

Stability Studies:[14]

Stability investigations of produced jelly at room temperature (25 °C ± 5 °C, -35 °C). The stability investigations were conducted for three weeks, and the formulations were examined for changes in physical parameters such as appearance and pH.

Syneresis: [16]

Syneresis is the contraction of the gel during storage, resulting in the separation of water from it. It is more noticeable in gels where smaller amounts of gelling chemicals are used.

 All jellies were examined for syneresis at room temperature (25 °C ± 5 °C) and 8 °C ± 1 °C.

In Vitro Dissolution Study: [17]

To conduct the dissolve test, 100 ml of pH 6.8 buffer was added to a 100 ml dissolution flask, and jelly was placed inside. The paddle was rotated at 50 rpm, and the temperature was kept at 37±1ºC. 1 ml aliquots were withdrawn at 5, 10, 15-, 20-, 25-, and 30-minutes intervals, with an equivalent volume of dissolution medium added to the dissolution flask after each withdrawal. The filtered samples were diluted and spectrophotometrically measured at 253 nm.

The FTIR method was used to test medication compatibility with polymers. FTIR was performed using a KBr disk in the region of 4000-400 cm-1.

       
           
       
    Fig 3. FTIR Result of Mecobalamin and Sugar

       
       
           
       
    
    Fig 5. FTIR Result of Mecobalamin and Citric Acid

Table 4: Drug and ingredients compatibility studies

Moisture Content Test:

Table 5: Moisture Content Test

Measurement Of pH:

Table 6: pH value

In Vitro Dissolution Study:

Table 7: In Vitro Dissolution Study
       
           
       
    

Table 8: Stability study data of the prepared formulation