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International Research Journal of Plant Science

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Research Article - International Research Journal of Plant Science ( 2022) Volume 13, Issue 5

Formulation And Development Of Herbal Jelly From Papaya Seeds For Anthelmintic Infection

Mrynal Chamoli1* and Shaffi Khurana Tangri2
 
1School of Pharmaceutical Sciences, SGRR University, Dehradun, India
2Assistant Professor, School of Pharmaceutical Sciences, SGRR University, Dehradun, India
 
*Corresponding Author:
Mrynal Chamoli, School of Pharmaceutical Sciences, SGRR University, Dehradun, India, Email: mrynal088@gmail.com

Received: 29-Sep-2022, Manuscript No. 77297; Editor assigned: 01-Oct-2022, Pre QC No. 77297; Reviewed: 15-Oct-2022, QC No. 77297; Revised: 20-Oct-2022, Manuscript No. 77297; Published: 27-Dec-2022, DOI: http:/dx.doi.org/10.14303/irjps.2022.031

Abstract

Papaya seeds are claimed to possess anthelmintic property in traditional system of medicines. Papaya seeds extract was incorporated in the jelly which is administered orally without water. The oral jelly was prepared by heating method by using various polymer with different concentration. As the extract was bitter in taste so taste masking is important parameter while designing the dosage forms, it is mainly done by adding sweeteners and flavors.

Keywords

Medicated jelly, Taste masking, Anthelmintic property, Gelling agents.

Introduction

Tropical plant Carica papaya Linn. A member of the Brassicales family and a member of the Caricaceae, is widely cultivated in tropical and subtropical regions. It is one of the most fertile fruits, the whole papaya includes the leaves, roots, barks, peels and seeds have the biological processes that include antioxidants, anti- inflammatory, anti-cancer, anti-bacterial and anti- fungal activity.( Gathuma et al., 2004), (Mhaskar et al., 2000), (Gill 1992), (Manivannan et al., 2009), (Adebiyi & Adaikan 2005), (Verma et al., 2006), (Cuña et al., 19997). The papaya fruits are tasty and healthy. Numerous amino acids and trace elements are present, Benzyl isothiocyanate (BITC), an active compound of papaya fruit, is an isothiocyanate (ITC). ITC are widely distributed naturally in cruciferous plant, including broccoli, watercress, and Brussels sprouts, cabbage, cauliflower, and sprouts. There are report of them, to possess qualities that benefit human health. These days BITC has also developed into a hub for its actions that are antibacterial, anticancer, and other. In 2017, in papaya, or study discovered that BITC had antifungal properties against Candida spp. In the course of ripening, papaya seeds and pulp undergo transformation.

The nutritional value and the action components of BITC are both significant. The amount of BITC present in papaya fruits must be closely monitored, Chromatography is the primary method used at the moment of analysis BITC in papaya fruits. In order to accomplish the goal of this approach, sample are often pretreated before examination technique such concurrent distillation and steam. There have been application of distillation and solvent extraction to papaya, extract BITC.(Arora et al., 2018), (Huang et al., 2019), (Azaiez et al., 2013), (Yang et al., 2020), (Nakamura et al., 2007), (He et al., 2017), (Almora et al., 2004), (Li et al., 2014), (da Rocha et al., 2017), (Soria et al., 2015), (Xie, Yu & Gong 2019) These techniques call for a lot of hazardous and hostile organic solvents and are typically time- consuming, labor-intensive, and poorly sensitive sensitive. To examine BITC in papaya pulp, headspace solid- phase microextraction (HS-SPME) has been used as an alternative. However, the material utilized in HS-SPME are pricy, transient, and frequently leave residuals behind. Therefore, creating a sample pretreatment procedure that is quick, precise, highly selective, and environmentally friendly is crucial for the determination of BITC in papaya fruits (Gimeno et al., 2018), (Khandelwal 1994).

Methodology

The papaya seeds were obtained from nearby market in premnagar, Uttarakhand. The gelatin, citric acid, methyl paraben, propyl paraben, dextrose was issued from the central store of our collage (SGRRU). All chemicals and reagents were used of analytical grade and were procured from authorized dealers

Extraction procedure

• The papaya seed was removed from the papaya fruit and rish it twice and dried in shade for 2 weeks.

• The dried seeds were grinded and then sieve through sieve no 40 and stored in air tight container separately for the further procedure.

• The powered seeds were filled in the thimble in the soxlet apparatus for the extraction process through hot percolation method.

• In this process methanol used as a solvent and reflux it for 3 hours.

• After 3 hours the obtained yellow color liquid extract was complete dried and stored in the air tight container for the further process and evaluation parameters testing (Nayak et al., 2016).

Preparation method of herbal jelly

i. The jellies were prepared by heating method using different polymers of different quantities.

ii. The sugar syrup will be prepared.

iii. To the sugar syrup the gelling agent is added with continuous stirring and heated.

iv. As the gelling agent dissolves completely, stabilizers and solubilizes are added to it and boiled for few min, thoroughly mixed.

v. When the mixture was completely dissolved with continuous stirring.

vi. Then, drug (herbal extract) was added to it with continuous stirring, colour and flavour was added, jellies could have settled down and thoroughly mixed.

vii. The final weight was adjusted with purified water

viii. Then, transferred into moulds and the mixture could cool to room temperature to form jelly (Dubey & Sheth 2015), (Ambedkar & Karthik 2015).

Evaluation parameter

The oral jelly was evaluated for clarity, odor, and color.

Weight Variation: This variable is based on the average weight of 10 jellies after they have been removed from their moulds, weighed, and mixed separately in a beaker.

To Determine Stickiness And Grittiness, Rub The Jelly Between Two: Fingers It is visually determined how sticky and gritty it is (Anand et al., 2015).

Pourability of The Mixture: The major characteristic of jelly is that it can be readily poured into the moulds by adding buffer salts that function as retardants, such as trisodium citrate. These retardants often elevate the pH of the formulation before the addition of acid, halting pregelation. As the retarder concentration is high, the lower the setting temperature and longer the setting time, which aids in setting and pouring the jelly.

pH Determination: The pH is determined by digital pH meters as jelly is dispersed in distilled water (50%) and 1%solution is prepared, the pH was noted.( Kumar et al., 2018), (Jadhav et al., 2017).

Content Uniformity: This assessment is carried out for each dosage form to guarantee the consistency of the drug substance's content. The jelly is crushed and then mixed, the extraction of this combination is carried out using appropriate media, and the amount of drug was calculated using an analytical approach (Ahire et al., 2016), (Prakash 2014).

Viscosity: A Brookfield viscometer is used to test viscosity, and a new sample is used each time (Nayak 2016).

It is computed as follows: Dial reading factor+viscosity in centipoise 2

Spreadability: Spreadability is assessed by sandwiching jelly between two glass slides, which is then uniformly flattened with a weight of 1000gm. The Spreadability of the two slides' separation time was calculated. it is determined by

a. S=m × L/T

b. Where m=weight tide to upper slide

c. T=time taken

d. L=length moved on glass slide (Prakash 2014)

Stability studies: Stability studies are carried out in accordance with ICH criteria and may be evaluated by storing the produced jelly for 90 days at room temperature and analyzing the physical changes that occur (Mathew 2015).

Syneresis: This process involves the separation of liquid by the contraction of a gel, and the jelly preparation was assessed after 24 hours at room temperature

Microbial investigations: These studies are critical in establishing the microbial composition of jellies. since jellies' high-water content makes them more susceptible to microbial development. E. coli, S. aureus, and P. aeruginosa were examined in the jellies' ability to cultivate infections on a particular medium.

The consistency of the gel was created by compressing 20 jellies. A predetermined amount of gel equal to 50mg of the medicine is added, and this is well mixed with the necessary amount of water. The solution was sonicated for 45 minutes, followed by the preparation of a 50ml volume, a filter, and a dilution. UV spectroscopy is used to verify the absorption as a result.

Invitro Taste Analysis: Prepared jelly's taste competence was evaluated using a 5-cc simulated salivary pH. One jelly from each batch is added to 5 ml of solution in a 50 ml beaker and stirred for 60 to 120 seconds before the solution is filtered. The presence of drugs was checked in filtrates using UV.

Dissolution Studies: Using a USP paddle device type 2 and 900 ml of phosphate buffer 6.8 as the dissolution medium at 50 rpm, jelly was successfully drug-dissolved in vitro. The temperature was maintained at 37 C plus or minus 0.5 C. At predetermined intervals of 5, 10, 15, 20, 25, 30, 35, and 40 minutes, 5 ml of sample was removed from the dissolving equipment and replaced with new dissolution medium. A U.V spectrometer was used to identify the release method, and the release study was computed using kinetic models.

Result and Discussion

Organoleptic properties of Herbal powder was observed by physical and visual method. The observed properties were matched with the given standard observed data. (Table 1)


Constituents
Aq. Extract
Flavonoids +
Tannins +
Alkaloids +
Phlobatannins -
Steroids +
Glycosides -

Table 1. Qualitative chemical tests for extracts of Anthelmintic drugs.

As per the observation Herbal powder is sparingly soluble in water, soluble in ethanol and soluble in phosphate buffer 6.8. (Table 2)


S.No.
Properties Result
1. Description Solid
2. Colour Brownish black
3. Odour Pungent

 Table 2. Organoleptic properties.

The standard calibration of Herbal powder was prepared in phosphate buffer 6.8: (Table 3-14)

S.No Solvents Concentration
(µg/ml)
Report
1 Water 12.5033 Sparingly soluble
2 Ethanol 65.4014 Soluble
3 Phosphate buffer 6.8 44.145 Soluble

Table 3. Solubility studies.


                   S.No
    Concentration(µg/ml)            Absorbance(nm)
1 2 0.1181
2 4 0.2243
3 6 0.3252
4 8 0.4520
5 10 0.5481
6 12 0.6295
7 14 0.7875
8 16 0.8730

Table 4. Calibration Curve of Herbal Powder.

S.No Concentration(µg/ml) Absorbance (nm)
1 0 0
2 5 0.2156
3 10 0.2864
4 15 0.3586
5 20 0.5316
6 25 0.6350
7 30 0.8522
8 35 0.9820

Table 5. The standard calibration of Herbal powder was prepared in water.


  S.No
    Concentration(µg/ml)            Absorbance(nm)
1 0 0
2 5 0.1270
3 10 0.2659
4 15 0.4287
5 20 0.6201
6 25 0.6838
7 30 0.9169
8 35 1.0801

Table 6. The standard calibration of Herbal powder was prepared in ethano.

S.No Herbal powder Herbal powder + gelatine Herbal Powder + sodium alginate Standard frequency range (cm¹) Interpretation
1 1598.84 1595.63 1598.98 1600-1200 Alkyl compound C=C          
2 722.22 765.85 776.11 900-650 Aromatic bending C=C
3 2924.27 2925.65 2925.67 3000-2850 C-H

Table 7. Interpretation data.


Ingredients
S1 S2 S3 S4
Herbal extracts mL 10 10 10 10
Gelatine (%) 1.5 2 2.5 3
Glycerine (ml) 2 2 2 2
Citric acid (%) 1 1 1 1
Propylene-glycol(ml) 3 3 3 3
Sugar (%) 60      
Colouring agent(ml) 0.5 0.5 0.50 0.5
Flavouring agent(ml) 1ml 1ml 1ml 1ml
Distilled water q.s q.s q.s q.s

Table 8. Formulation composition of Herbal Jelly.

Formulation code Appearance Texture Sugar crystallization Stickiness and grittiness
S1 Translucent but water bubbles are found Smooth No Slightly sticky & gritty
S2 Translucent with uniform consistency Smooth No Non-sticky & less gritty
S3 Translucent with uniform consistency Smooth No Non-sticky & less gritty
S4 Translucent but slightly thick Smooth No Non-sticky & less gritty

Table 9. Various evaluation parameters of Herbal Oral Jelly.

Organoleptic properties:

Formulation code
pH±S.D (n=3) Viscosity (cps) Spreadability
±S.D(n=3) cm²
Weight variation ± S.D (n=3) Syneresis Taste analysis Drug content ± S.D (n=3)
S1 7±0.404 35200 22.21±0.15 22.21±0.15 No 1.82% 98.66±0.428
S2 6.8±0.321 28200 18.70±0.09 18.70±0.09 No 0.97% 99.10±0.502
S3 6.7±0.267 44000 12.90±0.12 12.90±0.12 No 0.92% 96.66±0.297
S4 6.9±0.503 44600 13.56±0.14 13.56±0.14 No 0.87% 97.51±0.492

Table 10. Observation.

S.no. Time
(min)
Cumulative percent drug release (%C. R)
Formulation code-> SF1 SF2 SF3 SF4
1 0 0 0 0 0
2 5 23 20.28 14.28 11.5
3 10 28.43 28.04 19.8 18.14
4 15 33.65 39.81 23.95 26.94
5 20 43.57 52.26 31.28 31.94
6 25 59.33 64.50 40.71 34.32
7 30 74.85 77.69 45.71 39.54
8 35 87.44 89.81 59.99 44.44
9 40 96.21 97.08 69.39 58.52

Table 11. In-vitro drug release studies.

S.no. time Square root of time Log time Cumulative percent drug release Log cumulative percent drug release Log cumulative percent drug remaining
1 0 0 0 0 0 0
2. 5 2.23 0.698 23 1.36 1.886
3. 10 3.16 1 28.43 1.453 1.854
4. 15 3.87 1.17 33.65 1.526 1.821
5. 20 4.47 1.301 43.57 1.639 1.751
6. 25 5 1.397 59.33 1.726 1.609
7. 30 5.47 1.477 74.85 1.874 1.400
8. 35 5.91 1.544 87.44 1.941 1.098
9. 40 6.32 1.620 96.21 1.983 0.578

Kinetic studies
Table 12. Formulation SF1.


S.no.
Time Square root of time Log time Cumulative percent drug release Log cumulative percent drug release Log cumulative percent drug remaining
1 0 0 0 0 0 0
2. 5 2.23 0.698 20.28 1.3070 1.901
3. 10 3.16 1 28.04 1.4477 1.857
4. 15 3.87 1.17 39.81 1.599 1.779
5. 20 4.47 1.301 52.26 1.718 1.678
6. 25 5 1.397 64.50 1.809 1.550
7. 30 5.47 1.477 77.69 1.890 1.3484
8. 35 5.91 1.544 89.81 1.953 1.008
9. 40 6.32 1.620 97.08 1.9871 0.465

Table 13. Formulation SF2.


S.no.
Time Square root of time Log time Cumulative percent drug release Log cumulative percent drug release Log cumulative percent drug remaining
1 0 0 0 0 0 0
2. 5 2.23 0.698 14.28 0.1072 1.933
3. 10 3.16 1 19.8 1.296 1.904
4. 15 3.87 1.17 23.95 1.379 1.881
5. 20 4.47 1.301 31.28 1.495 1.837
6. 25 5 1.397 40.71 1.609 1.772
7. 30 5.47 1.477 45.56 1.658 1.735
8. 35 5.91 1.544 59.99 1.7749 1.602
9. 40 6.32 1.620 69.39 1.8412 1.485

Table 14. Formulation SF3.

The standard curve plot between concentration and absorbance. The value of R² was found to be 0.9971. So, the equation can be used for the further calculation (Figure 1)

plant-science-buffer

Figure 1. Calibration Curve in phosphate buffer.

The standard curve plot between concentration and absorbance. The value of R² was found to be 0.9833. So, the equation can be used for the further calculation (Figure 2)

plant-science-water

Figure 2. Calibration curve in water.

The standard curve plot between concentration and absorbance. The value of R² was found to be 0.9936. So, the equation can be used for the further calculations (Figure 3)

plant-science-ethanol

Figure 3. Calibration curve in ethanol.

Drug- excipient compatibility study was performed by using FTIR. By matching the main peak of drug with polymers, there is no significant difference observed in between the peaks of the herbal powder and polymer. So, it may be concluded that there was no possible interaction between drug and selected polymer. (Figure 4-6)

plant-science-extract

Figure 4.Standard FTIR of papaya seed extract.

plant-science-herbal

Figure 5.FTIR of herbal extract.

plant-science-gelatin

Figure 6.FTIR of Herbal powder and gelatin.

From all formulation we concluded that each batch having smooth texture. Although appearance is translucent in all formulation but the S1 contain little bubble in it, S4 is slightly thick and S2 & S3 formulation having uniform consistency. While formulation S2 to S4 exhibit no such stickiness and grittiness. The formulation S1&S2 show no sugar crystallization means sugar is properly dissolved in mixture i.e. no crunches are present. It was concluded that S2&S3 formulation showed acceptable jelly formulation. (Figure 7)

plant-science-formulation

Figure 7.Picture of jelly formulation from S1 to S2.

The pH determines the taste and stability of jellies formulation are found in the range 0f 6.9 ± 0.503 to 7 ± 0.404 which is near to neutral. So, minimum amount of citric acid is added to maintain pH (Figure 8)

plant-science-determination

Figure 8.pH determination of different formulation.

The viscosity was found in the range of 44600-28200 cps. As the viscosity is decrease the drug flow increases (Figure 9)

plant-science-formulation

Figure 9.Shows the viscosity determination of different formulation.

The Spreadability of formulation was found to decrease with the increase in the concentration of gelling agent. (Figure 10)

plant-science-viscosity

Figure 10.Show the viscosity determination of different formulation.

The weight variation varies from 0.82 gm to 0.91gm (Figure 11)

plant-science-formulate

Figure 11.Show the weight variation of different formulate.

There was no syneresis observed in the optimized formulation at the specified temperature The taste determination was found in the range of 0.87% to 1.82% which lies in scale range of no bitterness and threshold bitter. Hence, it can be co-related to taste feel.(Figure 12)

plant-science-drug

Figure 12.Shows the precent drug content.

The drug content of formulation S2 was found to be 99.1(Figure 13)

plant-science-model

Figure 13.Shows the in vitro drug release model between %CR and time.

The invitro drug release of formulation SF1 to S4 were studied. All formulation shows different level of drug release ranging from 58.52 to 97.08%. it has been evaluated that as the low concentration of gelling agent shows the significant drug release SF1 & SF2 (96.21 % & 97.08 %). The formulation SF1 and SF2 containing lowest concentration of gelling agent. (Figure 14).

plant-science-Cumulative

Figure 14.Kinetic release model of zero order release between Cumulative %drug release and time.

Drug release kinetic model are used to illustrate the drug release mechanism. For this various model are used like zero order, higuchi, first order, korsmeyer peppas to obtain the value of R2 value and n-value for the determination of best fit model. R2 value was compared for all the formulation which shows the bestfit model and by noticing n-value which is obtained from korsmeyer peppas model (Figure 15-17). Release mechanism was described by an equation:

Mt/M∞=ktn

The observed data of kinetic model shows the best fit model for prepared oral medicated jelly was determined by regression coefficient(r2) in all formulation. The highest r2 value determine the best fit model, the observed data shows the zero- order release in all formulation i.e, the drug release is independent of concentration. Formulation SF1, SF2 & SF4 shows the non-fickian diffusion and SF3 shows the supercase transport which depends upon the loss of polymeric chain and the release of drug takes place (Table 15-17).


S.no.
Time Square root of time Log time Cumulative percent drug release Log cumulative percent drug release Log cumulative percent drug remaining
1 0 0 0 0 0 0
2. 5 2.23 0.698 11.5 1.060 1.946
3. 10 3.16 1 18.14 1.258 1.913
4. 15 3.87 1.17 26.94 1.430 1.863
5. 20 4.47 1.301 31.94 1.504 1.832
6. 25 5 1.397 34.32 1.535 1.816
7. 30 5.47 1.477 39.54 1.597 1.781
8. 35 5.91 1.544 44.44 1.6477 1.744
9. 40 6.32 1.620 58.52 1.7673 1.617

Table 15. Formulation SF4.

  Formulation
Code

                 R                                  
     n value   Best fit model   Mechanism of release
Zero order First order Higuchi matrix
SF1 0.9813 0.8291 0.9026 0.727 Zero order Non- fickian
diffusion
SF2 0.9944 0.8586 0.937 0.795 Zero order Non- fickian
diffusion
SF3 0.9814 0.9182 0.8963 1.681 Zero order SupercaseⅡ transport
SF4 0.9686 0.9209 0.9376 0.73 Zero order Non- fickian
diffusion

Table 16. Drug release kinetic with model fitting.


n value
Release mechanism
0.5 Fickian diffusion
0.5<n<1 Non – fickian diffusion
1 Supercase Ⅱ transport

Table 17. Followed by standard release mechanism table.

Conclusion

To be concluded that prepared medicated herbal jelly is more organoleptically accepted particularly by patients with disability in ingestion of food and drink, in other words, those having difficulty in mastication and swallowing. The present study concludes that oral medicated jellies can be very promising for effective doses to systemic circulation. These may also provide an added advantage of circumventing the hepatic first pass metabolism. Prepared medicated jelly is cost wise cheap and acceptable and have gained relevance in pharmaceutical industry as a novel, patient friendly, convenient products.

Acknowledgements

We thank Assistant Prof. Shaffi Khurana Tangri, SGRR University, for their support during this work.

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Citation: Mrynal Chamoli (2022). Formulation and development of pediatric herbal jelly from papaya seeds for anthelmintic infection. IRJPS. 13: 031.

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