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| ORIGINAL ARTICLE |
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| Year : 2023 | Volume
: 8
| Issue : 3 | Page : 262-270 |
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Pharmaceutical evaluation of modified Kantakari Avaleha for pediatric use
Sagar Mahendrabhai Bhinde1, Sonam S Bhinde2, Vinay J Shukla3, Meera Cholera4, CR Harisha5, Virendra K Kori1
1 Department of Kaumarbhritya, ITRA, Rajkot, India
2 Department of RSBK, Indian Institute of Ayurved Research and Hospital, Rajkot, India
3 Department of Pharmaceutical Laboratory, ITRA, Jamnagar, Gujarat, India
4 Department of Microbiology Laboratory, ITRA, Jamnagar, Gujarat, India
5 Department of Pharmacognosy Laboratory, ITRA, Jamnagar, Gujarat, India
| Date of Submission | 16-Sep-2022 |
| Date of Acceptance | 03-Feb-2023 |
| Date of Web Publication | 16-Aug-2023 |
Correspondence Address:
Dr. Sagar Mahendrabhai Bhinde
Department of Kaumarbhritya, 533, 5th Floor, ITRA Institute Building, Jamnagar 361 008, Gujarat
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jdras.jdras_144_22
BACKGROUND: Kantakari Avaleha (KA) is a semisolid herbal drugs preparation recommended for various diseases like Hikka (hiccup), Kasa (cough), Shvasha (dyspnoea/asthma), and Shoola (colicky pain) in Sharangdhara Samhita. In this study, KA was slightly modified (after an experiment of classical and intermediate batches) by adding sugar and honey 1.5 and 2 times, respectively, in comparison to the classical method, to overcome its palatability issues in the pediatric age group. It is important to standardize the modified drug to make the drug formulation reproducible. Hence, the present study was aimed to evaluate pharmacognostical and pharmaceutical parameters of the modified Kantakari Avaleha (MKA) prepared for pediatric use. METHODS: Preauthenticated raw drugs were procured from pharmacy, ITRA, Jamnagar, Gujarat, India, and two pilot batches and final modified KA were prepared at RSBK Department, ITRA, Jamnagar. Samples from all three Avaleha were evaluated for organoleptic parameters and microbial study; samples from MKA were evaluated for pharmacognocy, physicochemical parameters, and high-performance thin-layer chromatography. RESULTS: Taste of MKA was improved compared to classical and intermediate formulations. Stability in terms of microbial overgrowth remains the same as the classical one. All the other evaluated parameters were comparable with Ayurveda Pharmacopeia of India standards except total, reducing and nonreducing sugar content. CONCLUSION: MKA was found to be palatable for pediatric use. The pharmacognostical and physico-chemical evaluation of final formulation revealed that this modified formulation meets almost all the pharmacopeial parameters (except sugar content) and hence data of the current study could be used as pharmaceutical standards for this specific MKA. Clinical study will be needed to determine whether the change in the proportion of sugar and honey has a favorable or negative impact on the clinical outcome. Keywords: Childhood asthma, HPTLC, Kantakari Avaleha, microbial safety, modified Kantakari Avaleha, pharmacognocy, physicochemical analysis
How to cite this article:
Bhinde SM, Bhinde SS, Shukla VJ, Cholera M, Harisha C R, Kori VK. Pharmaceutical evaluation of modified Kantakari Avaleha for pediatric use. J Drug Res Ayurvedic Sci 2023;8:262-70 |
How to cite this URL:
Bhinde SM, Bhinde SS, Shukla VJ, Cholera M, Harisha C R, Kori VK. Pharmaceutical evaluation of modified Kantakari Avaleha for pediatric use. J Drug Res Ayurvedic Sci [serial online] 2023 [cited 2023 Sep 23];8:262-70. Available from: http://www.jdrasccras.com/text.asp?2023/8/3/262/383696 |
| Introduction | |  |
Avaleha is the semi-solid dosage form, having long shelf-life in comparison to primary dosage forms, and can be administered to all the three age groups, that is, Bala (child), Yuva (young), and Vriddha (old). Kantakari Avaleha (KA) is a semisolid herbal drugs preparation recommended for various diseases like Hikka (hiccup), Kasa (cough), Shvasha (asthma), and Shoola (colicky pain). It is first mentioned in Sharangdhara Samhita.[1] KA contains Kantakari (Solanum xanthocarpum Schrad. & Wendl), Panchang (root, bark, leaves, flower, and fruit) as Kwatha Dravya (decoction material), 13 Prakshepa Dravya (various fine powders to be added at the end of procedure), sugar, ghee, oil, and honey. Comparing to other Avaleha forms; in KA, Prakshepa and Madhura Dravya is in equal quantity, and the oil amount is also approximately equal to the amount of Prakshepa Dravya. Due to specific contents, taste of this classical KA is bitter astringent, which is difficult to consume by pediatric patients. Noncompliance to medication due to bad taste is one of the common problems that pediatricians faced since long. Children stop taking medicine due to various reasons like bad taste, smell, inconvenient mode of drug delivery, long-term requirement of drug, etc. Noncompliance may lead to many consequences, such as increased doctor visit, treatment failure, toxicity, and medication interaction, especially in chronic diseases like asthma.[2] It was also seen that approximately 30%–70% of the patients with chronic illnesses (e.g., epilepsy, asthma, and diabetes) have poor adherence because of various reasons, but bad taste remains the prime culprit.[3] At least one-third of all children fail to complete even relatively short-term treatment regimens due to bad taste of medicines.[4]
So looking at this difficulty, few modifications were carried out in classical reference (CKA) to increase the palatability. Before reaching to the final modified version of KA, one intermediate modification (IKA) was also carried out. Finally, sugar and honey were added 1.5 and 2 times, respectively, in comparison to the classical method, to make final MKA mild bitter sweetish astringent in taste. But, it is also important to standardize the modified drug to make the drug formulation reproducible.[5] So, this study was aimed to evaluate the pharmacognostical and pharmaceutical parameters of the MKA prepared for pediatric use.
Objectives
- Organoleptic and microbial evaluation of CKA, IKA, and MKA.
- Pharmacognostical evaluation and physico-chemical analysis of MKA.
| Materials and Methods | | |
Collection and authentication of raw drugs
Preauthenticated raw drugs except honey and sugar were procured from the pharmacy, ITRA, Jamnagar. Honey and sugar were purchased from local market of Jamnagar, Gujarat. Ingredients of KA are mentioned in [Table 1].
Preparation of kantakari avaleha
CKA, IKA, and MKA were prepared by classical method as mentioned in Ayurveda Pharmacopeia of India at RSBK Department, ITRA, except step-by-step changes in the proportion of sugar and honey.
Whole process was divided into three stages.
Preparation of powder[
6]
Guduchi (Tinospora cordifolia (Willd.) Miers ex Hook.f. & Thomson), Chavya (Piper retrofractum Vahl.), Chitraka (Plumbago zeylanica L.), Musta (Cyperus rotundus L.), Karkatashringi (Pistacia integerrima J.L. Stewart), Shunthi (Zingiber officinale Roscoe.), Maricha (Piper nigrum L.), Pippali (Piper longum L.), Dhanvayasaka (Alhagi camelorum Fisch.), Bharangi (Clerodendrum serratum Moon), Rasna (Alpinia galangal (L.) Willd.), Shati (Hedycium specatium ham ex smith), and Tugaksiri (Bambusa arundinacea Retz.) were separately taken and physical impurities were removed from them. Then they were grinded by using minipulverizer and sieved through # 72. The powder that was not passed through # 72 sieve was grinded again by using mixture grinder and sieved to obtain fine powder.
Preparation of decoction[
7]
All physical impurities like stone and wood were removed from Kantakari Panchanga and soaked overnight by adding 8 times of water. This mixture was heated on medium temperature, until volume was reduced to 1/4th of its initial quantity. Then it was filtered through a clean cotton cloth to obtain decoction.
Preparation of Avaleha
The specific classical method for Kantakari Avaleha mentioned in Ayurveda Pharmacopeia of India (API) (adopted from Sharangadhara Samhita) was followed for the preparation of KA.[8] Sugar candy was added in filtered decoction and stirred over heating until sugar dissolved. Temperature of homogenous mixture was around 80°C. Then the mixture of sugar and decoction was filtered through double cloth to remove physical impurities of sugar candy. Then powdered ingredients [S.No. 3–14 in [Table 1]], ghee, and sesame oil were added to the filtrate. Heating process was maintained between 90 and 95°C with continuous stirring till it attains the semisolid consistency. It was confirmed by the formation of soft bolus, which does not disperse in water.[9] Then heating was stopped and allowed for self-cooling up to around 60°C temperature. After that fine powders of Vamsalochana and Pippali were added and stirred properly to get uniform mixture and allowed them to cool down to room temperature. Then honey was added and mixed thoroughly to obtain homogeneous blend. Final product was stored in airtight containers.
Method of modification
First batch of KA was prepared as per the classical proportion (CKA). Second batch was prepared with an increase in honey (2 times) in the proportion (IKA). And final modified KA was prepared by an increase in honey (2 times) and sugar (1.5 times) to achieve desired taste [Table 2].
Pharmacognostical evaluation
Organoleptic evaluation of all three samples was carried out by research scholars and volunteers. Microscopic study of the MKA was carried out at pharmacognocy laboratory, ITRA, Jamnagar. A small quantity of MKA was dissolved in distilled water, placed on slide, and observed under the microscope to get the microscopic characters of the ingredients of Avaleha. The sample was then stained with iodine solution, and Sudan III. Microphotographs were taken under the Carl Zeiss trinocular microscope attached with camera.[10]
Physicochemical analysis
MKA was analyzed by using standard qualitative and quantitative parameters at the Pharmaceutical Chemistry Lab, ITRA, Jamnagar. Loss on drying, water-soluble extract, methanol-soluble extract, pH, reducing, nonreducing, and total sugar were selected as the parameters. These physiochemical analyses were carried out by following standard procedures mentioned in API.[11] High-performance thin-layer chromatography (HPTLC) study was carried out with acid hydrolyzed methanolic extract on precoated silica gel GF 60254 aluminum plate as 5 mm bands, 5 mm apart, and 1 cm from the edge of the plates, by means of a Camag Linomate V applicator fitted with a 100 μL Hamilton syringe. The mobile phase used was toluene:ethyl acetate:glacial acetic acid: formic acid (5:5:1:0.5). The plates were developed in Camag twin trough chamber (20 × 10 cm2), and spots were detected in short UV (254 nm) and long UV (366 nm). Camag Scanner II (Ver. 3.17) was used for documentation.
Microbial study
CKA, IKA, and MKA were prepared on July 1, 2020, July 1, 2020, and July 10, 2020, respectively. Swab samples of all three Avaleha were subjected to microbial evaluation on every month till container become empty or microbial overgrowth comes positive (July 14, 2020, August 17, 2020, September 15, 2020, October 13, 2020, and November 9, 2020). Below-mentioned methods assessed microbial contamination at microbiology laboratory, ITRA, Jamnagar [Figure 1]. | Figure 1: Method of microbial study of KA. (A) Stained smear ready for examination. (B) Fungal culture media. (C) Aerobic culture media
Click here to view |
For smear preparation of 10% KOH Wet mount, samples were taken on grease free glass slides + 10% KOH and covered with clean cover slips for microscopic examination [Figure 1]A.
Gram’s stain test
A clean glass slide was taken to prepare a dry thick smear. The smear was fixed by heating it over the flame. Then Gram’s crystal violet (CV) solution was put on the fixed smear and left for a certain time as mentioned on the kit. The smear was later washed in running tap water to get rid of excessive CV solution. Then, Gram’s iodine solution was added to the smear and left for a certain time period as mentioned on the kit. Later, the smear was washed in running tap water to get rid of the excessive solution. Then, stream gram’s decolourizer (acetone) was put on the slide to remove the Gram’s crystal violet color or as per the kit; the smear was washed in running tap water to get rid of the excessive acetone. The smear was counterstained with Safranin solution and left for a certain time period as mentioned on the kit. Then, the smear was washed in running tap water to get rid of the excessive solution. The smear was left for drying. It was inspected under an oil immersion lens, and the findings were recorded.[12],[13]
Culture study
Samples were collected with sterile cotton swab for inoculation purpose on selected fungal and aerobic culture media [[Figure 1]B and C].
Fungal culture was prepared from Sabouraud modified (Dextrose Agar Base, Emmons) of HIMEDIA Laboratories Pvt. Ltd. It was kept for 5–7 days at 37°C.
Aerobic culture media was prepared from Mac Conkey Agar (MA) and Coulmbia Blood Agar of HIMEDIA Laboratories Pvt Ltd. It was kept for 24–48 h at 37°C for selective cultivation of pathogenic bacteria.
| Results | | |
Organoleptic characters
The organoleptic characters of CKA, IKA, and MKA are depicted and compared with available standards of API in [Table 3].
Microscopic evaluation
MKA showed the presence of circular crystal, stone cell, and starch grain of Rasna; lignified stone cell and black debris of Maricha; border pitted vessels, cork cells, starch grain, and collenchyma of Guduchi; cork cells, lignified fibers, and stone cells of Bharangi; lignified fibers and epidermal cells of Karkatashringi; group of stone cells of Chavya; lignified fibers, trichome, and stone cells of Dhanvayasa; lignified stone cells, rhomboidal crystal, stone cells, and pitted vessels of Chitraka; mesocarp cells and stone cell of Pippali: oil content of Ghrita; oil globules of sesame oil; scalariform vessels and fiber of Shunthi; silica deposition, Sclariform vessel, and starch grain of Musta; starch grain, trichome, yellow content, and tubes of Shati; and starch grain, tannin, and stellate trichome of Kantakari [Figure 2]. The diagnostic features obtained were found to be complying with the standards mentioned in API.
Physicochemical assay of MKA
Physicochemical parameters such as loss on drying, water-soluble extractive, methanol soluble extract, ash value, pH, and sugar content of MKA were assessed and compared with API. The results are cited in [Table 4].
HPTLC study
HPTLC study reveals that MKA has 10 peaks in 254 nm and 4 peaks in 366 nm UV lights [Table 5] and [Figure 3].
Microbial study
It was observed that CKA had observed fungal growth after 132 days; IKA had developed visible fungal growth after 75 days, while MKA had no any microbial contamination till container become empty (122 days) [Table 6].
| Discussion | | |
Preliminary step to establish pharmaceutical standards in traditional medicines is to perform pharmacognosy, physicochemical, microbial stability, and other analytical procedures.
Organoleptic parameters, specifically taste, were kept as primary factor for modification to make it palatable for pediatric use. After 2 pilot batches (CKA and IKA), final MKA was mild bitter sweetish astringent. All other organoleptic parameters were comparable with the API standard, indicating its authenticity in formulation method. Change in taste was deliberately made to make this formulation palatable for pediatric age group. Because Acharya Charaka means that the baby should be provided with drugs and food having sweet and mild astringent taste, due to tender nature, dependency, and inability to fully express themselves in speech and gestures.[14] Hence, step-by-step sweeteners were increased without altering any other drug component. Primarily CKA was bitter astringent, and hence it was modified by adding 2 times honey. That formulation (IKA) has introduced sweetness, but could not reduce its bitterness and become bitter sweetish astringent. Hence, IKA still remains bitter and smells of oil, making it unpalatable for kids. To reduce the bitterness, sugar was increased by 1.5 times than the classical proportion and then MKA had mildness in bitter taste.
Microscopic identification of the botanical ingredients is a standard for statutory purposes in several solid and semi-solid compound formulations. This study revealed the presence of various important microscopic compounds of its ingredients and hence proved its authenticity. This can be considered as fingerprinting for this modified Avaleha. Starch grains present in Avaleha are the main form by which plants store carbohydrate and is a major photosynthetic product in many species.[15]
The presence of more moisture content in any herbal drug may decrease the shelf-life. Hence, loss on drying was selected as one of the parameters for the standardization. 17% loss on drying was found to satisfy its quality in the current study.
Physicochemical parameters such as ash value, pH, water-soluble extractive value, and alcohol-soluble extractive value were comparable with that prescribed in API. This indicates that the modification does not affect the physicochemical nature of the formulation and hence could be hypothesized that efficacy might not be hampered with this modification.
Total ash values and extractive values are helpful in identifying and quantify the amount of the plant material present in the formulation. The total ash is particularly important in the evaluation of purity of drugs, that is, the presence or absence of inorganic matter such as metallic salts and/or silica. Total ash value helps in determining both physiological ash (plant tissue) and nonphysiological ash (extraneous matters like sand and soil). Extractive values help in determining the amount of active constituents concerning particular solvent system.[16]
pH of Avaleha was 5.5 suggesting little acidic nature of the drugs. This might be due to Shati (Amla Rasa—Raja Nighantu) and chemical constituents of other ingredients.
Since Avaleha contains significant quantity of sugar in its pharmaceutical procedure, sugar estimation was considered as another parameter. Total sugar was found (38%), and more than API standards were because of the modification we carried out by adding 1.5 times sugar than its classical reference. The idea behind increasing the sugar content is to enhance taste and increasing the shelf-life. Because previous researcher had also experienced that increase in sugar content resulted in significant increase in shelf-life of the product.[17] Though in this study, stability study carried out on MKA was for limited time; hence, maximum stability cannot be claimed.
The water-soluble extractive and methanol soluble extractive values were found to be 68.63% and 60.51%, respectively, indicating considerable amount of polar compounds in the sample.[18]
HPTLC data gathered here in this study can be used as fingerprinting of this modified formulation. In present study, 10 and 4 spots were observed in 254 and 366 nm, respectively. Similar findings of 8 and 5 spots in 254 and 366 UV light were also observed in previous study.[19]
Fungal growth was observed in CKA after 132 days, but when honey was doubled in that formulation (IKA), fungal growth took place even faster, that is, after 75 days only. That might be because of increased water content of honey in it. MKA had no microorganism even after 122 days of preparation, indicating that this drug’s shelf-life is at least for 122 days, and further long-term stability study or accelerated stability study is required to get exact idea of this MKA. These data also show that modification in sugar amount increased the shelf-life compared to IKA.
Limitation of the study
Data of multiple batches could not be performed in this study. Possibilities of change in therapeutic potential could not be denied after modification. Due to limited time and budgetary provisions, the accelerated stability study or long-term shelf life study could not be carried out in this study.
| Conclusion | | |
Modified Kantakari Avalehawas found to be palatable for pediatric use. The pharmacognostical and physico-chemical evaluation of modified Kantakari Avaleha revealed that it meets almost all the pharmacopeial parameters (except sugar content) and hence data of this study could be used as a reference for this specific modified Kantakari Avaleha. Modified Kantakari Avaleha found to have almost similar microbial stability to that of the classical one. Clinical study will be needed to determine whether the change in proportion of sugar and honey has a favorable or negative impact on the clinical outcome.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Srikanthamurthi KR Translator. Sharangadhara Samhita (A treatise on Ayurveda), Madhyama Khanda. Reprint ed. Ch. 08, Ver.4. Varanasi: Chaukhambha Orientalia; 2016. p. 111.  |
| 2. | Dawood OT, Izham M, Ibrahim M, Palaian S Medication compliance among children. World J Pediatrics 2010;6: 200-2. |
| 3. | Haynes RB, McDonald H, Garg AX, Montague P Interventions for helping patients to follow prescriptions for medications. Cochrane Database Syst Rev 2002;2:CD000011. Update in: Cochrane Database Syst Rev. 2005;4:CD000011. |
| 4. | Jones JG Compliance with pediatric therapy. Clin Pediatr 1983;22:262-5. |
| 5. | Anonymous. Guidelines on Safety Monitoring and Pharmacovigilance on Herbal Medicine. Geneva: World Health Organization; 2003. |
| 6. | Sharangdhara A Sharangdhara Samhita. Reprint ed. Chaukhambha Orientalia; 2009. p. 173. |
| 7. | Sharangdhara A Sharangdhara Samhita. Reprint ed. Chaukhambha Orientalia; 2009. p. 135. |
| 8. | Anonymous. The Ayurvedic Pharmacopoeia of India, Part 1. 2nd ed. Delhi: The Controller of Publications Civil Lines; 2003. p. 115-6. |
| 9. | Dalai SK What is Avalella Pakasidha Laksana—A matter of discussion. Ayurveda Mahasamelana Patrika 2008:39-40. |
| 10. | Wallis TE Practical Pharmacognosy. Gloucester Place, London: Published by J and A Churchill Ltd; 1953. p. 57-9. |
| 11. | Anonymous. The Ayurvedic Pharmacopoeia of India, Part 2, Vol. 4 (formulations): monographs. 2nd ed. Delhi: The Controller of Publications Civil Lines; 2003. p. 115-6. |
| 12. | Sharma R, Amin H, Shukla, VJ, Kartar D, Galib R, Prajapati PK Quality control evaluation of Guduchi Satva (solid aqueous extract of Tinospora cordifolia—Willd. Miers). An herbal formulation. Int J Green Pharm 2013;7:258-63. [Full text] |
| 13. | Sharma V, Sharma SK, Cholera MS, Pandya DH, Thakar A Stability study of Amalakibhavita nisha used in the management of type 2 diabetes (Madhumeha)-with respect to baseline microbial diagnostic modalities. Pharma Innov J 2019;8:811-7. |
| 14. | Trikamji AJ Agnivesa, Charaka Samhita, Chikitsa Sthana 30/283, Yonivyapada Chikitsa. Varanasi: Choukambha Publication; 2001. |
| 15. | Grennan AK PRegulation of starch metabolism in arabidopsis leaves. Plant Physiol 2006;142:1343-5. |
| 16. | Sharma R, Bolleddu R, Maji JK, Ruknuddin G, Prajapati PK In-vitro α-amylase, α-glucosidase inhibitory activities and in-vivo anti-hyperglycemic potential of different dosage forms of Guduchi ( Tinospora cordifolia [Willd.] Miers) prepared with ayurvedic bhavana process. Front Pharmacol 2021;12:642300. |
| 17. | Sidira M, Mitropoulou G, Galanis A, Kanellaki M, Kourkoutas Y Effect of sugar content on quality characteristics and shelf-life of probiotic dry-fermented sausages produced by free or immobilized Lactobacillus casei ATCC 393. Foods 2019;8:219. |
| 18. | Thirunavukkarasu MS, Galib R, Shukla VJ, Harisha CR, Thakar AB, Baghel MSA Preliminary physico chemical assay of Goksura granules—A pilot study. Int J Ayur Med 2010;1:100-8. |
| 19. | Senarathna U, Chaudhary S, Patgiri B Accelerated stability studies of kantakari avaleha and its granules. WJPR 2020;9:892-908. |
| 20. | Anonymous. The Ayurvedic Pharmacopoeia of India, Part 1, Vol. VII, Appendix 2. 1st ed. New Delhi: The Government of India; 2008. p. 233-348. |
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]
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