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| RESEARCH PAPER |
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| Ahead of print publication |
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Formulation, standardization, and evaluation of vaishvanara churna tablet
Rishi Kumar1, Saptarshi Samajdar2, Rupa Mazumder3, Amrish Chandra1
1 Amity Institute of Pharmacy, Amity University, Noida, Uttar Pradesh, India
2 School of Pharmacy, The Neotia University, Kolkata, West Bengal, India
3 Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida, Uttar Pradesh, India
| Date of Submission | 02-Sep-2022 |
| Date of Decision | 17-Nov-2022 |
| Date of Acceptance | 16-Dec-2022 |
| Date of Web Publication | 02-Mar-2023 |
Correspondence Address:
Amrish Chandra,
Amity Institute of Pharmacy, Amity University, Sector-125, Greater Noida - 201 313, Uttar Pradesh
India
 Source of Support: None, Conflict of Interest: None DOI: 10.4103/asl.asl_97_22
Background: The Vaishvanara Churna is an Ayurvedic formulation which finds its mention in the Ayurvedic Formulary of India. There are five natural ingredients in this preparation. Rheumatoid arthritis and other medical complications are treated with it. The Churna formulations are challenging to dose precisely, and patient compliance is generally low. Aim: The study was designed to formulate and standardize of Vaishvanara Churna tablet to improve patient compliance. Materials and Methods: The present study was carried out to characterize the coated tablet preparation of Vaishvanara Churna, a multiherbal formulation on the basis of pharmacognostic, physichochemical, microbiological, pharmaceutical, spectroscopic, and chromatographic parameters to identify the quality and purity of the tablets. Results: The selected tablet formulation (F5) was found within the limits of all pharmacopoeial parameters. Conclusion: The methods presented in this study can be used for production of this formulation at large scale to get better results in terms of quality, safety, and better therapeutic efficacy.
Keywords: High-performance thin-layer chromatography, microscopy, tablet, thermogravimetry, vaishvanara churna
| Introduction | |  |
The use and acceptability of traditional system of medicine are increasing day by day. The amalgamation of modern system of medicine with the traditional system has given its larger acceptance. The modern system of medicine is based on the latest methods of quality control. The modern methods are being used for the standardization of medicines from the traditional system. Large numbers of traditional medicines are based on the botanicals. The evaluations of these botanicals have opened up new approaches for the standardization of traditional medicines.[1] Many of the botanicals are being recognized as monographs in the various pharmacopoeias, in that case it becomes very important for regulators to devise standards for identity, purity and strength of botanicals. It not only improves the quality of the botanicals used in the preparation of traditional medicines available in Ayurveda, Siddha, Unani, and Sowa Rigpa, these standards also improve the safety and efficacy of botanicals. These botanicals are also being used for lead identification of New Chemical Entities. The plants mentioned in the traditional system of medicine can be used for the identification of lead compounds for further exploration of their therapeutic activities.[2] In the present study, authors selected the Vaishvanara churna an Ayurvedic formulation to convert it into film-coated tablet dosage form to improve the patient compliance according to the modern system of medicines.
Ayurvedic physicians prescribe Vaishvanara Churna, a polyherbal Churna formulation, to cure ailments such as gurgling flatulence (Adhmana), abdominal lumps (Gulma), duodenal ulcers (Parinamasula), rheumatism (Amavata), and heart disease (Hrdroga)[2] It contains five ingredients, Manimantha (Saindhava Lavana Active Pharmaceutical Ingredient [API]) Rock salt, Yamani (Yavani API) Trachyspermum ammi Fr., Ajmoda API Apium leptophyllum Fr., Nagara (Sunthi API) Zingiber officinale Rz, Haritaki API Terminalia Chebula P. mixed in Proportioned mentioned in the [Table 1].
The current work focuses on the conversion of Ayurvedic Vaishvanara churna, a traditional formulation, into tablet dosage form. In addition, Vaishvanara churna tablet has been thoroughly evaluated in accordance with the Ayurvedic Pharmacopoeia of India's requirements. For standardization of herbal products, guidelines have been provided by the WHO including US Pharmacopoeias, European Medicine Agency, and other renounced Organization. In India, the Indian Pharmacopoeia Commission and Pharmacopoeia Commission for Indian Medicine is taking the lead in developing the standards for the botanicals and other formulations mentioned in the traditional system of medicines such as Ayurveda, Siddha, Unani, and Sowa-rigpa including Homeopathic system of medicine.[3],[4],[5],[6],][7],[8],[9]
| Materials and Methods | | |
Materials
The raw herbs for the preparation of Vaishwanara churna were purchased from the local market of Ghaziabad, India. The individual herbs were authenticated by the Council of Scientific and Industrial Research-National Institute of Science Communication and Information Resources The voucher specimen of these ingredients was deposited in the Raw Material Herbarium and Museum, Delhi for future reference. The heavy metal was purchased from Merckbearing Lot no.HC271216. The mercury standards were purchased from Inorganics Ventures bearing Lot No-N2-HG672226.
Preparation of Vaishvanara churna granules
All the ingredients [Table 2] were taken as per Ayurvedic Formulary of India. Saindhava lavana was roasted in stainless steel pan at a low temperature till it becomes free from moisture. Other ingredients were powdered and passed through #85 sieve. All ingredients including disintegrating agent, binding agent, lubricants, and preservatives were weighed separately and then mixed together in specified ration as per the standard formula to obtain a homogenous blend. Then, it was packed in tightly closed containers to protect from light and moisture.[2]
The granules of Vaishvanara churna were prepared by the wet granulation technique. The wet granulation was done by using Isopropyl Alcohol; the binder agent used in the preparation of granules was Polyvinylpyrrolidone (PVP) (K30). The half of the binder was used as intra-granulating agents and half was added as extra-granulating agent. The mixture of churna was subjected to slugging for converting the powder mixture into slugs. The obtained slugs were passed through the granulator to get the granules. Finally, the tablets were prepared by Cadmach 16 Station Machine.[10]
Coating of Vaishvanara churna tablets
The tablets of Vaishvanara Churna were coated by using a coating machine (ACG Miniquest T) with coating solution of Opadry 03K15646 RED (Colorcon)(5%) and purified wáter (95%). Coating of 200 g tablet was carried out in a in 8-inch perforated coating pan with the following parameters: 1.0 mm nozzle, at 2.5 bar atomization; inlet temperature – 40°C–45°C; exhaust temperature – 38°C–40°C; spray rate - 3 rpm for process time (approx 1 h); drying was performed at 60°C for ~ 1 h.
Evaluation of the prepared tablets
Organoleptic evaluation
The formulation was also evaluated for organoleptic characters such as taste, odor, color, and texture.
Study of microscopic characteristics
The microscopic characteristics of Vaishvanara churna tablet formulation were studied and the photographs were captured using Nikon Inverted Microscope, Japan.
Physicochemical and micromeritic properties of the formulation
Physicochemical parameters for the evaluation of the Vaishvanara churna were performed on all the formulations using methods as mentioned by Mukhi et al. With slight modifications. The alcohol soluble extractive, water soluble extractive, total ash and acid soluble ash, and loss on drying were calculated.[11],[12]
Micromeritic parameters such as bulk density, tap density, angle of repose, Hausner ratio, and Carr's index were determined and expressed as an average representing the three batches of Vaishvnara churna formulation.
Qualitative phytochemical evaluation of vaishvanara churna
The phytochemical evaluation of the Churna preparation was performed as per the standard procedures. The preparation was screened for alkaloida, tannins, steroids, glycosides, flavanoids, saponins, carbohydrates, terpenoids, and proteins.
Determination of heavy metal content in vaishvanara churna
The heavy metal content of the formulation was estimated by using Inductively coupled plasma (ICP) Mass spectrometer (MS), Model NexION ×300 of Perkin Elmer. The standards of heavy metals selected for the study were multielement standard solution for ICP containing Cd, Pb, Cr, As, Ni, Cu, Co, and Zn.[13],[14]
Instrumentation
The ICP-MS operating conditions for the determination of Pb, Cd, As, and Hg were as follows: High purity (99.99%) argon was used as plasma and it was carried out in standard mode. The gas flows were kept at 18.0 l/min for plasma, 1.1 l/min for auxiliary, 1 l/min for nebulizer, the SAMPLE pump was kept at 25 rpm speed. The radiofrequency (RF) power was 1600 W.
Test sample preparation
Sample preparation is critical to the success of plasma-based analysis and is the first step in performing any analysis via ICP-MS. 0.2 g of sample was added to 5 ml of concentrated nitric acid of ICPMS grade. Then, it was allowed to sit loosely covered for 30 min in fume hood after Sample digestion was performed through a closed-vessel microwave digestion system Perkin Elmer (Anton Paar) with a multiwave 3000, and pressure sensor, provided with an auto pressure vent Quartz vessel. The maximum temperature for this system is 220°C and the sample can be digested with a maximum of 20 bar pressure.[15]
The most conventional means by which samples are introduced into the plasma is through solution nebulization. Sample was prepared in 1% nitric acid solutions, because there are minimal interferences with these solvents compared to other solvent choices.
Microbial limit test
Microbial analysis was carried out as per the standard procedure mentioned in the Indian Pharmacopoeia. It includes total bacterial count, total fungal count, presence of pathogens such as Escherichia coli, Salmonella ebony, Pseudomonas aeruginosa, and Staphylococus aureus.
Fourier transforms infrared spectrophotometric profiling
The Fourier transforms infrared (FTIR) spectroscopy was performed with the three batches of Vaishvanara churna using a FTIR Spectrometer of Perkin Elmer, Spectrum One. The range of spectra was kept at 4000-400 cm − 1. The pellet was prepared by mixing Vaishvanara Churna with KBr (FTIR grade) in a ratio of 1:100. The spectra were recorded by placing the pellet in the sample holder of the instrument.
In vitro dissolution studies on the Vaishvanara churna tablet
The dissolution study of coated Vaishvanara churna tablet was performed using an 8-station USP Type II dissolution apparatus with 900 mL of dissolution fluid at 37°C ± 0.5°C by rotating at 100 rpm using 0.1 N HCl (pH 1.2). Ten milliliter samples were collected at 15-, 30-, 45-, and 60-min time interval and were filtered using the 0.45 μm syringe filter. The sample was replaced by equal volume of the dissolution medium at 37°C. The sample was subjected to 10 times dilution and was tested under ultraviolet (UV) absorbance reading at 272 nm for determination of gallic acid.
High-performance thin-layer chromatography analysis
Preparation of the Sample
Accurately weighed 1 g of samples of Vaishvanara churna and crushed tablet were separately dissolved in 10 ml ethanol and refluxed on water bath at 90°–100° for 10 min. They were filtered and then taken for thin-layer chromatography profiling. Solvent system consisting of Toluene: Ethyl acetate: Glacial Acetic Acid in ratio of 93.5:6.5:3.5 v/v was used for volatile ingredients of the formulation. Solvent system consisting Toluene: Ethyl acetate: Glacial Acetic Acid: Methanol in ratio of 86:86:30:7 for better separation of phenolic ingredients in the formulation. The ethanolic extract were applied on 0.2 mm thick precoated Silica Gel 60F254 plates (Merck KGaA) and developed in the above-mentioned solvent system. The developed plates were examined under UV light at 254 and 366 nm. The photographs of both the wavelength were taken and RF values were calculated.
High-performance thin-layer chromatography analysis
Silica Gel 60 F254 precoated aluminium plates (Merck KGaA) of 10 cm × 10 cm with 0.2 mm thickness were used for high-performance thin-layer chromatography (HPTLC). The ethanolic extract of the in-house formulation, Marketed Formulation, coated tablet of Vaishvanara churna and Uncoated Tablet of the Vaishvanara churna were used for HPTLC profiling. Two microlitre of each formulation along with standards of 8 mm width was applied by autosampler system-CAMAG Linomat 5. The plates were developed in CAMAG glass twin through chamber (20 cm × 10 cm) previously saturated with the solvent for 60 min maintained at 60° and 40% relative humidity. The development distance was kept to be 9 cm. The Mobile phase used was Toluene: Ethyl acetate: Glacial Acetic Acid: Methanol (86:86:30:7 v/v) Visualization was done at 254 nm.[16],[17],[18],[19]
Thermo gravimetric analysis
The Thermogravimetric analysis (TGA) can used to evaluate the weight change of churna preparation due to excessive heat during the procedure. A defined quantity of the sample was taken and placed in alumina crucibles with a heating rate of 10°/min from room temperature to 600° in a nitrogen atmosphere using a thermogravimetric analyser TGA/differential scanning calorimetry (Mettler Toledo Switzerland). The calculation was done with help of STAR e Software (Mettler).
Statistical analysis
All the data reported are an average of triplicate observations. The data were expressed as means ± standard deviation (SD).
| Results and Discussion | | |
Six formulations (F1-F6) were prepared using Vaishvanara Churna with each tablet weighing 650 mg each. Tablet in all formulas showed appearance uniformity with flat texture and round shape and light pink in color [Table 3]. The tablets showed no signs of mottling indicating uniform mixture of the ingredients. The foreign matter content of the entire ingredient was found to be less 0.4% (w/w), which is below the maximum permissible limits of the Ayurvedic Pharmacopoeia of India.
Physical properties of vaishvanara churna tablet formulation
Weight of the formulations were found to be uniform at 650.1 ± 4.28 mg indicating uniformity of content, thus positively affect the uniformity of the dose in achieving the desired dose. The tablet's hardness reveals its resistance to mechanical stress, including shock, collision, and cracking during packaging, storage, shipping, and consumer delivery. According to the result obtained, all formulas have similar hardness values, which were 5.1 ± 0.25 kg [Table 4]. Other parameters were well within the range of pharmacopoeial limits.
Evaluation of vaishvanara churna tablet formulation
The tablets of Vishvanara churna were evaluated for the pharmacopoeial parameters [Table 4] as per the standard protocol available in Indian Pharmacopoeia. The flow property of formulation shown in [Table 6] has good flow. The disintegration time of the tablet was found to be 4 min 15 s in case of Formulation F5 which was considered to be best in terms of all parameters and considered for further studies.
The phytochemical screening of F5 formulation showed presence of all the tested phytochemical components like glycosides, carbohydrates, saponins, tannins, and flavonoids [Table 7]. Crude drugs may contain heavy metals due to soil contamination and air pollution. In addition, metals and minerals are employed to create Ayurvedic medicines. Hepatotoxicity, congenital paralysis and deafness, developmental delay, status epilepticus, fatal neonatal encephalopathy, and other harmful effects have all been linked to heavy metals. Heavy metals in Ayurvedic and other herbal medicines have been linked in numerous case studies to severe adverse consequences. Therefore, it is necessary to check for heavy metals in such preparations [Table 8]. All of the samples tested negative for the presence of heavy metals in this investigation, further demonstrating the preparation's nontoxic properties. Vaishvanara Churna tablet is a safe polyherbal formulation because it contains no hazardous ingredients. | Table 7: Phytochemical screening of coated Vaishvanara Churna tablet (F5)
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 | Table 8: Concentration of heavy metals in Vaishvanara Churna formulation
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Microbial analysis of vaishvanara churna formulation
Various microorganisms such as Staphylococcus aureus, P. aeruginosa, E. coli, and Salmonella typhi contaminate herbal drugs and cause serious health hazards. For the detection of such microorganisms, colonies obtained on specific media were subjected to suitable microbial tests along with pure strains to detect their presence or absence. The results obtained [Table 9] revealed the absence of these microorganisms thereby confirming the nontoxic nature of the formulation F5.
The FT-IR spectra of the Vaishvanara Churnatablet are displayed in [Figure 1] and [Figure 2] were found to be comparable to the FT-IR spectra of churna [Figure 2]. Infrared spectra of tablet appears as a very intense absorption ribbon, around 3421 cm − 1 due to OH group. A small absorption ribbon in between 2874 cm − 1 indicating CH group. At 1628 cm − 1 appears a characteristic peak of carbonyl group (C = O). At 1389 cm − 1 appears absorption ribbon from CH stretch. All the peaks were similar to spectra of only churna indicating no chemical changes due formulation and compression of tablets. | Figure 1: Photographs of Powder Microscopy of Vaishvanara Churnatablets (a) Fibers and Vessels Tachyspermumammi (×10). (b) Vittae and Endosperm (×40). (c) Endosperm (×40). (d) Endosperm (×40) Trachyspermum roxburghianum. (e) Vitae of Trachyspermumroxburghianum (×40). (f) Epidermal tissue with striated cuticle with papillose cells (×40). (g) Starch grains with eccentric hilum (×40) Zinziber officinale. (h) Vascular Bundles (×40). (i) Fiber (×40). (j) Calcium oxalate crystals Terminalia chebula (×40). (k) Vessles (×40). (l) Stone cells and Sclereid patch from Fruits (×40)
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 | Figure 2: Fourier transforms infrared spectra of different formulations of Vaishvanara churna
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In the Powder Microscopy of Vaishvanara Churna, the diagnostic characters of the formulation's each ingredient were identified and shown in [Figure 1]. The epidermal tissues with radially striated puckered papillose outgrowths were observed for Ajmoda (Trachyspermum roxburghianum Fr.); epidermal tissue with striated cuticle with papillose cells and short glandular outgrowths were observed for Yavani (T. ammi Fr.); broad, reticulate or pitted vessel debris, long non–lignified fibers with septae and dented along one side, starch grains large, up to 50 μ, oval with eccentric hilum were observed for Sunthi (Z. officinale Rz.); groups of sclereids with pits and broad lumen, fibres with crisscross thin wall and broad lumen and pegged tips were observed, polygonal cells in epidermal tissues, beaded walls and few of them showing thin septa were observed for Haritaki (T. chebula P.).
Physicochemical Analysis of Vaishvanara Churna (mean ± SD of three batches) showed in the following [Table 5]. The flowability of the granules of Vaishvanara Churna are depicted in the [Table 6].
The dissolution method for tablets
In vitro dissolution studies of the coated tablets reported in [Figure 3] revealed that % drug release of the F5 after 1 h at pH 1.2 was 99.33% ± 0.48%. Thus, this indicates the F5 Vaishvanara Churna coated tablet formulation is a rapid releasing in nature.[20],[21] | Figure 3: Release profile of gallic acid in Vaishvanara churna-coated tablet
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Thermo gravimetric analysis
The pyrolytic character of Vaishvanara churna tablet occurred in four stages. The First stage of Decomposition mainly attributed to loss of volatile oils mainly terpenes and water upto 130°C [Figure 4]. The Second Stage of Decomposition 130°C to 250°C indicates decomposition of plant material. The Third decomposition stage of 252°C to 357°C indicates turbostratic crystallites during pyrolysis. The Fourth Stage of 357°C to 600°C indicates biochar due to decomposition of more heat resistant components like lignins etc.[22] | Figure 4: Step wise degradation of Vaishvanara churna tablet during thermogravimetric analysis
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High performance thin layer chromatography analysis
The Analysis of HPTLC was done by using winCATS Planar Chromatography Manager Software as mentioned in [Figure 5], [Figure 6], [Figure 7], [Figure 8]. The concentration of the gallic acid in the uncoated formulation was found to be 124 ppm, whereas the concentration in coated formulation was found to be 184 ppm. The reason for more content of gallic acid in the coated formulation strengthens our objective of making a coated tablet of Vaishvanara churna. | Figure 5: Standard curve for gallic acid for HPTLC analysis of Vaishvanara Churna. HPTLC: High-performance thin-layer chromatography
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 | Figure 7: HPTLC Profile of Vaishvanara churna tablet at 272 nm. HPTLC: High-performance thin-layer chromatography
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 | Figure 8: Photograph of HPTLC plate: 1-5 calibration curve of gallic acid and others are different fraction of F5 sample. HPTLC: High performance thin layer chromatography
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The quality control parameter from the above study is summarized in [Table 10]. The authors suggest that it can be used for the quality control parameters for the preparation of Vaishvanara Churna tablets.
| Conclusion | | |
The results from the organoleptic, physical, physicochemical, and other tablet evaluation properties indicated that all F1-F6 formulations were in pharmacopoeial range. The formulation F5 showed the best disintegration properties so it was selected for further studies. The FTIR showed suggests that the absence of any chemical interaction between the churna and the excipients used in the coated tablet in F5 formulation. The F5 tablet formulation showed rapid releasing nature. The TGA shows four stages degradation while, HPTLC showed higher amount of gallic acid and thymol in F5 tablets. Thus, in this study we conclude that the tablet formulation of our Ayurvedic Churna is better option to measure the right dose and subsequently to improve patient compliance. The standardization parameters evaluated in this study can be used for identity, purity and safety of patients at large. The amalgamation of the traditional and modern system of medicine can improve therapeutic efficiency and overall acceptability of traditional medicines across the world.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Mukhi S, Bose A, Ray A, Swain PK. Analytical standards of Amrtadi churna: A classical Ayurvedic formulation. Indian J Pharm Sci 2017;79:227-40.  |
| 2. | The Ayurvedic Pharmacopoeia of India, Part-II, Volume-I, First Edition (Formulations). New Delhi: Government of India, Ministry of Health and Family Welfare, Department of Ayurveda, Yoga, and Naturopathy, Unani, Siddha and Homeopathy (AYUSH); 2007. p. 59. |
| 3. | Momin M, Amin AF, Pundarikakshudu K. Development and evaluation of Triphala formulations. Indian J Pharm Sci 2004;66:427. [Full text] |
| 4. | Bhope SG, Nagore DH, Kuber VV, Gupta PK, Patil MJ. Design and development of a stable polyherbal formulation based on the results of compatibility studies. Pharmacognosy Res 2011;3:122-9. |
| 5. | Heigl D, Franz G. Stability testing on typical flavonoid containing herbal drugs. Pharmazie 2003;58:881-5. |
| 6. | Surwade M, Kumar ST, Karkhanis A, Kumar M, Dasgupta S, Huebschmann HJ, et al. Analysis of multiresidue pesticides present in Ayurvedic Churna by GC-MS/MS. Thermo Fisher Scientific Application Note; 2013. p. 10361. |
| 7. | |
| 8. | Singh R, Gautam N, Mishra A, Gupta R. Heavy metals and living systems: An overview. Indian J Pharmacol 2011;43:246-53. [ PUBMED] [Full text] |
| 9. | Rasheed NM, Gupta VC. Standardization of a compound Unani herbal formulation "Qurs-e-Luk" with modern techniques. Pharmacognosy Res 2010;2:237-41. |
| 10. | Rathnam, G. Formulation and Evaluation of Colon Targeted Compression Coated Tablet of Mesalamine and Prednisolone for Ulcerative Colitis. Asian Journal of Pharmaceutics (AJP) 2017:11. |
| 11. | Mukhi S, Bose A, Panda P, Rao MM. Pharmacognostic, physicochemical and chromatographic characterization of Samasharkara Churna. J Ayurveda Integr Med 2016;7:88-99. |
| 12. | Mangilal T, Patnaik KR, Sunder RS, Bai SA. Preparation and evaluation of poly herbal anti-aging cream by using different synthetic polymers. Polymer 2017;4:4gm. |
| 13. | International Conference on Harmonisation Quidelines Q2A on: Validation of Analytical Methods: Definitions and Terminology. Geneva: ICH Harmonised Tripartite Guideline; 1994. |
| 14. | International Conference on Harmonisation Quidelines Q2B on: Validation of Analytical Procedures: Methodology. Geneva: ICH Harmonised Tripartite Guideline; 1996. |
| 15. | Sen I, Shrivastava D, Aggarwal M, Khandal RK. Development of a validated method for quantitative analysis of heavy metals in herbal medicines using inductively coupled plasma mass spectrometry. Development 2021;1:487-502. |
| 16. | Mudrić J, Arsenijević J, Maksimović Z, Ibrić S, Gopčević K, Đuriš J. Tablet and capsule formulations incorporating high doses of a dry optimized herbal extract: The case of Satureja Kitaibelii. J Drug Deliv Sci Technol 2021;66:102776. |
| 17. | Makhija IK, Shreedhara CS, Ram HH. Physico-chemical standardization of Sitopaladi Churna. Anc Sci Life 2012;31:107-16. |
| 18. | Aswatha Ram HN, Ujjwal K, Prachiti L, Shreedhara CS. Standardisation of Avipattikar Churna – A polyherbal formulation. Pharm Res 2009;1:224-7. |
| 19. | Bhandari P, Kumar N, Gupta AP, Singh B, Kaul VK. A rapid RP-HPTLC densitometry method for simultaneous determination of major flavonoids in important medicinal plants. J Sep Sci 2007;30:2092-6. |
| 20. | Santana CP, Medeiros FD, Correia LP, Diniz PH, Véras G, Medeiros AC. Dissolution and uniformity of content of tablets developed with extract of Ximenia Americana L. PLoS One 2018;13:e0197323. |
| 21. | Fereja TH, Seifu MF, Mola TY. UV-visible spectrophotometric method development and quantification of ciprofloxaciline in tablets dosage form. J Pharm Pharmacol 2015;2:1-8. |
| 22. | Coats AW, Redfern JP. Thermogravimetric analysis. A review. Analyst 1963;88:906-24. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7], [Table 8], [Table 9], [Table 10]
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