|Year : 2021 | Volume
| Issue : 1 | Page : 3-11
Critical review on pharmaceutico-analytical and safety profile of Swarna Makshika Bhasma (chalcopyrite calx)
Vandana Meena, Shakti Bhushan, Anand Chaudhary
Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India
|Date of Submission||19-Jul-2021|
|Date of Acceptance||13-Sep-2021|
|Date of Web Publication||14-Dec-2021|
Dr. Vandana Meena
Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh 221005.
Source of Support: None, Conflict of Interest: None
Swarna Makshika (chalcopyrite), an ore of copper, is used since ancient days in India to treat various ailments. Swarna Makshika Bhasma (SMB) preparation involves two main processes: Shodhana (detoxification) and Marana (incineration in a controlled manner). The present study is designed to compile and assess all the relevant and standard work done related to SMB preparation in addition to standardization in terms of its pharmaceutical, analytical, and safety parameters. These drugs may accumulate contaminants at various stages of manufacturing, transit, and storage, making them dangerous to administer and necessitating their detection and quantification. Analytical instrumentation and procedures are crucial in this regard. Sophisticated analytical analysis (X-ray diffraction, energy dispersive X-ray, Raman spectroscopy, Fourier-transform infrared spectroscopy, scanning electron microscope, transmission electron microscope, and nuclear magnetic resonance) may improvize our understanding on drugs’ overall response in terms of their structure, behavior, and response in the body. Relevant literatures of ancient India related to ayurvedic pharmaceutics for preparation of SMB along with contemporary research databases such as Scopus, PubMed, and various other appropriate contents on the internet were thoroughly searched. This work may provide an insight into its potential effect in characterization and therapeutics, eventually leading to the betterment of human life. Though this compilation has some limitations due to less standard works available, the concise perimeter may provide further quality studies to be done in near future.
Keywords: Bhasma, chalcopyrite, Marana, Shodhana, Swarna Makshika
|How to cite this article:|
Meena V, Bhushan S, Chaudhary A. Critical review on pharmaceutico-analytical and safety profile of Swarna Makshika Bhasma (chalcopyrite calx). J Drug Res Ayurvedic Sci 2021;6:3-11
|How to cite this URL:|
Meena V, Bhushan S, Chaudhary A. Critical review on pharmaceutico-analytical and safety profile of Swarna Makshika Bhasma (chalcopyrite calx). J Drug Res Ayurvedic Sci [serial online] 2021 [cited 2022 Aug 15];6:3-11. Available from: http://www.jdrasccras.com/text.asp?2021/6/1/3/332500
| Introduction|| |
Bhasmas are nano-sized medicines practiced in the Indian subcontinent since the seventh century and are widely used to treat several ailments. These are also added in traditional Ayurvedic polyherbal preparations to improve their potency.,,, In Ayurveda, Swarna Makshika Bhasma (SMB) is an incredibly admired medicine administered in past centuries till date. In various dosage forms, it is used to treat anemia, cardiac insufficiencies, poor intestinal capacity, icterus, chronic low-grade fever, eye burning, heartburn, micturition, nausea, reflux disease, headache, itching pain, leucorrhea, etc. The general dosage prescribed for SMB is 125–375 mg in adults.
Two primary processes for the processing of SMB involve detoxification in addition to purification with desired therapeutic properties, namely, Shodhana and Marana. Numerous Acharyas mentioned different media and methods for the Shodhana and Marana for the preparation of SMB. Shodhana incorporates numerous techniques such as Swedana (boiling), Bharjana (baking), Nirvapa (heating up and quenching in particular media), and Bhavana/Mardana (grinding). Marana (incineration) is a system of heating in which a specific quantum of heat (puta) is provided for a specific duration., SMB can be manufactured using different traditional putas. Cow dung cakes are used as fuel with their particular number or volume in a conventional system arranged in a particular dimension of the pit. Different herbal processing substances such as lime juice, castor oil, triphala decoction, banana stem juice, and sulfur as mineral origin are used during the manufacturing process of SMB. This variation in manufacturing creates confusion in standardization regarding the establishment of its quality, safety, and efficacy.
The selection of a particular methodology for Shodhana and Marana plays an important role in altering its pharmaceutical, analytical, toxicological, pharmacological, and therapeutic aspects of its formulations. Many research works had been done on Swarna Makshika (SM, chalcopyrites) regarding pharmaceutical validation, chemical characterization, safety profile, and therapeutic validation. In this present study, most of the available research works had been compiled on SM along with brief critical information about its pharmaceutical, analytical, toxicological, and pharmacological data, so that we can select a better option in the future for a superior result.
| Materials and Methods|| |
This review was prepared through literature searches using the keywords Makshika,Swarna Makshika, and Makshika Bhasma in the published articles on the internet. Range of databases such as PubMed, Medline, Google Scholar, and Scopus search engines and information from various Ayurvedic treatises and books were intensively searched.
| Classical collection|| |
Rasa shastra is an Ayurvedic branch devoted to therapeutics including ingredients of metal, mineral, and animal origin processed in herbal decoction/extract. SM (copper pyrites) is a popular Rasaushadhi commonly used as a rejuvenator, aphrodisiac, and used in the treatment of various ailments like kustha (skin disease), pandu (anemia) described in Charaka Samhita, Sushruta Samhita, and Rasa Ratna Sammuchya (an ancient classical text of rasa shastra/ayurvedic pharmaceutics, twelfth century), and various other Rasa Shastra texts. Various synonyms, desirable-undesirable characters, pharmaceutical processing (Shodhana and Marana), and Satvapatana (extraction of active ingredients) are depicted in [Figure 1].
Various procedures of Shodhana and Marana along with different media in original form/extract/decoctions mentioned in the diverse text of Rasaushadhis are depicted in [Table 1] and [Table 2].
|Table 2: Various Marana processes of Makshika mentioned in the different Ayurvedic texts|
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| Problem faced in standardization of SM|| |
SM has been mentioned since ancient times in India for its therapeutic activity against skin and gastrointestinal disorders. Due to the lack of proper standardization techniques, Bhasmas counters up with its safety and quality issues. Procurement and authentication of SM in its raw form is a tedious task and its rare availability poses serious concerns on standard manufacturing. Differences in raw material procurement to various pharmaceutical procedures adopted eventually produce bhasmas with variable characters. Hence, desirable reproducibility is not achieved. Numerous times it is seen that industrial pharmacies do not adopt standard fundamentals of traditional method and adopt short-cut methods and use a substitute or substandard material to produce large quantities of products in less time. If basic principles of manufacturing and standard test at the end of the product formation (Bhasma pariksha) get compromised, then it eventually leads to the accumulation of toxic substances exceeding permissible limits. Sometimes, it becomes difficult to procure the ingredients used in media processing (shodhana and marana) as per the season and hence hampers the process of manufacturing. Fuel consumption in traditional heating usually consumes cow dung cakes; therefore to standardize in terms of electrical heating in an electrical muffle furnace becomes a herculean task. Temperature standardization for a controlled quantum of heat (puta) along with its ascending and descending pattern needs precise operative procedures. Subsequently, in order to minimize variability and to sustain quality, efficacy, and safety, we need standard operative procedures for the preparation of bhasma along with its quality control and quality assurance.
| Pharmaceutical validation|| |
Different kinds of laws can be used for explaining the thermodynamics of Puta. Puta is a precise arrangement of heating for the incineration of metals and minerals of different densities and properties. According to the fuel quantity and nature of raw material to be incinerated, various putas are described, namely, Mahaputa, Gajaputa, Varahputa, Kukkutaputa, Bhandaputa, etc. Each puta has different dimensional measurements for specific intensity, temperature mode, duration, and heat resistance as per the nature of raw materials. Different laws of thermodynamics are used to explain the mechanism of conduction of heat flow. Fourier law and Hess’s law explain the rate of flow of heat through uniform materials as circular pellets are prepared during the puta process. Several physiochemical changes occur inside the closed system. Nowadays, electric muffle furnaces of two types, vertical and horizontal, are used frequently with maximum working temperature till 1200°C in a controlled manner.
Standardization and regulation of temperature are tedious tasks while preparing metal/mineral Bhasmas, and this article focusses on standard temperature pattern for the preparation of classical SMB. In one study, SMB was given conventional heating instructions in line with criteria quoted in Ayurvedic Formulary of India. Intended for SM incineration, Varaha Puta or Gaja Puta is recommended. Four kilograms of cow dung cake for a 100 g sample was procured. It was observed that even after 10 puta desirable color as per SMB was not obtained, stating that there was no proper conversion of material into Bhasma. On discussion with the expertise of this field (as mentioned in the study), the mass of cake prepared from cow dung was enhanced to 6 kg. After three puta, the desired color, that is, Raktotpala (reddish brown) color, was obtained. Bhasma’s cumulative production was 91.98%. The conclusion was that 6 kg of cow dung cake was sufficient for 100 g of sample regarding SMB’s preparations.
A study entitled “Swarna Makshika Bhasma preparation using an alternative heating method to traditional Varaha Puta” was intended to obtain the conventional Varaha Puta’s temperature profile and to generate a complementary temperature profile inside the muffle furnace. Varaha Puta’s temperature profile was measured using dried cow dung cakes (created cow dung and sun-dried paddy cakes) at a heat flux rate of 15.44 MJ/kg. The temperature profile was then mapped with an electric muffle furnace to the conventional Varaha Puta, and SMB (chalcopyrite) was produced using both the traditional oven and an electric muffle furnace.
Methods prepared for SMBs produce particles in the diameter range of 0.05–92.57 μm. About 35.71% of the entire Bhasma made with conventional Varaha Puta is below 10 μm in diameter, and 47.03% of the particles in Bhasma made with a muffled furnace was below 10 μm in diameter. In addition, it is shown that 50% of Bhasmas particles are less than 20 μm.
The original composition of SM formulated with external CuS addition was 15% Fe2O3, 38% Cu, and 1.8% SiO2. During this preparation, the key aspect of SM is the retention of a proper copper (Cu) percentage in the initial sample. Fe, Cu, and SiO2 compositions in pellets were around half the first raw mineral composition as SM was blended in the pellet preparation with the same amount of sulfur. After Marana, Fe, Cu, and SiO2 content in Bhasma prepared at Varaha Puta amounted to 47%, 44%, and 2%, respectively, compared with 38%, 35%, and traces present in the Bhasma prepared in an electric muffle furnace.
Bhasma made with both Varaha Puta and muffle furnace showed similar properties based on conventional ayurvedic studies and recent laboratory techniques. The findings revealed that the SMB can be prepared equally with an electric muffle oven over conventional Varaha Puta.
System standardization and regulation of output is a compulsory activity for sound industrial practices to ensure the quality and volume of the finished product. Methods described in Rasa Ratna Samuchhaya (a classical textbook of Ayurveda) were followed to perform Shodhana (detoxification) process. Repetitive quenching in Triphala decoction imparts some microelements that can nullify the toxicity of primary raw content and improve SM’s therapeutic properties. Shodhana of SM was carried out in three batches (600 g in each batch) by quenching seven times in Triphala Kwatha (a decoction of three ingredients Phyllanthus emblica, Terminalia bellirica, and Terminalia chebula). The method would conclude that an average of 532 g of Shodhita SM (88.67%) from 600 g of SM was obtained. The average time required for achieving the red hot stage was 24.81 min. Media research has shown that pH, basic gravity, and overall solid content have been improved. On completion of Shodhana, average return was 88.67%. The findings of this analysis ensure the standardization of the operating procedures implemented in SM Shodhana.
| Analytical validation|| |
Ancient pharmaceutical methods have been able to turn metals and minerals into therapeutic medicines that have been in common usage over the years. However, the physical and chemical character of raw materials and finished goods must also be clarified. In the standardization of drugs, analytical analysis plays a significant role. The lack of standard quality control profiles impedes the adoption of the traditional methods of drug development. Efficacy and safety are influenced by drug consistency, that is, the profile of the ingredients in the finished product.
A trial for raw and refined SM was performed to produce a pharmacological fingerprint. In an iron vessel, powdered SM was heated with lemon juice for 3 days, before sulfur fumes ceased. Bhasma was obtained by triturating Shodhit (purified) SM (copper pyrites) with purified Gandhaka (sulfur) and lemon juice. This mixture was heat-regulated with nine putas and was used as fuel in 4 kg of cow droppings cakes. To ensure quality management parameters for Bhasma according to the Rasa Shastra (ancient Indian classical text for the preparation of Bhasmas for therapeutical use) book, classic tests such as Nischandratva (loss of metallic luster), Varitara (after sprinkling float on the surface of the water), Rekha-purnatva (particle should be really tiny that it can get into the finger pores), etc. were used. The desired observation was passed by the Bhasma, and the final result was analyzed with X-ray diffraction (XRD). Raw SM and SM Bhasma study showed that raw SM contains CuFeS2 and that SM Bhasma contains Fe2O3, FeS2 and CuS mixture, and SiO2 combination.
Electron scanning microscopic studies have shown that SMB grain is reliably arranged in 1–2 µm size agglomerates in contrast to the raw SM grain, which showed an increased grain arrangement of 6–8 µm grain size. The author appears to be the first to record SMB’s fingerprinting by this specific method.
SM is one of the most important minerals containing iron (Fe), copper (Cu), and sulfur (S), along with other therapeutically important trace elements.
There are a few studies concerning SM characterization. In the present study, the transmission electron microscope (TEM) and energy dispersive X-ray (EDAX) research have analyzed SM and SMB.
Analysis indicates that Fe, Cu, and S are found in SM. Besides these elements, potassium, magnesium, aluminum, and silicone are present in trace amounts in SMB. The TEM analysis indicates substantial reduction to 50–200 nm of grain size of SM (5–10 µm).
In another study “X-ray diffraction of different samples of Swarna Makshika Bhasma,” the analysis was prepared with various media and methods to determine chemical changes in SMB. This research was conducted using various media and processes, raw SM, SM distilled (purified), and four forms of SMB (lemon juice, Shodhita Gandhaka and lemon juice, 1/8th part of Shodhita Hingula triturated with lemon juice, and Kajjali triturated with lemon juice). XRD analysis has been evaluated. XRD of SMB separate samples following comparison with the Joint Committee on Powder Diffraction Standards data indicates that raw SM has CuFeS2, which, after Shodhana, has been transformed into copper sulfides with iron and oxide and iron sulfate. Significant compounds of numerous samples found in Bhasma were Fe3O4, Fe2O3, FeS2, FeSO4, and Cu2S. The Bhasma prepared by Kupipaka followed by Putapaka revealed that strongest peaks of Fe2O3, Cu2O, and FeSO4 were identified. The XRD analysis shows the easier, more convenient, and more time-saving SMB prepared with Kupipakwa methods.
| Safety validation|| |
An analysis called “Evaluation of Swarna Makshika Bhasma’s subchronic genotoxic potential” was carried out with the goal of producing and evaluating 14 days’ therapeutic administered genotoxic potential in SMB (mineral preparation). In this analysis, chromosomal aberrations and irregular criteria for sperm testing were taken. As a positive group, cyclophosphamide (CP) has been taken and findings were compared. The findings indicated a lack of structural malformation in the above parameters in contrast to the CP-treated community with the studied drugs. Observed results suggested that under laboratory conditions, tested Bhasmas were non-genotoxic.
One research examined the results on various biochemical parameters in laboratory animals of the conventionally prepared SMB for the empirical evidence basis for logical use in clinical practice. Test animals (rats) were split into two classes. The SMB combined with diluted honey was delivered orally at medicinal doses in group SMB, and only the diluted honey was given to the vehicles control group for 30 days. After 15 and 30 days of drug management, separate biochemical tests were conducted, and the blood samples are obtained twice. Based on references to ayurvedic classics and contemporary medicine, the biochemical criteria were selected. There was a substantial rise in the percentage of hemoglobin; low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) were observed in group SMB to be slightly lower when compared with the vehicle control group. This experimental evidence allows doctors to use SMB in a variety of conditions with outcomes such as low Hb% and elevated LDL and VLDL levels in multiple illnesses.
| Limitation and future perspectives|| |
Quality control parameters were more developed in ancient days as per their time, but they have certain limitations in the present era. The use of sophisticated tools in the present era may be helpful in the standardization of Bhasmas. The majority of the old texts set out such protocols to analyze Bhasmas, according to the range, mass, and physical and chemical stability of their particles. But these experiments are only observational and have no detail on the chemistry of these phases. Nowadays, we have included and we may add sophisticated analytical techniques regarding data gathering and structural mapping. After judgment with classical control parameters of Bhasma Pariksha and later on following these techniques are becoming important resources to standardize the intermediate and final products, which includes TEM, infrared spectroscopy, X-ray fluorescence, particle-induced X-ray emission, matrix-assisted laser desorption/ionization, atomic force microscopy, electron spectroscopy for chemical analysis, nuclear magnetic resonance, EDAX, and electron probe micro-analyzer, etc. These procedures of analysis provide in-depth view of the geometrical and cellular functions of the drug at the subatomic level. Safety and toxicity concerns on metal or mineral-based medicines have been raised by several scholars., Therefore, toxicity studies should be done on international parameters to assess the safety of Bhasmas and permissible levels can also be accessed via these procedures. These methods along with other complementary procedures of basic laboratory sciences can be helpful to generate fingerprints characterization and to establish the standard operative procedures/standard manufacturing procedure of Bhasma preparations.
| Conclusion|| |
SM is a copper-containing mineral that has been used in the treatment of various ailments in Ayurveda tradition, but nowadays due to proper unavailability of genuine samples standardization is need of the hour. Pharmaceutical characterization in terms of validation, safety evaluation, and analytical standardization becomes important. Sophisticated analysis of the data is need of the hour in ayurvedic drug standardization to develop a standard protocol of analysis and a better understanding of the behavior of drug by using contemporary tools of analysis. This article may help us to better understand the work done in relation to SM standard operative procedures along with different advanced/sophisticated analytical techniques.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]