The system of Ayurveda has a long history and is approximately as old as the Vedic age. At present, most people prefer Ayurveda as an alternative to allopathic medicines because it is significantly cheaper and has fewer side effects.¹  The products obtained from natural resources have been essential for maintaining and healing life for millennia. They are used following the processing or formation of raw materials from which robust chemical structures with promising biological activity are isolated. Nowadays, products from natural resources are becoming increasingly essential as complementary and alternative medicines and sources of pharmaco-therapeutics.²  Almost half of the population of the United States has tried natural medicines to prevent and/or treat diseases.³  Chemicals posing medicinal values are considered as active ingredients of natural therapies. For new drug development, natural products have been used as a primary resource. Nearly half of the Food and Drug Administration (FDA)-approved drugs from the 1940s to the end of 2020 were developed from natural products.^4–6  In natural medicine, the active ingredients are relatively low in quantity, and cumbersome extraction and isolation processes have been the limiting factor in applying natural drug development products. Therefore, the development of efficient methods for extracting and isolating natural bioactive products is appealing.³ 

The minerals and metallic preparations with healing properties occupy a significant area in the Ayurvedic pharmacopeia, which has been practiced in different parts of India for many centuries. Interestingly, those preparations are safe and, even in minute doses, are effective, provided that they are manufactured and used following the specified classical guidelines. However, over the past decade, several concerns have been expressed by the scientific community in the West regarding the safety of Ayurvedic preparations, including various minerals and metallic medical products.⁷  Ayurvedic medicines are based on plants, extracts of animals, and by-products of minerals as single drugs and/or compound formulations. Moreover, in Ayurveda, all substances are regarded as a potential source of medicine.⁸  With the aid of different manufacturing processes, Ayurvedic herbal dosage forms are formulated. Ayurvedic compound formulations mainly originate from plants (Kasthausadhi) and metals and minerals (Rasausadhi). Plant formulations such as Asavaristra, Avleha, Grafa Churena, and Taila, and metal and mineral formulations such as Bhasma, Lauha Kapibadkva, and Rasayana are described in Ayurveda.⁹ 

Arista and Asava are made by drenching the herbs in the form of powder or decoction in a solution of sugar or jaggery for a specific period. Over a period of time, it undergoes a process of fermentation that leads to the generation of alcohol, which aids in extracting the active constituents in the herbs.¹⁰  To manufacture essential liquid, medicines such as juices or decoctions, as indicated in the classics, are kept for fermentation. Ethyl alcohol is produced as an outcome of the manufacturing procedure and is not included from an outside source. In addition to ethyl alcohol, many other organic compounds, such as alcohol and acetic acid, are generated; in turn, herbal drugs are extracted. These formulations have a longer half-life, more rapid absorption and activity, and higher therapeutic efficacy than other Ayurvedic herbal medicines. The Ayurvedic system relies on specific dosage forms, Sadhana Kalpana (Asava, Arishta, and kanji), to treat diseases in day-to-day practice.¹¹  Similarly, in European countries, different stimulants such as wine and beer are formulated and used for pleasure. Interestingly, the preparation principles of fermented products were similar in ancient times to modern days, and few differences were observed in machinery, resource, and sterilization techniques. However, a marked improvement is observed in parameters which are tested to assess the quality of the end products.¹¹ 

In Ayurveda, use of mineral drugs is called Rasa Rasayana or Ras-yoga. Rasibhavana refers to the ability of Bhasma to act on the body, which mimics fluid containing nutrients that are circulating inside the body.¹²  The impurified states of mercury, gold, silver, copper, iron, and sulfur are used to convert to Bhasma form; subsequently, other herbs are added in aliquots and grounded to form a fine powder. Drugs such as Gandhaka and Manaḥaśila are used in purified form. Rasa and Gandhakaare, the components of a formulation of Kajjalī, are prepared, and fine powders of other specified drugs are added in specified quantities. The color and smell of the formula depend on the type of metal.¹³ 

The Laura Kalpa is formed following mixing powders of active drugs with Loha Bhasma. The powder mixture (churnas) is prepared by sieving the dry drugs through a fine cloth. Laura Kalpa in Churna form is prepared following the addition of finely powdered herbal medicines to the Lauha Bhasma. Until a homogeneous mixture is formulated it is triturated.¹⁴  Physicians mastered the art of Bhasma preparation relatively safely and effectively. The processing of Bhasma was remarkable, with the whole idea being to remove the toxicity of the minerals and metals in the therapeutic doses. To assess the safety of these formulations, physical and chemical tests have been developed, and the ancient texts discuss such tests. Interestingly, they considered the size of the particle, its density, and its chemical and physical stability under high temperature.⁸  The characteristics of properly processed Bhasma should include: once rubbed between the thumb and the index finger Bhasma particles are powdered to settle in the ridges of fingers; it should float on the surface of water; once mixed with the jaggery, fruits of Abrus precatorious Linn., ghee, honey, and borax and subjected to intense heating it should never re-appear as the original mineral or metal used to prepare the Bhasma. Special attention is required to keep the temperature below the temperature used to test the quality of Bhasma.⁸ 

Moreover, the Bhasma is placed in a crucible with an equally weighted piece of silver metal, and the crucible is heated for 3 hours, at the exact temperature used for the preparation of Bhasma. Thus, heating should not change the weight of the silver metal pieces, with any change indicating that the Bhasma has not been correctly prepared. Bhasma that fails to retain the described physical and chemical parameters is considered to be toxic. It is worth noting the harmful and poisonous effects of mercury and other minerals and metals for the therapeutics following improper or inadequate processing.^7,8 

Shodhana (purification) and Maarana are regarded as the two main steps in Bhasma preparation. Some minerals and metals, such as Biotite mica and copper, may undergo additional steps such as Amrutikarna and Lohitikarna.⁸ 

Shodhana is regarded as the process of purification. The aspects of Shodhana are broad and are not restricted to physical or chemical purification and are mainly focused on the therapeutic utility. Sometimes the processed material may contain foreign molecules. A summary of the objectives of shodhana is as follows: macroscopically remove foreign matter like dust and gravel; biologically eliminate the harmful activities of the drug; the physical and chemical modifications lead to improvement of its therapeutic action; and finally, preparation for further processing.⁸  At the end of shodhana, sulfur, hematite, and alum are suitable for use as a mono-drug or material for a herbal mixture. Other minerals and metals require further processing to be suitable as a drug, and this further processing is termed Maarana.⁸ 

Mica, pyrite ores, and metals are hard in consistency and following shodhana their consistency is reduced to a reasonable extent; however to make them edible further processing is required. In addition to making the materials soft and palatable, this augments the intended therapeutic efficacy.⁸  The objective of maarana is to obtain the material in powder form and as Bhasma that is as fine and as soft as collyrium. Collyrium is applied in the eye, is fine and soft in consistency, and does not cause chemical or physical injury to the cornea. To minimize toxic effects, the material is required to be further processed. The prescribed procedure is maarana, which is an outcome following the processes of incineration and calcination. It is carried out following wet grinding (Bhaavana) and incineration (Putapaaka).⁸ 

The end product of the shodhana process is termed shuddha dravya (cleaned products), which is used as the raw material for the process of maarana. Those raw materials are subjected to wet grinding, and initially, using the prescribed liquid media, the material is wholly soaked until the liquid is evaporated. When the grinder contents became doughy, the process of wet grinding is stopped, and pellets of the required size are cut from the dough. These pellets are dried in air, and further processing, called Putapaaka, is carried out. The incineration must be carried out appropriately using pellets. A specific device called a puta is used for incineration, and as fuel, cow dung cakes are used.⁸  Once dried pellets are obtained, they are sealed in two shallow earthenware plates using an appropriate sealing material. Then, the surrounding cow dung cakes are ignited, left to burn to ashes, and left to cool on their own. The sealed pot is later opened, and the contents are ground using a mortar to prepare fine powder.¹⁵  One puta describes the process from wet grinding to incineration. The process must be repeated until Bhasma in the required quality is obtained. However, following the prescribed number of puta, if the Bhasma fails in the prescribed tests, the puta process must be continued until Bhasma has been reached.¹⁵ 

In regards to the therapeutic activity of metal Bhasma, metal with mercury contains the highest activity. In contrast, medium activity is ascertained following metal with plant material, and the lowest following metal with sulfur. Metal Bhasma prepared by blending metals with opposing characters are thought to be toxic. In contrast, modern medicine strongly prohibits the internal use of mercury and its derivatives. Also, to avoid physical contact with mercury and its compounds, extra caution is recommended.¹⁵  Mercuric sulfide, an inorganic form, is the form that is primarily used in Ayurveda. Occasionally, mercuric chloride is used, and such use is limited and always advised with caution due to its toxicity. A negligible amount of mercuric sulfide is absorbed through the gastric mucosa and hence is nontoxic. In contrast, mercury in organic form has been often highly toxic and known to damage the brain and liver.¹⁶ 

The first reference to mercury and its utility in the classics is controversial, and its use is rarely mentioned in Charaka. Only a few scholars interpret Rasa in the verse chikitsasthana as mercury. In Dwivraniya Chikitsa, Rasa is interpreted as mercury by Chakrapani, the commentator. Interestingly, both these formulations are recommended only for external application.¹⁷  Rasausadhies, which were named after mercury, were classified into two separate classes: mercurials and nonmercurials. The use of mercury has changed the direction of the management of disease. Mercury was regarded as a bio-enhancer and not as a drug. When any medication is combined with mercury, it is supposed to increase its efficacy and reduce its dose manyfold.¹⁵  Initially, mercury is purified and converted into an effective, stable, and nontoxic compound. The primary material used to prepare most mercury-based drugs is a combination of mercury and sulfur, which are ground together. This fine powder is black and termed kajjali which mimics collyrium due to its color and softness. Depending on the preparation methods, mercury-based herbals are categorized as Khalvi Rasa, Parpati Rasa, Kupipakwa Rasa, and Pottali Rasa.^15,16 

A finely powdered formula is formed using a mortar by grinding mercury and sulfur with other herbal, mineral, and metal ingredients. After being ground in a mortar, termed Khalva, in Ayurveda the formulation is classified as Khalvi Rasa.¹⁵ 

A homogeneous black-colored fine powder termed Kajjali is formed using a ground mixture of mercury and sulfur mixed with or without a specified metal Bhasma. Then a molten mass is obtained using an iron spatula following the application of heat in a controlled manner. The molten mass then is poured immediately onto a flat soft surface, with a banana leaf placed on a smooth-surfaced platform made using fresh wet cow dung or mud and spread evenly. Then, the poured mass is covered immediately with a banana leaf and hand-pressed to create an even and thin flat sheet of the material termed parpati.¹⁵ 

Kupipakva Rasa is formed using mercurial drugs prepared by kajjali and is heated using a long narrow-necked glass flask (kupi). The drug is designed in the following stages: the kajjali, mercury, sulfur, and other required raw materials are subjected to the purification procedure; using a suitable mortar the purified metal is grounded with pure mercury to obtain a homogeneous mass.¹⁵ 

Kajjali appropriately mixed with other metals or herbs can alleviate most symptoms and cure diseases. Following administration, the herbs spread rapidly through the body, which in turn clears the obstructed vessels in diseased organs and enhances the properties of other metallic or herbal medications.¹⁸  In Ayurveda the toxicity of mercury is immensely reduced following its combination with sulfur therefore reducing its bioavailability. The preparation of Kajjali by mixing purified mercury and sulfur is the initial step in preparing any herb mineral formulations. The gradual and homogeneous application of heat for the preparation of Kajjali has been described. A layer of clayed fabric is wrapped around a flask or bottle, assuring that there is no air gap between the clayed fabric and the outer surface of the flask or bottle, and then it is left to dry. Soon after the first layer dries, the second layer of clayed fabric is wrapped around the flask. Successively, the flask is covered with seven layers of clayed fabrics, and once all the wrappings are entirely dried it is ready to use. Heating starts with a low flame at between 100–200 °C, and the apparatus is left to cool on its own. Therefore, the heating must be continued for a number of hours.¹⁵  Safe drug storage is mentioned in an ancient text as being in the form of a fine powder in an airtight container.^15,16 

Kajjali is wrapped in a silk cloth to prepare a tight bundle (pottali). Sulfur powder in the prescribed quantity is placed in a stainless steel or wide-mouthed earthenware pan, kept on a fire, and allowed to melt. Then the bundle of kajjali is immersed in the melted sulfur while an adequate temperature is maintained to keep the sulfur in a molten state for a reasonable period of time. The wrapped silk cloth is burnt and wrapped around the hardened ball. In a circular motion, the hardball is rubbed on a moist stone slab, and the accumulated paste is prescribed for licking. The drug's prescribed dose is decided following several rounds of rubbing.¹⁵ 

The Pottali Rasa is prescribed in medical emergencies and is regarded as an instantly acting drug formulation. Caution has also been issued for Rasa rasayana regarding the toxic effects of mercury and mercury toxicity treatment and its usability in Ayurveda texts has been intensely argued about. In Rasa therapy, mercury is regarded as the most unstable and chemically reactive substance. Mercury absorbs atmospheric impurities passively and tends to react with other metals and form amalgams quickly. Due to reactions, purified mercury is challenging to obtain.^15–17 

Since antiquity, gold has been described as a noble metal. It can be referred to as Charaka and Sushruta Samhita. The Bhasma form of gold is a mixture of metallic gold (96.76%), silica (1.14%), ferric oxide (0.14%), phosphates (0.78%), potash (0.16%), salt (0.078%), and traces of copper and magnesium. Various formulations of gold are helpful as disease alleviators, particularly in chronic debilitating diseases. The Swarna Bhasma dose is between 15–30 mg.¹⁷ 

According to the classics, the therapeutic use of silver is limited. Classical alchemy describes silver as clear and heavy with a metallic sheen. Following heating or cutting, it becomes bright white.¹⁶  The Bhasma form of silver is a combination of metallic silver (52–59%), free sulfur (0.675%), ferric oxide (14.33%), calcium (10.769%), silver chloride (0.479%), and traces of Na, K, and Al. The silver Bhasma dose is from 30 mg to 120 mg.^16,17 

Since pre-Vedic times, copper has been routinely used, and it is the best known metal for preparing the more robust brass and bronze alloy metals. A characteristic metallic sheen, smooth and bright reddish color with good tensile strength are observed in copper. Moreover, impurities are rarely identified and so it is very suitable for medicinal purposes. Formulations of copper are used to cure a broad spectrum of diseases including worm infestation and hemorrhoids. The use of copper vessels for various pharmaceutical procedures has been described in Charaka. The copper Bhasma dose is between 15–60 mg.^16,17 

After gold, silver, and copper, iron is another well-known metal that has been used for millennia. During Charaka, iron was used in various topical and oral formulations for many diseases. Compounds of iron were mainly used for anemia. Further classics describe iron as an excellent rejuvenator that stimulates all organ functions and promotes life, helping to regain mental and physical strength.^16,17  Iron has a large number of therapeutic applications in Ayurveda, and during purification and incineration, proper care should be taken. A procedure to convert thin metal into a fine digestible form was described by Charaka. In addition, the use of iron vessels for various pharmaceutical procedures has been described. Iron in Bhasma form is a combination of ferric oxide (96.5%), ferrous oxide (2.5%), magnesium oxide (0.8%), copper oxide (0.3%), with trace amounts of phosphorus and potassium. Various iron formulations are used in a broad spectrum of diseases including hemorrhoids and different types of pain. The iron Bhasma dose is between 30–240 mg.¹⁶ 

In Ayurveda the Mandura, another form of iron Bhasma, is well known for its use in a wide array of therapeutic procedures. Madhava Upadhyaya defines it as a collection of debris around a blacksmith's anvil, collected after heating and beating for many years. If anvils are 100 years old, they are regarded as the most useful, while those 60–80 years old are considered average and less efficacious. Mandura is smooth to touch, heavy, firm, devoid of fissures, and useful as a therapeutic.^17,18  Following purification Mandura is useful for inflammations, edema, jaundice, and anemia. Mandura is a combination of ferric oxide (59.14%), ferrous oxide (26.7%), chlorides (4.4%), magnesium (3.9%), sodium (1.7%), and a few other elements in small quantities. Its constituents play a major role in curing anemia. The Mandura Bhasma dose is between 30–240 mg.^17,18 

Since ancient times lead has been known as an important loha. Lead Bhasma topically, in particular for rashes, has been advocated by Charaka. Lead quickly melts and is heavy, externally black, and when cut shines a bright black. Quantitatively, lead Bhasma contains lead oxide (75.6%), ferric oxide (7.5%), and small amounts of calcium and magnesium chlorides and carbonates.^16,17  Various formulations are useful for obesity, pre-diabetes and diabetes, various abdominal lumps, and leucorrhea. The lead Bhasma dose is between 30–120 mg.^17,18 

The use of tin, a loha, has been well described in Ayurveda. The Rasa Vagbhata, an influential Ayurvedic writer, described two varieties of tin (Khurana and Mishraka), with the former being the accepted form of therapy. Khurana that is bright white, smooth, melts at low temperature, and heavy is identified as Khurana that is preferred for therapy. Tin in the form of Bhasma is a combination of stannic oxide (91.4%), ferric oxide (2.9%), potassium (2.9%), calcium oxide (2%), aluminum (2%), and magnesium oxides (0.6%).¹⁹  Tin Bhasma formation is used as a therapy for diabetes, respiratory tract disease, asthma, microbes, and bone dislocation. Alone, or in combination, it is beneficial for genitourinary tract pathologies. Also, it is the drug of choice for the treatment of obesity. The tin Bhasma dose is between 120–240 mg.²⁰ 

Brass is a mixed metal alloy of copper and zinc. Formulations of brass are beneficial in diseases such as various abdominal lumps, rashes, and jaundice. The brass dose is between 60–120 mg.²¹ 

Bronze, the bell metal, is made by mixing copper and tin. According to Ayurveda, there are two bronze varieties called Pushpa and Talika, and only Pushpa is used for therapy. When tapped bronze produces a sharp sound, and is soft to touch, gray in color, devoid of impurities, and following heating, it turns red. Formulations of bronze are used in the treatment of various types of abdominal lumps and rashes. The bronze Bhasma dose is from 60 mg to 120 mg.²²  The method of preparation of bronze Bhasma is described by Charaka. It is initiated following metal powder preparation and as with Carla, a 7.4 × 7.4 cm thin sheet of metal, penetrable with a thorn prick, is heated until it is red hot. The red-hot sheet is sequentially drenched till a delicate powder is formed in the decoction of Triphala (a mixture of dried Emblica officinalis, Terminalia bellirica, and Terminalia chebula), cow excreta (urine), Hordeum vulgare (Linn.) ash in water, rock salt, Balanites aegyptiaca (Linn.) ash in water, and Butea frondosa Koen Ex (Roxb.) ash in water.²³ 

The soft powder is subsequently mixed with honey and Phyllanthus emblica fruit juice and kept for a year. Once a month it is stirred and yields a semi-solid mixture which is the final form. This applies to gold, silver, copper, or iron as well.²⁴  In Sushruta Samhita, the concepts of Lohaadi Rasayana, chemistry in metals, is converted to powder form using a slightly different procedure described by Charaka. Here, thin metal sheets are softened using different mineral salts and made red hot following intense heating. These sheets are then drenched to make a powder in Triphala and decoction Shorea robusta Gaertn. f., Acacia catechu, Betula utilis D. Don, Gymnema sylvestre R. Br. 16 times. The powder is sieved using a fabric that is then used as a drug.^25,26 

The tablet or pill form in Ayurveda is known as Vati or Gutika. It is made using one or more plant drugs or purified materials from animals or purified minerals. When the dosage is in a circular mass it is called Gutika. This is comparable to pills in modern pharmaceutics. Vati is similar to a tablet that can be swallowed, while Ghanavati has to be chewed before swallowing.²⁷  Generally, the consumption of Ayurvedic medicines is a significant challenge for most patients due to their bitter and astringent taste. Most will accept this challenge to cure their diseases, however some are unable to. Vati is the most basic and palatable form of Ayurvedic medicine and is very easy to consume due to not having an unpleasant taste.²⁸  Vati can be modified into a long oval shape form called Varti. It is suitable for local administration in the anal or vaginal canals, penis, or eye. Another form, modaka, is circular and has a considerable size, having a weight of around 20–50 g.²⁹  Two types of vati preparation methods are described in Ayurveda, Agnisadhya vati and Anagnisadhya vati. Agnisadhya vati is made using sugar or jaggery or Guggulu on a warm fire. Contrary, Anagnisadhya vati is made without heat.³⁰  The vati or Gulika, made of herbal raw materials kept in airtight containers, can be used for two years. Vati or gulika, which contains minerals, can be used indefinitely if preserved properly, meaning that they do not have any expiry date. Vati should not lose their original color, smell, taste, or form. When sugar, jaggery, salt, or kshara are ingredients, the vati should be kept away from moisture.³¹ 

The fine powder formulation in Ayurveda is termed churna. The herbs are cleaned, dried, and powdered mechanically using a fine mesh. If churna is preserved in an airtight container, it can keep for one year without losing its potency.³² 

Semi-solid formulations are called Avaleha. These are prepared by adding jaggery, sugar, or sugar candy, and boiled with the prescribed decoction. When cold and well-mixed, honey is added. Various Avaleha are mentioned in Ayurvedic classics and they are the most popular Ayurvedic dosage form. They are easy to administer, palatable, and pose a long shelf-life.³³  According to various formulations, the percentage of sugar, sugar candy, and jaggery varied, and additionally sugar acts as a preservative. Once Avaleha is incorporated into a lipid medium using Ghrita it becomes soft. Moreover, honey, gingelly oil, salts, alkalis, milk and milk products, and Bhasma are added according to formulations and contain specific timeframes to develop it into a finished drug.³⁴ 

When ghee is boiled with the prescribed decoction, Ghrita is developed. Ghee contains 100% fat, and routine consumption may increase the likelihood of coronary artery diseases. Many therapeutic forms are described in Ayurvedic classics, such as tablets and powder, and it additionally contains self-generated alcohol. There are more than 55–60 medicated Ghrita described in the Ayurvedic classics. Drugs given in the form of Ghrita are digested and absorbed quickly and reach some of the most distant areas of the body, including the central nervous system.³⁵  The described preparation procedures used to produce Ghrita rely upon heating at temperatures from 105–118 °C to remove the water. Studies have been conducted on Ayurvedic medicated Ghrita to explore its effects in various conditions. A study conducted on Saraswati ghrita (a polyherbal formulation containing Bacopa monnieri as the main content with Curcuma longa, Phyllanthus emblica, Operculina turpethum, Terminalia chebula, and Piper longum embelia ribes and cow's Ghrita) demonstrated that Ghrita had exquisite potential for the management of disorders like Alzheimer's diseases and dementia.³⁶  Anticonvulsant activities have also been reported in medicated Unmadnashak Ghrita (an Ayurvedic formulation containing Ferula narthex (6 g).³⁷ 

According to the formula, various oils are formed following boiling with the prescribed decoction. The formation of lipophilic fluid ensures extraction of the active ingredients from the raw herbal materials. Taila generally has the color, odor, and taste of the herbs used, and has the consistency of an oil. When milk is used in a considerable quantity in the preparation, the oil becomes thick.³⁸  In Ayurveda, it is claimed that medicated Taila has greater power of healing and half-life than crude Taila. Taila can increase the level of energy and the body's anabolism.³⁹  For the preparation of Taila, precautions should be taken, such as the intensity of the fire should be maintained throughout the process to assure a consistent temperature. The mixture has to be carefully stirred throughout to ensure that the extract does not stick to the vessel. A moist-free container is used to preserve the Taila and to develop a favorable odor when Taila is lukewarm, also, the materials added should stir well.⁴⁰ 

Guggulu is prepared from exudates obtained from the plant Commiphora mukul. Small pieces of exudates are wrapped with a cloth and boiled in Triphala or other herbals till they pass into the solution through the cloth. Further, it is boiled to form a solid mass and left to dry. Once dried, ghee is added to form a waxy paste.^39,40  Ayurvedic physicians have used Guggulu for centuries to treat different diseases. It contains oils which vaporize rapidly, Gugu lipids, guggul-sterones, guggul-sterols, mukolol, and other steroids. Guggulu is used as an antiseptic, expectorant, antispasmodic, and emmenagogue. It is renowned as a fat-burning agent and is used as a slimming aid. It reduces total body cholesterol and triglycerides.⁴⁰  It is used to treat rheumatoid arthritis, gout, and sciatica and also for steatohepatitis, neuronal disorders, bronchial mucus congestion, and cardiac and circulatory problems. It stimulates digestion and libido and is useful in treating skin ulcers, local abscess, bone fractures, gynecological problems, and multiple skin diseases.⁴⁰ 

Extraction is the initial step to select active natural products from raw materials.⁴¹  According to the principle of extraction, different extraction methods are used, and solvent extraction, distillation, pressing, and sublimation are known methods; however, solvent extraction is most the commonly employed method. The liquid solvent has to penetrate the solid matrix, and subsequently, the active ingredients dissolve. Anything which enhances the diffusion and its solubility facilitates the process of extraction.⁴¹  Moreover, the efficiency of extraction relies on the characteristics of the solvent used for the extraction, particle diameter of raw material, solvent-to-solid ratio, temperature used for the extraction, and the duration.^41,42  For efficient solvent extraction, the proper solvent selection is essential, and solubility, cost, and safety characters also are required to be considered. For phytochemical extraction, alcohols are regarded as the universal solvents.^41,42  Currently, based on the required extraction in the phytochemical investigation, alcohol in the appropriate concentration and known strength is used; however, Ayurveda follows unique methods based on different scales and measurements. In Arista and Asava, alcohol extraction was used to extract essential herbs from the herbal formulary. Moreover, alcohol was formed following fermentation within Arista and Asava and consumers may take herbals in addition to formed alcohol.^41,42  Once the duration of extraction increases, the extraction efficiency increases; however, once equilibrium is reached between the inside of the solid material and outside the solvent, increased time barely affects the extraction. For the formation of different Arista and Asava specifically applied periods have been described in the ancient scripts.⁴³ 

The utility of different metals for modern medicine was identified in the 17th century, and was introduced following the use of iron salts for anemia. The roles of metals in the functions of metalloenzymes and metalloproteins are well known, and trace amounts of cobalt, copper, iron, selenium, zinc, and magnesium are essential. The use of selenium, copper, and gold in cancer treatment has been practiced for decades.⁴⁴  When considering the concepts of Rasa Rasayan, mercury or other metals in the form of Bhasma, the bioavailability of the drug is increased. According to modern medicine, mercury use is often limited to a few topical applications, dental fillings, and contact lenses. Compared to the organic form and various compounds, its elementary form is less toxic.⁴⁵  The various Ayurvedic formulations and their Western medicine counterparts are included in Table 1.1.

Over the centuries, gold in its elementary form was used as an antipruritic agent. Clinical trials have been conducted to assess the therapeutic potential of gold on arthritis and systemic lupus erythematosus.⁴⁶  Following the use of gold compounds, the concentration of rheumatic factor is decreased, and its influence on immunological response was remarkable. Compared to glucocorticoids, gold strongly suppresses the release of histamine following a type-1 hypersensitivity reaction. Sodium aurothiomalate, in a water-soluble form, was discovered around two decades ago, and is useful for treating arthritis.⁴⁷  However, its pharmacokinetics and dynamics properties are not well established, and its antiinflammatory and stimulatory effects on the reticuloendothelial system could be the reason for the above-described actions. Gold-based medications can be use as an analgesic, and an antioxidant effect also has been described.

Copper-based formulas have liver-protective- antioxidant- and gastroprotective effects. Zinc-based formulas arrest myopia and iron-based ones are hepatic- and gastro-protective. Often, Bhasma forms can be regarded as different complex compounds and have been shown to have a number of essential activities, especially a cytoprotective effect against different types of ulcers.^47,48 

Silver has the highest thermal and electrical conductivity and is the most reflective metal. Most importantly, silver can be used to prevent the growth of potentially harmful bacteria. At present, silver nanoparticles are used as antimicrobial products; however, the concepts of infection and infectious agents are not described in detail in Ayurveda.^46–48 

The consumption of mineral materials is impossible due to their hard consistency. However, chemical and physical processing change their consistency to make them smooth and palatable. This applies to the preparation of various modern-day metallic formulations by utilizing the knowledge of chemistry and physics combined with the battery of knowledge from the ancient era. The preparation of metal-based formulations involves the conversion of a thin sheet of metal into a powder. Heat and various acidic and alkaline preparations in a particular sequence are used for this conversion.^48,49 

Moreover, Ayurveda includes various herbs and purifying techniques to increase the quality of the desired herbal formulations. Often these are in the semi-solid phase, and those preparations are topically applied to the eyes as a therapy. However, Western medicine remains reluctant to use topical semisolid preparations on the eyes, only using liquids in the form of eye drops.⁵⁰  The use of metal-based herbal formulas for therapy is considered to be controversial. Two schools of thought exist, with practitioners of metallic Bhasma representing one while the other is represented by the scientific community holding Western beliefs. The practitioners of metallic Bhasma are invariably in favor of its use and argue that it has been used as a medication for thousands of years. However, in Ayurvedic classics it is mentioned that these drugs should be used with caution.⁵¹ 

General observations illustrate that metals are toxic; however, in therapeutic doses, compounds such as metal sulfides are nontoxic. The main concern is whether the metal-based preparations mentioned in the Ayurvedic classics are safe and efficacious.⁵²  Several studies have been carried out over the years, and many recent studies have shown that toxicity is not generally observed at the therapeutic dose level if used properly.^47–51  However, a great deal of data were gathered in the last century that oppose the above findings.^44–52  Often toxicity potential is inherent, if metal-based products are used inappropriately under unacceptable conditions, with fatal outcomes being relatively high. Such toxicity is generally not related to the active pharmaceutical ingredients and instead is often related to the manufacturing process. Since the manufacturing process is cumbersome, lengthy, and requires a high level of skill, only a few experts have gathered and retained the required knowledge. Following the loss of those experts, the retained knowledge has been gradually lost, resulting in a deficiency in the standard operating procedures and standardization has reduced its reproducibility.^50,51  There is a demand to standardize all aspects of herbal preparation.⁵³  Moreover, observations and facts are sufficient to claim that metal-based preparations used in Ayurveda contain essential biological effects. Therefore, these should not be discarded without an in-depth analysis to decide on the usability and safety.⁵⁴ 

Complexes of mercury and sulfur are prepared using different methods. During the preparation of Kajjali sulfur is provided in excess compared with that required for the stoichiometric arrangement of HgS. The idea behind this is to minimize oxidation. The processing of mercury reduces its toxicity and the adopted methods of purification are unique. Allium sativum (Rasona), which contains sulfur, is used for the purification of mercury. Also, for processing, heat is applied and then it is subsequently boiled in a liquid bath. Later grinding, sublimation, and distillation are carried out.^53,54  The solubility of HgS is low. Therefore, the toxic threshold is also low. While passage along the gastrointestinal tract due to the interaction with enzymes in the digestive tract and a change of pH leads to the development of complex biomolecules in food. As a result, the solubility of HgS would increase greatly. By using scanning electron microscopy and X-ray diffraction, the results of mercury and sulfur mixing have been elucidated. Following 60 min of grinding it slowly forms black HgS, which contains mercury globules. Interestingly, following 90 min of grinding, free mercury was not detected; however, after 120 min of grinding, particles were formed containing 2–15 weight % of mercuric oxide. It was also found that sulfur particles surround the HgS particles. In Kajjali free sulfur in excess is detected and often trapped in the mesh of HgS.⁵⁵ 

Biomolecules including methionine, cysteine, taurine, and enzymes act as antioxidants, and those such as glutathione are rich in sulfur.^54,55  Most Ayurveda formulas contain excess amounts of antioxidants, and their influence on its therapeutic effect is remarkable. Antioxidants protect cells following free radical-induced damage. Based on its antioxidant properties, it is possible to explain the rejuvenating effects and antiaging effects of metal-Bhasma. Mercury in Bhasma may serve as a transient catalyst also.^53–55 

The trituration of the prescribed powder of herb with Kajjali develops a unique molecular layer which is capable of acting as a sustained-release formulation. When consumed, it gradually releases an effective dose, that is adsorbed and acts on the target area. Preparations with sustained-release are advancements in modern medicine, which can improve the therapeutic activity. With regards to the concept of slow-release, Ayurveda classics pose similar concepts.^54,55 

During the formation of metal Bhasma, quality assurance and quality control are carried out to assure the quality and efficacy of the formulation. This is compatible with the concepts of modern-day quality control; however, they should be reassessed and reassured. Also, modern techniques could be introduced to make it safer. Also, drug formulation knowledge is kept secret and hidden. Nevertheless, it has been kept and protected through various modes, such as in the form of sloka (poetic form in Sanskrit) and phrases. These forms provide the methods in the correct order and can be considered as ancient standard operational procedures.^53,54 

Compressed single or multiple powdered ingredients form hard tablets or smooth-coated capsules that following ingestion break down in the digestive tract. Most tablets contain additives and active ingredients, which hold the pill together and improve the taste, texture, and appearance. Tablets can be round, oblong, or disc-shaped. Oblong tablets are known as caplets, which can be easier to swallow. Similarly, in Ayurveda, vati has been prepared as a single or mixture of medications required for ingestion. The size and the shape of tablets are considered to be important for ingestion and insertion to the gastrointestinal tract through mouth or anus.^51,55  Moreover, Ayurveda has considered the importance of a base to ensure the stability, taste, and texture of the final product. Most are swallowed, while some have to be chewed before swallowing. This is similar to concepts in modern tablets. However, based on pharmacokinetics and pharmacodynamics properties, in-depth studies on such Ayurvedic preparations are required to assess their bioavailability and efficacy.^51,52,55  Other formularies, churna, are similar to powdered formulations in modern medicine. Depending on their use, the physical, chemical, and biological characteristics can vary.⁵⁶ 

The oral transmucosal route is useful for the absorption of drugs, both systemically and locally. Avala is a formulation intended to be administered through the oral cavity. Ayurveda has developed such a formulation that can bypass the first-pass metabolism of the liver to enhance its bioavailability.^56,57  Ghrita is an almost anhydrous milk fat prominent in the Indian diet and that is given great importance. Ghrita is used as a food and is the main ingredient for many Ayurveda medicines and is an excellent vehicle for the administration of drugs. Its spreading nature facilitates the dispersion of all medicinal properties to the deepest tissues. In this context, it is also referred to as a catalytic agent. Ghrita made from cows’ milk is considered superior to all other Ghrita. Like many dairy products, Ghrita is composed almost entirely of fat, with 62% saturated fats. Plant-based oils are generally rich in unsaturated fatty acids, while the products derived from animals are rich in saturated fatty acids.⁵⁷ 

Saturated fatty acids (SFAs) are produced as a result of ruminant biochemical hydrogenation, producing mostly the cis configuration of SFAs, and it differs quite extensively from the FAs (fatty acids) produced by industrial hydrogenation, which converts some cis FAs to trans FAs through cis–trans isomerization. The trans configuration of SFAs is not recognized by the enzymes present in the biological systems of humans and other animals and so they tend to collect in the body, thus being associated with higher coronary vascular disease risk.⁵⁸ 

Most of the activities described for Ghrita in the classics are known to be imparted by antioxidants and docosahexaenoic acid (DHA), an essential fatty acid. Several studies have proved that using traditional methods to produce Ghrita results in a higher amount of DHA and omega-3 long-chain polyunsaturated fatty acid (PFA). Dietary DHA reduces the risk of ischemic heart disease, malignancy, type-2 diabetes mellitus, and arthritis.⁵⁹  For years, Ghrita has been considered to be fattening and unhealthy and it has been associated with many diseases and increased mortality. Several studies have revealed Ghrita has saturated fatty acids and that heated products contain a high level of oxidative products of cholesterol which would increase the prevalence of ischemic heart diseases in Asians, particularly Indians.⁶⁰  Studies have shown that up to 10% Ghrita in the diet positively affects the serum lipid profile. There was a dose-dependent decrease in triacylglycerol, low-density lipoprotein, and VLDL cholesterol and triacylglycerol when Ghrita was given at a rate higher than 2.5% in the diet. The level of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in microsomes of the liver was not affected by dietary Ghrita, indicating that cholesterol biosynthesis was not affected by it, but instead, the excretion of bile constituents was increased by 18–30%, lowering the serum cholesterol levels.⁶¹ 

Moreover, conventional herbal extraction methods have several drawbacks, such as excess time consumption, solvents with residual effects, stickiness, and handling difficulty of highly inflammable solvents. Hence, it is necessary to develop a novel method for extracting the phytoconstituents utilizing traditional knowledge. In regard to oil preparations, the decoction was mixed with different seed or plant oils. Depending on the source of the oil, the duration and intensity of heating were prescribed. These oils often act as a base and soluble media for lipophilic herbs, which helps in the better absorption for lipid-soluble substances and allowing greater affinity through the cell membrane when used for different mucosa.⁶² 

Guggulu contains a mixture of steroids, diterpenoids, triterpenes, aliphatic esters, alcohols, carbohydrates, amino acids, cholesterol, Guggulu-sterol, flavonoid, and a variety of inorganic compounds. Guggulu has antiplatelet activity, cardiac protective activity, antioxidant activity, reducing the pro-inflammatory cytokines and antibacterial activities. l-arabinose is a good source of sugar ferulic acid esters and has antitumor properties. Guggulu and Guggulu-lipid are used for cardiovascular diseases, including dyslipidemia and atherosclerosis. Guggulu is generally used in compound dosage forms such as Ayurveda tablets, oils, and topical preparations. The different choices of therapy are based on soluble alkaloid and the insoluble resinous gum content of Guggulu. The formulation concept is also designed for better pharmacokinetics of Guggulu in clinical practice in Ayurveda.⁶³  Gum Guggulu acts as a binder in the preparation of pills and tablets, while it acts as a suspending and emulsifying agent in the case of liquid dosage forms. The solid dosage forms thus have a longer disintegration time, which delays the therapeutic action of Guggulu formulations. Possibly considering this in view, the seers of ancient times advised dissolving Guggulu completely in suitable liquids before its consumption, and Ayurvedic physicians in the present scenario advise breaking Guggulu solid dosage forms like pills and tablets before oral administration for proper assimilation and absorption in the gastrointestinal tract.^64,65 

The possible modes of action of Ayurvedic formulations can be multidimensional and include scavenging of free radicals, antioxidation, antimicrobial, pro-enzymatic, and immunomodulation. The kajjali complex is more effective due to its sustained release.⁶⁶  In Ayurveda, herbal mixtures have been used, and concepts of the molecule, its size, weight, and intermolecular interactions were not considered. Moreover, thermodynamics and other characteristics were not considered explicitly in Ayurveda drug preparation. However, for the preparation of different herbal formularies, the intensity and duration of heat were specifically considered following changing characteristics of fire by using different types of firewood and other fire sources.⁶⁷ 

In Ayurveda, raw herbal plant materials were used by volume to volume, weight to weight, or volume to weight ratios to extract herbs efficiently. The Ayurveda disease management system was mainly practiced on a small scale as a service without industrial measures. Herbal preparations were created using abundant herbal plants; concepts of efficient extraction would not have been considered to any great extent.^68–70  In Ayurveda, the quality of the final drug subjective parameters is assessed, while in modern medicine, multiple analytical and advanced biotechniques are employed.⁷¹  The development of herbal formulations and the methods used to assess their therapeutic usability and validity were not described in Ayurveda and it is generally believed that spiritual activities were relied upon. In contrast, laboratory studies, clinical assays, and trials in various phases have been done to assess their validity and safety.^69,72,73  The Ayurveda system poses different scales and parameters and can be compared easily with those in current scientific scales. In-depth scientific studies are required to ascertain the essence of Ayurveda concepts to make them more applicable to modern medicine.