Critical review on the pharmaceutical vistas of Lauha Kalpas (Iron formulations).

Iron is one among the major metals present in the earth's crust and is essential for sound sustenance of human body. Its deficiency leads to various health ailments. Contemporary medicine advises iron supplements in iron deficiency anemia. Ayurvedic classics also quote significant information about administration of iron. Lauha Kalpas are the unique compound herbo-mineral formulations where iron (Lauha) is used as a major ingredient. Relevant literature (Bhaishajya Ratnavali, Charaka Samhita, Rasendra Sara Samgraha etc.) reviewed to gather information about Lauha Kalpas. Critical analysis of these Lauha Kalpas reveals that ancient seers administered iron in a better acceptable form. Unlike popular understanding these are not only Khalviya preparations; but Churna (powders), Avaleha (confectionaries), Rasakriya (solidified decoctions), and Putapaka (incinerated) form of preparations are also found. Apart from solid dosage forms, semisolid dosage forms mentioned in classics are very much useful. Unfortunately most of the formulations are not found in the market. Hence Pharmaceutical firms may bring these unique dosage forms in to the market to supply the healthcare needs of the community. It is interesting that iron preparations are used in Ayurveda in different medical conditions apart from anemia (Pandu). This leaves a scope for further researches on different dosage forms of iron and their indications.

INTRODUCTION

Ayurveda is a well-documented Traditional system of Indian Medicine (TIM). Rasa Shastra, an offshoot of Ayurveda popular from medieval period, mostly deals with therapeutic utilization of metals and minerals.[12] Hundreds of formulations are explained in classical texts with the permutation combination of Bhasmas along with herbal ingredients. Careful review shows that there are around 30 types of Bhasmas, which are frequently used. A simple change in the method of preparation and ingredients can bring a change in the action, indication, and efficacy. Hence, it is the need of the hour to critically analyze the formulations and the rationality behind it. This may be a guideline for further research to unravel Ayurveda. Iron is a noncontroversial metal for therapeutic use since centuries in east as well as west. Iron containing drugs are widely used in modern medicine as hematinics. These drugs are known to induce some adverse drug reactions -- gastro intestinal symptoms (nausea, vomiting, epigastric pain, eructation, pyrosis, meteorism, borborygami, colic pain, flatulence, constipation, black feces, and diarrhea)[3] The hematinics market in India is currently worth around Rs. 900 crore and is growing at 15% per annum.[4] Hence it is the need of the hour to search some alternative from other systems of medicine like Ayurveda. Lauha Kalpas can be a better alternative from Ayurveda. Till date, no scientific comprehensive review has been done on Lauha Kalpas. Hence this study is undertaken.

Lauha Kalpas(LK) are formulations which possess Lauha Bhasma (calx of iron) as the major ingredient along with the other herbal ingredients. These formulations have “Lauha” as suffix in their name. Some Lauha Kalpas possess other mineral ingredients including mercury along with Lauha as main ingredient.

Background

Charaka Samhita quotes the nonexistence of any entity which is not a medicine (Nanaushadhi) in the universe. Acharya Charaka further elucidates that every object can be a medicine if used wisely with a logical thought (Yukthi).[5] Considering this fact, the three forms of natural materials -- herbal, mineral, and animal origins were subjected to trials and their therapeutic values were established. Due to the toxic nature of the minerals and metals, they were less used for the internal administration compared to herbs. Conversion of metals into suitable consumable medicinal form is found in the preparation of Lohadi Rasayana[6] and Ayaskriti.[7] In the Samhita period, iron (Ayas-Lauha) was used in the form of fine powder. Later Rasa shastra classical texts explained the Shodhana[i] and Marana[ii] methods.

Some researches have been carried out on individual Lauha Kalpas like Navayasa Lauha,[8] Nayanamrita Lauha,[9] Sapthamrita Lauha.[10]

According to Ayurvedic Formulary of India, Lauha Kalpas are the formulations of Lauha Bhasma (LB)f as main ingredient added to other drugs. The drugs are reduced to fine powder and mixed with Lauha Bhasma. The Bhavana process is carried out with prescribed liquids if mentioned.[11] When well protected from moisture and heat, they preserve their potency for a period of about 10 years. Preparations containing mercury or its compounds preserve their potency indefinitely.[12]

MATERIALS AND METHODS

Important texts of Ayurveda commencing from Charaka Samhita (CS) to Rasa Ratna Samucchaya (RRS), Rasendra Sara Samgraha (RSS), and Bhaishajya Ratnavali (BR) have been the sources for Lauha Kalpas. BR being a comprehensive source for LK's was the main source and the other important formulations are selected from other classics and enumerated according to the method of preparation.

Only the formulations having suffix as Lauha are considered for the study. The other Lauha Bhasma containing dosage forms such as Asava and Arishta (alcoholic formulations) are excluded from the study.

Quantity of Lauha Bhasma in few formulations is quoted as “Sarva dravya samam Lauham” which means 50% of the formulation will be Lauha Bhasma. In other formulations the quantity is calculated in accordance with the solid constituents, where in the ingredients like decoctions (Kwatha), fresh juices (Swarasa), ghee (Ghrita -clarified butter), and honey (Madhu) are not taken into consideration. Calculation is based on the raw ingredients taken prior to the pharmaceutical processes. Hence the percentage in the final product may change except in Churnas.

Method of calculation

Percentage of LB =100×weight of LB/weight of total solid ingredients (including LB). E.g., in Mahamrityunjaya Lauha (BR 41/136-45) total weight of all ingredients (mineral and herbal) is 17 Tola[iii], i.e., 17×12 = 204 g out of which 2 Tola (24 g) is LB. Bhavana Dravya, Guduchi, and Ardraka Swarasa are not considered for calculation.

Percentage of LB is 100×24 g/204 g = 11.76, i.e., approximately 12%

Churna Lauha Kalpa (Powder mixtures)

Churnas[13] (powder mixtures) are prepared by pounding the dry drugs and then sieving through a fine cloth or sieves. Lauha Kalpa in Churna form are prepared by adding the fine powder of the herbal drugs to the Lauha Bhasma and triturated (dry) until homogenous mixture is obtained [Table 1].

Table 1

Churna Lauha Kalpas

Khalviya Lauha Kalpa

Herbal juices advocated are added to mixture of the metals--minerals (Bhasmas) and herbs and then triturated till the liquid portion is totally dried. The liquid added should be optimum to form soft or soggy mass[15] [Table 2].

Table 2

Khalviya formulations: Prepared by using water for Bhavana

Some formulations do not contain herbal ingredients. The mineral ingredients are triturated with advocated herbal juices [Tables 3–6].

Table 3

Khalviya formulations: Prepared by Bhavana with herbal juices having only mineral ingredients

Table 6

Khalviya formulations: Prepared with mercurial ingredients (Kajjali and Rasa Sindhura) and Bhavana with herbal juices

Lauha Rasakriya Kalpa

When primary liquid dosage forms are boiled until thicker consistency is attained, so that they can be rolled as pills, it is called Rasakriya. Here Lauha Bhasma is boiled along with different herbal juices and decoctions until it converts to solid dosage form[19] [Table 7].

Table 7

Rasa Kriya Lauha Kalpas: Formulations prepared by boiling decoctions until solidification

Lauha Avaleha Kalpa

Literally, Lehya refers to that which is consumed by licking. It is a semisolid dosage form, prepared by solidifying the decoctions, etc. primary liquid dosage forms by boiling along with sugar-, jaggery-like sweetening agents and after it attains proper consistency fine powders of drugs (Prakshepa Dravya), ghee, and honey are added[21] [Table 8].

Table 8

Avaleha Lauha Kalpas: Prepared by boiling decoctions with sugar or jaggery

Putapaka Lauha Kalpa

The formulations which are prepared by the incineration method (Puta Paka) are included under this group. Puta indicates the specific quantum of heat required for conversion of a particular metal--mineral into an assimilable medicine using the suitable incineration method[22] [Table 9].

Table 9

Formulations prepared with Puta Paka method

DISCUSSION

Ancient Ayurveda even after centuries is an inspiration for the researchers to think beyond their imagination and knowledge. The same is true with pharmaceutical aspects. A better understanding of Ayurveda is adding up new things to the existent pharmaceutical excellence. Rasaushadhis are the formulations which are discussed in present era for right or wrong reasons. Even after this hue and cry it is impossible to discard them due to their effectiveness. Rasaushadhis (herbomineral formulations) are being prescribed by Ayurvedic physicians since long with a rare mention of toxicity. It is observed that herb--mineral complexes are more stable and more interactive compared to plain herbs as these result in faster therapeutic action and have a longer shelf life.[25] Lauha Kalpas are formulations which are safe, effective, and noteworthy compound formulations of iron. Prior to the period of Rasa Shastra, Lauha was used in the form of ultra fine powders (Anjana sadrisha -- collyrium like). A number of references for internal administration of Lauha and noble metals like gold and silver are found in our classics, as they are relatively less toxic than other metals in elemental form.[2627] In the medieval period, the internal administration of all metals and minerals became possible because of the invention of pharmaceutical technology of converting metals and minerals into Bhasmas, i.e., detoxification, (Shodhana) converting into powders (Jarana, causing decay of metals) and incineration (Marana, killing metallic properties) methods.

After careful review of Lauha Kalpas, it is found that unlike popular understanding they all are not only Khalviya preparations but can be classified based on the methods of preparation into Churna Lauha Kalpa, Khalviya Lauha Kalpa, Rasa Kriya Lauha Kalpa, Avaleha Lauha Kalpa, and Puta Paka Lauha Kalpa. Other than these listed formulations, special pharmaceutical preparations like Parpati (e.g., Rasa Parpati, Panchamrita Parpati), Asava, and Arishta are also described.

The percentage of LB varies from as less as 2–75% (Jwarantaka Lauha -- 1.7%, Vidangadi Lauha -- 2%, Tandavari Lauha -- 75%) in Lauha Kalpas. Many formulations contain 50% of LB. Herbal ingredients found in maximum formulations are Trika Traya.[vi]

Khalviya Lauha Kalpas are prepared by wet trituration (Bhavana, impregnation) with liquid ingredients, i.e., decoctions and herbal juices. In few formulations, water is used as a media for Bhavana. Wet trituration (Toya Sannikarsha) facilitates particle size reduction and homogenization leading to modification of properties (Gunantharadhana) of the end product.[28] In the pharmaceutical preparation of Chaushashta Prahara Pippali, it was observed that the number of Bhavanas with Pippali Kwatha, was inversely proportional to the piperine content.[29] With this information inference can be drawn that reduction of piperine is anticipated in this particular formulation, justifying the significance of the Bhavana process. In another work, which was intended for the study of shelf life and interactions of Vidanga with iron-in-iron containing formulations like Vidangadi Lauha, Chandanadi Lauha, and Navayasa Churna showed the reduction of embelin content observed in 6 months shelf life studies. Navayasa Lauha decreases less compared with other two formulations. This study concludes that iron can interact and can react with embelin and form a complex.[30]

Triphala mainly consists of tannin, gallic acid, ascorbic acid (vitamin c), and phenolics. Ascorbic acid increases the bioavailability of iron by converting Fe3+ to Fe2+, while phenolics can reduce the iron by binding to it. The presence of ascorbic acid or a lack of dietary tannins has both been suggested as contributing to clinical/pathological iron storage disease. Too much iron is toxic. It can damage the liver, heart, and pancreas and irritate the stomach and gut, causing constipation and diarrhea. In other words, this may also be taken as the various constituents of Triphala have antagonizing activity. Thus, too much iron absorption is prevented.[31] Triphala is a mild laxative and thereby counteracts the constipating property of iron and thus be beneficial due to which Acharyas might have mentioned Triphala in maximum Lauha formulations.

The findings from one study suggested that Triphala and its individual constituents have an inhibitory effect on metabolic enzymes when consumed along with therapeutic products. Further the inhibitory effects were relatively comparable to all the constituents tested, despite the variability of the content of biomarker. Triphala and its ingredients are likely to inhibit drug metabolizing enzymes, but less likely to produce significant drug interactions. Certain major factors of metabolism such as competition between coadministered drugs, unspecific interactions with proteins, and enzyme induction due to chronic intake are not addressed in that in vitro assay. However, one study clearly suggested that herbal products containing gallic acid may have the potential to inhibit the metabolism of certain coadministered drugs.[32] Hence a conclusion can be drawn that the presence of Triphala is a facilitator in the formulations.

Many formulations are said to be triturated with honey and sugar, due to which it becomes difficult to store them in tablet form, as honey and sugar (as liquids added while preparation) are hygroscopic and they become semisolid. Hence they have to be stored and consumed in semisolid form. Same is the problem with formulations containing Cow's ghee. Sapthamrita Lauha and Madhukadi Lauha both comprise Triphala, Yashti as ingredients. Honey and Cow's ghee are ingredients in Sapthamrita Lauha but they are Anupana (vehicle, adjuvant) in Madhukadi Lauha. Ideally Sapthamrita Lauha has to be prepared by adding honey and ghee and should be in semisolid dosage form and Madhukadi Lauha should be solid dosage form. But Sapthamrita Lauha, which is available in the market, is in solid dosage form[33] and devoid of honey and ghee; hence it will be rational to name it as Madhukadi Lauha.

It is understood that many proteins play significant role in absorption of iron from intestine (such as hespidin, DMT-1, ceruloplasmin) and are also required for efflux of iron from enterocytes. Iron supplements require bioavailability enhancers to minimize the side effects. Herbomineral formulations can be used to reduce various side effects as the processing of various herbal juices with already processed and micro-fined minerals lead to the formation of herbomineral complexes. These complexes upon interaction with digestive juices adopt a colloidal form, for faster absorption. Sometimes they play a catalytic role facilitating absorption of other nutrients and correcting a disease process.[34]

Few Khalviya Lauha Kalpas comprise Parada (Hg), Gandhaka (S) as ingredients. Initially Kajjali (HgS -- black) has to be prepared, later remaining powders are subjected for wet trituration and pills are to be made. These two types of formulations can be made into pills and stored; hence these are solid dosage forms. Few are prepared by adding mineral ingredients in decoctions, fresh juices and cow's urine, etc. and boiled, after it obtains proper consistency the remaining herbal ingredients (Prakshepa dravya) are to be added and pills are to be made. Cow's urine if taken has to be eight times to that of the quantity of LB.

Most of the LKs do not comprise mercury as an ingredient (with few exceptions). Dhanvanthari Bhaga (share of the physician in the medicine prepared) has been told separately for Loha Yogas and Rasa Yogas.[35] Hence some may doubt the inclusion of Lauha Kalpas in Rasaushadhis. But while explaining the novel nature of Rasaushadhis, Rasa Vagbhata describes that Rasaushadhis are effective in low dose with better acceptability and potent to reinstate health in short duration in a diseased individual. The author defines Rasaushadhis as the formulations which possess Rasa (Parada, Maharasa, Uparasa, and Sadharana Rasa) or any metal and mineral or poisonous roots as an ingredient,[36] All Lauha Kalpas possess LB, an iron metal Bhasma as a major ingredient hence LK can be termed as Rasaushadhis.

Lauha by virtue of its potential can be administered in various dosage forms (Bahu Kalpam) and thus fulfilling the criteria of an ideal medicine.[37] It is understood that iron and its salts produce gastric intolerance. Hence Acharyas have used iron as a part of formulations. It is evident that other ingredients of LK, processes and dosage forms explained are in line to improve the acceptability by patients of different body types and ages in indicated disease conditions.

Lauha Kalpas are mentioned for different ailments like Pandu (anemia), Arsha (hemorroids), Rakta Pitta (bleeding disorders), Shula (pain of different origin), Jwara (fevers), Yakrit Pliha Roga (diseases of liver and spleen), Udara (dropsy), Amavata (rheumatic arthritis), Vata Rakta (gout), Kushta (skin disorders), Medo Roga (obesity), Tandava Roga, Gulma, Kasa (cough) and Shwasa (dyspnoea). The role of Lauha in a specific formulation has to be ascertained by an erudite researcher in a respective disease condition. There are many LKs, especially semisolid dosage forms which are mentioned in classical texts but these are not available in the market. It is need of the hour for the pharmaceutical houses to work in this aspect and make these formulations available to the needy population.

CONCLUSION

From pharmaceutical viewpoint all Lauha Kalpas are not only Khalviya Aushadhis (prepared by Bhavana, impregnation -- wet trituration with simple water to different herbal juices). They are Churnas (mixtures -- prepared by dry trituration), Rasakriya (solidified formulations -- prepared by boiling of decoctions, herbal juices and even cows urine), Avaleha (confectionery), and Puta Paka (calcination products) formulations. Based on the method of preparation, shelf life, pharmacological action, indication varies. There are number of formulations which are not available in the market and but suits the present day healthcare demand. Hence pharmaceutical houses can manufacture and make them available.

Herbs found repeatedly in the formulations irrespective of indication are Trika Traya. These might have some role (bio enhancer) in absorption, distribution, metabolism, and excretion of iron. This work may serve as preliminary data and can be a torch bearer for the further studies on Lauha Kalpas.

Table 4

Khalviya formulations: Prepared with Bhavana of Sneha dravya (oil and ghee) and Madhura dravya (Sugars, Jaggery, and Honey) and Drava Dravya (Herbal juices and decoctions)

Table 5

Khalviya formulations: prepared by Bhavana of both mineral and herbal ingredients (solid dosage form)