Basic Principles in Siddha Pharmaceutical Science - An Overview

Pharmaceutics in Siddha system of medicine is an important component with scientific background. As per the mode of application and medicinal forms, the pharmaceutical products in Siddha system have been classified into 32 internal and 32 external formulations. Basically the formulations are designed as per the concept of five elements and six tastes employing the principles of synergism, antagonism and transformation into atomic or ionic form for the production of effective molecules. This review paper highlights the GMP and guidelines mentioned in the Siddha literature along with the scientific background of the same. One part of this paper is devoted to the discussion on the influence of different factors in the expression of pharmacological activity of drugs. The paper also discusses the noteworthy endeavours in the standardization and commercialisation of Siddha formulations and contemplates on the quality control aspects of traditional medicines. The aim of this review paper is to illustrate the scientific advancements in the ancient drug processing methods of the Siddha system of medicine.

The Siddha system of medicine is a complex system of science as it has treatises on medicine, alchemy and an extensive set of pharmacopoeia. It has its own fundamental principles of therapy and pharmaceuticals with specialization in iatrochemistry well before the development of modern science.

As per Siddha, the human body is the replica of the universe; food and drugs irrespective of their origin are made of five basic elements namely, Earth, Water, Fire, Air and Ether.1 The proportion of the elements present in the drugs vary and their preponderance or otherwise is responsible for their actions and therapeutic results.

According to basic Siddha concept the Pancha bhootham (five elements), Arusuvai(Six tastes) and Uyirthathu (three humours) are interlinked. That is , predominance of fire and water element expresses salty taste; fire and air element expresses pungent taste. Both are having hot potency and intake of them results in vitiation of Azhal humour. Similarly, the earth element with water element produces sweet tasting substance which can vitiate Iyya humour.2 Hence, Siddha formulations are designed based on the understanding of these reactions.

The knowledge of plants and minerals from all the branches of science is used in the preparation of medicine in Siddha. In Siddha system the knowledge of chemistry had been honed into a science complementary to medicine. Moreover the knowledge in this system is not static and is inherently dynamic in nature and evolves in response to challenges posed by the environment. The practitioners of Siddha applies several procedures divided into processes such as calcination, sublimation, distillation, fusion, separation, conjunction/combination, fermentation, purification, incineration of metals, liquefaction and extraction for the preparation of formulations.

Drugs In Siddha System
The source of pharmaceutical preparations in Siddha system comprises Thadhu (metals, minerals & arsenical compounds), Thavara (herbs), and Jeeva (materials and products of animal origin) elements. Apart from the vast herbal sources, Gunapadam(Materia Medica) describes the detailed classification of Thadhu drugs as well.

For example, the verse: 'Kaelappa kaaramodu yirunoorodu yirupa thaache' - Bohar Karasarathurai, denotes the types of Thadhu drugs; they are: 11 types of metals, 25 types of karasaram (i.e. different types of salts), 64 types of Pashana drugs that do not dissolve in water but emit vapours when put in fire, 120 Uparasa (mineral) drugs.3

The system has a classification of metals and alloys, which melts on heating and solidifies on cooling. These include gold, silver, copper, tin, lead and iron. These are incinerated by special processes and are used in medicine after purification or ore dressing. There is a group of drugs that exhibit sublimation on heating, which includes mercury and its different forms like red sulfide of mercury, mercuric chloride and red oxide of mercury etc. Sulphur, which is insoluble in water, finds a crucial place in Siddha Materia Medica along with mercury for usage in therapeutics and in maintenance of good health. In addition there are drugs obtained from animal sources like milk and milk products, conch, bones, teeth, bile, etc.

Even though the usage of Thadhu ingredients are more advanced in Siddha system, it was mentioned that the application of metallic preparations is preferred only after the use of herbal preparations as mentioned in the following verse: 'Vaerpaaru thazhaipaaru minjinakkal mella mella parpam chendhooram paaru'4

The Siddhars (experts) applied the Pancha bhoothic principles for raw materials and classified them as Panchabhootha ulogam, Pancha bhootha uppu, Panchabhootha Pashanam, Panchabhootha uparasam, and formulated the preparations according to the dominating Pootham, Suvai and Veeriyam.3



Basically the drugs are explained in five characteristics namely Suvai (taste), Gunam(quality), Veeriyam (potency), Vibaham(class) and Ceykai (action). The details regarding antagonistic - agonistic (chathru - mithru) compounds of drugs, dose, duration, season for ingestion, its compliance with geographical location and food restriction are well explicated in the Siddha Materia Medica.

As per the sorting in Siddha texts, 32 types of internal medicines based on the form, methods of preparation, shelf life, etc and 32 types of external medicines based on the modes of application have been elucidated and practiced since ages.3 Certain medicines, method of preparation and therapeutic procedures are unique to the Siddha system of medicine. Lakhs of formulations are available in Siddha literature though only a few are documented whilst a vast number are still in palm leaves recorded in the classical script.

Designing of Formulations In Siddha
The formulations and treatment methods in Siddha system are not uniform for all cases or patients. It has to be customized and modified in accordance with the climate, habitat, body constitution and individual body conditions. Hence the quality control of the final product is an exigent task of this system.

Siddha formulations are in natural form and contain in unison the active ingredients, inactive fibres, debris, etc. The functional principles of Siddha do not attempt to haul out the active ingredients and are disinclined to the concept of employing drugs as chemicals. This adds to the therapeutic value to these drugs by way of either neutralizing the toxic material, if any or facilitating the excretion of unwanted chemicals by entrapping them within fibres, debris, etc. 5

The inorganic substances occurring in nature have to be brought into atomic form for their effective usage as medicine. The Siddhars developed the knowledge of transforming inorganic substances into atomic and ionic form through specific processes, whereby they can be easily absorbed in the desired pathways resulting in a highly efficacious product. The ideology behind the customised formulations as practiced in Siddha is to circumvent side effects / after effects.5

Siddhars have followed various methods for medicinal preparations. Important among them are4:
  • 1. Process involving drugs based on combined ratio of five elements - Aeaga mooligai prayogam
  • 2. Process involving antagonism and synergism - Maarana prayogam
  • 3. Process involving distilled acids(Dhravagam)
  • 4. Process involving Ceyneer
  • 5. Process involving Muppu.
Uloga maaranam is the process for detoxification of metals and to increase the efficacy and potency of metallic compounds. Certain drugs are combined systematically and changed into liquid form known as Ceyneer. This Ceyneer helps to convert the drugs of combustible nature into noncombustible nature. The salt Pooneeru, the melted salt prepared from Fuller's earth is converted into calcine powder form and used in Muppu processing.4

Preparation of specialized drugs like Kattu, Urukku, Kalangu and Chunnam which have long shelf life and the medicinal forms like Chatthu, Gurukuligai of infinite life span, are accomplished by such ingenious processing methods.

Factors Affecting the Pharmacological Actions of Drug
The pharmaceutical procedures for any drug involve various steps starting from identification and collection of authentic raw material, application of standardised processing techniques for purification and formulation, packaging and storage of prepared drug, usage of adjuvant on application. In each step, the factors influencing and/or detaining the expression of pharmacological activity of drugs has to be considered.

The season of collection of raw drugs and geographical area of collection have great impact in the expression of pharmacological activity. According to ancient Siddha classics, the geographical areas (Kurinji - mountains, Mullai - forests, Marutham - cultivation area, Neithal - seashore and Palai - deserts)6 have features that are specific to that area.7 As per Siddha, the plants usually collected in Marutham and Kurinji areas are highly nutritive and possess medicinal value; but the herbs from other areas imbalances three humours and paves the way for certain pathological conditions.4

Genetic variants lead to the variability in the chemical composition of the population. Geography, altitude, soil composition, microbial load, climate, temperature, season, etc can cause fluctuation in the phytochemical ratio. A variation in the alkaloid composition in the leaves of Adhatoda vasica seasonally has been recorded. It is lowest in February - March and highest in August - October. Similarly, variation of alkaloid contents based on the age of the plant is reported in Holarrhena antidysenterica.8



The pharmaceutical processing of drug depends upon nature of the raw material - fresh or dry, solubility and heat stability of ingredients, route of administration, shelf life of drug, etc. Alteration in the drug processing method has a strong adverse impact on the formulation. Thus, misprocessing may lead to adverse effects of Siddha drugs. For example, while processing Rasam, if the impurities namely Thodam/Chattai are not properly removed, it may lead to disorders like skin ailments, haemorrhoids, neurological disorders, respiratory ailments and seldom death also.3

The adjuvant or vehicle used along with the drugs may not be inert and per se may produce significant pharmacological activity. For example, usage of honey while treating anaemia supports the therapeutic efficacy of drug. This is due to the presence of minerals like iron and vitamins like ascorbic acid in it.9 Most of the adjuvants enhance the activity of drugs, some of them neutralizes the toxic reactions while others balance the humours, etc.

Hence, while making changes in the classical formulations, the impact factors should be noted. The modification in classical formulations (form, ingredients, adjuvant, etc) should not be made without any valid reason or supporting information.

GMP In Siddha Literature
The techniques and instruments used for the preparation of Siddha drugs are clearly explained in the literature. Raw materials used in the manufacture of drugs should be authentic, of prescribed quality and free from contamination. The impurities (Thodam) in each of the drug and methods for the purification of drugs, etc are clearly elucidated in the classical Siddha texts. As per the classical texts, it is essential that the principles regarding the collection of raw material (eg: collection of the roots of plants directed towards north [Vadakku ver]10, collection of plant parts in the morning, etc), purification procedures, preparatory time, etc should be followed strictly to ensure the safety and efficacy of the drug.

Tools of Siddha drug processing
Kalvam (stone mortar) is being used for grinding drugs in Siddha pharmacy. As per the classics, black coloured stone mortar is preferred for the grinding process. This type of mortar will not release particles and thus the medicines may be obtained without impurities.11 On the other hand, use of yellow or white coloured mortar results in neutralisation of the activity of the drug and ends with inactive substance.3

medicines from Kalvam and also for stirring or mixing of ingredients while processing. Steel or silver spoon is utthamam (good). Spoon made of wood or horn is matthimam (moderate). As iron has a tendency to rust, the usage of iron spoon may reduce the effectiveness of the drug.3 The ladle to be used in the preparation of oils and ghees should be made of coconut shell (akappai); churning sticks made of wood for churning; wooden spatula for the preparation of elagam. Iron ladles should not be used for preparing perfumed oils, medicated ghee, lime juice and decoctions made of milk, butter milk, etc. It should also not be used in preparations that involve mercury, arsenic and toxic herbs because of the demineralisation of iron on exposure to such chemicals.4

The mud pot used for the preparation of decoction and distillation processes is made by using astringent and sour materials. For sublimation, vapourising , mezhugu processing, etc, the mouth of the processing vessel should be narrow; for roasting process, the mud vessel used should be of shallow surface with brim and the vessel for decoction preparation should have a deep bottom. The vessels made of Navaloga (nine metals) are not suitable for preparation of decoctions, medicinal ghee and distillation process. Also, the vessel used for the preparation of a particular medicated oil should not be used in the processing of other oils, because it not only spoils the medicine, but also the health of the patient and the reputation of the physician. In case of a new pot, care should be taken that the ghee does not percolate too deep4.

Temperature for drug processing is also accomplished by various methods like Pudam - which can be classified according to the number/type of dung cakes used; Kaadai pudam - 1 cow dung cake, Kavuthaari pudam - 3 cow dung cakes, Kukkuda pudam - 10 cow dung cakes, Varaaka pudam - 50 cow dung cakes, Manalmaraivu pudam - 90 cow dung cakes, Keja pudam - 1000 cow dung cakes and Bhoomi pudam - sheep or goat dung. In the processing of medicinal preparations the source of fire, type of fire and method of exposure to heat is basically designed according to the nature of the drug material and the application of the drug.

A few of the unique processes used in the preparation of some Siddha medicines are namely, Thanyapudam - keeping the drug immersed in grains, Umipudam - keeping the drug immersed in husk/ chaff, Pattaipudam - keeping the drug within tree bark, Sooriyapudam - keeping the drug under sunlight, Chandrapudam - keeping the drug under moonlight, Panipudam - exposing the drugs to dew.3

In Pudam processing method, the usage of naturally occurring dung material is vital. Dried cow dung cakes from the forest are good for preparing medicine while the dung of buffalos is second preference. The use of dung mixed with straw and dust will reduce the potency of the drug. Based upon the necessity of temperature, Calcium stones or sand or soil or ash can also be used in the processing of heavy metals and arsenic compounds like Yellow Orpiment, etc.3

While using firewood for Thailam processing, the type of fire (Dheepakkini, Kamalakkini, Kathaliyakkini, Kaadakkini) is decided as per the stage of processing, whereas the type of firewood is decided according to the ingredients of the formulation. For example, the firewood of Neem, Coconut palm and Palmyra palm is apt for Mercury preparations while Indian Arabic tree and Indian Kino tree is suitable for preparations containing Iron.3

On the other hand, the type of firewood to be used is also decided as per the application of the drug. Tanner's Cassia and Country Mallow is preferred for the processing of medicated oil for fever while firewood of Indian Jujube and Black Siris tree is ideal for the processing of medicated oil for auricular, nasal and ophthalmic applications. Firewood of South Indian Mahua and Tamarind is applicable for the processing of external therapeutic oils. If the notified firewood is unavailable, then the alternative is determined on the basis of the character or contents of the oil being processed.12

Firewood of dead trees is of no use, whereas firewood cut before three months is good and freshly cut wood is to be avoided as it tends to spoil the drug. Pittha would aggravate if the firewood of very old tree is used for medicinal preparations. If the bark of such a tree is used as fuel, then the drug being processed may cause itching on application.4

Guidelines of Siddha drug processing
1. The preparations like Utkali, Maathirai, etc should be in the non-sticky stage, i.e. the materials should not adhere to the fingers after the product is fully processed.3
2. The stages of the processing oil are expressed on the surface as froth and at the end of the processing stage, the sediment should not be sticky and should burn vigorously without any crackling noise when exposed to fire.12 The oil processing has to be finished in three stages namely, soft stage (Mirudu pakam), waxy stage (Mezhugu pakam) and gritty stage (Karakarappu pakam). The medicated oil of Mirudu pakam is for the internal application in Vali humour imbalance, medicated oil of Mezhugu pakam is for external application and Azhal diseases while the medicated oil of Karakarappu pakam is for application on the scalp and Iyya diseases.12
3. As the effectiveness of drug depends upon the tiny or microscopic nature of the particles, a sieve of highly fine mesh is mandatory in the processing of chooranam. The chooranam prepared by the use of mechanical devices like pulverizer should be allowed to cool down by way of spreading and then mixed well for storage and packing.12
4. As there is a chance of plenty of microbes inhabiting the Choornam, it should be subjected to the process of purification (Choorana thooimai). This involves baking of Chooranam and then processing it into fine powder.3
5. While processing preparations like manappagu, large spatula or ladle is to be used to stir continuously, otherwise the mixture will deposit in the bottom and get charred. This may lead to burnt smell and bitter taste to the product.
6. Whilst processing nei, at certain stage of boiling froth will appear on the surface of the ghee. At that moment, the sediment should be analyzed by hands. If it is well processed, the sediment would be nonsticky. The ghee should be then filtered off and preserved.12
7. In the processing of elagam (lehiyam), honey should be added only after oven and then mixed well into the elagam for suitable consistency.12
8. As the colour, characteristics and fineness of parpam is based on the quality of grinding process, it should be done in the proper way. While processing, if there is any moisture content in the tablet (villai) material , the colour of the parpam may differ and hence proper drying is mandatory. 12
9. In Pudam method of processing, the cake materials should be placed in earthen bowl properly so that the temperature is spread evenly over the materials. The size of the bowl depends on the quantity of material; bowls with too much depth and breadth should be avoided. 12
10.Place of reasonable air circulation should be selected for pudam processing. A crater of defined breadth and depth is to be dug out in the earth and the circumference is to be modulated by bricks to prevent the seepage of soil in the mixture. Half of the defined cowdung cakes are to be filled up in the crater and the earthen bowl containing the material is to be placed on that, while the remaining cowdung cakes are to be spread on the said bowl and fired.12
11.Even though the cowdung cakes are the usual burning materials in pudam processing, some herbal barks or dung of goats have been specified for the processing of certain drugs. Dung may also contain certain sand or waste materials and hence the number or quantity should be modified as per the necessity of temperature in the process
12.Certain substances like Ganthagam(Sulphur), Thalakam (Yellow Orpiment) are vulnerable to high temperature, and hence ash or sand is to be used for calcination/pudam process. Suitable quantity of ash is to be spread in the bowl and the material in villai (tablet) form is to be placed within the bowl and covered further with ash.12
13. The disassembling of the processing setup should be carried out only after all the materials have cooled down.
14.Medicines once prepared should not be reheated. This principle applies for elagam, decoctions, boiled juices, etc.4

3. Quality Assessment of Drug
Quality of drugs like parpam, chendhooram, etc shall be assessed by the analysis of physical characteristics. Properly finished parpam and chendhooram is tasteless, fine, smooth and devoid of shine or glitter. The finished parpam or chendhooram is said to be as per standards, if a small amount of the mixture when placed on water does not sink. The perfect parpam or chendhooram will not degenerate to the base elements when exposed to fire .12 The preparations like chooranam should be devoid of moisture content and its particles should be minute.11

Standardization of Siddha Drugs
Standardization of Siddha formulations is one of the mandatory requirements in order to develop quality drugs on a large scale and market it. The effectiveness of the formulations is completely dependent on the raw materials used and also on the quality control of the processes employed. The raw materials such as herbs cultivated in different environmental conditions and geographical areas possess different types of chemical constituents. Hence, harmonization of chemical constituents is complex in nature and therefore fingerprinting profiles of phytoconstitutents is the easiest and cost effective procedure to analyse raw drugs.

Also, the assay of a particular chemical constituent can be done through the identification of chemical markers and their quantification. The analytical reference standard can then be prepared based on this data. Macroscopic, microscopic and physico-chemical tests are now part of the routine analyses in any quality control laboratories pertaining to herbal drugs. Lately, sophisticated analytical tandem techniques such LC-MS and GC-MS are being used for molecular fingerprinting. NMR metabolic profiling is also a good tool for the quantification of chemical markers without isolation. The volatile and low boiling chemical constituents can be identified and quantified through GC-MS and non-volatile constituents can be profiled through LC-MS.

The DNA fingerprinting methodologies can be effectively used for raw materials of different origin. The test for heavy metals is another critical test with reference to traditional medicine and the same can be done through elemental analysis techniques. The preparative HPLC techniques can be used to isolate major constituents and through lyophilisation processes, the purest single molecule can be obtained and complete characterization of the molecule would help to identify the structure. This would enhance the ability to study drugdrug interactions and to find out the mode of action of the drugs.

While attempting to commercialize a product belonging to Siddha system, the issues regarding portability of the drug and shelf life of the drug arises, as most of the herbal medicines are in unsophisticated form, having short shelf life and the addition of preservatives for the purpose of marketing results in the reduced efficacy of the drug. In the case of preparations like parpam, chendooram, karuppu, etc, there is no critical issues regarding the shelf life and portability, but the issue is regarding the adjuvant of the drug and dosage, as most of these kinds of drugs are in nano-particulate form and the dosage are in micro or milligram levels. Any minor variation may generate unwanted reactions and also the efficacy of the drug is based on the precise dose and the specific adjuvant5.

Modification in the route of administration or change of form for portability or adjustments for palatability shows strong adverse impact on the activity of the drug. Hence, further studies are needed to adapt the Siddha formulations as per the needs of the market.

Conclusion
Pharmaceutics in Siddha system is essentially a personalised or customized scientific system wherein the collection of raw materials and processing has to be done as per strict guidelines, principally based on experiential wisdom. Transformation of this ancient system into a generalised and commercial system has led to poor quality assurance. Therefore, more research and development efforts are required to optimise the formulation aspects in order to ensure constant availability of standardised products with consistent composition and efficacy.

References
1] Dr. Jayaprakash Narayanan, et al; Siddha Medicine - Fundamentals; Volume =II; Thamil Valarchi Kalagam; Madras University; Page 1.
[2] S. Shanmugavelan; Noinaadal Noimuthalnaadal Thirattu Part-1; Department of Indian Medicine and Homeopathy; Pages 20-23.
[3] R. Thiagarajan, Gunapadam - Thathu- Jeeva Vaguppu; Department of Indian Medicine and Homeopathy; Pages 1-23, 44.
[4] Dr. C. S. Utthamaroyan; A Compendium of Siddha Doctrine; Department of Indian Medicine and Homeopathy; Pages 10, 46, 437-439.
[5] G. S. Lekha, Patenting of Siddha formulations- Scope and Issues; STM Journal of Ayush; Volume 1, Issue 2, August 2012; Pages 50-62
[6] Dr. K. Durai rajan; Noyilla Neri; Department of Indian Medicine and Homeopathy; Page 2.
[7] G. S. Lekha, P. Sathiyarajeswaran; Management of NCD by Siddha system; Ayushdhara - An International Journal of Research in AYUSH and Allied Systems; July-August 2015, Vol 2, Issue 4; Pages 1-8.
[8]. Palpu Pushpangadan; Raw material: Sustainable availability and concern regarding medicinal plants on negative list; International Conclave on Traditional Medicine 16th & 17th Nov 2006; New Delhi.
[9]. Chemical composition of honey - The Wealth of India; Raw materials - Volume 2: B - A Dictionary of hidden raw materials & Industrial products; CSIR, New Delhi; Page 91.
[10]. Pillai pini Maruthuvam - Part -2; Department of Indian Medicine and Homeopathy; Page 445.
[11].Thanigavelan.V, et al, Antibacterial and haemostatic activities of a Siddha formulation - Pavala Parpam; Pharmacologyonline 1; Pages 613-624 (2011)
[12]. The Siddha formulary of India; Part 2(Tamil Version); Department of AYUSH, New Delhi; Pages 17, 43, 63, 94, 95, 14, 229, 230. [Dr. Shyamala Rajkumar, Research Officer (Siddha), Central Council for Research in Siddha, Chennai & G.S. Lekha, Medical Consultant, Siddha Central Research Institute (SCRI), Chennai.]