INTRODUCTION: - The science of Ayurveda has been framed upon “Trisutras”1. Among them Oushadha is most important.
That which contains rasa (active ingredient) is known as aushadhi & because taste of drug may be considered responsible for achieving health or curing disease. Hence these are known as aushadhis. The drug is like an instrumental aid for a physician. That is why it has been placed next to the physician amongst the quadruples of treatment4.
Well, to explain the fundamental definition of what is a dosage, it is the physical type and amount of a medication further Drug design, also sometimes referred to as rational drug design or structure based drug design, is the ingenious process of finding new medications based on the knowledge of the biological target5.
Ancient Indian Ayurvedic Pharmaceutics is an abode of rational drug designs. Today the drug designing is a major form of conception as it should be a comprehensible technique. The advantages & disadvantages of all these innovations have been complex & exceedingly costly. The Pharmaceutical companies are bound to unearth new drug dosages with safety & effective profile. Our ancient seers were well known to observe such facts for which they proved to generate each & every formulation which could accomplish the necessary properties. On an account the safety, quality & efficacy kept in mind but on the other hand the drug was also target oriented.
MüsmÉlÉÇ rÉÉåeÉlÉÇ CirÉjÉïÈ| (AÂhÉS¨É) 6 is the statement not only indicating the formulation technique but also the intellectual skill in which the seers could visualize. The drug mechanism when applied on Human beings in different situations concerned with place, time, season, sex, age, strength of the person ,strength of the disease, food habits, congeniality, quantity of dosage, prodrug’s or adjuvant’s to be given along was very essential. Because the treatment was not only to cure symptoms but holistically it was about rooting out the diseases at the core & look forward for “Swasthya lakshana7”.
Rasashastra & Bhaishajya Kalpana, distinctive branches in Ancient Indian Pharmaceutics is two faces of a same coin sustaining the Ayurvedic therapeutics. The facts regarding drugs, their processing techniques, pharmacological & therapeutic properties & method of their uses come under the facet of pharmaceutical science.
Major Ayurvedic treatises of Charaka, Sushrutha & Vagbhata also mention about the preparation of medicine from design to administration pattern along with the indications & contraindications as they were aware of drug safety. Later after 15th century some new formulations like Sarbats, malhars, arkas etc got introduced in Ayurvedic pharmaceutics8. Through these ages many of the instruments, standardization techniques have been introduced into the Ayurvedic field but no new principles of Pharmaceutics have been added. Thus till today the same fundamental preparations & principles of Ayurvedic pharmaceutics mentioned are in practice. Only modern techniques, equipments, standardization procedures have been introduced into Ayurvedic Pharmaceutics.
Review on Literature:- According to Sayana, the commentator of Vedas Rasa means juice of a drug used to treat a disease9. This shows that the dosage Swarasa (juice/ extract) was commonly prepared & used for treating the disease.
Up to 7th century herbal preparations were only in vogue. Later even metals & minerals & drugs of animal origin also were used. By this time the seers thought to have a specialized technical knowledge for conversion of various metals & minerals as medicinal forms like Bhasmas etc. Hence the concept for separate branch of learning known as Rasashastra emerged in the field of AYURVEDA. The latter part Bhaishajya kalpana also was of much concern wherein Sharangadhara, a great scholar seems to have done a detailed study10.
The pre-historic texts like Rig veda11 & Atharva veda12 have mentioned some of the medicinal values of the metals like Gold, Silver etc. The great Indian alchemist Nagarjuna who flourished in India is credited for starting the use of metals, minerals& mercury in Ayurveda and named Rasashastra as Daivi chikithsa. 13
ÍxÉ®å UxÉå MüËUwrÉÉÍqÉ ÌlÉSìÉïËU±(nirogam)ÍqÉSÇ eÉaÉiÉç|14is quoted by him which means the purpose of eradicating diseases from the world. The perception of Rasa shastra mainly originated saying Rasa as: UxÉlÉÉixÉuÉïkÉÉiÉÔlÉÉÇ UxÉ CirÉÍpÉkÉÏrÉiÉå | eÉUÉÂXqÉçØirÉÑlÉÉzÉÉrÉ UxrÉiÉå uÉÉ UxÉÉå qÉiÉÈ||15 Rasayana /Deha vada where the mineral & metallic drugs were meant not only for eradicating diseases but also for the purpose of rejuvenation & in case of casualties.
Conversely, Bhaishajya kalpana emphasized much upon the herbal & dietic preparations.Kalpa means “Tena Kimkim sadhayatam shakyam iti tat kartwata samarthanam nama kalpaha”16
What actions could be performed and which is capable of doing that is known as Kalpa.
Analysis & Understanding
A. The imperatives prior Drug design:-
1. Paribhasha17: - This part enlightens the meaning of a subject clearly with minimum word & help understanding the matter better. E.g.:- Triphala.
2. Mana18:-Mana or Parimana is essential to quantify the ingredients in a preparation & in the fixation of the dose of a drug or diet.
3. Dravya sangrahana & samrakshana19:-The season, ideal soil for & the method of collection, the part actively potent which is completely matured is also described well to procure the potent drugs. An usna virya dravya is collected in usna kala (hot season) & from agneya maha bhutha pradhana bhumi like Vindya pradesha whereas sita dravyas from Saumya bhumi like Himachal Pradesh.The Jangama dravyas like blood hair, nails etc are collected from young & strong animals but milk, urine, dung is collected after they completely digest the food. Even the Pharmacy & store room design is also well described so as to protect & preserve the potent drug against dust, smoke, pests & other contamination. Regular fumigation using herbs was in practice.
4. Panchabhautikatwa20. - The guna (quality) and the Karma (action on target) are based upon the facts of permutations & combinations of Pancha bhutas. Though the rasa (taste) guna (inherent quality) virya (potency) vipaka (final metabolic state) of many drugs especially in metals & minerals aren’t mentioned in classics it is the physician who uses his intellect-Yukti.
5. Anukta Visesokta Vishaya Grahana21:- Some of the general principles mentioned by Acharyas when the name of the drug ,its quantity, time of administration etc are not specified:-
a) If the time of intake of medicine is not mentioned then it should be taken early in the morning.
b) While preparing a medicine, if the bhavana/drava dravya is not specified then water should be used.
c) When the useful part of any plant is not mentioned then its root must be used.
d) The mention of no name of oil is seen then it is considered to be tila taila (sesame oil).
e) If the type of vessel is not specified then take earthen pot.
f) When the quantity of the ingredients is not mentioned then each drug is taken in equal quantities.
g) In any preparation if the drug is mentioned twice it means the quantity should be double.
h) The wet drug must be taken in double quantity to the dry form.
i) The dose of any preparation mentioned in our classics indicates it to a middle aged person having a moderate digestive capacity & physical strength, keeping these points in mind, as per need one can earlier increase or decrease the dose of a preparation.
j) According to the principles of Ayurveda, the pratinidhi (substitute) can be selected only for those drugs which are not main drugs of the formulation.
B. Fundamental Principles of processing in Drug design:-
Each & every dosage form, ingredients naturally procured undergoes series of processes & screening to make it a target oriented bio-available drug. The Gunantaradhana or the transition of a material from one form to another through any process is accomplished only by SAMSKARAS23 which also happens in a rational drug design. In Charaka Samhitha the Gunantaradhana is elaborately elucidated with an account of following techniques 24.-
a) Toya Sannikarsa (treatment with water/fluids)
b) Agni Sannikarsa ( heat treatment)
c) Toyagni Sannikarsa ( fluid & heat treatment)
d) Sauca (Purification/detoxification)
e) Desa (Place)
f) Kala (Season/duration)
g) Mantha (churning/ grinding for dispersion & disintegration of materials)
h) Vasana (flavouring)
i) Bhavana (trituration with plant extracts)
j) Bhajana (Use of different containers/ equipments/ instruments) etc.
It is said that a simple drug could be made into most powerful one by simple procedures like addition or deletion of certain drugs, by keeping the drugs in certain process for specific time, by collecting the drugs during scheduled period & by processing it with various techniques for the enhancement of the potency of the drug which will be made fit for therapeutic administration .Eg:- Shadanga Paniya churna Vina shunti (without Shunti) in case of diseases of Pitta origin.
C. Development of important Pharmaceutical Process:-
During the time of development of Rasashastra, a number of important pharmaceutical processes, treatment & techniques necessary for conversion of metallic & mineral drugs into suitable dosage form have been evolved. Some of them are as follows26:-
a) Shodhana (Purification/detoxification process)
b) Jarana (Conversion of molten metal into fine powder form)
c) Marana (Incineration /conversion of metals, minerals into ashes form)
d) Jaranaa (Digestion & assimilation of grasa / metal content into mercury)
e) Satva patana (extraction of metal content of minerals through strong heating )
f) Druti (Stable liquefaction of metals with/ without heat treatment )
Ashta samskaras27:- This is considered to be highly significant procedure to remove various doshas (toxins) & enhance the potency & efficiency of Mercury from therapeutic as well as alchemical point of view.
a) Swedanam-heating through boiling liquid especially weak acidic.
b) Mardanam,-Grinding with the same acidic liquid.
c) Murchanam,-Grinding in Iron mortar till it attains nasta pistatwa (quality of mercury).
d) Utthapanam,-Bringing back to the original stage.
e) Patana- Sublimation / distillation
f) Bodhana, Niyamana, Dipana- Mercury potentiating processes.
D. Pharmaco -dynamics & kinetics in Ayurveda:-A detailed pharmacology & toxicological studies were carried out even during that time to produce one final dosage form. Accordingly even animals were used for such experiments.
iÉ§É cÉiÉÑÌuÉïkÉ pÉÔiÉaÉëÉqÉÈ xÉÇxuÉåSeÉ eÉUÉrÉÑeÉ AhQûeÉ AÉæΰeÉ xÉÇ¥ÉÉÈ | iÉ§É mÉÑÂwÉÈ mÉëkÉÉlÉÉÇ iÉxrÉÉåmÉMüUhÉqÉlrÉiÉç ||28 xÉÑ.xÉÔ 1/22
Acharya Charaka defines the Pharmacology through following principles29 :-
rÉiÉç MÑüuÉïÎliÉ iÉiÉç MüqÉï |
(Action of the drug)
rÉãlÉ MÑüuÉïÎliÉ iÉiÉç uÉÏrÉï |
(Potency of the drug)
rÉ§É MÑüuÉïÎliÉ iÉiÉç AÍkÉMüUhÉqÉç |
(Site of action)
rÉSÉ MÑüuÉïÎliÉ xÉ MüÉsÉ: |
(Time for bioavailability)
rÉjÉÉ MÑüuÉïÎliÉ xÉ EmÉÉrÉ: |
(Mode of action)
rÉiÉç xÉÉkÉrÉÎliÉ iÉiÉç TüsÉqÉç | (Thérapeutiques)
Ayurveda describes the dravya (drug) on the basis of Panchamahabhootha(five elements) predominance in it. The QSAR (quantity structure activity relationship) of a drug is quite similar to pharmacological action of dravya resulting from its panchabhouthik configuration.
Achievement of Rasibhavana:- The ancient scholars have also mentioned that mrita lohas (metallo-mineral formulas) should be converted to Rasibhavana state means it should be changed in absorbable form i.e. organo metallic compound form as in that form only the absorption is possible30 .
The Rasaparivartana31 or the absorption,metabolism, distribution & the excretion of a drug happens by 6-7 days for its complete action. But some of the drugs are an exception to this statement as they show the action according to their attributes. The advice of Mandala (21 days/48 days) for drug mechanism also shows its magnitude towards the task.
E. An array of Drug Dosage:-
Not all the dosage forms were meant for preservation for longer periods. Instead for the potent action at the earliest which otherwise would be ineffectual.
The drug dosage forms mentioned in classics like swarasa (juice extract), Kalka (pastes), churna (powders), Kashaya (decoctions), Hima (a cold infusion), Phanta (a hot infusion), Ksheerapaka (medicated milk), Arka (liquid distillate), Ghanasatwa (the solid extract), Guda & Khanda kalpana (jaggery/ sugar based solid preparations), Phanitha (Highly concentrated juice), Avaleha (linctus), Vati (solid dosage forms by adding powders & liquids), Guti (Smaller sized solid dosage form), Modaka (bolus sort of dosage), Pindi (pea sized solid dosage), Varti (suppositories), Anjana (microfine paste only for eyes), Masi (carbon form of a drug), Lavana (granule salt form), Ayaskriti (Metallo-mineral liquid dosage), Satva (starchy extract), Ksara (alkaline powders), Dhupana (fumigative powders), Dravaka (acidic/alkaline distillates), Ghrutha (medicated ghee), taila (medicated oil),taila nishkasana (extraction of taila) Asava & arishta (fermented liquids), Lepa (creams), Malahara (ointments), upanaha (poultices) etc. are found in Bhaishajya kalpana.
The drug dosage forms in the domain of Rasashastra are Bhasmas (calcined/incineratd forms of metals& minerals), Parpati (crispy thin wafers), Pottalis (Kupi pakwa rasayanas as Sindooras (Sulphide/oxide forms of Hg), Rasas (powder/vati/guti forms), Manduras (Iron preparations), Pisti (microfine calcium mixtures), in the form of powders or gutis , Satva (metallic extracts), Dhruti (liquified metals), Pushpa / Karpoora (non-sulphuric mercurial forms), Bandhas (Mixture of Hg with herbs & minerals), Suchikabharana rasa (injectables).
Brand names for tagging the formulation32: - In Ayurvedic pharmaceutics, while naming the formulation following principles are found to be followed.
a) By the name of the first ingredient e.g.:- Sitopaladi churna
b) On the basis of the therapeutic use of the drug:- Eg Jwarari rasa,
c) Preparations could be called by the name of their inventor:-Agastya Haritaki rasayana
d) Few preparations are found to be named on the basis of their properties & actions. Eg:- Arogya vardini rasa
e) As per the external appearance also the preparations could be named :- Suvarna vanga
f) Few yogas are named by the name of their main ingredient.eg:-Triphala guggulu
g) Dose is also criteria used to denote a preparation:- Sadbindu taila.
h) On the basis of the method of the preparation a drug could be named: - Sata dhoutha ghrutha.
F. Dosage Canon:-The necessity of Matra Kala & Anupana was emphasized by seers for a drug to act on its target.
Matra (Posology): - The drug can cause complications or some untoward effects when administered in too small quantity or in too high dose33.
Charaka says an Ideal drug is that which is formulated in such a way that even in small dose within a short time, without causing any discomfort, it should correct most of the vitiated doshas .It must be lighter for digestion .It must contain good taste & must nourish the body too. It should have the capacity to cure diseases. It should not cause any untoward or side effects or complications.
Kala35: - The time of administration of a drug is equally important to obtain the benefits of the drug.
a) Abhaktha (in empty stomach)
b) Prakbhaktha (before taking food),
c) Adhobhaktha (after taking food),
d) Madhya Bhaktha (in between 2 meals)
e) Antara Bhaktha (soon after taking food),
f) Sabhaktha (along with meals),
g) Samudgam (By mixing the bolus of the food.),
h) Muhur Muhu (Repeatedly),
i) Grasam (along with every bolus of food),
j) Grasantaram (in between two bolus of the meal),
k) Nishi (night/ bed time).
ANUPANA (Adjuvant):-
The drug is said to be administered with appropriate anupana, the drug spreads & exhibits its effect very fast like that of oil spreading on the surface of water. By changing anupana a single drug can have various effects. These anupanas can act like catalysts & enhance the therapeutic efficacy of the drug with which they are used.Eg:-Hot water after medicated ghee.
Anupana should not be dhathu virodhis37. Eg: - Hot water after Bhallataka taila (oil of semecarpus anacardium). It should not inhibit the property of the main drug instead it should enhance the activity of the main drug which indicates the potentiation38.
Eg:-Dashamoolarishta for trayodashanga guggulu.
Dosage also depends upon:-
· Tridoshas & Saptha dooshyaas: The quantum of doshas & seven dhatus in the body which are affected.
· Desha – The country/place geographically & also the deha desha or anatomically affected area.
· Kala–Both nityaga & avasthika kala.The kala of the disease (Kriya kalas) & the season in which the treatment is adopted.
· Bala – The roga & rogi bala i.e the strength of the disease & the strength of the person are essential to be estimated for its management or recovery.
· Prakruthi – The constitution of the person apart from the vikruti seen whether hampers the situation or raises the antagonism mechanism inherently.
· Sathmya- The congeniality of certain drugs if not then it may worsen the condition of the diseased.
· Avastha – The condition of the disease whether easily curable, moderate for treatment or just manageable.
· Vyaadi-To diagnose the actual disease whether laghu or guru i.e. acute / chronic.
· Dravya-The rasa guna veerya vipaka, prabhava (attributes of drug) of the drug for its necessary action.
· Vaya & Linga – The age & sex of the person w.r.t Matra (quantity) & selection of drugs & treatment method.
Discussion & conclusion: - The concept of drug design & dosage in ancient Indian Ayurvedic Pharmaceutics is a reserve of facts & figures. The understanding of these novel ideas & its application is sometimes manoeuvered in its own way for better usage in present day. Drug design means not only the mixture of mere drugs of various origins but is the idea postulated, experimented standardized, then finally presented with all necessary prerequisites. Dosage does not stop only in prescription of the brand names but the suitable quantity, specific time & the adjuvant to be used along. Today even in alternate medical science these concepts are obvious. The concept of “chronobiotics” which follows the time of the drug administration, the prodrug concept for the synergistic action of the main drug is evidenced.
Though major part of medicaments is in the form of vatis /gutis having taken the form of tablets & churnas filled in capsules & swarasas / rasakriyas having replaced by syrups are only in vogue, the dynamics (what drug does to the body) & kinetics (what body does to the drug) of the drug dosage forms are still precise with its distinctive properties. The principle behind ancient drug design & dosage forms whether it was a single drug or a combination (samyoga) was:-
· Nature of the drug to be selected concerned with the part used, time of collection etc.
· Potentiating through various processes.
· Disintegration & dissolution using the adjuvant drugs as anupana or sahapana.
· Onset & Duration of action was used & so an array of dosages was used.
· Synergism & Antagonism in a formulation to enhance the drug activity & at the same time inhibit the toxic property of the drug.Eg: Tankana (borax) in Vatsanabha (aconitum ferox) formulations..
· Stability was also observed for which the shelf life of all the drugs are well documented.
· EasyADME(absorption,distribution,metabolism,excretion) where drugs with its action from its rasa (taste ) to the Karma(action ) are recorded.
· Bioavailability for the drugs which had to have a sustained/immediate release.
· Biotransformation or the rasibhavana state where the drug enters into the target cell organelles.
· Drug affinity towards one another when given in a formulation.
· Palatability as it should be acceptable to all the ages & vulnerable.
· Magical bullet technique or Prabhava was cited to see for the mysterious action.
The everlasting intellectual skills of the ancient seers who examined the biophysics & biochemical concepts of molecular interactions between ligands & their receptors & resulting applications for a rational drug design is estimable. From the perception of a drug to the balanced condition of the individual was the aim of the vaidyas & it was not mere the chemical laboratories, animal experiments, & colorful generics.
1. “ kLpn. yojn. [Ty4R: |” A=`d%
2. “ t5 ctuivR2 wUtg/am: s.Svedj jrayuj A~Dj AOi²j s¥na: |
t5 pu=8: p/2ana. tSyopkr`mNyt\ ||” su , sU 1/22
3. “ icikiTst. Vyai2hr. p$y. sa2n. AO82m\ |
p/ayiXc%. p/xmn. p/k<itS4apn. ihtm\ ||” c , ic 1/3
