Śodhana: An Ayurvedic process for detoxification and modification of therapeutic activities of poisonous medicinal plants.

Ayurveda involves the use of drugs obtained from plants, animals, and mineral origin. All the three sources of drugs can be divided under poisonous and nonpoisonous category. There are various crude drugs, which generally possess unwanted impurities and toxic substances, which can lead to harmful health problems. Many authors have reported that not all medicinal plants are safe to use since they can bear many toxic and harmful phytoconstituents in them. Śodhana (detoxification/purification) is the process, which involves the conversion of any poisonous drug into beneficial, nonpoisonous/nontoxic ones. Vatsanābha (Aconitum species), Semecarpus anacardium, Strychnos nux-vomica, Acorus calamus, Abrus precatorius etc., are some of the interesting examples of toxic plants, which are still used in the Indian system of medicine. Aconite, bhilawanols, strychnine, β-asarone, abrin are some of the toxic components present in these plants and are relatively toxic in nature. Śodhana process involves the purification as well as reduction in the levels of toxic principles which sometimes results in an enhanced therapeutic efficacy. The present review is designed to extensively discuss and understand the scientific basis of the alternative use of toxic plants as a medicine after their purification process.

INTRODUCTION

Plants are the prime source of medicine in Ayurveda. Several compounds have been isolated from medicinal plants and introduced for the service of mankind; however most of these medicines have been withdrawn due to their toxicity or side-effects.[123] Traditionally, plants having various classes of phytochemicals are still in use either in their crude form or after proper processing. Though most of the plant drugs are safe, yet few are toxic for human health. These poisonous/toxic plants are categorized as viṣa (poison) and upaviṣa (toxic but not lethal for human health) in Ayurvedic texts[4] [Table 1] and also listed in the schedule-E of Drugs and Cosmetics Act 1940[5] [Table 2]. Hence, to promote and introduce their use for medicine, such plant drugs must be detoxified or purified before their use.[6] The detoxification or purification process of any toxic material used for medicinal purposes is termed as “Śodhana”. In Ayurveda, Śodhana is in practice since the times of Caraka Saṃhitā, but its use expanded with the development of Rasaśāstra since 8th century CE. Śodhana process is specially designed for the drugs from mineral origin; however, it is recommended for all kinds of drugs to remove their doṣās (impurities or toxic content). It is cited in the treatises of Ayurveda that by the used of proper method of processing, viṣa can be converted into amṛta (nectar) and on other hand on adoption of inappropriate methods, nontoxic materials become a toxic.[7] The concept of Śodhana in Ayurveda not only covers the process of purification/detoxifcation of physical as well as chemical impurities but also covers the minimization of side effects and improving the potency/therapeutic efficacy of the purified drugs.[8]

Table 1

Viṣa and Upaviṣa

Table 2

Ayurvedic poisonous plant listed in the schedule E of drugs and cosmetics Act 1940 and rule 1945

Active constituents of many plant drugs may exert severe toxic effect at high concentrations.[91011] The purification processes are basically intended to reduce the toxicity level to a body sustainable limit and to reduce the toxic constituents to some extent or by potentiating their chemical transformation to nontoxic or relatively less toxic substances by enhancing their biological efficacy. Ayurvedic classics have emphasized various methods of Śodhana to overcome the undesired effects from various poisonous and nonpoisons drugs,[121314] involving different media specific to substances such as Godugdha (milk of Bos indicus), Gomūtra (urine of Bos indicus), Triphalā (combination of three fruits, Terminalia chebula, Terminalia bellarica and Emblica officinalis) and lemon juice etc.[1516] [Table 3]. A number of toxicological and pharmacological studies have been investigated on the active phytochemicals of many poisonous plants after their Śodhana. The objective of the present study is to review the state of knowledge about the Śodhana process of many poisonous plants. The present review also describes up to date information regarding the different process of detoxification (Śodhana) in Ayurvedic system of medicines.

Table 3

Śodhana procedures: Classical view

VARIOUS TOXIC MEDICINAL PLANTS AND THEIR ŚODHANA PROCESS

Aconitum species

Many species of the genus Aconitum viz., Aconitum ferox Wall., Aconitum napellus Linn., and Aconitum chasmanthum Holmes ex. Stapf. are known under the common name “Vatsanābha” in Sanskrit and “Aconite” in English. The roots of all the three plants are extremely poisonous but useful in the treatment of various diseases such as fever, rheumatoid arthritis, sciatica, hypertension, and acts as “rasāyana” (immunomodulators) after their detoxification.[171819] Most of the alkaloids present in the root of Aconitum species at higher doses are reported to have cardiotoxic and neurotoxic effects. Severe Aconite poisoning results mainly due to the accidental ingestion of wild plant or excess consumption of herbal decoction made from the Aconite roots.[2021] Isolated compound (Aconite) from Vatsanābha at a dose of 2 mg can cause death, while 1 g of Vatsanābha is fatal for human being.[22] The root of Vatsanābha was used as poison for hunting animals in ancient times by tribals.[23] Overdosing of traditional Ayurvedic formulations of Vatsanābha may cause hypotension, bradycardia or bidirectional tachycardia.[222425] Due to such reasons, the therapeutic dose of Vatsanābha mentioned in Ayurvedic system of medicine is 8 mg to 16 mg/day.[26] Its purification process includes svedana (boiling) in dola yantra using Godugdha for 3 h daily for three continuous days, followed by washing with water thrice and drying under sun light.[2728] After Śodhana process, the total alkaloid content decreases,[11] but the contents of less toxic substances such as aconine, hypoaconine, and benzylhypoaconine increases[2930] possibly due to conversion of the toxic aconitine into aconine or hydrolysis of the alkaloids to their respective amino alcohols after Śodhana process.[3132] In another study, it has been reported that the purified form of A. carmichaeli produces cholinergic stimulation which prevents the cold-stress-induced hypothermia and immuno–suppression.[18] Moreover, the unpurified root of A. napellus has been reported to cause a significant rise in heart rate and changes in electrocardiogram as compared to purified Aconite. It has been reported that Gomūtra converts Aconite to a compound with cardiac stimulant property, whereas, raw Aconite showed cardiac depressant properties.[19293334] Śodhana by both Gomūtra and Godugdha makes Aconite devoid of cardiac and neuro–muscular toxic effects without affecting its antipyretic activity.[11] A. chasmanthum is another species which is well known for its cardiac and neuro-toxicity. According to Sarkar et al.[35] A. chasmanthum showed toxic effects, which leads to the impairment in kidney and liver functions. Śodhana with Gomūtra reduces the toxic effects of Aconite significantly.[3035]

In vivo and in vitro studies on frog heart showed that A. ferox has potential effect to depress the heart rate by its positive inotropic and negative chronotropic effects and these effects may be mediated through cholinergic stimulation or by direct action on the heart muscle.[36]

Guñjā

Guñjā (Abrus precatorius Linn., Family: Fabaceae) roots, seeds, and leaves have been used traditionally for their purgative, emetic, tonic, aphrodisiac, and hair growth promoting properties after being processed through Śodhana.[3738] Since ancient times, it has been used as fish poison, arrow poison and also for criminal purposes of poisoning both humans and cattle.[39] Abrus seeds contain a toxic lectin, abrin (an albumotoxin), a fat-splitting enzyme, a glucoside (abrussic acid), urease, abarnin, trigonelline, choline, hypaphorine, and steroidal oil that have abortive effects.[404142] Abrin has a fatal dose of 0.1–1 μg/kg in humans and it is reported that boiling renders the seed harmless.[4344] In Śodhana of Guñjā seeds, they are subjected to the svedana in dolā yantra with Godugdha or Kāñji for 3–6 h. The Śodhita material is then subjected to washing with hot water and drying under shade.[28] During the Śodhana process, color of the media changes due to the removal of colored materials from the endosperm of the seeds and subsequently there is loss in weight.[45] According to Singh et al.[46] High performance liquid chromatography (HPLC) study of the Guñjā extract before and after the Śodhana process showed that the level of toxic hypaphorine decreases, whereas the less toxic alkaloid abrine increases. Perhaps during Śodhana process, a major part of hypaphorine might have undergone transformation into abrine by reduction of its tertiary amino group into the primary amino group. Percentage of protein present in Guñjā also reduces after Śodhana.[46] In another study, chromatographic evaluation confirms the absence of the steroidal oil in Śodhita Guñjā seed, which is responsible for the abortifacient effect. The LD50 dose of Guñjā was reported to increase from 2 to 5 g/kg (aśodhita) to ≥5 g/kg (Śodhita). The efficacy studies on hair growth and antibacterial effect of the Śodhita Guñjā show significant result.[4547]

Kupīlu

Kupīlu (Strychnos nux-vomica Linn., Family: Loganiaceae) is extensively used in various conditions such as nervous debility, paralysis, and weakness of limbs, sexual weakness, dyspepsia, dysentery, and rheumatism after proper Śodhana.[4849] It is used as a potent rasāyana drug for old age problems.[50] Kupīlu has been reported to contain active alkaloids (strychnine and brucine), which are highly poisonous.[5152] Different techniques[5354555657] have been used for the analysis and quantification of strychnine and brucine in its raw and processed seeds. Kupīlu is used not only in Ayurveda but also in Chinese and Unani system of medicine after processing.[585960] There are several specific Śodhana procedures, which have been adopted to purify the toxic materials from the seeds of Kupīlu.[2861] Classical method of purification includes soaking of Kupīlu seeds in liquid media (one after another) for 3–20 days. The liquid media include kāñji (soaking for 3 days), Godugdha (boiling for 3 h), Gomūtra (7 days soaking) and Goghṛta (fried till brownish red in color and swollen)[3] whereas traditional practitioners use castor oil (Eraṇḍa taila) instead of grita to fry[62] or immerse the seeds in the exudates scraped from the fresh leaves and stems of Aloe vera (ghṛtakumārī) for 15 days, followed by ginger juice (Ārdraka svarasa) for 7 days[63] for purification. After Śodhana process, the seeds are washed with lukewarm water where the outer seed coat and embryo are removed from the cotyledons.[64] Similarly in Chinese system of medicine, nux-vomica is fried with sesame oil for detoxification.[5465] Kupīlu after Śodhana exhibits low percentage of total alkaloid content (strychnine and brucine); and the toxic loganin glycoside is eliminated.[9646667] Detoxification of Kupīlu might be due to the chemical changes that causes the enhance N–oxidation and conversion of strychnine and brucine into less toxic derivatives such as isostrychnine, isobrucine, strychnine N–oxide, brucine N–oxide, and reduced level of loganic acid content of the seeds.[95458686970] The preliminary phytochemical investigation also shows significant changes in the level of phytoconstituents in different methods of Śodhana. Being acidic in nature, kāñji is a better extraction medium because it may facilitate the extraction of alkaloids and other phytochemicals. Ādraka svarasa also produces better results in reducing the toxic constituents (alkaloids) present in the seeds.[9] Though larger doses of strychnine are known to be lethal,[71] in lower doses it is known to be a stimulator.[72] Gomūtra Śodhita Kupīlu shows better pharmacological potency than the raw seeds.[7374] It has also been reported that Śodhana processes of Kupīlu enhances its hepatoprotective potency.[64]

The detoxification study of S. nux-vomica seeds was performed by Katiyar et al.[62] by traditional methods using aloe and ginger juice, by frying in cow ghee and by boiling in cow milk. All the treated samples were extracted with ethanol. Ethanol extracts were used for the evaluation of spontaneous motor acting (SMA), pentobarbitone-induced hypnosis, pentylenetetrazole (PTZ)-induced convoulsions, diazepam-assisted protection and morphine induced catalepsy. Ethanolic extracts of all the samples reduced SMA and inhibiting catalepsy, but seeds processed in milk showed the lowest content of strychnine, exhibited marked inhibition of PTZ induced convulsion and maximum potentiation of hypnosis. Seeds of nux-vomica were also processed in castor oil by Mitra et al.[63] where the strychnine and brucine contents in processed and unprocessed seed of nux-vomica were estimated by HPLC. Strychnine and brucine content in the processed seed reduced up to 67.40% and 46.58% respectively as compared to unprocessed seeds. In another experiment, Mitra et al.[75] also performed the detoxification study of nux-vomica seeds by using cow urine, cow milk and both. After the treatment, strychnine and brucine contents were determined by HPLC. Maximum reduction in the alkaloids content was found when seeds were purified in cow urine (soaking for 7 days), followed by boiling in cow milk for 3 h.

Dhattūra

Dhattūra (Datura metel Linn., Family: Solanaceae) seeds are highly toxic and may be fatal, due to the presence of alkaloids in them.[76777879] Most of the side-effects (dryness of the mouth, excessive thirst, cramps, unconsciousness, and giddiness) are due to anticholinergic property of the alkaloids present in this plant. In the purification process of Dhattūra, seeds are soaked in freshly collected Gomūtra and kept aside for 12 h. After washing, the seeds are transferred to the dolā yantra for svedana process for 3 h. The seeds are again washed with lukewarm water, allowed to dry and the seeds testa are removed.[1228] Reduction in total alkaloid content and increase in total protein content of seed were observed after Śodhana. Complete removal of scopolamine and partial removal of hyosciamine reflects the importance of Śodhana of Dhattūra by means of which the toxic effects are removed.[10]

Bhallātaka

The fruit of Bhallātaka (Semecarpus anacardium Linn., Family: Anacardiaceae) is a potent drug for nervous debility, rheumatism, epilepsy, sciatica, asthma, and many more diseases.[80] Pericarp of the fruit contains tarry oil consisting of anacardic acid 90% and cardol 10%. Other isolated chemical constituents are bhilawanols (urushiols), semecarpol, and anacardol.[818283] Bhilawanol and anacardic acids are the phytoconstituents responsible for the irritation, blisters, toxicity and contact dermatitis.[848586] The Śodhana procedure of Bhallātaka includes soaking the fruits in Gomūtra, Godugdha and rubbing it on brick gravels. After removing the thalamus portions, the fruits are kept either in Gomūtra (for 7 days) or Godugdha (for 7 days), which are finally washed with water. The seeds are then shifted to a bag containing brick gravels (for 3 days), rubbed thoroughly and dried.[1628] During the process of Śodhana of Bhāllataka, coconut oil is applied on the exposed body parts of the persons involved in the processing to reduce the chances of dermatitis.[87] Weight loss observed after Śodhana may be due to the reduction of the oil content of the fruits. It reveals that after Śodhana the polar constituents decrease from the plant materials. The increase in ash value may be due to the addition of brick powder with plant material.[88] Increase level of anacardol is observed in Śodhita fruits in comparison to the raw fruits. Recent studies prove the changes of Rf values of phytoconstituents in Śodhita samples of Bhallātaka as compared to raw Bhallātaka.[8889] Due to the decarboxylation of the oil, the anacardic acid gets converted into the less toxic anacardol. Decarboxylation process may start right from the point of cutting of the fruit and will be catalyzed in further processing.[90] It is possible that a greater percentage of oil might get reduced by soaking the fruits in the Gomūtra or Godugdha. Brick powder has adsorbent property because of which it absorbs irritant oils in the fruit. Śodhana does not affect the amount of total flavonoids and the total carbohydrate content; however, considerable decrease in total phenolic content was reported after the Śodhana process.[91] Antioxidant activity of S. anacardium decreases but the safety profile of the drug increases as the toxic phenolic oil is removed during Śodhana.[92] In addition, after Śodhana, the plant showed normal anti-artharitic activity, that is, there was no effect of Śodhana on a desirable property.[93]

Karavīra

Karavīra (Nerium indicum; Family: Apocynaceae) has anti-stress, anti-inflammatory, antifungal, cardiotonic, neuroprotective, and anticancer activities.[94] This plant contains a mixture of toxic cardiac glycosides, the cardenolides[9596] particularly oleandrin and neriine.[97] Roots of N. indicum are purified by svedana process in dolā yantra using Godugdha for 3 h. After Śodhana, the roots are washed with water and dried.[12] There is a decrease in the cardenolide and oleandrin content of the Śodhita Karavīra. Hence, the removal of these compounds may be responsible for the reduction in their effects. It was also observed that Śodhita dravya showed no reported toxicity in animal models.[98]

Guggula

Guggula (Commiphora mukul Hook. Ex. Stocks. Engl., Family: Burseraceae) is an oleo-gum resin containing dust, dry leaves, and other foreign materials. It is recommended that it should be used after purification, which makes it safer and more effective for use.[1499] Its purification process involves svedana in dolā yantra by using various media such as distilled water, Triphalā kvātha, Godugdha and Gomūtra. When all the Guggula dissolves in media, poṭṭalī is to be removed and the liquid is evaporated to collect Śodhita Guggula.[28] It is indicated in the literature that Śodhana of guggula may enhance specific action such as increasing mobile property, body tonic property, and bioavailability.[100101]Śodhita Guggula shows considerable antispasmodic activity against spasms induced by acetylcholine, histamine and barium chloride on ileum of guinea pig and Wistar rats, which are absent in aśodhita guggula.[15] The study demonstrates that purification processes significantly modified the anti-inflammatory activities of Guggula.[102] On the basis of toxicity study, it is concluded that after Śodhana process the toxicity of purified Guggula reduces as compare to crude Guggula.[103]

Vacā

The rhizome of Vacā (Acorus calamus Linn., Family: Araceae) finds use as brain tonic, appetizer, emetic, and antiepileptic.[83104] It also possesses tranquilizing, antimicrobial, antidiarrheal, antidyslipidemic, neuroprotective, antioxidant, anticholinesterase, spasmolytic, antiulcer, anthelmintic, anti-inflammatory, and analgesic activities.[105106107108] Though vacā does not come under poisonous drug category, yet some Ayurvedic texts and Ayurvedic Pharmacopoeia of India have recommended Śodhana process for Vacā rhizome.[104108109] The reason behind the Śodhana of Vacā though not clearly mentioned in any of the texts, may be surmised to be to reduce the tīkṣṇa, emetic and strong carminative actions of rhizome. The major active principles present in the A. calamus oil are α and β–asarone, calamene, calamenenol, calameone, α–pinene, camphene, and eugenol.[110111] Most of the pharmacological actions of A. calamus are attributed to aromatic oils and β–asarone,[112] but it is carcinogenic in rodents and potentially genotoxic. The content of β–asarone in A. calamus depends on the ploidy level of the plant. The diploid variety found in North America is free from β–asarone. The triploid variety found in Europe contains 9–13% of β–asarone. The tetraploid variety of A. calamus found in India contains around 75% of β–asarone.[113] However, it may not be ruled out that ancient Indian physicians were well aware of its toxic effects such as carcinogenicity and mutagenecity and to overcome these effects they might have recommended the Śodhana procedure.[12114] The Śodhana procedure involves boiling of Vacā successively by Gomūtra, Muṇḍīkvātha (decoction prepared from whole plant of Sphaeranthus indicus) and Pañcapallava kvātha for 3 h. After that it is treated with Gandhodaka for 1 h.[108] After Śodhana process, the rhizomes are shade dried for 12 days. Multiple processes of heating with different media lead to the decrease in the content of β–asarone due to its volatilization.[115] As per the study conducted by Bhat et al.,[114] pretreatment of rats with both raw and Śodhita Vacā exhibit significant anticonvulsant activity by decreasing the duration of tonic extensor phase. Further, Śodhita Vacā significantly decreases the duration of convulsion and stupor phases of MES–induced seizures. Raw Vacā shows 31.76% protection, while Śodhita Vacā show 36.48% protection at 5% level of significance. Both the samples of Vacā shorten other phases of MES–induced seizures, such as flexion, convulsion, and stupor, however, only the observed decrease of clonus and stupor in Śodhita Vacā treated group was found to be statistically significant. Subjecting to classical Śodhana procedure did not reduce the efficacy of Vacā rhizomes, instead it enhanced the activity profile of the Vacā.[114] Toxicity studies indicate that oral administration of rhizomes of both Śodhita and raw Vacā powder at 2000 mg/kg in albino rats is relatively safe.[116]

Lāṅgalī

Gloriosa superba Linn. (Family: Liliaceae) is a semi-woody herbaceous climber which is used in inflammations, gout, rheumatoid arthritis, gonorrhea, fever and in promoting labor pains.[83] The colchicine present in this plant is reported for its toxic effects, particular cardiotoxicity.[117118119120121] The species also contains another toxic alkaloid, gloriosine.[122123] The Śodhana/detoxification process involve the soaking of roots and seeds in Gomūtra for 24 h and then washing with warm water.[11] After the Śodhana process the level of colchicine significantly reduces as colchicine is polar in nature and therefore soluble in Gomūtra and water.[124]

Citraka

Citraka (Plumbago zeylanica Linn., Family: Plumbagi-naceae) is commonly used as appetizer, digestive, in irritable bowel disease, pain and piles.[83] Plumbagin at higher doses has been reported to be highly cytotoxic.[125] Citraka in higher dose may causes paralysis due to presence of plumbagin, and the minimum lethal dose in frog, mice and rabbits were reported to be 0.5, 0.1 and 10 mg/kg respectively. For purification process, Citraka is soaked in lime mixed with water for 24 h. The same procedure is repeated for another 24 h.[28] It has been reported that Śodhana of Citraka, removed 50% of plumbagin.[126] In another comparative study it has been reported that after the Śodhana, plumbagin content is comparatively reduced in the roots of P. zeylanica significantly as compared to roots of P. indica.[127]

Kumbhinī

Kumbhinī (Croton tiglium) is widely used for constipation, dyspepsia, dysenteria, intestinal inflammation, and other gastrointestinal disorders.[83] Seeds contain an irritating oil, a toxic protein constituent, “crotin” (composed of a “crotonglobulin” and a “crotonalbumin”)[128] and also strong purgative principles such as phorbol esters and crotonic acid.[129130] Kumbhinī seeds are purified by svedana with Godugdha in a dolā yantra for 3 h, after removing its raphae which are later triturated with lemon juice.[12] The phorbol content and toxicity of the croton oil has been reported to significantly reduced, whereas its pharmacological potency increased after the Śodhana process.[131] Significant changes were observed in the physicochemical parameters of seeds after Śodhana.[132] The quantity of major purgative principles phorbol ester and crotonic acid in unpurified and purified samples were determined by HPLC. The content of the phorbol ester in unpurified and purified sample was found to be 5.2 mg/100 g and 1.8 mg/100 g of dried seeds of C. tiglium, respectively. The quantity of crotonic acid in unpurified seeds of C. tiglium was found to be 0.102 mg/100 g of dried seeds. Crotonic acid content was found to be absent in the purified seed extract of C. tiglium.[133]

Ahiphena

The opium obtained from the fruits of Papaver somniferum Linn. is bitter, astringent, sweet, constipating, aphrodisiac, sedative, somniferous, narcotic, myotic, and antispasmodic. It is used for the treatment of cough, fever, inflammatory affections of eye, proctalgia and low back pain due to diarrhea and dysentery, migraine, malaria, dysmenorrhea, cystitis, menorrhagia, and other painful conditions.[134] Major constituents of opium are morphine and papavarine. Large dose of opium exhibited toxic effects of central nervous system, induces sleep, relieves pain and develops euphoria. Toxic effects of opium can be reduced by steeping in cold water for 5–6 h. After this process, the insoluble brown latex obtained is used in the Ayurvedic medicine.[135] Severe toxicity of opium can also be reduced by triturating with ginger juice. This process is repeated 21 times.[61228]

Bhangā

Leaves of Cannabis seativa Linn. are bitter, astringent, tonic, aphrodisiac, alterative, intoxicating, stomachic, analgesic, and abortifacient. It is used for the treatment of convulsions, otalgia, abdominal disorders, malarial fever, dysentery, diarrhea, skin diseases, hysteria, insomnia, gonorrhea, colic, tetanus, and hydrophobia. Its excessive use causes dyspepsia, cough, impotence, melancholy, dropsy, restlessness, and insanity.[48] In order to reduce these toxic effects, Bhangā is boiled with Babbula Tvak kvātha for 3 h and the powder obtained is triturated with Godugdha.[612] Toxic effects of Bhangā can also be reduced by triturating with Babbula Tvak kvātha and frying the powder obtained in Cow Ghee.[28]

CONCLUSION

As per the concept of Ayurveda, “even a strong poison can be converted to an excellent medicine if processed and administrated properly. On the other hand, even the most useful medicine may become a poison if handled incorrectly.” Over time Ayurvedic practioners have tried to develop a number of traditional methods to convert toxic medicinal plants to useful medicines. Ancient healers, who developed formulations based on medicinal herbs, were probably not aware of the chemical composition of the herbs. Ayurveda uses many toxic natural drugs either in their crude form or after subjecting them to Śodhana processes for treating human ailments. It may be concluded that the traditional system of purification (Śodhana) can influence the phytochemical, pharmacological, and toxicological profile of the plant drugs and thereby useful in increasing safety profile and efficacy of the drugs. It is worthwhile to adopt Śodhana processes as per Indian system of medicine in the development of herbal formulations with application of modern technology to assess its safety and efficacy. Studies have shown that the toxic constituents are transferred into media rendering the drug nontoxic. Specific media has definitely an important role in making a drug act without causing side-effects/adverse effects.

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