This review has been done under the expert guidance of Dr Surekha .S. Medikeri on the various possibilities for pharmacological advances in Guggulu Kalpana . It is the need of the hour as , Researches are going on to bypass the drawbacks associated with available conventional formulations, as not much of study has been performed in relevance to new approaches like liposomes, phytosomes, niosomes, dendrites, microspheres etc.This advanced technology can prove to be as useful marker due to its numerous pharmacological effects.

1. Guggulu Kalpana
Dr J Janani , 2nd year PG Scholar , Dept of RSBK , GAMC Bengaluru
Under the guidance of HOD and Professor Dr Surekha S Medikeri

2. Introduction
 Definition Guggulu is an exudate (Niryasa) obtained from the plant
Commiphora mukul .Preparations having the exudate as main effective
ingredient are known as Guggulu.
 belongs to the family Burseraceae.
 It is also popularly known as Indian bellidium, and it is found in northern parts
of India, Bangladesh and Pakistan.
 The Sanskrit meaning of the word guggulu is “one that protects against
disease”.
 Guggulu has been used in treating many kinds of diseases and it has a wide
range of action when compared to other drugs, the main action being to
lower the cholesterol and triglycerides level and in treating joint diseases.

3. Synonyms
 guggulu, devdhoop, kaushik, pur,mahishaksha, palanksha, kumbh,
ullukhal, gum-guggul, Indian bedellium etc

4. Historical & Literary Review
 The reference of guggulu is found in the Atharva veda which mentions its use as a
dhupa (fumigant).
 Here it has been mentioned that disease like yaksma will not spread to the places
where the fumigation of guggulu is done. It was a well known dhupana dravya
(fumigating agent) and was also used for treating disease of the cattle.
 It was widely used during Vedic period but its use increased substantially during the
Samitha period.
 The reference of guggulu is found in Charaka Samhitha where it has been mentioned
it under the Sangyasthapana mahakashaya and also in kashayaskanda.

5.  Sushruta Samhita- mentioned in Eladi gana .
 Bhavaprakash Nighantu- Karpuradi varga.
 Acharaya Kashypa has given different dosage forms of guggulu like
taila, avaleha, doopana, vati etc. for treating balaroga.
 And Maharishi Bhela has described that dhoomapana of guggulu
should be taken after bath and after taking meals.

6.  Maharishri Haritha due to wide range of action of guggulu have
mentioned this drug as a separate chapter named as guggulu kalpana.

 The reference of it is mainly found in Sharangadhara Samhita where he
has described guggulu kalpana under vati kalpana.

7. Morphology
 Morphology- It grows upto 2-3 metres as a woody tree and shows spine-
scent branches on pale yellow to brownish stem. It has characteristic
silvery and paper like bark peelings. It bears compound leaves with oval
sub-sessile leaflets and they are serrated with smooth upper surface.

8. Method of collection
 The trees are tapped by making an incision on the bark. The resin, which flows out,
is allowed to harden before it is collected.
 The tree is tapped from November to January and the resin is collected through
May to June.
 Average 250-500g of drug resin is collected from Guggul tree per year .

9. Shodhana
 Process of shodhana-
 (1) Sand stone, glass etc. are first removed.
 (2) It is then broken into small pieces.
 (3) It is thereafter bundled in a piece of the cloth and boiled in Dola Yantra
containing any one of the following fluids.
 (a) Gomutra
 (b) Triphala kashaya.
 (c) vasa patra swarasa
 (d) vasa patra kashaya.
 (e) Nirgundi patra Svarasa with haridra churna ; And (f) Dugdha.

10.  The boiling is continued till the Guggulu becomes a soft mass.
 It is then taken out of the cloth and spread over a smooth wooden board smeared
with ghee or oil.
 By pressing with fingers the sand and other remaining foreign impurities are
removed.
 It is taken out and again fried with ghee and ground in a stone mortar (khalva).

11.  The other method is to suspend the bundle of Guggulu in
Dola Yantra so as to remain immersed in the specified
as it is boiled untill all the Guggulu passes into the fluid
through the cloth.
 The residue in the bundle is discarded.
 The fluid is filtered and again boiled till it forms a mass.
 This mass is dried in sun light and then pounded with a pestle
in a stone 203 mortar, adding ghee in small quantities till
becomes waxy.

12. Preservation and Storage
It should be kept in glass or porcelain jars free
from moisture and stored in a cool place.
The potency is maintained for two years when
prepared with ingredients of plant origin and
indefinitely when prepared with metals and
minerals

13. Note as per AFI
 There is also another practice of steaming the Guggulu in vapour by suspending
it in the Dola Yantra without actually immersing it in water.
 2. Sharangadhara’s commentator, Kashiram, in his gudartha deepika mentions that
Guggulu should be dissolved in any Vatahara warm kashaya and then dried. It
should be pounded (Kuttanam) with Ghee till it becomes waxy This is possible in 24
hours.

14. Types of guggulu
 Bhavmishra and Kaidev have classified the guggulu on the basis of its
colour. These are-
 Mahishaksha (Krishna),
 Mahaneel (Neel),
 Kumud (Kapish),
 Padm (Rakt)
 Kanak (Peet). The Kanak type of guggulu having brightness, madhur
gandhi and stickiness considered as best variety and used in human being.
 Mahishaksha And Kanaka Guggulu are usually preferred for medicinal
preparations.
 Mahishaksha Guggulu is dark greenish brown and Kanaka Guggulu is
yellowish brown in colour.

15.  Bhava prakash nighantu- 2 types

 1. Nava Guggulu

 2. Purana Guggulu


16.  Properties and action –

18. Preliminary phytochemical study of nava and
purana guggulu (Commiphora mukul)
 The preliminary tests were made by using the four different
extracts of Commiphora mukul.
 Observations and discussion –
 Similarities
Nava and purana guggulu shows presence of proteins,
carbohydrates, glycosides, flavonoids in all the four extracts
(aqueous, petroleum ether, ethanol and chloroform extract).

19. aqueous petroleum
ether
ethanol chloroform
Anthrocyanins N P N X N P
saponins N P N X
phenol X P X P N P X P
Steroid X P N P N P
alkaloid X P N P N P

20.  Anthrocyanins are also present in petroleum ether and chloroform extract of nava and
purana guggulu and absent in aqueous extract.
 They also show presence of saponins in aqueous extract, phenols in ethanol extract,
extract, steroids in ethanol and chloroform extracts and alkaloids in ethanol and
chloroform extracts of nava and purana guggulu.
 Anthrocyanins are absent in aqueous extract, saponins are absent in petroleum ether
and chloroform extracts, steroids are absent in aqueous extract and alkaloids are
in petroleum ether extract of nava and purana
guggulu.

21.  Dissimilarities
Anthrocyanins and saponins are present in ethanol extract of nava guggulu which
is absent in purana guggulu.
 Phenols are present in only ethanol extract of nava guggulu where as it is present
in all four extracts of purana guggulu.
Steroids are absent in petroleum ether extract of nava guggulu and they are
present in the same in purana guggulu.
Alkaloids are absent in aqueous extract of nava guggulu and present in the same
purana guggulu.

23.  Karma: Balya, Rasayana, Varnya, Vatabalasajit,
Bhagnasandhanakrit, Medohara
 Note-Guggulu older than 5 years is considered as purana
Guggulu .
 Doshakarma- vata kapha shamaka.



24.  Indications - vatavyadhi,
 sthaulya(obesity),
 amavata(rheumatoid arthritis),
 urusthambha,
 shotha(oedema),
 vatarakta(gout),
 vidradhi(abcess)

 Therapeutic dose- Niryasa(gum resin)- 2 to 4gm

25. Prashasta guggulu- snigdha(unctuous), mrudu(soft),
picchila(slimy), madhura Gandhi(good smell),
tikta(bitter), pitabha(yellowish in colour).

26. Shushka(dry), durgandhi(bad odour),
vivarna(discoloured), and nirvirya(devoid of potency)
guggulu should not be used in medicine.

27. Pharmacology and Phytochemistry of Oleo-
Gum Resin of Commiphora wightii (Guggulu) –
 Guggulu occurs in vermicular pieces of pale yellow or brown coloured
mass with aromatic odour and bitter astringent taste; when fresh it is
viscid and golden coloured.
 It should produce not more than 5 percent of total ash and
 1 percent of acid-insoluble ash.
 It yields not less than 27 percent of alcohol-soluble matter and
 not less than 53 percent of water-soluble matter.
 The genuine samples of guggulu contain 1 percent of volatile oil
 and between 1.0 and 1.5 percent of guggulsterones (Z and E)

28.  Contraindications during guggulu administration-
 amla food (sour), tikshna(penetrating), madya(alcoholic
drinks), ajirna bhojana(indigestion), maithuna(intercourse),
vyayama(exercise), atapasevana(exposure to hot climatic
condition), krodha(anger)


29.  Excessive and long term use of guggulu leads to timira,
mukhashosha(dryness in mouth), klaibya(infertility),
krushata(lean), murcha(giddiness), shithilya(losseness),
roukshya(dryness).

30. Chemical Constituents
Chemical study of guggulu revealed that it is a complex
mixture of steroids, diterpenoids, triterpenes, aliphatic
esters, alcohols, carbohydrates, amino acids, cholesterol,
guggulusterol, flavonoid and variety of inorganic compounds.
Steam distillation of guggulu gives pale yellow volatile oil
containing the terpenes like myrcene and caryophylline.
Guggulu contains Z-guggulusterone, E-guggulusterone and
three new sterols viz. guggulusterol I, II, III.

32. Pharmacological activities
 Guggulsterones i.e. E & Z guggulsterones are the major constituents responsible
for its pharmacological use.
 hypocholesterolemic activity,
 thyroid-stimulant, like all oleo-resins, it causes an increase of leucocytes in the
blood and stimulates phagocytosis.
 thyroid stimulatory agent, Platelet aggregation, fibrinolytic agent and the cytotoxic
agent.
 antiarthritic,
 anti- inflammatory,

33.  osteoarthritic activity,
 antiseptic, antibacterial antifungal activity,
 anti- diabetic,
 nervous diseases ,
 cardiovascular diseases.
 demulcent, aphrodisiac,

34.  liver tonic, antispasmodic,
 anti-suppurative, anthelmintic,
 urinary disorders, vulnerary etc.
 In a recent study, C. mukul and guggulsterone were found to be effective
antioxidant.

37. Method of preparation of Guggulu Vati –
Guggulu vati prepared by paka method is as follows:
First the guggulu is to be taken and small quantity of
water, kashaya, swarasa is to be added to dissolve the
guggulu in it.
It is then heated till it attains the paka lakshana and later
the fine powder of all the ingredients is to be added and
Boiled.

38. It is then rolled into vati form with little ghee and dried
properly.
The colour and other characteristics of guggulu kalpana
vary from preparation to preparation depending upon the
ingredients added to the specific formulation.

39.  Guggulu Paka Lakshana –
The paka lakshna of guggulu can be classified into 2 types
1. Pakakaleene (during the time of paka)
• The paka material sticks strongly to the spoon while
stirring.
• It attains three to four thread consistencies.
• It settles down in the bowl of water without spreading.
• It remains very soft and sticky to touch.

40.  Pakaanantara (after paka ) –
Desired colour, odour, and taste of the ingredients are to be obtained
Finger prints are imparted over the paka material.

41. Dose adjuvant and shelf life –
• One karsha (approx. 12 g)
• It can be given along with go- dugdha (cow’s milk), jala
(water) or liquid preparation.
• It can be used for 1 year from the date of manufacture.

42. Ayurvedic formulations of guggulu

54.  In present study, it has been observed that purified guggulu is used in
61 different imperative guggulu formulations used in the Ayurveda
of which are named with suffix ‘guggulu’.
 The review advocates that guggulu is generally used in compound
dosage forms like vati, guti, pills, churna, kvatha, lepa, taila and ghrita
Ayurvedic medical practice.
 However, various functional limitations and constant improvisations
seemed to have shaped the guggulu Kalpana in its today’s form like tablet.
The difference in choice of Kalpana is explained on the basis of soluble
alkaloid content and insoluble resinous gum content of guggulu.

55.  Guggulu augments the formulations with the other drugs in it without
losing its potency and it acts effectively in treating the diseases.
 It is Characterised by polyvalent actions and interpreted as additives or in
some cases they synergistically produce the observed therapeutic effect.
 The formulation concept also designed for better pharmacokinetics of
guggulu in clinical practice in Ayurveda.

56. The dose of purified guggulu is 2-4 gm however, it
is observed that even after formulating guggulu
with different ingredients the dose remain same
for many formulations - between 1-3 gm except
certain rasa preparation like Vranatak Guggulu
dose is lower as 250 mg while for lepa external
preparation like Vranari Guggulu the dose is high
up to 12 gm.

57.  Guggulu act as-binder in preparation of vati, pills and tablet while act as
suspending and emulsifying agent in case of liquid dosage forms.
 The solid dosage forms thus developed more disintegration time
which delay therapeutic action of guggulu formulations.
 Possibly considering this in view; the seers of ancient time had advised
dissolving guggulu completely in suitable liquids Before its
and Ayurvedic physicians in scenario advice to break guggulu solid
dosage forms like vati, pills and tablet before oral administration for
proper assimilation and absorption in GI tract.

59. Amavatari Rasa

63. In this ratio eranda taila obtains highest
quantity that is 4 times more than
gandhak and guggulu.
Cannot get vati form. To solve this issue
we took trial in different batches and ratio
was reduced to ¼ for all ingredients. We
have tried this classical formulation in
6(Method 1 -6) {Explain theses method
[table No 2]} different batches with 6
different methods like different heating
pattern, changing in sequence of adding
ingredients, different form of triphala
kwath. In this all 6 batches we took
ingredients in same quantity like
shudhdha Guggulu-12 gms, shudhdha
Gandhaka-12 gms (Powder form), Eranda
taila- 48 gms, Triphala in different form-
36 gms.

66. With variation in anupana, guggulu kalpana will also be beneficial
in treating many diseases as the mode of action depends on the
type of anupana (adjuvant) used.
Finally, it is observed that no data on bioavailability, metabolism, and
pharmacokinetics of Guggulu in animal models or humans are currently
available. The knowledge of these basic parameters is needed for proper
evaluation of the clinical findings with guggulu and its formulations. The
challenge in this venture is finding genuine raw drugs - guggulu and the
media of shodhana selected.

68. Drawbacks of conventional dosage forms
 Though conventional dosage form shows the dominance as patient compliance
and easy availability, yet it has found to pose the problems like dose fluctuation,
peak-valley effect, non-adjustment of the administered drug, invasiveness etc.
 Guggulu lacks its desired effect due to its low bioavailability and less water
solubility. This makes it a partial or a deficient therapy for remedy of many
signs and symptoms.

69. Novel drug delivery system (NDDS)
 Novel drug delivery system (NDDS), a new approach in the pharma sector has
excluded many of drawbacks exhibited by conventional dosage forms. Some of the
novel dosage forms of guggul has been formed like nanoparticles, nanovesicles,
gugglusomes and proniosomal gel microspheres, micro emulsion.
 But still, the novel formulations for guggulu is less outspread in the market.
Guggulu can be executed as a profitable drug using NDDS.

70. Gugglusomes
 newer kind of vesicles in which guggul is used as a carrier.
 These are commercially used for transdermal as well as topical delivery of other
anti-inflammatory drugs.
 reported to show their acceptable results without any irritation.
 sustain release and better entrapment of drug.
 This Enlighted the concept of gugglusomes for systemic as well as topical
delivery of drugs omitting the side effects produced by conventional dosage
forms.

71. Nanoparticles
 approach for transporting the drugs across blood-brain barrier inside the CNS.
 antineoplastics, antipsychotics, CNS active drugs etc.
 Solid lipid nanoparticles are characterized as lipid based nanoparticles. They
show good physical stability, protection to labile drugs from degradation,
provides site-specific and controlled release of a drug. They can be employed in
any dosage form like for topical, oral, parenteral and rectal.

72. Proniosomal gel
 Proniosomes are pro vesicular carriers.
 Device of proniosomes has overcome the physical stability issues (aggregation,
fusion, leakage, sedimentation) and chemical instability such as hydrolysis by
water, provided ease of sterilization and improved bioavailability.
 immense potential for developing herbal anti-inflammatory products.

73. CYP3A4 mediated pharmacokinetics drug
interaction potential of Maha-Yogaraj Gugglu
and E, Z guggulsterone

74.  Cytochrome enzymes play a crucial role in drug metabolism, and the majority of
the drugs are metabolized by CYP3A4 enzyme.
 Inhibition/Induction of drug metabolism is a common cause of clinically important
pharmacokinetic herb-drug interactions.
 The specific substrate of CYP450 enzyme may interact with the active
phytochemical compounds of herbal medication and which can diminish the
metabolic clearance of a co-administered conventional medicine.
 This issue is significantly safety concern, especially important with drugs
narrow therapeutic index such as warfarin or digoxin

76.  Aim:
 To evaluate TG tablets to meet modern pharmaceutical approaches and
also standardization processes.
 Materials and Methods:
 Shodhana of Guggulu was performed using Triphala Kwatha (decoction)
mentioned in ayurvedic texts.
 This processed material was dried using spray drying technique, blended
with other herbal powders as per formula and using suitable excipients
was incorporated for compressing into tablets.
 Excipients and their concentrations were evaluated for various
micromeritics properties and the formula that met the requirements was
compressed.

77.  USP informs about the limits for powder flow properties, which helps for
evaluating the flowability of powders, which is intended for compression
into tablet dosage form.
 Using approved excipients in different combinations, were able to
achieve the required flow property as per USP.
 Based on these results of micromeritics properties, blend TGF-3 was
selected for compression.
 Compressed tablets were evaluated for their physical tablet characteristics
and found to meet the USP requirements . Interestingly, the tablet
disintegration time was <30 min and was pharmaceutically well
limit. This preparation is from Guggulu and hence is expected to show
higher disintegration time.
 The Ayurvedic Pharmacopoeia of India (API) limit is of maximum 60
and the presence of markers such as guggulsterone and piperine is
ascertained using thin layer chromatography profile in both before
after derivatization.

78. Synergistic and sustained anti-inflammatory activity of Guggulu
with the Ibuprofen: A preliminary study
 Guggulosomes prepared using guggul by bath sonication and trituration
methods were studied for optical microscopy, in vitro release profile,
entrapment efficiency of drugs and anti-inflammatory activity.
 Average particle size determined was between 0.1 μm to 0.2 μm.
 Guggulosomes sustained the drug release for a period of 9 hrs and more in bath
sonification method.
 Ibuprofen loaded guggulosomes showed maximum entrapment efficiency of
26.0 % in bath sonication method.
 Anti-inflammatory study of Guggulosomes revealed that it is having more efficacy
than Ibuprofen and guggul shows that guggulosomes produced synergistic effect
with ibuprofen. Thus from the studies conducted so far we can conclude that
guggulu could serve as a carrier for entrapping drugs and shows sustained
release action.

79. Points to ponder
 Researches are going on to bypass the drawbacks associated with available
conventional formulations, as not much of study has been performed in relevance
to new approaches like liposomes, phytosomes, niosomes, dendrites,
microspheres etc.
 This advanced technology can prove to be as useful marker due to its numerous
pharmacological effects.

80. THANK YOU