Sneha Kalpana : Its probable co-relation with Liposomal drug delivery System. (Glycerosome)
- 1. Sneha Kalpana: its probable co-relation with Liposomal drug delivery System. (Glycerosome) Presenter: Dr. Saumya Gulati Junior resident- III Dept of Rasashastra & Bhaishajya Kalpana, Faculty of Ayurveda, IMS, BHU, Varanasi.
- 2. Introduction Concept of Murcchana methodology Seven Rules Completion tests Route of administration Dosage/Shelf life Liposomes Composition/types of liposome Mode of Action / variants Similarities/ dissimilarities Discussion/ conclusion
- 3. Sneha Kalpana can be defined as a pharmaceutical process to prepare oleaginous medicaments from the substances like Kalka , Kwatha or Drava Dravya taken in specific proportion and by subjecting them to unique heating pattern and duration to fulfill certain pharmaceutical parameters, according to the need of therapeutics. कल्काच्चतुर्ुुणीकृ त्य घृतं वा तैलमेव वा । चतुर्ुुणे द्रवे साध्यं तस्य मात्रा पलोन्ममता ॥ (S.M.K 9/1)
- 4. Its Endeavor To extract lipid soluble active principles from the drugs. To make use of therapeutic values of oil/ ghrita. To enhance the shelf life of Sneha preparation. To enhance drug absorption. To make the preparation more palatable with good odour.
- 5. Concept of murcchana Sneha Murchana is the procedure in which raw Sneha (Taila and Ghrita) is boiled with the fine powder of selected medicinal drugs and desired quantity of water to get rid of Aama Dosha and bad odour present in it. Rationality : This process probably helps in removal of free fatty acids, undesirable color, moisture and solids from crude Ghrita. May alters the solubility pattern and absorbability, which is desired to get maximum medicinal properties. Specific group of plant material perhaps alter the chemical composition of Sneha Change in physico-chemical characteristics.
- 6. Ghrita/ taila murcchana Kept it for mild heating. Fumes start appearing, Add Drava Dravya followed by Kalka Dravya Boiling is continued with frequent stirring.. Sneha Siddhi Lakshana should be attained.. Filtered through clean cloth & preserved in container… METHODOLOGY
- 7. Kwathapreparation (Depending on nature of drugs) Soft drugs • 4 times Medium & hard drugs • 8 times Very hard drugs • 16 times Rationality : Harder the drug, more the time required for the water molecules to act upon it, in order to facilitate transfer of active principles from drug to the liquid media.
- 8. Rationality To extract active constituents from more number of drug molecules, more the requirement of water molecules. More time duration to evaporate excess water molecules . Should be economically feasible. Depending on Quantity of drugs. Contd..
- 10. Rule 1 • The quantity of kalka dravya differs from general ratio depending on different drava-dravyas used. In case of Jala, Kwatha, swarasa, the kalka quantity will be 1/4th, 1/6th and 1/8th respectively. Rule 2 • In case of Godugdha, dadhi, mamsarasa, takra used as drava dravya the quantity of Kalka dravya the quantity of Kalka dravya should be 1/8th. However, 4 times of water is also added. Rule 3 • If number of drava-dravyas are 5 or more than 5 , Quantity of each should be equal to that of sneha. • If less than 5 then total quantity of all of them should be 4 times to that of sneha.. Rule 4 • If only Dravyas are mentioned for a Sneha preparation, then Kalka of the same drugs is prepared and used.
- 11. Rule 5 • If only Kwatha dravyas are given in a sneha preparation then Kalka of the same drugs is added. Rule 6 • In case Kalka is either not indicated or restricted , then Sneha can be prepared without Kalka. Rule 7 • In case of Pushpa Kalka, it should be taken in 1/8th part to that of Sneha Contd..
- 12. SnehaSiddhilakshnaS वर्तुवत स्नेहकल्कः यदामर्ुल्या ववमर्दुतः| शब्दहीनो अन्ननर्नक्षिप्त:| फे नोद्र्मस्तैले फे नशान्मतश्च सवपुवि | र्मधवणुरसोत्पवि: | (S.M.K 9/12-14)
- 13. Different Types of paka Mrdu paka -- Ishat Rasakalkastu Madhyam Paka– Kalke Neerasa komale Khara Paka – Ishat kathina kalkashcha Aam Paka– Nirvirya, vahnimandakaro guru. Dagdha Paka– Dahakrita, nishprayoganam Therapeutic Usage Should be discarded Mrdu paka For Nasya (Nasal administration ) Madhyama Paka For all purpose (Pana, Abhyanga, Basti, Nasya, Karnapurana, Netra purana.) Khara Paka Abhyanga
- 14. Route of drug Administration Enteral (Abhyantara ) Topical (Bahya ) Enteral Nasya Tarpana Karna purana Basti Pichu • AbhyangaTopical
- 15. Dosage/shelf life Dose : 1 pala ( Sharngdhar Samhita , madhyam khand) Depending upon the Digestive capacity of patient Uttam matra= 1 pala Madhyam matra= 3 pala Jaghanya matra= 2 karsha Shelf life: Sharangdhar samhita Deepika tika: 16 months D&C Rule 1945, , Part XVI- Rule 161-B (Shelf life or date of expiry of medicine) Ghrita = 2 years Taila = 3 years Purana ghrita 1 to 11 years Prapurana ghrita10 to 100 years Kumbha sarpi 100 to 111 years Maha ghrita older than 111 years
- 16. Liposomal drug delivery system
- 17. Liposomes are micro-particulate or colloidal carriers, usually 0.05-5.0 /~m in diameter which form spontaneously when certain lipids are hydrated in aqueous media. They are composed of relatively biocompatible and biodegradable material, and they consist of an aqueous volume entrapped by one or more bilayers of natural and/or synthetic lipids. Drugs with widely varying lipophilicities can be encapsulated in liposome, either in the phospholipids bilayer, in the entrapped aqueous volume or at the bilayer interface. Liposome & its structure
- 19. various mechanism of intracellular drug delivery by liposome
- 21. Advantage of liposomal Drug delivery Certain Limitations 1. Entrapment 2. Penetration 3. Fluidity 4. Stability 5. Immunogenic
- 22. Variants of Liposome (clinical implications ). Liposome Navo somes Glycero somes Vaso somes Archeo some Nio somes Crypto somes Emul somes
- 23. Glycerosome The concept of glycerosomes was introduced by Manca et al. for the delivery of diclofenac to skin. Glycerosomes represent a novel drug delivery systems composed of phospholipids, water and glycerol in varying amount. They are upgraded versions of liposomes meant for topical and transdermal drug delivery. These drug delivery systems manifest improved stability, fluidity, entrapment and penetration in comparison to conventional liposome. Increasing the concentration of glycerol by 10, 20 or 30 % leads to a drastic increase in glycerosome stability. These vesicles deliver the active ingredients to skin with high efficiency.
- 24. Nontoxic topical drug delivery system. Do not depend on transition temperatures for their formation unlike conventional liposomes. Improved entrapment, fluidity and stability. Glycerol, being viscous in nature homogenously spreads on skin , prevents the leakage of API. Change the plasticity of the skin layer and improve it. These increase the water content in the stratum corneum and minimise the obstacles in transdermal drug delivery. Vesicles of less than 20 % glycerol possess low viscosity, reduced penetration and low flexibility. Increased entrapment of glycerol in vesicles lead to delayed drug release as glycerol disturbs the osmotic balance between receptor and donor sides. Addition of glycerol to vesicles lead to increased particle size and reduced drug release. Glycerosome viscosity on one hand results in improved stability but on other hand it may prolong the time for vesicles to reach the skin surface from the formulation. Advantages Disadvantages
- 26. Probable co-relation of liposome (Glycerosome )with sneha -Kalpana Both are oleganious in nature, hence absorption is faster because cells are made up of lipid bilayer, hence faster cellular uptake. In liposomes, drug is present both in aqueous phase and between lipid bilayer, in the same way one can propose that the medicines in the form of kalka and kwatha leave their water and lipid soluble active constituent when processed them with ghrita/oil. Both can be used orally as well as topically. Liposomes are made up of natural lipids. There are certain oils and ghritas such as Shadbindu Taila administered nasally , indicated for Urdhajatrugata rogas , might cross the BBB and shows its therapeutic effects due to its lipoidal structure.
- 27. Disimilarities Sneha Kalpana is itself a medication , while liposomes are mere carriers that deliver the drug to a particular site. Oil/ Ghritas have their own therapeutic value and when kalka and kwatha dravyas are processed in them , their therapeutic property will enhance by the process of “Samskara”. As one research showed that , Ghrita of Guduchi is therapeutically more efficacious than swarasa and Kwatha of Guduchi. Liposomes are inert and get degraded after delivering the drug to target site. In Ayurveda, the concept of targeted drug delivery can’t be possible because the disease manifests due to imbalance among the Doshas, Dhatus, Malas , Agni vaishamya and Aaamotpatti. Hence one cannot fix the target organ for any disease manifestation. Till now there are no such researches done, that can reveal the Pharmaco-dynanmics of oleganious medications. Henceforth, there will be a need to explore the unrevealed facts in the field of oleganious medicaments of Ayurveda.
- 28. Discussion / Conclusion Sneha Kalpana is pharamaceutical dosage form involving mass transfer of the aqueous and lipid-soluble active principles of all treated herbal drugs and material of animal and mineral origin. Both oil/ ghrita have their own therapeutic indications , when processed with herbal drugs enhance their therapeutic efficacy as evidenced by various researches. As cell wall is made up of phospholipids , hence the cellular uptake of oleganious preparation is enchanced, either applied topically or taken per oral. Liposomes are a targeted drug delivery system, consist of an aqueous volume entrapped by one or more bilayers of natural and/or synthetic lipids. They release the drug to the target site and get degraded, having no therapeutic efficacy. Liposomes are also available in sustained and controlled released forms, they enhance the bioavailability of a drug because enteric absorption and degradation is trounced.
- 29. Glycerosome is one of its variant of Liposome having certain advantages over it such as improved stability, fluidity, entrapment and penetration in comparison to conventional liposome. Glycerosome are only meant for topical and transdermal drug delivery. There are certain similarities among liposome and Sneha – kalpana, like their structure and penetration to the deeper tissues. However, liposome is meant to administer drug to the target site , having no therapeutic action while Sneha- Kalpana is itself a form of drug having both water and lipid soluble active constituents of herbal drugs. There is need to understand the PK/ PD of Sneha Kalpana and then any co- relation can be justified.
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