BASIC INFRASTRUCTURE REQUIREMENTS FOR HERBAL BASED INDUSTRIES

BASIC INFRASTRUCTURE REQUIREMENTS FOR HERBAL BASED INDUSTRIES

STANDARDIZED EXTRACTS AND AYURVEDIC VARIOUS DOSAGE FORMS

          Ayurvedic dosage forms (formulations) can also give grouped into four types depending upon their physical form i.e.

1. Solid dosage forms – Gutika, Vatika etc
2. Semi Solid dosage forms – Avleha, Paka, Lepa, Ghrita, etc
3. Liquid dosage forms – Arista, Asava, Arka, Taila, etc
4. Powder dosage forms – Bhasma, Satva, Mandura, Pisti, etc

          Ayurvedic therapeutics is based in five pharmacological principles (panchsheel) of the drug. These principles are Rasa, Guna, Virya, Vipaka and Prabhava.

          With an objective of obtaining maximum therapeutic benefit and making the formulation palatable, different pharmaceutical processes are prescribed in Ayurveda. The important are as follows

Asavas and Arishta

          Asavas and Arishtas are the medicinal preparations processed by soaking the drugs in the powdered forms or in the form of their decoction (known as Kasaya in ayurveda) in a solution of sugar or jaggery (Gur), for a specified period of time. During soaking, it undergoes fermentation generating alcohol and in process facilitating extraction of active constituents contained in the drugs, Alcohol so generated also serves as a preservative in the product.

          In the preparation of Asava, required quantity of water and jaggery or sugar is taken, boiled, cooled and transferred to fermentation vessel or barrel. Finely powdered crude drugs and other ingredients as mentioned in the formula (Patha) are then added to it. The container is covered with the lid and edges are sealed with clay-smeared cloth, wrapped in seven consecutive layers. Further processing is identical to that of arishta.

          Filtered Asava and Arishta should be clear and without any froth (foam) at the top it should not become sour on standing. It has characteristic. Aromatic and alcoholic odour.

Example: Kumariasava, Madhukasava, Punarvasava

Arka

          It is the liquid preparation obtained by distillation of certain crude drugs soaked in water using the distillation unit (Arkayantra).

          The coarsely powdered crude drug is soaked in adequate quantity of water and kept overnight, which softens the drug and releases the volatile principles during distillation.

          Arka is suspension of the distillate in water with slight turbidity and colour, depending upon the nature of crude drug undergoing the distillation. It has characteristics aromatic odour.

Example: Ajmodarka, Kaparady arka, Jatamansyarka

Avaleha or Leha and Paka

          Avaleha or leha is a semisolid preparation of drugs prepared by addition of sugar, jaggery (Gur), or sugar candy and boiled with  prescribed drug juice or decoction.

          Jaggery/Gur or sugar candy is dissolved in liquid, boiled and strained. The powdered drugs in small quantities are added and stirred continuously to form the homogeneous mass. Ghee or oil is added while preparation is hot.

Example: Kutajavelaha, Draksavaleha, Bilvadileha

Kvatha (Decoction)

          This is prepared by boiling the powdered crude drugs in water. According to the hardness of crude drugs, four, eight or sixteen times quantity of water is added to the drug and boiled to one fourth volume. The decoction is filtered and used. Sometimes butter, honey, sugar, jaggery or oils are added before intake.

Churna

          Fine powder of drug or drugs is known as churna, drugs mentioned in Patha, are cleaned properly, dried thoroughly, pulverized and then sieved. The churna is free flowing and retains potency for one year, if preserved in airtight container.

Example: Triphala churna, Trikatu churna, Drakshadi churna

Dravaka

          The preparation obtained from lavanas or Ksharas are known as Dravakas.

          They are prepared by distillation process with or without additions of any fluids. These should be stored in glass bottles and are quite stable products.

Example: Sankha dravaka

Ksharas

          Alkaline (basic) substances obtained from the ash of drugs are known as Ksharas. The crude drugs is cut into pieces and burnt to ash. The ash is dissolved in water, strained and again evaporated to remove water while salty solid contained is known as Kshara.

          Kshar becomes moist, if exposed to atmospheric conditions. It is quite stable for years together. The taste of Kshar is salty.

Examples: Apamarga Ksara, Palasa Ksara, Vasa Ksara and Yavaksara

Lepa

          The preparation in the form of paste meant for external application on the body is known as lepa. The crude drugs in the powdered form are mixed with cows urine, water, oil or ghee and made into paste.

          Lepas prepared from vegetables powders are stable only for one month, while lepas containing minerals or metals long last.

Example: Sinduradi lepa. Pathyadi lepa. Dasanga lepa and Doshaghna lepa

Vatika and Gutika

          Medicaments in the form of tablets or pills are known Vatika and Gutika respectively. These are made by using single or combinations of vegetable, minerals or animal drugs.

          These preparations can be used up to two years. Pills with mineral ingredients can be used indefinitely.  

          These formulations should not loose their original color, odour, taste, and form on standing. They should be kept away from moisture, if they contain salt, ksara or sugar.

Examples: Gandhaka vati, Lasunadi Gutika, Marma Gutika

Netrabindu and Anjana

          Netrabindu is processed by dissolving the specified crude drugs in Kasaya or honey and used as eye drops.

          Anjanas are very fine powders of medicaments to be applied with netrasalaka. Their potency depends upon the drugs used in their separation. Normally, they are used within one year.

Example: Muktadi mahanjana, Chandroaday vartti

Sattva

          Water extractable solid substance obtained from a drug is known as sattava. Crude drug is cut into pieces, soaked in water, kept overnight and strained. It is allowed to settle. The supernant liquid is decanted and Sattva (extracted) is dried and powdered.

Example: Guduchi sattava

Pisti

          Pisti is obtained by triturating the drug with the specified liquids and exposing the same to sun or moonlight.  Pisties are as fine as bhasma, and retain their potency indefinitely, they are stored in bottles.

Example: Praval pisti, Mukta pisti, Manikya pisti

Ghrita (Snehkapla)

          Ghritas are the preparations in which ghee is boiled with the prescribed quantity of the decoction (Kasaya) and fine paste (Kalka) of the drug as specified in the formula.

Example: Ashoka Ghrita, Nirgundi Ghrita, Brahmi Ghrita, Sukumara Ghrita

          For preparing medicated oil, the fine paste of the drug, liquid and oil together, cooked, stirred, constantly to the paste at the bottom and prevented from getting charred.

          Tailas can be used internally and topically. They retain poteny for about sixteen months. They are taken internally with warm or warm milk.

Example: Bhringaraj taila, Maha Narayana taila, Laghu visgarbha taila

Bhasma

          The powdered form of the substance, obtained by calcinations of metals, minerals or animal products by a special process in closed crucibles or in pits covered with cow dung cakes (puta), is known as bhasma.

Exmples: Tamra – bhasma, Godanti bhasma, Mukta bhasma

Rasa Yoga

          The meidicinal preparations containing mineral drugs as their main ingredients, in the form of powder or pills are known as Rasa Yoga.

Examples: Karpura rasa. Tribhuvana Kirti – Rasa

Kupipakva Rasayana

          The minerals and drugs of metallic origin in the powdered form are mixed together and placed in a glass flask (Kachkupi i.e. glass vessel)

Examples: Rasa karpura, Rasa sindhura, Makaradhvaja

Fant

          These are prepared by pouring hot water over the dry crude drugs. Normally crude drugs are leaves but roots and fruits may also be used at times. The pulverized crude drugs are placed in the clean and dry metal vessels and the hot water (jut to boil) is poured and is placed.

Nikhada

          The residue or marc obtained in Kadha or Kashaya is treated with boiling water and strained.  The filtrate thus obtained is known as Nikhata.

Ghana Saar

          The decoction obtained in preparation of Kadha or Nikadha is further evaporated to semi-solid mass is known as Ghana saar (Ghan means solid)

Kalka

          When fresh or dry crude drug is powdered and pounded with water hot or cold to give a very fine paste then it is termed Kalak.

Swarsa

          When the Kalka is pressed in between the palms of the hand or is expressed through the layers of cloth to produce a thick juice then it called as Swaras. Swaras is generally prepared from crushed leaves or the roots of the herbs.

Parpati Kalpas

          The mineral or herbal drugs are processed by special techniques of roasting and are converted into flattened scales or thin layers parpati – kalpas are claimed to have long shelf life.

Siddha Milks

          The drops obtained by burning medicinal substances like roots or fruits (marking nut) or wicks impregnated with medicinal extracts (Sulphur preparations)  are allowed to fall in the boiling milk and are thoroughly  mixed by stirring. The drops getting mixed with milk are enriched with medicinal activity are further used for treatment. Siddha milk are specially useful for invalid as correctives or tonics.

Kajjali

          An amalgam used in Ayurvedic system of medicine as a vehicle for other medicines is prepared by mixing equal quantity of mercury and sulphur. Before the sulphur and mercury are mixed together every care is taken to see that both the ingredients are of highest purity. Stone mortar and Pestal are used for uniform rubbing and coverting them into very fine  blackish grey powder.

Matras

          Highly potent, stick like preparations are known as Matras. They are rubbed over the sand stone in a vehicle like honey or milk. The rubbing on the sand stone is termed as turn. Turms deiced the dose of the medicament. The out come of turns is collected on the fingertips and is applied to the tongue where from the drug gets absorbed and offers its therapeutic activity.

Nassayas

          These are the nasal preparations and may be very fine powders, aqueous or oily preparations. They are either directly blown into the nostrils or applied by dropper if in the liquid form.

Praash

          They are semi solid preparations like jams. These are highly palatable preparations used for refreshing or rejuvenations of body i.e. Chyavanaprash.

Space requirements for manufacturing of Ayurveda and Siddha Medicines

1200 sq ft covered area with separate cabins/partitions for each activity is required if Unani medicine are manufactured in the same premises an additional area of 400sq ft will be required. Minimum space requirement for manufacturing individual category of medicine of Ayurveda/Siddhas as per GMP requirements has been further explained in Table below.

Sl. No.	Category of Medicine	Minimum space required
1.	Anjana/pisti	100 sq ft
2.	Churna/Nasya, Manjan/Lepa, Kwatha, Churna	200 sq ft
3.	Pills/Vatti/Gutika, Matirai	100 sq ft
4.	Tablets	100 sq ft
5.	Kupipakva/Ksaram/Parpati/Lavana. Bhasma, Satva/Sindura Karpu/Uppu/Param	150 sq ft
6.	Kajal	100 sq ft
7.	Capsule	100 sq ft
8.	Ointment / Marham Pasai	100 sq ft
9.	Pak/Avaleh/Khand/Modak/Lakayam	100 sq ft
10.	Panak, Syrup/Pravahi, Kwath Manapaku	150 sq ft
11.	Asava/Arista	200 sq ft
12.	Sura	100 sq ft
13.	Ark Tinir	100 sq ft
14.	Taila/GhritNey	100 sq ft
15.	Aschoyotan/Netra, Malham, Panir	100 sq ft

MACHINERY AND EQUIPMENTS

          Machinery and equipment should be according to the size of operations and nature of product. Manufacturing process could be manual, semi-automatic or automatic. In an ISM manufacturing unit different processes are – crushing, grinding powdering, boiling, mashing, burning, roasting, filtering, drying, filling, labeling and packing etc. There should be adequate space between machines to facilitate the cleaning and maintenance operations.

          Machinery and equipment for manufacturing of Ayurveda and Siddha medicine.

Sl. No.	Category of Medicine	Machinery and Equipment Required
1.	Anajana/Pisti	Kharel-merchanized/motorized, Kharel, end runner / ball mill, sieves/sifter
2.	Pills/Vatti/Gutika matirai	Ballmill, mass mixer, powder mixer pill/vati cutting machine, stainless steel trays/containers for storage, driers/mechanized chattee (for mixing guggul) where required
3.	Tablets	Ball mill, mass mixer, powder mixer granulator, tablets compressing machine and sugar coating, merchandized chatte (for mixing of guggulu) where required
4.	Churna/Nasya, Manjan/Lepa, Kwath churn	Grinder, disintegrator, pulverizer, powder mixer, sieves/shifter
5.	Kupi pakva/Ksara/ Parpati/Lavana, Bhasma Satva/Sindura karpu/ Uppu /param	Bhatti, karahi/stainless steel vessels/patila flask multani matti/plaster of paris, copper road earthen container, gaj put bhatti, muffle furnace (electrically operated) end/edge runner, exhaust fan, wooden/SS spatula
6.	Kajal	Earthen lamps for collection of kajal, tipple roller mill, end runner, sieves, SS patila, filling / packing and manufacturing room should be provided with exhaust fan and ultravioler lamps
7.	Ointment/Marham Pasai	Tube filling machine, crimping machine/ointment mixer, end runner/mill (where required) SS storage container SS patila
8.	Pak/Avaleh/Khand/ Modak/Lakayam	Bhatti section fitted with exhaust fan and should be fly proof, iron kadahi/SS patila and SS storage container

9.	Panak,Syrup/Pravahi, Kwath, Manapaku	Tincture press, exhaust fan fitted and fly proof, bhatti section bottle washing machine, filter press/gra filter liquid filling tan with tap/liquid filling machine, PP capping machine
10.	Asava/Arishta	Same as mentioned above, fermentation tanks, containers and distillation plant where necessary filter press
11.	Sura	Same as mentioned above, fermentation tanks, containers and distillation plant where necessary filter press
12.	Ark Tinir	Maceration tank, distillation plant, liquid filing tank with tap/gravity liter/filter press, visual inspection box
13.	Tail,Ghrit,Ney	Bhatti, Kadahi/SS patila SS storage container, filtration with tap/liquid filling machine
14.	Aschoyotan/Netra, Malham, Panir	Hot air oven electrically head with thermostatic control, kettle, gas or electrically heated with suitable mixing arrangements colloid mill or ointment: mill, tube filling equipments, mixing and storage tanks of stainless or of other suitable material sintered glass funnel, seitz filter or filter candle, liquid filling equipment, autoclave.

OTHER BASIC RESOURCES SUCH AS MANUFACTURING UNIT

Buildings

          The factory building is an important aspect. The total building plan should have due consideration for dosage forms to be manufactured (product range), scale of operation, (small medium and large) and type of equipments (manufacturing of medicine should qualify following conditions along with conformity with the Factory act.

i.                    Building should be designed constructed and maintained in such way to prevent entry of insects/rodents, files and dust

ii.                  Proper sanitary and drainage system in the unit

iii.                Adequate provision of light, electrical fixtures, proper ventilation/chimney and fire safety measures/exits

Water Supply

          Water used in manufacturing should be pure and of potable quality. Adequate provision for washing of premises should be made. Potable water should conform to prescribed standards (ICMR standards)

Requirements for the Sterile Products

          There should be provision of separate enclosed area specifically designed for sterile products. Salient points for the production of sterile products are given below

a) Manufacturing Area

i.                    Air locks for entry

ii.                  Free from dust and ventilated with an air supply

Raw Material Stores

          For the storage of raw materials appropriate containers as per material (physical and chemical properties) may be used to prevent from dampness, microbiological contamination, rodents and insect infestation, In ISM manufacturing unit raw material may be categorized as follows for their appropriate storage:

1.     Fresh herbs

2.     Dry herbs

3.     Plant extracts and exudates/resins etc

4.     Volatile oils/perfumes and flavours

5.     Animal origin

6.     Metallic origin

7.     Mineral origin

8.     Excipients

Packing Materials Stores

          There should be separate space for storage of bottles, jars, capsules, etc. All the containers and closures lids should be adequately cleaned and dried before packing the products.

Finished Goods Store

          The finished products from the production area after proper packaging should be stored in the finished goods store

REGULATORY REQUIREMENT FOR HERBAL INDUSTRIES

QUALITY CONTROL OF HERBAL DRUGS

          The pharmacopoeias of different countries include monographs indicating quality parameters and standards for various herbal drugs and also for some of their products.

1. Morphological or organolaptic evaluation:

     It refers to evaluation of drugs by  colour, odour, taste, size, shape and special features, like touch, texture,  etc. It is a technique of qualitative  evaluation  based on the study of morphological  and sensory  profiles  of whole drugs.

2. Microscopic Evaluation:

Determination of stomatal number, stomatal index and trichomes (leaf constant)

3. Chemical Evaluation:

Phytochemical investigation test like

Alkaloid test: Dragendrofot reagent test

Carbohydrate and Glycoside test: Fehling test

Liebermann – Buchard’s test: Legal test

Phytosterols, fixed oils, saponins, phenolic compounds and tannins, amino acids, volatile oils, gums and mucilage identifying test 

4. Physical Evaluation

Moisture content: Ex: Aloe – not more than 10% w/w

Viscosity : Ex: Liquid paraffin - not less 64 centistokes at 37.8₀

Melting point: Ex: Colophony 75 – 85⁰ C

Solubility : Ex: Caster oil soluble only in 3 volume of 90% alcohol

Optical rotation

Ex: Carway oil + 75⁰ – 80⁰

Refractive Index: Ex: Carway oil 1.4838 to 1.4858

Ash value is extractive, volatile oil content

5. Detection of Foreign Organic matter or Impurities

Qualitative evaluation by HPLC, HPTLC, GC

6. Estimation of Assay by UV Spectroscopy, IR Spectroscopy, Fluorescence analysis, NMR (Nuclear Magnetic Resonance Spectroscopy) mass spectroscopy, x-ray diffraction, radio imino assay.
7. Biological Evaluation

Determination Hepato protective activity, Hypoglasmic activity, antifertility activity, anti inflammatory, neuro pharmacological activity

8. Microbiological assay

By Cylinder Plate Method (CUP)

9. Determination Microbiological Contamination

Total viable aeriobic count should be underspecified limit

Ex: Ecoli, salmonella should not more than 5000/g

10. Radioactive Contamination

A typical monograph for herbal drugs as per regulatory specifications.

Monograph title

Botanical

Sensory Evaluation :        Visual Macroscopy/Touch/Odour/Taste

Foreign Matter        :        Foreign plants, foreign animals, foreign minerals etc

Microscopy             :        Histological observation, Histochemical detection

                                      measurement etc

Physiochemical  

TLC

Ash                       :        Total, Acid insoluble, water soluble

Extractable matter   :        In hot water, cold water and ethanol

Water content and volatile matter : LOD, Azeotropic

Volatile oils             :        By steam distillation

Pharmacological

Bitterness value       :        Units eq. To bitterness of std. Soln. Of quinine

                                      hydrochloride

Haemolytic activity :        On ox blood by comparison with std. Ref. Saponin

Astringency             :        Fraction (Tannins) that binds to std. hide powder

Swelling Index        :        In water

Foaming Index        :        Foam height produced by 1 gm material under

                                      specified conditions

Toxicological

Pesticide Residues   :        Total organic chloride and Total organic phosphorus

Arsenic                  :        Strain produced on HgBr₂ paper in comparison std.

                                      stain

Heavy Metals          :        Cadmium and Lead

Microbial Contamination

Total viable aerobic count

Pathogens : Enterobacteriaceae, E.coli

Salmonella, P.aerogenosa, S.aureus

Aflatoxins: By TLC using std. Aflatoxins (B₁, B₂, G₁, G₂) mixture.