AP-CF/Guidelines-GMCL & LAB/Final

GUIDELINES FOR HARVESTING, STORAGE, DRYING AND GRADING & STRUCTURES REQUIRED FOR VALUE ADDITION AND STORAGE

PREPARED FOR ANDHRA PRADESH FOREST DEPARTMENT

GMCL & LAB

JULY 2002

AP-CF/Guidelines-GMCL & LAB/Final

GUIDELINES FOR HARVESTING, STORAGE, DRYING AND GRADING & STRUCTURES REQUIRED FOR VALUE ADDITION AND STORAGE

PREPARED FOR ANDHRA PRADESH FOREST DEPARTMENT

Contributors :

G. RAJU Dr. M.S. Sastry

GMCL & LAB

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Value Addition to Raw drugs

In the Report on Value Addition Techniques for commercially important medicinal plants of Andhra Pradesh including Pharmacoepial standards for 61 species , discussion on good storage practices, drying methods etc., have been provided.

The following section discusses the value addition route to raw drugs. Ayurvedic formulation: This route can ensure a value addition in the range of 4-10 times or more. Ayurvedic formulation can be made from the Ayurvedic Formulary of India, a standard reference for this purpose. The technology involved is simple. There are a plethora of products and the consumer may have a problem in differentiating a good quality product from a spurious one. The market survey reveals that the products are not formulated on any standards. Each company makes its own formulations and the claims are not substantiated. Even if the enterprise was to make genuine products the challenge will be to build an image of quality. It is expected that the market for herbal products will grow to about Rs 4000 crores by about 2002 AD. So while there is space for introducing formulations the challenge will be to build a brand image. Export of such products is another avenue of opportunity. The table 1 gives an idea of market of different products that are produced from the species that we have identified.
Table:1 Sl. no Prices of Sample Products plant name price of crude drug A. paniculata 20.00 M. pruriens 30.00 C. borivilianum H. antidysentrica 200.0 13.00

single product churan churan

Price

Mixed product

Price

1 2 3 4

70.00

With H.a* Vanari kalpa Capsule 200ml containing 25gms

300.00 225.00 240.00 per 100 40.00

5 G. sylvestre 10.00 churan 80.00 * H.antidysentrica Source: Raju and Singh (1997) : Feasibility Study of a Non-timber forest produce enterprise. Working paper. Institute of Rural Management, Anand

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The table 2 gives the number of formulations that are possible based on the Ayurvedic Formulary of India that was mentioned earlier. Table:2 Ayurvedic formulations containing selected medicinal plants

Sl.No. Medicinal Plants 1 2 3 4 5 6 7 8 9 10 11 12 13 Andrographis paniculata Butea monosperma Cassia fistula Cassia tora Chlorophytum tuberosum Curculigo orchioides Hemidesmus indicus Holarrhena antidysenterica Mucuna pruriens Phyllanthus amarus Semecarpus anacardium Strychnos nux-vomica Woodfordia fruticosa

No. of Formulations 24 8 10 3 5 2 41 30 7 9 15 1 36

Source: Raju and Singh (1997) : Feasibility Study of a Non-timber forest produce enterprise. Working paper. Institute of Rural Management, Anand

The table 3 gives a general break-up of the market share of categories of products (ITCOT, 1996). Based on this table one can decide the categories of products that can be made and sold.

Table 3 Market share of products Product category Arishtas Medicated oils Lehas Kashayams Medicated ghee Pills, powders and raskariyas % share 30 20 20 10 10 10

Source: Raju and Singh (1997) : Feasibility Study of a Non-timber forest produce enterprise. Working paper. Institute of Rural Management, Anand

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Extracts: This route requires a more sophisticated technology. The following plants yield extractions that have a demand in the market place. A. paniculata, G. sylvestre, Strychnos nux-vomica, P. amarus, M. pruriens and others such as B. monosperma, S. anacardium yield extracts that have industrial applications. In this route value addition to the extent of 10 times is possible. The technology required is one of solvents extraction with various solvents required for extraction purposes. The extracts also have a demand in the export segment.
Table 4: Export Potential

Sl. no 1 2 3 4 5

Item of export Sarasparilla* Nux-vomica salts and derivatives Strychnine alkaloids Emetine alkaloids** Emetine salts and derivatives

Value in Rs in lakhs per tonne 0.645 11.494 7.67 422 317

* S. zeylanica is used as a substitute. ** The plants Holarrhena antidysentrica have emetic properties. Source: Raju and Singh (1997) : Feasibility Study of a Non-timber forest produce enterprise. Working paper. Institute of Rural Management, Anand

Table 4 gives a picture regarding the export market and the table 5 gives an idea of the domestic market prices. In the domestic market likewise in crude drug market the quality of extracts is also considered a problem. The enterprise could use it as an advantage and supply good quality extracts to other companies that make formulations based on these extracts. In this sector not many players are there and hence an image could be more easily established as compared to the crude drug segment.

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Table 5 Some market price of Extracts Plant name Price per kg of concentrated Price of Extracts of Company B extracts of Company A 1=25kg of crude drug 435.00 420.00 225.00 495.00 165.00 435.00 1=100kg crude drug 1380.00 1290.00 480.00 1584.00 303.00 1380.00 of Product type Price

Ipomea nil Mucuna pruriens Gymnema sylvestre P. niruri W. fruticosa C. angustifolia S. nux-vomica H. antidysentrica A. paniculata

8% L-Dopa 1=10kg

35.00* 450.00 1250.00 (15% senocide) 95.00 per % 30.00 per % 35.00* per %

4-8% striccine 525.00 1695.00

8% Andrographali de Source: Raju and Singh (1997) : Feasibility Study of a Non-timber forest produce enterprise. Working paper. Institute of Rural Management, Anand

Technological Process: Crude Drugs: In case of the crude drugs plant material is collected in the appropriate season and time of the day. Leaves are collected from plants during the flowering season when the plant is very active. The sap movement and photosynthetic activity are at a maximum and leaves contain maximum of the active constituents. Bark is collected in spring or early summer. In this season cambium is very active and since its cell walls are very thin bark gets separated very easily. Flowers are collected about the time of pollination in dry weather in the forenoon when the dew has disappeared and dried in shade. Roots and tubers are collected in autumn when the plant is inactive and the vegetative process has ceased and contain the maximum active constituents. Once the plant material is collected it is dried either in shade or in sun and stored. Impurities are then removed. Then the plant material is ready to be packed and transported as crude drugs to the end user companies.

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Ayurvedic Formulations: Ayurvedic formulations are made in the form of choorna, lehya, gutika, rasayans, ointment, oils etc. Use of modern technology in the manufacturing process like grinding, crushing, mixing, tabletting, packing could be made. The entire process could also be done manually using kitchen equipment of large capacity. The Ayurvedic Formulary of India, like a recipe, gives the individual ingredients that are required and the quantity required of each constituent and the process involved. Hence no difficulty is anticipated in its manufacture. The Government of India has prescribed Good Manufacturing Practices (GMP) which is dealt in a separate section.

Extraction Technology: The process involves pulverising the crude drug, extraction with solvents such as water, alcohol, chloroform, acetone etc and the concentration of extract to a paste constituency, vacuum drying, centrifuging in the case of some products, pressure filtration, spray drying, powdering to a fine mesh and vacuum packing. As the products are utilised for pharmaceutical and cosmetic industry a great deal of care needs to be given to the Goods Manufacturing Practices, such as the use of stainless steel equipment, quality of process water used, maintenance of sterile manufacturing facility, quality control and quality assurance and the continuous analysis of products throughout the manufacturing cycle.

Some extraction processes are illustrated in Annexure-I

Good Manufacturing Practices (GMP): Some Salient Features: The Good Manufacturing Practices are prescribed to ensure that: 1. Raw materials used in the manufacture of drugs are authentic, of prescribed quality and are free from contamination. 2. The manufacturing process is as has been prescribed to maintain the standards 3. Adequate control measures are adopted and 4. The manufactured drug which is released for sale is of acceptable quality. 5. To achieve the above objectives listed , each licenses shall evolve methodology and procedures for following the prescribed process of manufacturing the which should be documented as manual and kept for reference and inspection.

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Factory Premises: The manufacturing plant should have adequate space for

a) Receiving and storage of raw material b) Manufacturing process areas c) Quality control section d) Finished goods store e) Office f) Rejected goods/drug store

General Requirements
Location and Surroundings The factory buildings for manufacture of ayurveda, siddha and unani medicines shall be so situated and shall have such construction as to avoid contamination from open sewage, drain, public lavatory or any factory which produces disagreeable or obnoxious odour or fumes or excessive soot, dust or smoke.

Buildings The building used for factory shall be as such as to permit production of drugs under hygienic conditions and should be free from cobwebs and insects/rodents. It should have adequate provision of light and ventilation. The floor and the walls should not be damp or moist. The premises used for manufacturing, processing, packaging and labelling will be in conformity with the provisions of the Factory Act. It shall be located as to be :

a) Compatible with other manufacturing operations that may be carried out in the same way or adjacent premises. b) Adequately provided with working space to allow orderly and logical placement of equipment and materials to avoid the risk of mix up between different drugs or components thereof and control the possibility of cross contamination by other drugs or substances and avoid the risk of omission of any manufacturing or control step:

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c) Designed, constructed and maintained to prevent entry of insects/rodents. Interior surface (walls, floors and ceilings) shall be smooth and free from cracks and permit easy cleaning and dis-infection. The walls of the room in which the manufacturing operations are carried out shall be impervious to and be capable of being kept clean. The flooring shall be smooth and even and shall be such as not to permit retention or accumulation of dust or waste products. d) Provided with proper drainage system in the processing area. The sanitary fitting and electrical fixtures in the manufacturing area shall be proper and safe. e) Furnace/bhatti section could be covered with tin roof and proper ventilation, but sufficient cares should be taken to prevent flies and dust. f) There should be fire safety measures and proper exits should be there.

Water supply The water used in manufacture shall be pure and of potable quality. Adequate provision of water for washing the premises shall be made.

Disposal of waste From the manufacturing sections and laboratories the waste water and the residues which might be prejudicial to the workers or public health shall be disposed off after suitable treatment as per guidelines of pollution control authorities to render them harmless.

Containers Cleaning In factories where operations involving the use of containers such as bottles, vials and jars are conducted, there shall be adequate arrangements separated from the manufacturing operations for washing, cleaning and drying of such containers.

Stores Storage should have proper ventilation and shall be free from dampness. It should provide independent adequate space for storage of different types of material, such as raw material, packaging material and finished products.

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Raw Materials All raw materials procured for manufacturing will be stores in the raw materials store. The manufacture based on the experience and the characteristics of the particular raw material used in ISM system shall decide the use of appropriate containers which would protect quality of the raw material. (See Good storage practice). The raw material should be segregated depending on the source as follows: metallic origin, animal, mineral, fresh, dry, volatile oils etc and plant extracts. Labelling as suggested should be adhered to.

Packaging Materials All packaging material shall be stored properly. All packing material should be cleaned before use for packing and storing.

Finished Goods Stores The finished goods transferred from the production area after proper packaging shall be restored in the finished goods stores within an area marked Quarantine. After the quality control laboratory and the experts have checked the correctness of finished goods with reference to its packing/labelling as well as the finished good quality as prescribed, then it will be moved to approved finished goods stock area. Only approved finished goods shall be dispatched as per marketing requirements. Distribution records shall be maintained as required.

Equipments For carrying out manufacturing depending on the size of operation and the nature of product manufactured suitable equipment either manually operated or operated semiautomatically or fully automatic machinery shall be made available. These equipments have to be properly installed and maintained with proper cleaning. Proper standard operational procedures for cleaning, maintaining and performance of every machine should be laid down.

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Quality Control Every licensee is required to provide facility for quality control section in his own premises or through Government approved testing laboratory. The tests shall be as prescribed in ISM pharmacopoeial standards. The quality control section shall verify all the raw materials, monitor in process quality checks and control the quality of finished product released to finished goods store/warehouse. Further the GMP norms defines the space and other requirements of such a facility.

(The GMP further discusses on working space, health clothing, sanitation and hygiene of workers, medical services to workers, Requirement of sterile product manufacturing area, batch manufacturing records, record of market complaints,. For brevity sake the details are not provided. The GMP can be obtained from ISM Department, Ministry of Health)

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ANNEXURE I SEMI PROCESSING OF THE MEDICINAL PLANTS NATIVE TO ANDHRA PRADESH FOR VALUE ADDITION Acorus calamus Extract : The rhizomes are extracted with ethyl alcohol or methyl alcohol at 65 70 0 C after soaking the material for 2 hours. The solvent from the extract is completely removed under vacuum and the residue mixed with excipients is dried under vacuum. The dried product is powdered. Aloe barbadensis The plant yields two commercially important products: 1. Aloe :The latex from the Pericyclic cells beneath the skin of the leaves is evaporated and the solid residue so obtained is the commercial aloe. It is bitter and used as a purgative. It is a thin gelatinous material obtained by crushing the mucilagenous cells in the inner tissue of the leaf. The epidermis of the leaves is removed to get mucilagenous parenchyma and homogenised. It is diluted with water, filtered and concentrated under reduced pressure to obtain 5% solids or as per requirements. This gel is used in cosmetics. Aloe gel obtained as above is concentrated under reduced pressure to contain 15% solids and then spray dried to convert it into aloe gel powder. Andrographis paniculata Extract: The crushed plant material is extracted with 70% alcohol and after removing the solvent at 55 0 C under vacuum, the extract is homogenised and spray dried.

2. Aloe gel:-

FRLHT

Source : Standardisation of Botanicals Vol 1 (2002) Eastern Publishers, New Delhi

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Bacopa monnieri Extract: The crushed plant material is extracted with 70% alcohol in counter current extractors. The extract so obtained is concentrated and the resinous matter is separated. The resin free extract is further concentrated in a falling film evaporator to a consistency of 30% solids and spray dried. Boswellia serrata Gum: The gum collected from the medicinal plant is cleared from the adhering material and extracted with alcohol. These extracts are partially distilled and pH adjusted to slightly above 7. It is then extracted with petroleum ether in a liquid liquid extractor. Alcoholic fraction is concentrated to contain 35% solids and poured into deminerlised water with stirring to precipitate Boswellic acid, rich fraction. This precipitate is separated and dried under vacuum. Cassia senna Extract: Senna leaves powder containing about 2.5% sennosides are extracted with acetone and then with 70% alcohol or methyl alcohol pre-adjusted to pH 3.9 with citric acid. The extract is treated with lime water and pH is adjusted to 6.0 6.2 and concentrated to a paste with 65 70% solids content in a multiple effect evaporator. The paste is then dried in a rotary vacuum evaporator at 50 550C. Centella asiatica Extract: Powdered plant material is extracted with alcohol and then with water. The combined extracts are concentrated to a thick paste under vacuum at 550C in a falling film evaporator. The paste is defatted with n-hexane under reflux for one hour. The defatted material is mixed with suitable additives and the paste is dried under vacuum in a rotary dryer.

FRLHT

Source : Standardisation of Botanicals Vol 1 (2002) Eastern Publishers, New Delhi

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Eclipta alla Extract: Plant material is extracted with 90% methanol and then with 50% methanol. The extract is concentrated and dried under vacuum. The flakes obtained are powdered. Gymnema sylvestre Extract: Powdered leaves are extracted with 55% alcohol and the extract concentrated under reduced pressure to contain 30% solids. The concentrated extract is dried in spray dryer to obtain homogenised powder. Mucuna pruriens Extract: Powdered seeds are extracted with demineralised water containing 1% acetic acid. The concentrated extract is spray dried. The moisture content of the powder is maintained below 3%. Phyllanthus amarus Extract: The plant material generally found to be contaminated with fungus and bacteria is first decontaminated and extracted with a pure polar solvent followed with a dilute solvent. Both the extracts are concentrated separately and mixed in a definite strength to get the extract in a paste form. The paste is then dried at reduced pressure after mixing with water soluble starch and pulverised. Moisture content should not be more than 4%. Tinospora cordifolia The well matured stems are powdered and extracted with 50% alcohol followed with demineralised water. The extracts are concentrated separately, mixed and further concentrated. The concentrate is spray dried to a thick paste containing 65 70% solids, which is then dried in a vacuum tray dryer and powdered.

FRLHT

Source : Standardisation of Botanicals Vol 1 (2002) Eastern Publishers, New Delhi

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Tribulus terrestris Extract: The powdered fruits are soaked in 55% alcohol and then extracted repeatedly with the same solvent. The extract is concentrated to attain a consistency of 30-35% solids contents and sterlised. The sterlised extract is spray dried and powdered. Withania somnifera Extract: Powdered roots are extracted with 55% alcohol in a counter current extractor and the extract is concentrated under vacuum at 550C and then spray dried.

FRLHT

Source : Standardisation of Botanicals Vol 1 (2002) Eastern Publishers, New Delhi