INTRODUCTION

Granulation may be defined as a size enlargement process which converts small particles into physically stronger & larger agglomerates.

Granulation method can be broadly classified into two types: Wet granulation and Dry granulation

Ideal characteristics of granules:-

The ideal characteristics of granules include spherical shape, smaller particle size distribution with sufficient fines to fill void spaces between granules, adequate moisture (between 1-2%), good flow, good compressibility and sufficient hardness.

The effectiveness of granulation depends on the following properties

i) Particle size of the drug and excipients

ii) Type of binder (strong or weak)

iii) Volume of binder (less or more)

iv) Wet massing time ( less or more)

v) Amount of shear applied

vi) Drying rate ( Hydrate formation and polymorphism)

(1)Wet granulation:-

The most widely used process of agglomeration in pharmaceutical industry is wet granulation. Wet granulation process simply involves wet massing of the powder blend with a granulating liquid, wet sizing and drying.

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Characters:-

i) Mixing of the drug(s) and excipients

ii) Preparation of binder solution

iii) Mixing of binder solution with powder mixture to form wet mass.

iv) Coarse screening of wet mass using a suitable sieve

v) Drying of moist granules.

(vi) Screening of dry granules through a suitable sieve (14-20 )

(vii) Mixing of screened granules with disintegrant, glidant, and lubricant.

Limitaton of wet granulation:-

i)The greatest disadvantage of wet granulation is its cost. It is an expensive process because of labor, time, equipment, energy and space requirements.

ii)Loss of material during various stages of processing

iii)Stability may be major concern for moisture sensitive or thermo labile drugs

iv)Multiple processing steps add complexity and make validation and control difficult

v)An inherent limitation of wet granulation is that any incompatibility between formulation components is aggravated.

Special wet granulation techniques:-

i) High shear mixture granulation

ii) Fluid bed granulation

iii) Extrusion-spheronization

iv) Spray drying

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i. High shear mixture granulation:-

High shear mixture has been widely used in Pharmaceutical industries for blending and granulation. Blending and wet massing is accompanied by high mechanical agitation by an impeller and a chopper. Mixing, densification and agglomeration are achieved through shear and compaction force exerted by the impeller.

Advantages:

i) Short processing time

ii) Less amount of liquid binders required compared with fluid bed.

iii) Highly cohesive material can be granulated.

 

ii. Fluid bed granulation:-

Fluidization is the operation by which fine solids are transformed into a fluid like state through contact with a gas. At certain gas velocity the fluid will support the particles giving them free mobility without entrapment.

Fluid bed granulation is a process by which granules are produced in a single equipment by spraying a binder solution onto a fluidized powder bed. The material processed by fluid bed granulation are finer, free flowing and homogeneous.

iii. Extrusion and Spheronization:-

It is a multiple step process capable of making uniform sized spherical particles. It is primarily used as a method to produce multi-particulates for controlled release application.

Advantages:-

i) Ability to incorporate higher levels of active components without producing excessively larger particles.

ii) Applicable to both immediate and controlled release dosage form.

 

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iv. Spray drying granulation:-

It is a unique granulation technique that directly converts liquids into dry powder in a single step. This method removes moisture instantly and converts pumpable liquids into a dry powder.

Advantages:

i) Rapid process

ii) Ability to be operated continuously

iii) Suitable for heat sensitive product

 

Lists of equipments for wet granulation

(1)High Shear granulation:-

i)Little ford Lodgie granulator

ii)Little ford MGT granulator

iii)Diosna granulator

iv)Gral mixer

(2)Granulator with drying facility:-

i) Fluidized bed granulator

ii) Day nauta mixer processor

iii) Double cone or twin shell processor

iv) Topo granulator

(3)Special granulator:-

i) Roto granulator

ii) Marumerizer

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Current topics related to wet granulation

I.Hydrate formation

For example, theophylline anhydrous during high shear wet granulation transfers to theophylline monohydrate. The midpoint conversion occurs in three minutes after the binder solution is added.

For online monitoring of the transformation from one form to another, Raman spectroscopy is most widely used.

II.Polymorphic transformation

The drying phase of wet granulation plays a vital role for conversion of one form to another.

For example, glycine which exist in three polymorphs that is α β γ . γ is the most stable form and αis the metastable form. The stable Glycine polymorph (γ) converts to metastable form (α) when wet granulated with microcrystalline cellulose.

 

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(2) Dry granulation:-

In dry granulation process the powder mixture is compressed without the use of heat and solvent. It is the least desirable of all methods of granulation. The two basic procedures are to form a compact of material by compression and then to mill the compact to obtain a granules. Two methods are used for dry granulation. The more widely used method is slugging, where the powder is precompressed and the resulting tablet or slug are milled to yield the granules. The other method is to precompress the powder with pressure rolls using a machine such as Chilosonator.

Advantages:-

The main advantages of dry granulation or slugging are that it uses less equipments and space. It eliminates the need for binder solution, heavy mixing equipment and the costly and time consuming drying step required for wet granulation. Slugging can be used for advantages in the following situations:

i) For moisture sensitive material

ii) For heat sensitive material

iii) For improved disintegration since powder particles are not bonded together by a binder

Disadvantages:-

i) It requires a specialized heavy duty tablet press to form slug

ii) It does not permit uniform colour distribution as can be

iii) Achieved with wet granulation where the dye can be incorporated into binder liquid.

iv) The process tends to create more dust than wet granulation, increasing the potential contamination.

Steps in dry granulation:-

i) Milling of drugs and excipients

ii) Mixing of milled powders

iii) Compression into large, hard tablets to make slug

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iv) Screening of slugs

v) Mixing with lubricant and disintegrating agent

vi) Tablet compression

Two main dry granulation processes:-

(a)Slugging process:-

Granulation by slugging is the process of compressing dry powder of tablet formulation with tablet press having die cavity large enough in diameter to fill quickly. The accuracy or condition of slug is not too important. Only sufficient pressure to compact the powder into uniform slugs should be used. Once slugs are produced they are reduced to appropriate granule size for final compression by screening and milling.

Factors which determine how well a material may slug

i) Compressibility or cohesiveness of the mater

ii) Compression ratio of powder

iii) Density of the powder

iv) Machine type

v) Punch and die size

vi) Slug thickness

vii) Speed of compression

viii) Pressure used to produce slug

 

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(b)Roller compaction:-

The compaction of powder by means of pressure roll can also be accomplished by a machine called chilsonator. Unlike tablet machine, the chilsonator turns out a compacted mass in a steady continuous flow. The powder is fed down between the rollers from the hopper which contains a spiral auger to feed the powder into the compaction zone. Like slugs, the aggregates are screened or milled for production into granules.

Formulation for dry granulation:-

The excipients used for dry granulation are basically same as that of wet granulation or that of direct compression. With dry granulation it is often possible to compact the active ingredient with a minor addition of lubricant and disintegrating agent. Fillers that are used in dry granulation include the following examples: Lactose, dextrose, sucrose, MCC, calcium sulphate, Sta-Rx® etc.

 

Advancement in Granulations:-

(a)Steam Granulation:-

It is modification of wet granulation. Here steam is used as a binder instead of water. Its several benefits includes higher distribution uniformity, higher diffusion rate into powders, more favourable thermal balance during drying step, steam granules are more spherical, have large surface area hence increased dissolution rate of the drug from granules, processing time is shorter therefore more number of tablets are produced per batch, compared to the use of organic solvent water vapour is environmentally friendly, no health hazards to operators, no restriction by ICH on traces left in the granules, freshly distilled steam is sterile and therefore the total count can be kept under control, lowers dissolution rate so can be used for preparation of taste masked granules without modifying availability of the drug. But the limitation is that it is unsuitable for thermolabile drugs. Moreover special equipments are required and are unsuitable for binders that cannot be later activated by contact with water vapour.

 

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(b)Melt Granulation / Thermoplastic Granulation:-

Here granulation is achieved by the addition of meltable binder. That is binder is in solid state at room temperature but melts in the temperature range of 50 – 80˚C. Melted binder then acts like a binding liquid. There is no need of drying phase since dried granules are obtained by cooling it to room temperature. Moreover, amount of liquid binder can be controlled precisely and the production and equipment costs are reduced. It is useful for granulating water sensitive material and producing SR granulation or solid dispersion. But this method is not suitable for thermolabile substances. When water soluble binders are needed, Polyethylene Glycol (PEG) is used as melting binders. When water insoluble binders are needed, Stearic acid, cetyl or stearyl alcohol, various waxes and mono-, di-, & triglycerides are used as melting binders.

(c)Moisture Activated Dry Granulation (MADG):-

It involves moisture distribution and agglomeration. Tablets prepared using MADG method has better content uniformity. This method utilizes very little granulating fluid. It decreases drying time and produces granules with excellent flowability.

(d)Moist Granulation Technique (MGT):-

A small amount granulating fluid is added to activate dry binder and to facilitate agglomeration. Then a moisture absorbing material like Microcrystalline Cellulose (MCC) is added to absorb any excess moisture. By adding MCC in this way drying step is not necessary. It is applicable for developing a controlled release formulation.

(e)Thermal Adhesion Granulation Process (TAGP):-

It is applicable for preparing direct tableting formulations. TAGP is performed under low moisture content or low content of pharmaceutically acceptable solvent by subjecting a mixture containing excipients to heating at a temperature in the range from about 30ºC to about 130ºC in a closed system under mixing by tumble rotation until the formation of granules. This method utilizes less water or solvent than traditional wet granulation method. It provides granules with good flow properties and binding capacity to form tablets of low friability, adequate hardness and have a high uptake capacity for active substances whose tableting is poor.

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(f)Foam Granulation:-

Here liquid binders are added as aqueous foam. It has several benefits over spray(wet) granulation such as it requires less binder than Spray Granulation, requires less water to wet granulate, rate of addition of foam is greater than rate of addition of sprayed liquids, no detrimental effects on granulate, tablet, or invitro drug dissolution properties, no plugging problems since use of spray nozzles is eliminated, no overwetting, useful for granulating water sensitive formulations, reduces drying time, uniform distribution of binder throughout the powder bed, reduce manufacturing time, less binder required for Immediate Release (IR) and Controlled Release (CR) formulations.

 

 

 

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HERBALFORMULATION: -

INTRODUCTION : -

Typically, therapeutic herbal formulations based on several Chinese medicinal herbs are designed to stimulate and enhance the functionality of each ingredient. At the same time, herbal formulations also aim at suppressing and counteracting toxicity, as well as avoiding incompatibility of each ingredient. Therefore, the balance and interaction of all the ingredients are considered more important than the effect of the individual ingredients. In contrast to a typical Western medication, which focuses on a single chemical entity that targets a single organism or organ, herbal formulations often rely on the combined and synergetic effects of the several herbs to target multiple indications of a disease.

 

"Herb" refers to a plant's matter, including its flower, barks, leaves, fruit, green stems, rhizome and roots, that contains one or more pharmacologically active substances.

"Extraction" refers to a process in which one or more substances having pharmacological activities, or "active substances", are isolated from an herb or a mixture of herbs. Typically, the active substances in the herb(s) preferentially dissolve into a liquid medium. The liquid medium containing the active substances extracted from one or more herbs, also referred to "liquid phase", can thereafter be separated from the herb(s) to provide an "herbal extract" or "extract".

"Infusion" refers to a process to carry out the extraction, in which the herbs are soaked in a liquid medium to enable the active substances to enter the liquid medium. Typically, the herbs are allowed to infuse for a sufficient amount of time for the active substances in the liquid phase to reach an equilibrium, such that no more active substances can be further extracted even with prolonged infusion.

The nature and the yield of an active substance extracted are dependent upon its solubility in a given liquid medium. A liquid medium may be polar or non-polar. Examples of the polar liquid medium include water, alcohols, acetone, or a mixture thereof. Examples of the non-polar liquid medium (or lipophilic solvent) include an oil, such a plant-based oil, an animal- based oil or a mineral oil. In certain embodiments, an active substance may be preferentially soluble in one type of medium over another. For example, Doscin, an active substance in Paris, is soluble in methanol, ethanol, n-butanol, water, hydrate methanol and ethanol, but insoluble in lipophilic organic solvent. An active substance is "soluble" in a liquid medium if its solubility in the liquid medium is at least 0.1 mg/ml (w/v) at room temperature (about 25°C).

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A liquid medium may be volatile, having a boiling point of no more than 1600C. Examples of volatile liquid media include water, an alcohol, acetone or a mixture thereof. Examples of the alcohol include methanol, ethanol, isopropanol, butanol, and combinations thereof.

"Extracted substances" refers to one or more active substances isolated from the herbs. In certain embodiments, the extracted substances are in a concentrated form by removing the liquid medium. For example, the extract of Paris and Sanguisorba can be concentrated by allowing the liquid medium to evaporate. Once the liquid medium is removed, the concentrated extract may be in the form of a liquid, for example, an oily substance. It may also take the form of a semi-solid or solid. The concentrated extract can be further formulated into various forms by combining with a carrier material, such as a cream, an oil or a gel. In other embodiments, the extract can be used directly or further formulated without the removal of the liquid medium.

"Aqueous extract" refers to an extract of active substances extracted from an herb or a mixture of herbs by infusing the herbs in water.

As noted herein, the biological activity of the herbal formulation is the combined result of a mixture of the active substances. Without wishing to be bound by any particular theory, it is believed that the extract of Paris and Sanguisorba comprises active substances that separate necrotic tissue from healthy tissue at the burn site. The active substances may be of a chemical or a biological nature. "Necrotic tissue" refers to damaged and unviable tissue in any layer of skin caused by a burn, an infection or complications ensuing thereafter. Necrotic tissue tends to adhere to the burn site and provides a breeding ground for bacterial growth. As noted herein, removal of the necrotic tissue (debridement) is critical in preventing infection, control inflammation and promoting tissue regeneration.

In addition, the extract of Paris and Sanguisorba comprises active substances having pain-relieving, hemostatic, broad-spectrum antimicrobial, anti-virus and anti-inflammatory activities. Testing has shown that Paris contains a variety of glycosides having hemostatic ability, and saponins having pain-relieving and anti-inflammatory functions. In a certain embodiment, Sanguisorba extract in the liquid medium as defined herein contains saponins and other glycosides, as well as a variety of tannin compounds. The combined effects of the extract of Paris and Sanguisorba therefore target multiple indications of a typical burn injury, such as local infection, hemorrhage and edema.

 

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 Chinese Herbal Formulation:-

 

Herb tablets are made with high quality ingredients. Spring Wind has a unique lot-based program to test the most commonly used herbs for harmful chemical contaminants. Herbs are purchased in small quantities to insure freshness since Spring Wind is commitment to an uncompromising standard of quality. Herbs that are free of pesticides, fungicides and herbicides are clearly identified on the label. Equally important, each herb is selected for correct genus, species and plant part. Because of the expertise of the staff at Spring Wind Herbs, you can be certain that the herbs are correctly identified. Golden Flower Chinese Herbs carries the entire line of Spring Wind brand raw herbs.

 

1. Herb Selection and Identification:-

Since the beginning of the aristolochic acid controversy, proper herb identification has become a major issue for herbalists and manufacturers alike. Many of the aristolochic acid-related problems that occurred in the industry could have been avoided if the herbs had been properly identified before formulation. The herb identification protocol we use was instituted by Andy Ellis in 1995 and was the key for Golden Flower avoiding misidentification problems.

The ID protocol is in a constant state of upgrade. We are proud to announce the addition of a staff botanist at the manufacturing site, who will help ensure quality and accuracy. Some of the features of the best, most accurate herb identification protocol in the industry include:

Expert macroscopic inspection to weed out common substitutes Microscopic examination to ascertain species (and sometimes even

variety) authenticity TLC (Thin Layer Chromatography), a chemical “fingerprint” unique to each

species

 

2. Herbs Are Cooked:-

After each herb had been properly identified they are thoroughly cleaned and prepared. They are picked through, washed and agitated according to the specific protocol of each herb. After all foreign materials are meticulously removed the ingredients are assembled and cooked together in a vat called a rotary extractor. Fifty percent more herbs than our standard formulations are added to the EC (Extra-Concentrated) formulas to help them achieve a potent

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concentration. A continuous rotary motion thoroughly mixes the decoction liquid with strict control of the extraction temperature and timing. This unique extractor includes an essential oil retrieval system for which our manufacturer holds the patent. This retrieval system allows the vat to capture and preserve the volatile oils, which are reintroduced later in the flow coater phase.

3. Evaporation

Once extraction is complete, a valve is opened in the rotary extractor and the decoction flows directly into a state-of-the-art low temperature vacuum evaporation system. This low temperature system eliminates the damaging effects that high temperatures can have on formula potency.

4. Granulation & Tableting

Still in its airtight chamber, there is a 0% chance of cross-contamination as the flow coater (granulator) sprays the concentrate onto minute particles of base material and dries them to create concentrated granules. In the vast majority of our formulas, the base material consists of powdered herbs from the ingredients of the formulas themselves. Occasionally, when the formula has an especially cloying nature, non-GMO potato starch is used. Potato starch is chosen because it is hypoallergenic, unlike the cornstarch commonly used by other processing facilities. The granules are later precisely measured and pressed into smooth, scored tablets for easy swallowing and convenient dose adjustment. Only 2.5% of the finished EC (Extra-Concentrated) tablet is binder material, far less than most herb tablets available.

5. Lab Tests

A battery of laboratory tests check samples from each batch to assure Potency and Safety. These tests include:

Microbial testing to screen for E. coli, salmonella, and various other possible bio-contaminants such as molds and yeasts.

GC (Gas Chromatography) ensures safety by testing for the presence of over 200 potentially harmful substances such as pesticides, herbicides and fungicides.

HPLC (High Pressure Liquid Chromatography) measures potency by substantiating the presence of active ingredients.

ICP-MS (Inductively Coupled Plasma-Mass Spectrometry) is the future of non-organic (heavy metal) testing.

 

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 Granulation Method For Herbal Formulation

There are a no. of method of granulation, which are widely used in herbal formulation.these methods are:-

Fluid-Bed Granulating (Granulation)

There are a number of granulation technologies available to pharmaceutical manufacturers. Given the importance of granulation in the production of oral dosage forms, this paper offers advice on various process and looks at the implications of two different applications.

Granulation is one of the most important unit operations in the production of pharmaceutical oral dosage forms. However, there are many different technologies each having different strengths and weaknesses. Most companies choose which one to use simply based on their own experience.This article introduces different processes, compares them objectively and offers unbiased advice on the merits of each system. It then looks at the implications of selection on two different applications.

Different Fluid-Bed Granulating  Method for Herbal Formulation:-

Granulation methods:-

Single pot Fluid bed top spray granulation High shear granulation/fluid bed drying combination Continuous fluid bed granulation Fluidized spray drying Pellet production line

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(1) Single Pot Granulator :-

 A mixer/granulator that dries granules in the same equipment without discharging is commonly called a single pot (Figure 1).The granulation is done in a normal high shear processor; however, care must be taken to avoid the formation of lumps as they cannot be broken down before drying.

There are various options for drying in single pots. The traditional heat source comes from the dryer walls, which are heated; the boiling temperature and vacuum are used to reduce and remove vapours.The heat transfer is related to the surface area of the dryer walls and the volume of product treated. Therefore, this direct heating method is only effective for small scale use.

Introducing stripping gas into the pot allows large scale operation. A small quantity of gas is introduced in the bottom of the equipment, which passes through the product bed, improving the heat flow from the wall into the product.The gas also improves the efficiency of vapour removal. However, as the heated wall is the only source of drying energy, linear scale-up is not possible.This problem is exacerbated if the material to be processed is heat sensitive (as this limits the wall temperature); if water is used as a granulation liquid (it has a high boiling temperature under vacuum and a high heat of evaporation); and if used for larger-scale production (the surface/volume ratio deteriorates as the volume increases).

Microwave energy can be used to overcome these limitations.This provides a further source of energy and has the additional advantage, with organic solvents, that only pure organic vapours must be treated on the exhaust side, and not a mixture of solvent and large volumes of process gas.

Fig.1 A Typical Single Pot Set-Up

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(2)Fluid Bed Top Spray Granulation :-

Granulation can be performed using fluid beds fitted with spray nozzles. During the last 10 years, fluid beds have improved dramatically in response to single pot technology competition. It is possible to have completely closed material handling by a closed linking with upstream and downstream equipment (Figure 2). Also, fully automatic cleaning (cleaning-in- place [CIP] and wash-in-place [WIP]) in fluid beds using stainless steel filters now compares favourably with what is possible in a single pot.

Figure 2 Fluid Bed Top Spray Granulation

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(3)High Shear Granulation :-

This is the most common configuration used at an industrial scale for the production of pharmaceutical granules (Figure 3). Again, this system allows full integration with upstream and downstream equipment, and even includes a wet mill between the granulator and dryer. With modern control systems it is easy to load, mix and granulate a second batch in the high shear granulator whilst drying the previous batch in the fluid bed prior to discharge. All equipment can be CIP in a single automatic process.Whereas a single shaker might be acceptable for drying applications, a twin shaker or blowback filter design should be used for granulation processes.

FIG.3 High shear granulation

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(4)Continuous Fluid Bed Granulation :-

 A configuration enabling this process is shown in Figure 4. For start-up, the equipment is filled with raw material similar to a batch unit. After the material has been granulated, the process is switched to the continuous mode allowing material to be introduced via the rotary inlet valve and discharged as granules by a second outlet valve. The process can be controlled by monitoring the pressure drop over the product bed. The inlet air is segmented, which allows the product in different areas to be treated with different temperatures. Although the process is essentially plug flow, a significant amount of back mixing occurs during processing.

fig. 4 continuous fluid-bed granulation

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(5)Fluidized Spray Drying :-

FSD. Fluidized spray drying (FSD) produces granules from a liquid in a one-step process (Figure 5). One option is to produce the active in the primary production as granules, so that it only requires blending with excipients suitable for direct compression for secondary processing. This can only be done with actives that are tacky (in a wet state), otherwise the addition of a binder is necessary. Another possible use of FSD technology is to mix all the ingredients into a solution or suspension and to produce granules in a one-step operation.

During the FSD process, the liquid feed is atomized at the top of the tower in a cocurrent mode. After the liquid is evaporated, the particles generated leave the drying chamber together with the exhaust air. These particles are then separated in a cyclone or filter and reintroduced into the drying chamber where they come into contact with wet droplets and form agglomerates. After these agglomerates have reached a certain weight they cannot leave via the top of the tower with the exhaust air, but fall down into the integrated fluid bed at the bottom of the drying chamber. Here they are dried and cooled before being discharged.

However, this type of equipment is difficult to clean, particularly the external pipework, when changing to another product. Systems have, therefore, been developed where the external pipework does not come into contact with the product

Fig. 5 Fluidized Spray Drying

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Pellet Production Line :-

Pellet production line To form granules from powders, granulation liquid and mechanical energy are needed. Alternatively, an extruder may be used similar to that used for pellet manufacture. In a typical set-up, all ingredients are preblended in a container after dispensing. Depending on the extruder design, the liquid can be added in the extruder or mixed separately to the correct consistency. The material produced is transferred directly into a continuous fluid bed where it is dried to the desired moisture level rather than rounded in a spheronizer (as it would be for pellet manufacture).

Methods of Preparing Herbal Drugs:-

In traditional herbal medicine systems, herbal remedies are prepared in several rather standardized ways which usually vary based upon the plant utilized, and sometimes, what condition is being treated. Some of these methods include: infusions (hot teas), decoctions (boiled teas), tinctures (alcohol and water extracts), and macerations (cold-soaking) which are detailed more fully herein. In indigenous Indian medicine systems, medicine men or shamans generally use these same methods in addition to others. Others include preparing plants in hot baths (in which the patient is soaked in it or bathed with it), inhalation of powdered plants (like snuff), steam inhalation of various aromatic plants boiled in hot water, and even aromatherapy. The well-trained herbalist will always throughly review the time-honored method in which a plant has been traditionally prepared—it holds important information for preparing an effective herbal remedy.

Preparing Your Own Remedies:-

While a bit more trouble and time consuming, making your own natural remedies is usually much more economical than purchasing manufactured products. They can also be much more effective when prepared properly and by following time-honored traditional preparation methods. The first step is sourcing the good raw plant materials. Most coming from South America and the Amazon (featured in this book) will only be available in a dried state, and in either a cut herb or ground powder form. Find a reputable supplier who exports regularly from the region and PLEASE, ask questions about their harvesting practices. Many South American plants are harvested unsustainably - causing more rainforest destruction, rather than helping to preserve it. Again, do the research required to find a good supplier, ask questions, and make sure you are obtaining the correct species of plant, it is fresh, and it has been sustainably harvested.

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If you don't plan on using the plant(s) immediately, it's best to keep them unopened, in their original packaging, and away from direct sunlight (just put them in a closed cupboard/cabinet). Many plants will absorb moisture and humidity from the air, so if they are opened, reseal them tightly, or put them into glass jars with a tight-fitting lid (avoid metal containers). Most will never require refrigeration or freezing - just keep them at average room temperature (70-80 degrees). Generally, the "shelf-life" for optimum freshness will be about a year for a dried leaves, and two years for dried barks and roots if stored properly. If you live in a warm, high humidity area, it may be impossible to keep moisture out of regularly opened and closed glass containers, and the plants may become moldy. If this happens, discard them and purchase fresh ones. Next time, try storing them in paper lunch bags so they can "breathe" (although this will reduce the shelf-life significantly).

It is not always necessary to find a tea-cut plant to prepare a tea; ground powders can be used to make teas, tinctures and decoctions just as well. Since the plant is finely ground, it usually makes a stronger remedy as more surface area of the plant is available to extract in the liquid. Extra time filtering is normally required when working with plant powders, but many herbalists prefer working with powders instead of bulky cut herbs since they make stronger extracts. It is also recommended to use distilled or purified water when extracting medicinal plants. Regular tap water can contain chlorine and other chemicals which might have an interaction or chain reaction with one or more of the many chemicals found in plants.

Instructions for the main preparation methods used in the reference guides and in the main plant section are as follows.

Infusions:-Infusions are typically used for delicate herbs, leaves and fresh tender plants. Preparing an infusion is much like making a cup of tea. Water is brought just to a boil and then poured over an herb (or combination of herbs), it is covered and allowed to sit/steep for 10-15 minutes or so. It can be prepared in the drinking cup (by just pouring the heated water over the herb in the cup) or by dropping the herb into the pot which the water was heated in. Empty gauze tea-bags are even available at some herb stores which can be filled with herbs and then sealed with a iron. If an infusion is prepared in the heating pan/pot, it's best to use a ceramic pot with a lid (avoid metal pots). Stirring it a few times while steeping (especially with cut herbs) is helpful. Keeping the infusion covered while steeping is generally recommended as well (place a saucer on top of the cup, or a lid on top of the pot). The ratio of herb to water can vary depending on the remedy, the plant, and whether cut herb or powdered herb is used. Generally using 1 teaspoon of powdered herb or 2 teaspoons of more bulky cut herb in a 6-8 ounce cup of water is sufficient. If using a powdered herb; stir once halfway through the seeping time and let the powder settle to the bottom of the cup, then drink the infusion off the top (leaving the sediment in the bottom of the cup). If using a cut

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herb, strain the infusion with a tea-strainer after seeping. Infusions are best prepared as needed and taken the same day it was prepared and can be taken hot, warm, or cold. Standard dosages of infusions are generally one teacup (6-8 ounces), two or three times daily. The entire day's dosage can be prepared in the morning (2-3 cups at one time), and the remainder refrigerated until ready to use. The exceptions are the more aromatic plants with active essential oils. These are best prepared in single dosages (by the cupful) as needed and taken immediately (and while still hot/warm).

Decoctions:-

Decoctions are usually the method of choice when working with tougher and more fibrous plants, barks and roots (and which have water soluble chemicals). Instead of just steeping it in hot water, the plant material is boiled for a longer period of time to soften the harder woody material and release its active constituents. To prepare a decoction, select a ceramic pot with a snug fitting lid. Measure the amount of herb needed (usually the same ratio of 1 teaspoon powdered herb or 2 teaspoons of cut herb per 8 ounces of water) into the pot and add the proper amount of cold water depending on how many cups of the decoction you wish to prepare. Turn on the heat to medium high and bring to a roiling boil. Place the lid on the pot and reduce the heat to medium or medium-low so that the mixture stays at a good simmer. Simmer it covered for 20 minutes. If you can see steam escaping or smell the aroma of the herb, your lid is not tight enough and valuable essential oils are escaping. After 20 minutes, remove from heat and cool slightly. If using cut herbs, strain the mixture through a tea strainer into a teacup. When straining, make sure to press on the cut herb pieces in the strainer to get as much liquid/decoction out of the herb pieces as possible. If using powdered herb, allow the powder to settle to the bottom of the pot and then pour off the decoction from the top into a teacup (any sediment missed will settle to the bottom of the teacup). Standard dosages for decoction are generally one-half to one cup, two or three times daily. Again, the entire day's dosage can be prepared in the morning (2-3 cups at one time), and the remainder refrigerated until ready to use later in the day.

Strong Decoctions:-

Depending on the type of plant material used, strong decoctions are prepared in two general ways. The first involves boiling the mixture longer. This is usually indicated when working with larger woody pieces of bark. Longer boiling time, up to 2 hours or more, is sometimes necessary to break down, soften, and extract the larger pieces. Alternatively, when smaller woody pieces are used yet a stronger remedy is wanted, the decoction is prepared as above (boiling 20 minutes), then it is allowed to sit/soak overnight before straining out the herb. When straining, again, make sure to press on the cut herb pieces in the strainer to get as much moisture/decoction out of the herb pieces.

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Tinctures:-

A tincture is an alcohol and water extract which is used when plants have active chemicals that are not very soluble in water, and/or when a larger quantity is prepared for convenience and wanted for longer term storage. Many properly prepared plant tinctures can last several years or more without losing potency. The percentage of alcohol usually helps determine its shelf-life: the more alcohol used, the longer the shelf life. Sometimes the percentage of alcohol and water is unique to the herbs that are used as some active ingredients are more soluble in alcohol and others more soluble in water. The type of alcohol can vary. . . from vodka, rum, or 90 to 180 proof grain alcohol (sold as "everclear" in liquor stores and sometimes cheaper than vodka). Vodka is fine, but remember if it says 80 proof; it is 40% alcohol and the rest is water. In the Amazon, a sugar-cane alcohol resembling rum and called aguardiente is often used to prepare plant tinctures and it is 40 to 50% alchohol (or 80 to 90 proof). To prepare a tincture with a shelf-life of at least one year, plan on using a minimum of 40% alcohol (so you can extract an herb in a bottle of 80 proof vodka or rum without adding any water). Use a clean glass bottle or jar with tight fitting lid or cork. Use a dark colored bottle (like a recycled green/amber wine bottle) or plan on storing the bottle out of the sunlight. When working with dried plants, use two ounces of plant material (cut or powder) for every 8 ounces (1 cup) of liquid. Since many cut herbs can be bulky, measure the amount of cut herb by weight and not volume (ie; most cooks would tell you 2 tablespoons of butter is 1 ounce... however a lightweight bulky leaf is not as heavy as butter in the same volume or by the tablespoon). A "standard 4:1 tincture" usually means 1 part herb to 4 parts liquid (or as above, 1 ounce herb to 4 ounces of liquid). To prepare approximately 1 cup of tincture (some of the liquid will be absorbed by the dry plant material) place 2 ounces of the herb (cut up or powdered) into your clean glass container. Pour ½ cup (4 ounces) of distilled water and ½ cup (4 ounces) of 180 proof alcohol into the container (or just use 1 cup of straight 80 proof vodka and no water). Seal the container and store at room temperature away from direct sunlight. Shake the bottle/jar at least once daily while allowing it to soak/extract for at least two weeks (larger woody cut herb pieces may need to soak for 4 weeks). At the end of two weeks, filter the tincture through a strainer to remove the plant parts (pressing hard on the plant material to get as much liquid out as possible) and pour into a fresh clean glass container and seal. Some like to pour it through a cheese cloth and then use the cheese cloth to more easily wring out the liquid from the plant material. If using a powdered plant for the tincture, stop shaking for three days and the powder will settle to the bottom. Pour the tincture off the top through a piece of cheesecloth to filter it.

Since this method uses a higher ratio of plant to liquid and helps concentrate the chemicals through the use of alcohol, dosages needed for tinctures are usually much less than infusions and decoctions. Average dosages for tinctures are about 1-2 milliliters (about 30 to 60 drops) two to three times daily. The tincture can be placed directly in the mouth for immediate absorption, or placed in a small

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amount of water or juice. If you dislike the alcohol content (or want to give the remedy to a child), place the dosage in about 1-2 ounces of very hot water and most of the alcohol will be evaporated in the hot water in a minute or two. (Let cool before taking). Store the tincture at room temperature and away from direct sunlight.

Macerations:-This method of preparation is certainly the easiest. The fresh or dried plant material is simply covered in cool water and soaked overnight. The herb is strained out and the liquid is taken. Normally this is used for very tender plants and/or fresh plants, or those with delicate chemicals that might be harmed by heating or which might be degraded in strong alcohol. This is also the easiest to adapt to western methods, since tablets or capsules can be used instead. Alternatively, just stir the ground plant powder into juice, water or smoothies and drink.

Poultices and Compresses:-

Many herbal remedies are applied directly to the skin as poultices - usually on rashes and wounds and as topical pain-relieving remedies. Poultices are prepared in various ways... from the jungle shaman chewing up fresh leaves or roots and spitting them out onto the skin, to mashing up fresh leaves or roots by hand or with a mortar and pestle. Sometimes just enough hot water is poured over dried or fresh plant material to soften them. Then the wet herbs are placed directly on the skin or between two pieces of cloth and laid on the skin. A light cotton bandage to bind the poultice to the area is generally used (or in the jungle, a nice large flexible leaf is commonly employed and tied with a bit of twine). Compresses are simply soaking a cloth in a prepared infusion, tincture or decoction and laying the cloth onto the affected part of the body/skin. Since most American readers of this book will only have access to dried plant materials to work with, using compresses instead of poultices will suffice for many of the describe indigenous poultice remedies. More specific adaptations and directions where applicable are found in the main plant section under "Traditional Remedy" where it might say to apply an infusion or decoction topically.

 

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Herbal Preparation Technique:-

Briefly, this is how the spagyric technique works:

The raw plant material is soaked in water and alcohol, the two best solvents known. These natural solvents dissolve the compound into a solution that extracts otherwise insoluble elements.

Next, the solution is put under heavy pressure in a 100,000-pound press. This separates the liquid from the “mark” -- the material left in the press.

In other processes the “mark” is discarded. But we know this cellulose fiber contains a wealth of phyto-nutrients. We save the “mark” and reduce it to mineral ash, retaining all of its valuable components.

We then re-combine the mineral ash with the “mother” solution.

By using this rare and superior process, no part of the plant is wasted. No essence of the plant is lost. The finished formula retains the plant’s original constitution, but with much more strength, absorbability and healing potential than a raw plant.

 

 

 

 

 

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The Granulation Process (Basic Technologies for Tablet Making)

 This article presents the basic technologies for preparing powders for tablet making. Granulation is the process of collecting particles together by creating bonds between them. Bonds are formed by compression or by using a binding agent. If one were to  make tablets from granulated sugar versus powdered sugar, for example, powdered   sugar would be difficult to compress into a tablet and granulated sugar would be easy     to compress. Powdered sugar’s small particles have poor flow and compression characteristics. These small particles would have to be compressed very slowly for a long period of time to make a worthwhile tablet. Unless the powdered sugar is granulated, it could not efficiently be made into a tablet that has good tablet characteristics such as uniform content or consistent hardness. The granulation process combines one or more powders and forms a granule that will allow the tableting process to be predictable and will produce quality tablets within the required tablet-press speed range.

A tablet formulation contains several ingredients, and the active ingredient is the most important among them. The remaining ingredients are necessary because a suitable tablet cannot be composed of active ingredients alone. The tablet may require variations such as additional bulk, improved flow, better compressibility, flavoring, improved disintegration characteristics, or enhanced appearance. If the active ingredient in a formulation represents a very small portion of the overall tablet, then the challenge is to ensure that each tablet has the same amount of active ingredient. Sometimes, blending the ingredients is not enough. The active ingredient may segregate from the other ingredients in the blending process. The ingredients may be incompatible because of particle size, particle density, flow characteristics, compressibility, and moisture content. These incompatibilities can cause problems such as segregation during blending or during transfer of the product to the press as well as separation of the active on the tablet press.

Granulating the active by itself and then blending it with the rest of the ingredients is one solution to the segregation problem. Or, all or most of the ingredients could be granulated together. The best course of action to ensure that each tablet contains the correct amount of active ingredient, especially if the active is only a small percentage of the tablet ingredients, is to mix the active thoroughly with some or most of the other ingredients and then granulate the blend (i.e., form the blend into granules). Each granule would contain a little of each of the ingredients,and the active ingredient would be distributed evenly.

 

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Formulations:-

(a) Direct compression:

Direct compression is used when a group of ingredients can be blended, placed onto a tablet press, and made into a perfect tablet without any of the ingredients having to be changed. Powders that can be blended and compressed are commonly referred to

as directly compressible or as direct-blend formulations. Blending the powders, putting them onto a tablet press, and seeing what happens is the most direct way to make a tablet. Sometimes the tablet will fall apart, the active ingredient won’t be in all the tablets (no content uniformity), or all the powders won’t fit into the die cavity (the place where powders are filled on the tablet press). Simply blending powders does not form a granule.When powders do not compress correctly, they must be granulated.

Nevertheless, not all products must be granulated.Many processes are unnecessarily implemented because the objective and reason for choosing a process path were incorrect. Before choosing a means to process a formula, the best course of action is to put the product on the press to see what happens.

 

(b )Excipients:

Ingredients in a tablet other than the active ingredient are called excipients. Excipients can help powders become more fluid. This fluid motion is very important for transferring powders into the die cavity for compaction. Many years ago a high-speed tablet press could produce 50 tablets/min. Now a tablet pressthat runs this slowly is called a laboratory development press, and it is good only for basic feasibility studies. Today’s highspeed tablet presses can produce up to 12,000 tablets/min, and the average tablet press speed is 3000 tablets/min. Therefore, excipients are used not only to enhance the performance of active ingredients, but also to simply make the active work better on the tablet press. Many types of excipients are used in tablet formulations to help in other ways. They include :-  

● binders, which help powders fuse or link particles to one another

● fillers, which bulk up a tablet

● lubricants, which prevent powders from sticking to the metal components of the tablet  press  and tablet-press tooling

● disintegrants, which help the tablet break up after it is ingested by the patient

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Several other excipients can be added to a formula to improve flow, compression, hardness, taste, and tablet performance:-

(a) Flowability: -

As mentioned previously, press speed requires powders to be very fluid, a property commonly referred to as product flowability. Good flow characteristics are necessary because the mechanical action of the tablet press requires a volume of fill. As

shown in Figure 1, the volume of fill represents the actual tablet weight. A tablet press does not weigh the precise amount of powder for each tablet. To achieve consistent tablet weights, the formula must be designed to flow consistently and to fill volumetrically.

Thus the powders in the formula must possess a consistent particle-size distribution and density to attain proper flow and achieve volume of fill (i.e., tablet weight). In other words, the powders must flow consistently to attain consistent results.

 (b) Compressibility:

Other excipients in a formula enhance the ability of the powders to compact. All powders have very different characteristics.

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Herbal Tablet

Defintion:-Herbal tablets are the solid unit dosage forms containing a medicament or mixture of medicament and excipients compressed or moulded into solid cylindrical shape having either flat or convex surfaces.

Method of Herbal Tablet Preparation:-

The manufacture of granulations of herbal tablet compression may follow one or a combination of three established methods.

(1)Direct Compression:-

Crystalline substances like sodium chloride ,sod. Bromide and pot.chloride ,may be compressed directly. The vast majority of medicinal agents are rarely so easy to tablet,however,in addition the compression of a single substance may produce tablets that do not disintegrate.direct compression materials should possess good flow and compressibility and must be inert,tasteless,able to disintegrate and inexpensive

Direct compression method:- Drug + Filler + Disintegrant + Lubricant + Glidant

↓ Blending

↓ Compresion

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(2)Dry Granulation:-

Dry Granulation has been used for many years and is a valuable technique in situation where the effective dose of a drug is too high for direct compaction and the drug is sensitive to heart ,moisture or both which precludes wet granulation.Many aspirin and vitamin formulation are prepared for tableting by dry granulation.

Dry Granulation or compression or slugging method :- Drug +

Filler + → Blending

Lubricant ↓ Precompression

↓ Comminution Glidant + ↓ Lubricant+ → Sizing

Disintegrant ↓ Blending

(3)Wet Granulation:-

Wet granulation form the granules by blending the powder together with an adhesive ,instead of by compaction .the solubility of binder has a good influence on the choice of methods,since the solution should be fluid enough to disperse readily in the mass .Liquid bridges are developed between particles ,and the tensile strength of these bonds increases as the amount of the liquid added is increased.A drying process is required in all wet granulation to remove the solvent and to reduce the moisture content.After drying ,the granulation is screened again,followed by compression.

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Drug+ Filler → Blending ↓ Wetting ←Adhesive& ↓ Water Granulation ↓ Drying Lubricant → ↓ Glidant Sizing Disintegrant ↓ Blending ↓ Compression

Reason for Granulation:-

The reason why granulation is often necessary are as follows:

(1)To prevent segregation of the constituents in the powder mix

Segregation is primarily due to differences in the size or density of the components, the smaller particles concentrating at the base of a container with the large particles above them. an ideal granulation will contain all the constituents of the mix in each granule and segregation of the ingredients will not occur.It is also important to control the particle size distribution of the granules because, although the individual components may not segregate , if there is a wide side distribution, the granules them selves may segregate. If this occur in hoppers of sachet filling machine or tablets machines products having large weight variation will result.

(2) To improve the flow properties of mix

Many powders, because of there small size or surface characteristics, are cohesive and do not flow well . Poor flow will often result in a wide weight variation within the final product due to the variable flow of tablets dies etc.Granules produced from such a cohesive system will be larger and more isodaimetric, both factors contributing to improve the flow properties.

(3) To improve the compression charecterstics of the mix

Some powders are difficult to compress even if a really compressed adhesive is included in the mix but granules of the same formulation are often more easily compressed and produced stronger.

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(4) Other reason

These are the primary reason for the granulation of pharmaceutical products but there are other reasons which may necessitate the granulation of powdered material;-

(a) The granulation of toxic materials will reduce the hazard of the generation of toxic dust, which, may arise when handling powder. Suitable precaution must be taken to ensure that such dust is not a hazard during the granulation process.

(b) Materials which are slightly hygroscopic may adhere and form a cake if stored as powder. Granulation may reduce this hazard as the granules will be able to absorb some moisture and airs retain their flow ability because of their size.

(c) Granules, being denser than the parent powder mix, occupy less volume per unit weight. They are therefore more convenient for storage or shipment.

Effect of granulation methods on granule structure:-

The type and capacity of granulating mixtures significantly influences the work important and time necessary to produce a cohesive mass, adequate liquid distribution and intragranular porosity of the granular mass. The method and condition of granulation effect intragranular pore structure by changing the degree of packing within the granules. Granules prepared by the wet massing consisted of intact drug particles held together in a sponge like matrix of binder. Fluidized- bed granules were similar to granules prepared by the wet massing process, but process greater porosity and the granules surface pass covered by a film of binding agent. With spray dried systems the granules consisited of spherical particles composed of an outer shell with an inner core of particles.

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Bibliography:-

1. Kawai S.  Granulation and drying of powdery or liquid materials by fluidized-bed technology. Drying Tech. 

2. Watano S, Ta kashima H, Miyanami K.  Control of moisture content in fluidized bed granulation by neural network. J Chem Eng Japan.

3. Gore AY, McFarland DW, Batuyios NH.  Fluid-bed granulation: factors affecting the process in a laboratory development and production scale-up. Pharm Tech. .

4. O. Worts, Wet Granulation - Fluidized Bed and High Shear Techniques Compared, Pharm. Tech. Europe

5. K.T. Walter, A Process for Granulation of a Particulate Material. European Patent

6. T. Kawaguchi, H. Sunada, Y. Yonezawa, K. Danjo, M. Hasegawa, T. Makino, H. Sakamoto, K. Fujita, T. Tanino and H. Kokubo,Granulation of  Acetaminophen by a Rotating Fluidized-Bed Granulator, Pharm. Dev. Tech.

7.Product Alert. Jul. 22, 1996. Alvita Herbal RemeTeas—Lancaster County Migra-Wonder. PROMT Abstract.

8.Castleman, M. 1991. The Healing Herbs. Publ: Rodale Press, Emmaus, PA. pp. 186-189.

9.PDR for Herbal Medicines, 1st ed. Spring 1998. Publ: Mecial Econ. Co., Montvale, NJ, pp. 746-748 and 1222-1223.

10. Lachman & Liberman Et Al; The Theory And Practice Of Industrual Pharmacy,Fourth Indian Reprint 1994, Varghesh Publishing House, Page No-687.

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