Introduction to Powders and Granules – Pharmaceutics – I B. Pharma 1st Semester

Introduction to Powders and Granules

Introduction to Powders and Granules

Introduction to Powders and Granules

Learning objectives

At the end of this lecture, student will be able to:

      Define the term powders and granules

      List the advantages and disadvantages of powder dosage form

      Classify powders

      Give appropriate examples for various classes of powders

      List the methods for blending of powders

      Explain the methods used for blending of powders

      Explain bulk powders for internal use

      Explain cachets and types of cachets

      Discuss preparation of cachets

      Explain seidlitz powder

      Explain the significance of granules

      List the advantages of granules as solid dosage form

      Explain effervescent granules

      Explain methods of preparation of effervescent granules

      Explain powders having dispensing problems

      Indicate the remedial measures for packing such special powders

Powders

q  A powder is a homogeneous mixture

q  More or less finely divided drugs or chemicals in dry form

q  May be intended for internal (oral powders) or external (topical powders) use

q  Pharmaceutical powders à size between 0.1 and 10µ

q   Constituted powders

Advantages

q  Physically and chemically more stable when compared to liquid dosage form Eg: Does not undergo hydrolysis

q   Insoluble medicaments and those susceptible to microbial attack can be dispensed in powder dosage form

q  Easy drug administration for very large dose of drugs Eg: Indigestion, constipation, diarrhea

q  It is well accepted by pediatric and geriatric patients Eg: Small children have difficulty in swallowing tablets and capsules, powders can overcome this difficulty with instructions to mix them with a sweet substance such as syrup, honey or jam

q   The rate of dissolution and absorption is faster in powder dosage form when compared to any other solid dosage forms

Disadvantages

q  Bulk dosage forms cause difficulty in handling and transport

q  They are not easily transferrable from a container and may spill

q  In bulk dosage forms, medicaments often have same weight but different volumes and hence this method is inaccurate and therefore potent substances should not be dispensed in bulk powders

q  The method of preparation and packaging are time consuming

q  Drug substances that are having an unpleasant taste are not suitable to administer in powder form

q  The substances that are hygroscopic, deliquescent, volatile and oxygen sensitive are not suitable to be administered in powder form

Classification of Powders

q  According to division of prescribed dose

      Divided powders

      Bulk powders for internal use

      Bulk powders for external use

      Effervescent powders/ Granules

      Powders enclosed within an edible shell (like cachets and capsules)

q  According to composition

      Simple powders

      Compound powders

Divided Powders / Single Dose Powders

q  Divided powders are unit dose powders

q   Packed in properly folded papers and dispensed in envelops, metal foil, small heat sealed plastic bags or other containers

Divided Powders / Single Dose Powders

q  The number of active ingredients may be one (Simple powders) or more than one (Compound powders)

q   Manipulative losses are inevitable; therefore it is necessary to prepare for atleast one powder packet extra to requirement

Preparation of Divided Powders

Step 1. The ingredients are weighed correctly

Step 2. Blended by geometric dilution in ascending order of weights

Step 3. Mixture is then either divided into blocks of equal size (dose) or

Step 4. Packed in paper which is folded according to the pharmaceutical art

Step 5. Placed in envelope or powder box and dispensed

Colourless Powders

Step 1. If all the materials present in the powders are white in color 

Step 2. Add a drop amaranth alcoholic solution to the powders and mix it

Step 3. The end point of mixing would be even spreading of the pink colour of amaranth

Mixing of Powders

q  When two or more powdered substances are to be combined to form a uniform mixture

q  It is best to reduce the particle size of each powder individually before weighing and blending

q  Depending on

      –    The nature of the ingredients

        The amount of powder to prepare

        The equipment available, powders may be blended by

q  Spatulation

q  Trituration

q  Sifting

q  Tumbling

Spatulation

q  The blending of powders with a spatula on a tile or paper used for small quantities 

q  Used when the mortar and pestle technique is undesirable

q  The method is not suitable for large quantities of powders

q  The method is not suitable for powders containing one or more potent substance

q   because homogenous blending is not certain

q  There is no particle size reduction, so the powders to be mixed must be fine and of uniform size

q  Because no pressure is used, the resulting powder is usually light and is not compacted

q  This method should be used when hard trituration is to be avoided, such as when blending powders that liquefies on trituration

q  Eg: phenol, camphor, menthol, thymol, aspirin, phenyl salicylate etc.

Trituration

q  Trituration Applied both to comminute and to mix powders

q  When a small amount of a potent substance is to be mixed with a large amount of diluent, The geometric dilution method is used to ensure the uniform distribution of the potent drug

q  When the potent and non-potent ingredients are of the same color and a visible sign of mixing is lacking, trituration is preferred

Geometric Dilution Method

Step 1. Equal volume of potent drug + dilulent in a mortar

Step 2. Mixed thoroughly by trituration

Step 3. A second portion of diluent equal in volume to the mixture is added

Step 4. The trituration is repeated

Step 5. Process is continued by adding equal volumes of diluent to the powder mixture and repeating until all of the diluent is incorporated

q  If 100mg of potent drug is required to be mixed with 900mg lactose,

100mg of drug       +    100mg of lactose   =  200mg mixture

200mg of mixture  +   200mg of lactose    =  400mg mixture

400mg of mixture   + 400mg of lactose      =  800mg mixture

800mg of mixture   + remaining mg of lactose = 1000mg mixture

Sifting

q  Powders may also be mixed by passing them through sifters

q   Sifting results in light fluffy product

q  The process is not acceptable for incorporation of potent drugs into a diluent powder

Tumbling

q  Tumbling of the powders are carried out in an enclosed rotating chamber / container

q  Special small scale and large scale motorized powder blenders have been developed which mix powder by tumbling motion

q  Mixing by this process is time – consuming

                Eg: Twin shell blender

Divided Powders

q  If the powder contains a potent medicine, Then dilute them with a suitable diluent ,In the case of codeine phosphate we dilute them with lactose to bring them enough weight.

q  If a powder is hygroscopic in nature, the final powder is double wrapped.

q  If a powder contains materials are eutectic mixture, The eutectic formation is allowed, Absorbed onto a diluents, The final powder is double wrapped.

q  If a powder contains an effervescent mixture, The acid and the alkaline salts are separately packed, Dispensed with suitable directions.

q  After a powder has been properly blended (using the geometric dilution method for potent substances)

q  It may be divided into individual dosing units based on the amount to be taken or used at a single time

q  Each divided portion of powder may be placed on a small piece of paper that is folded to enclose the medication

q  Some commercially prepared premeasured products are available in folded papers or packets, including headache powders, powdered laxatives, and douche powders

Bulk Internal Powders

q Bulk powders are usually a simple mixture of the prescribed medicament without additional ingredients

q  It is preferable to administer large quantities with food or drinks

q  Fine particles dissolve quickly and the onset of action can be seen rapidly

q  The powders for internal use are sometimes converted into granules of desired size

q The main additives needed for powders are

q diluents like lactose, sucrose, sorbitol, micro crystalline cellulose (MCC)

q organoleptic additives like flavoring and sweetening agents are must while colors may or may not be used

q Bulk powders contain many doses in a wide mouth container i.e., suitable to remove the powder by a teaspoon

q The non-potent and light/ bulky powders are used in bulk powder form

q Examples :

q Antacid, laxative, purgative etc.,

q Eg: Rhubarb powder, light magnesium carbonate, heavy magnesium carbonate, ginger powder etc.,

Compound Magnesium Trisilicate Oral Powder BP

q Contains

      Magnesium tricilicate

      Chalk in powder

      Sodium bicarbonate

      Heavy magnesium carbonate

q Procedure

    The powders are mixed in a mortar in order of increasing bulk volume

    Pass the resulting mix through a 250µm sieve

    Lightly mix and pack

q Storage and container-

                In an amber color glass screw capped bottle in a dry place

q Directions

                The powder should be taken mixed with a little water or other fluid between meals

q Uses-

                Adsorbent

                Antacid for the treatment of dyspepsia

Cachets

q Solid unit dosage forms of the medicament

q The drug is enclosed in a tasteless sheet made by pouring a mixture of rice flour and water

q The water evaporates and a sheet of wafer is formed

q They are also known as wafer capsules or capsula amyacea

q Cachets are used to enclose nauseous powders and can hold 0.2 to 1.5 g of powders

q Cachets are hard to swallow

q Before administration the cachets should be dipped in water for a few seconds

q Then placed on the tongue and swallowed with the help of water.

q After swallowing, the cachet will disintegrate and the powder will be released.

Advantages

q Can be made with simple machinery.

q Large doses of drugs can be enclosed in cachets.

q  Large sizes of cachets are easy to swallow once they have been softened by immersion in water.

q Disintegrate quickly in the stomach.

q Nauseous drugs and those with an unpleasant taste can be dispensed.

Disadvantage

q Easily damaged

q Give poor protection from light and moisture

q Must be softened before swallowing

q Occupy more space than capsule and tablet strips

q Not very suitable for filling by large-scale machinery

Types of Cachets

q There are two types of cachets

q Wet seal cachets

q Dry seal cachets

Wet Seal Cachets

q These are sealed by moistening the edges with water

q They are made up of two similar halves having flat edges

q Preparation-

              Step 1. The weighed amount of powder is placed in one half

              Step 2. the edges of the other half is moistened with water

              Step 3. moistened half is placed exactly over the 1st half containing the powder

              Step 4. The flat edges of both the halves are pressed together

              Step 5. A perfect seal and powder is completely enclosed

Cachet Mould

       The standard cachet machine consisted of three metal plates

       Drilled with holes of different diameter for the size of the cachet used.

       The first half of the cachet was then fitted in the base plate.

       The centre plate was then used to mask the rims of the cachets to prevent powder deposit.

Cachet Mould

Preparation of Cachets

q Funnels were then used to deposit an appropriate dose of the powdered drug into the lower part of the cachet

q When the cachets were filled, moisture was applied to the rims of the cachet halves in the top plate

q The centre plate was then removed and the two cachet halves brought together

q After a few minutes the cachets were dry and could be removed

Dry Seal Cachets

q They do not require moisture for sealing

q They consists of 2 halves the upper half and the lower half

q Labelling

                                Immerse in water for few seconds and then swallow with the help of water

q Preparation

              Step 1. They consists of 2 halves the upper half and the lower half

              Step 2. The diameter of the upper half is slightly larger than the lower one

              Step 3. The powdered drug is filled in the lower half and the upper half is fitted over the lower half

              Step 4. The filled cachets are then sealed in a machine by pressing the two halves, removed and packed

Seidlitz Powder
(Compound Effervescent Powder)

q Seidlitz powders are administered as effervescent draught

q It consists of two powders

q Powder No. 1 (both wrapped in blue paper)

                Sodium potassium tartrate                         

                Sodium bicarbonate

q Powder No. 2 (wrapped in white paper)

                Tartaric acid                                       

Seidlitz Powder – Directions

q The contents of the blue paper are dissolved in a tumblerful of cold or warm water, the contents of the whitepaper are added, the mixture is stirred the product is taken while effervescing

q As sodium bicarbonate and tartaric acid are both hygroscopic at high humidities

q An inner wrapper of waxed paper is used

q  This preparation is slightly acidic due to the excess of tartaric acid

q Tartaric acid is added to overcome the salty taste of the preparation

Granules

q Bulk granules can be used to deliver bulky medicaments of low potency

q Granules packed in individual sachets have accurate dosage and protection from the atmosphere

q Granules containing potent substances should not be supplied in bulk because of the risk of wrong dosage

Granules

q Granulation of a powder allows addition of flavouring agents and coloring agents

q Easily handled

q Attractive product

Need for Granules

q Solid medicaments which are required to be administered orally in large doses can be given as granules

q They cannot be prescribed in tablets and capsules because for a single dose more than one have to be take

q Some medicaments are difficult to dispense as such in powder form because of its bitter, nauseous and unpleasant taste

q It is also difficult to convert it into liquid dosage form due to stability problem

q The only alternative is to convert these powdered medicaments into granular form

q Solid medicaments are mixed with sweetening, flavouring and colouring agent

Preparation of Granules

q A suitable granulating agent is added to moisten the powders so as to make a coherent mass

Preparation of Granules

q These coherent mass will be passed through sieve no. 10 or 16 to make granules

q Granules will be dried in a hot air oven at a temp not exceeding 60°C

q The dried granules are passed through sieve no. 20 or 24 and stored in a dry well closed wide mouthed bottles

Advantages

q Free flowing

q They are more stable to the effects of atmosphere humidity as their surface area is less than of powder

q Less likely to cake or harden upon standing

q Easily wetted by liquids than certain light and fluffy powders (which tend to float on the surface)

q Preferred for dry powders intended to be constituted into solutions or suspensions

Reconstituted Granules

Drug + suspending, sweetening, flavouring, colouring and granulating agents

Granules prepared

Packed in bottles

Directions on its label for reconstitution.

Reconstituted Granules

q A number of commercial products containing antibiotic drugs that are unstable in aqueous solution

q Prepared as small granules for constitution with purified water before use

                                Eg: Erythromycin, phenoxy methyl penicillin, ampicillin

q Label should state the time limit within which reconstituted preparation should be used

Effervescent Granules

q Specially prepared solid dosage form of medicament, meant for internal use

q They contain a medicinal agent in a dry mixture composed of sodium bicarbonate, citric acid and tartaric acid

q When added to water, the acids and the base react to liberate CO2 resulting in effervescence

q The resulting carbonated mixture masks an undesirable taste of any medical agent present

Effervescent Granules Vs Effervescent Powders

Effervescent Granules

Effervescent Powders

Coarse particles of mixed powder

Small powder particles

Rate of dissolution less

Rate of dissolution more

No violent and uncontrollable
effervescence

violent and uncontrollable
effervescence

q Sudden and rapid effervescence could overflow the glass and leave little residual carbonate in the solution

q Contains –

                                A medicinal agent

                                Sodium bicarbonate

                                Citric acid

                                Tartaric acid

Why two acids..?

q Combination of two acids avoids certain difficulties

q When tartaric acid is used alone, the resulting granules lose their firmness and readily crumble

q When Citric acid used alone results in sticky mixture difficult to granules

Reaction involved in Effervescent Granules

3NaHCO3   +   C6H8O7.H2O —————–à Na3C6H5O7 + 4 H2O +3CO2  á

Sodium                  Citric acid                           Sodium

Bicarbonate                                                          Citrate

2 Na HCO3   +  C4H6O6 —————–à Na2C4H4O6  +  2H2O + 2CO2 á

Sodium                  tartaric acid                 Sodium

Bicarbonate                                                 Tartarate

Methods of Preparation

q Effervescent granules are prepared by two general methods

      The dry or fusion method

      The wet method

Fusion Method / The Dry Method

q Each molecule of citric acid contains one molecule of water

                Acts as the binding agent for the powder mixture

q Before mixing the powders,

                The citric acid crystals are powdered

                Then mixed with the other powders of the same sieve size

                Gives uniformity of the mixture

q Sieves and other mixing equipment should be made of stainless steel or other material resistant to the effects of the acids

q The mixing of the powders is performed rapidly

q This is to avoid premature chemical reaction [Which occurs by absorbing moisture from a low humidity environment]

q After mixing the powder is placed on a china dish in an oven at 34-40°C

q During the heating process, an acid resistant spatula is used to turn the powder

q The heat causes the release of the water of crystallization from the citric acid

q which in turn dissolves a portion of the powder mixture setting of the chemical reaction

q consequent release of some CO2

q This causes the softened mass of powder to become spongy

q When of the proper consistency (as bread dough) is formed

q It is removed from the oven(heat source) and rubbed through a sieve to produce granules of the desired size

q The granules are dried at a temp not exceeding 54°C and immediately placed in containers and tightly sealed

                Sieve no. #4            ——————                             large granules

                Sieve no. #8            ——————                             medium

                Sieve no. #10          ——————                             small granules

Wet Method

The source of binding agent is not the water of crystallization from the citric acid

Alcohol  is added to moisten the anhydrous powders and helps them to form a pliable (flexible) mass for granulation

Just enough liquid is added to prepare a mass of proper consistency

then granules are prepared and dried

Special Powders

Dispensing of Powders involving Special Problems.

q Volatile Substance

q Hygroscopic And Deliquescent Powders

q Efflorescent Powders

q Eutectic Mixtures

q Liquids

q Explosive Powders

q Potent Drugs

Volatile Substance

q Certain vegetable powders contain volatile oils.

q To prevent the loss of volatile oils, these vegetable drugs must be powdered lightly in a mortar.

q Volatization of substances like menthol, camphor and essential oils may take place on incorporation in powders.

Volatile Substance – Dispensing Remedies

q This is prevented or minimized by the use of double wrapping.

q The inner wrapper should be wax paper

q Outer wrapper may be of any thick paper.

Hygroscopic and Deliquescent Powders

q The powders which absorb moisture from the atmosphere are called hygroscopic powders

q Certain powders absorbs moisture to such a great extent that they go into solutions form and are called as deliquescent powders.

q Calcium chloride, potassium acetate, iron, ammonium chloride, ammonium citrate, pepsin, phenobaritone, sodium bromide, sodium iodide, potassium citrate, zinc chloride etc.

Hygroscopic and Deliquescent Powders -Dispensing Remedy

q Such substances are supplied in granular form

Ø Expose less surface area to the atmosphere.

q These powders should not be very finely divided

q Should be double wrapped.

q Further wrapping in aluminium foil or plastic cover.

q Whether the tendency of the hygroscopic materials to absorb water can be countered ?

q Yes…

q How ?

q By incorporation of finely subdivided substances like magnesium oxide, magnesium carbonate, calcium carbonate, talc, colloidal silica

q Complete for moisture and take it up before it can harm the medicament.

Efflorescent Powders

q Some crystalline substances liberate water of crystallization wholly or partly…

q When ??

q On exposure to atmosphere or during trituration

q  Thus become wet or liquefy

q Eg: caffeine, citric acid, ferrous sulphate, sodium borate etc.,

Dispensing Remedy

q This difficulty may be overcome

q By using either corresponding anhydrous salt or an inert substance

q Which have to be mixed with efflorescent substances before incorporating with other ingredients.

Eutectic Mixtures

When two or more substances having low melting point are mixed together,

they liquefy due to the formation of a  new compound

which has a lower melting point than room temperature.

q  Eg: Menthol, thymol, camphor, phenol, salol, aspirin, phenacetin, chloral hydrate, salicylic acid, phenyl salicylate.

q  These substances can be dispensed by two methods

o  Dispense as separate set of powders with directions that one set of each kind shall be taken as a dose

o  An equal amount of any of inert absorbent like magnesium carbonate, light magnesium oxide, kaolin, starch, lactose, calcium phosphate etc., may be mixed with eutectic substances and then blended together lightly with a spatula on a sheet of paper

Formula

q Dispense 50g of the following insufflations

                                Menthol

                                Camphor

                                Ammonium chloride

                                Light magnesium carbonate

q Dispense 50g of the following Antipruritic preparation

                                Menthol

                                Camphor

                                Light magnesium carbonate

Method of Preparation

Step 1. Separately powder each ingredient

Step 2. Weigh required quantity of menthol, camphor and ammonium chloride.

Step 3. Mix them in ascending order of their weight in a mortar to form a liquid.

Step 4. Add light magnesium carbonate to make a free flowing powder.

Step 5. Pass through sieve no. 85 and dispense in air tight container.

Liquids

q  In certain prescription, the liquid medicaments are also incorporated in dispensing powers.

q  If the quantity of the liquid is small, It may be triturated with an equal amount of powder, then the rest of the ingredients are incorporated in small portions with continuous trituration.

q  If the quantity of the liquid is larger, Then an absorbent must be added. 

q  Eg: Liquid extracts and tinctures are evaporated to a syrupy mass.

                 Lactose/ some other diluents is mixed

                Then continue the evaporation to dryness.

                Mix other ingredients or substitute the liquid extract by a dry extract.

Explosive Powders

When an oxidizing substances such as potassium chlorate, Mixed with reducing agents such as tannic acid,  There are chances of violent explosion which may lead to serious consequences.

Eg :

Rx

                Potassium chlorate

                Tannic acid                            used as gargle

                Sucrose                               

Method of Preparation

Step 1. Powder each ingredient separately in a mortar

Step 2. Mix them lightly with other ingredients. OR Powder each ingredient separately

Step 3. Dispense them in separate powder paper with suitable directions regarding the use.

Eg for oxidizing agents                  Eg for reducing agents

Potassium chlorate                                         Charcoal

Potassium dichlorate                                      Sulphur

Potassium nitrate                                            Sulphides

Potassium permanganate                            Tannic acid

Silver nitrate

Potent Drugs

q The substances having minimum dose of less than one grain (60 mg) and poisonous

q A larger response at low concentrations

q The potent drug is triturated with some diluents to make a weighable quantity for each powder packet (mixed by geometric dilution method).

                                Eg: codeine phosphate 10mg

                                Minimum weighable quantity = 120mg.

 Summary

q  A powder is a homogeneous mixture

q  May be intended for internal (oral powders) or external (topical powders) use

q  In presence of potent drug, diluents should be added

q  Trituration, Sifting, Tumbling are methods for mixing of powders

q  Spatulation for powders which are fine and uniform size

q  Trituration reduces the powder size along with mixing

q  Tumbling of the powders are carried out in an enclosed rotating chamber / container and suitable for large scale

q  Divided powders are unit dose powders which may or may not contain potent drug.

q  Bulk powders contain many doses in a wide mouth container i.e., suitable to remove the powder by a teaspoon.

q  Cachets – solid unit dosage forms of the medicament, in which the drug is enclosed in a tasteless sheet made by pouring a mixture of rice flour and water.

q  Seidlitz powders are administered as effervescent draught.

q  Seidlitz powder

Powder No. 1

Sodium potassium tartrate                         

Sodium bicarbonate

Powder No. 2

Tartaric acid                                       

q  Some commercial products containing antibiotic drugs that are unstable in aqueous solution are dispensed as reconstituted powders

q  Effervescent Granules contain a medicinal agent in a dry mixture composed of sodium bicarbonate, citric acid and tartaric acid

q  Effervescent Granules can be prepared by wet method or dry method

q  In wet method anhydrous citric acid is used and in dry method hydrated citric acid is used

q  Volatile substances like menthol, camphor and essential oils may volatilize on incorporation in powders. Therefore double wrapped.

q  The powders which absorb moisture from the atmosphere are called hygroscopic powders

q  Certain powders absorbs moisture to such a great extent that they go into solutions form and are called as deliquescent powders.

q  Efflorescent Powders – on exposure to atmosphere liberate water of crystallization wholly or partly.

q  Eutectic mixtures – When two or more substances having low melting point are mixed together, they liquefy due to the formation of a  new compound which has a melting point lesser than room temperature.

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