Introduction The term ‘Galenicals’ is derived by ‘Galen’ the name of Greek Physician. Galenicals: Crude medicinal products made from animal or vegetable drugs. Extraction: Treatment of plant or animal tissue with solvents to saperate soluble active materials from the insoluble residue like cell tissues and most of inactive or inert components.

Importance of Extraction Isolation of the active principle Reduces the bulk of the crude drug consumption Reduces the side effects / adverse effects Produces specific therapeutic effect

Menstrum: Solvent used for extraction. Marc: The residue left after extracting the desired constituents. An ideal menstrum should have the following properties: It should be selective It should be cheap It should be chemically inert and non-toxic It should be easily available

Salient Features of Different Menstrums 1. Water: Suitable for extraction of drugs containing proteins, alkaloidal salts, colouring matters, glycosides, gums sugars, anthraquinone derivatives and tannins Act as menstrum for enzymes, many organic acids and small proportion of volatile oils Not suitable for drugs like waxes, fats, fixed oils, and alkaloidal bases

Advantages Cheap Solvent for wide range of drugs Non-toxic It is non-inflammable It is plentily available

Disadvantages Good media for growth of microbes Stabilization or sterilization is must Hydrolysis is promoted Enzymatic degradation

2. Alcohol: Suitable for drugs like alkaloids, alkaloidal salts, glycosides, volatile oils, resins, tannins Not suitable for drugs containing gums, waxes, fats, and fixed oils

Advantages Disadvantages Fairly selective More stable products are obtained Non - toxic Disadvantages Costly Used according to excise duties Act

Other Solvents for Extraction of Drugs Soluble constituents Properties Examples Ether Oils, fats, waxes, resins and alkaloidal based Highly inflammable produces physiological effects, fairly costly. Chloroform Non- inflammable produces physiological effects. Glycerin Tannins Non-inflammable viscous liquid, costly Wild cherry syrup

Light petroleum Oils, fats, waxes, resins and alkaloidal based Very volatile, highly inflammable, cheaper than the chloroform Tincture of strophanthus, B.P. Fixed oils (Arachis oils) Calciferol, camphor Non-flammable, viscous. Solution of Calciferol. Propylene glycol Progesterone, phenobarbitone Clear, colorless, odourless, viscous liquid, sweet in taste, hygroscopic, miscible with water alcohol and chloroform, soluble 1 in 10 in ether Intramuscular injection of progesterone and phenobarbitone sodium.

Methods of Extraction The efficiency of drug extraction depends on the following factors: Nature of the drug and its solubility in the solvents Particle size of drug powder Nature of the solvent The state of contact between the drug particles and solvent

The various processes used for extraction are Infusion Decoction Digestion Maceration Percolation

Infusion Drug is kept in contact with water for the stated period, 15 minutes, with occasional stirring and finally filtering the liquid. Marc is not pressed. Coffee pot or tea can be used. Drug is placed at the bottom of the pot water is added. Stirred for three or four times

Muslin bag can also be used Drug is put in the bag Bag is suspended below the level of water in a beaker Stirring is not required Water slowly circulates due to increase in specific gravity of water near the drug

When the active constituents dissolve water becomes heavier Heavier layers come down Fresh water replaces Special pots- infusion pots are used Consists of loose perforated shelf Drug is placed on the perforated shelf Pot is filled with water Perforated shelf is adjusted below the surface of water

Common apparatus used is coffee or tea pot There are two types of infusions: Fresh infusions Concentrated infusions

Fresh infusions: Aqueous solutions of active constituents of a vegetable drug prepared by the process of infusion Ex: Fresh infusion of Quassia Should be used within 12 hours of its preparation

2. Concentrated infusions. Prepared by double or triple maceration process They are 8 times stronger than the fresh infusions Can be stored for longer period Alcohol -20% to -25% is used Ex: Concentrated infusion of Quassia Concentrated Compound Infusion of Chirata. 1 volume ------ diluted to 7volumes of water

Decoction Used for extracting the hard and woody crude drugs Water is used as menstum Drugs are boiled with water for stated period usually 10 minutes [ Freshly prepared decoctions should only be dispensed ] Liquid is strained Water is passed through the contents of the strainer

Comparison Between ‘Infusion’ and ‘Decoction’ 1.Cold or boiling water is used as menstruum. 1.Drug is boiled in water. 2.Drug having soft tissue is used 2.Drug of a hard tissue is used. 3.Drug constituents may be volatile. 3.Drug constituents should be non-volatile. 4.Final volume is not adjusted. 4. Adjustment to volume is done. 5.When boiling water is used as menstruum, precautions are taken to prevent the escape of heat by covering the vessel with a cloth. 5.No such precaution is required because the final volume is adjusted at the end.

Digestion Drug is extracted by heating at a particular pressure and low temperature for a lengthy period. Penetration power of menstum is increased Digester is used for extraction of drugs

Maceration: Organised drugs Apparatus: Wide mouthed bottle of any container with stopper Closed container prevents evaporation of menstruum like alcohol Evaporation of menstruum leads to variation

Method: Drug + menstruum placed in closed vessel for 7days Shaken occasionally Strained after 7days Marc is pressed Expressed liquid is mixed with strained liquid Filtered Final volume is not adjusted

Explanation: Shaking is essential to replace the saturated layers around the drug Marc is pressed in a filter press, hydraulic press or hand press If final adjustments is made, concentration varies Filtration removes insoluble cell contents E.g: Compound Tincture of Gentian . Tincture of lemon Tincture of squill, BPC

Officially, maceration process is used for: Tinctures made from organized drugs Tinctures made from unorganized drugs Concentrated preparations, involving double and triple maceration

Percentage w/v of soluble matter in case of unadjusted and adjusted volume of tinctures extracted by maceration by three different workers Expression of marc by 1 Expression of marc by 2 Expression of marc by 3 Strained liquid (uniform in all cases) 860 ml Expression liquid (by pressing of marc) 40 ml 900 ml 60 ml 920 ml 90 ml 950 ml % of soluble matter present 90% 92% 95% % of soluble matter assuming that the drug had 10% of soluble matter (uniform in all cases) 1% % of soluble matter after adjusting to 1000 ml. (different in all cases) 0.90% 0.92% 0.95% PH 101. 44

Maceration Process for Tinctures Made from Unorganized drugs Place unorganised drug + 4/5 of menstruum in a closed vessel Keep for 2 – 7 days Shake occasionally Filter the liquid Make the final volume with 1/5 of the menstruum Marc is not pressed

Explanation Unorganised drugs dissolve in the solvent very easily and quickly Time can be reduced from 7days Marc is compact gummy mater Does not retain the menstruum Not necessary to press the marc All active constituents of drug get dissolved in menstruum

Ex:- Tincture of Benzoin, BPC; Tincture of Myrrh, BPC; Tincture of Tolu, BPC;

Maceration Process for Concentrated Preparations Double Maceration: Drug is extracted twice by the menstruum, which is divided into two parts and each part is separately used for maceration Different macerations are later mixed and processed further

Double maceration: Drug is macerated twice by using the menstruum menstruum is divided into two parts Volume of menstruum to be retained by the drug is determined by experiment Known volume of menstruum + known weight of the drug

After maceration : Strain Press the marc Measure the volumes of liquid obtained Difference in volume obtained and volume used is the volume of menstruum retained by the drug

Process Drug + menstruum for first maceration Macerate for 48 hours Strain the liquid Press the marc Macerate again Drug + menstruum for 2nd maceration in accurate for 24 hours

Strain the liquid Press the marc Mix the liquids Allow to stand for 14 days Filter it

Volume for 1st maceration Vol. for 1st maceration = T.V. of M - V. R by D +V.R 2 T.V of M = Total volume of menstruum V.R by D = Volume to be retained by drug V.R = Volume retained Drug retains menstruum equal to half of its weight even after being pressed

Problem: In double maceration, 400 gram of drug is to be extracted with 1200 ml of menstruum,. Each 2 g of drug is supposed to retain 1 ml of menstruum.

Solution: First of all, find out the volumes of menstruum for first maceration and second maceration Applying the below formula: Vol. for 1st maceration= T.V of M - V. R by D+V.R 2 T.V of M = Total volume of menstruum V.R by D = Volume retained by drug V.R = Volume retained

Volume for first maceration Volume of menstruum for second maceration

Drug extraction by first maceration 700 ml menstruum is added to 400 g of drug 200 ml menstruum is retained by drug Volume of combined strained and expressed liquid is 500 ml; representing = 71.4% soluble matter

Drug extraction by second maceration Remaining 500 ml of menstruum is added to marc already containing 200 ml of menstruum Volume combined strained and expressed liquid is 500 ml; representing 500/700 of 28.6% of soluble matter i.e.,20.4% soluble matter The total soluble matter extracted will be 71.4+20.4=91.8%

If the same drug is extracted by a single maceration using 1200 ml menstruum at a time, Then, Volume of combined strained and expressed liquid is 1000 ml representing; 1000/1200 x100=83.3% of soluble matter Double maceration has therefore extracted more soluble matter than single maceration. The percentage gain is (91.8-83.3) x100 =10.2%. 83.3

Triple Maceration Drug is extracted thrice menstruum is divided into three equal parts Whole drug + menstruum Macerate for 1 hour Strain Drug + 2nd part of menstruum strain

Triple Maceration Drug + 3rd part of menstruum Macerate for 1 hour strain Press the marc lightly Combine the liquid obtained from 2nd & 3rd macerations Evaporate Mix the liquid obtained from 1st maceration

Triple Maceration Add 90% alcohol equal to ¼ of volume of finished product. Adjust volume with water. Allow to stand for 14 days, filter.

Triple Maceration Drug is extracted trice menstruum is divided into three parts Equation for calculating the volume of the first part of menstruum is calculated as: Vol. for 1st maceration= T.V. of M. - V. R. by D. +V.R. 3 T.V of M = Total volume of menstruum V.R by D = Volume retained by drug V.R = Volume retained

Let us take the extraction of same 400g of drug with 1200 menstruum by triple maceration instead of double maceration Solution Drug is extracted trice. (three times) menstruum is divided into three parts. Equation for calculating the volume of the first part of menstruum is calculated as:

Vol. for 1st maceration= T.V. of M. - V. R. by D. +V.R. 3 T.V. of M. = Total volume of menstruum V.R. by D. = Volume retained by drug V.R. = Volume retained Volume for 1st maceration = 1200-200+200=533.3ml 3 Volumes for the 2nd and 3rd maceration will be 1200-534 =333 ml. 2

Drug extraction by first maceration 534 ml menstruum is added to 400 g of drug. 200 ml menstruum is retained by drug. Volume of combined strained and expressed liquid is 334 ml; representing 334 x100 = 62.5% soluble matter 534

Drug extraction by second maceration 333 ml menstruum is added to 400 g of drug 200 ml menstruum is retained by drug Volume combined strained and expressed liquid is 334 ml; representing 333/533 of 27.5% of soluble matter i.e., 17.5% soluble matter

Drug extraction by third maceration 333 ml menstruum is added to marc already containing 200 ml menstruum. Volume combined, strained and expressed liquid is 33 ml; representing 333/533 of 20% of soluble matter = 12.5% soluble matter Therefore, the total soluble extracted by triple maceration is 62.5+17.2+12.5=92.2% soluble matter

Percentage soluble matter extracted by Comparative results of extraction of drug by different maceration processes. Total drug Total menstruum used menstruum retained by drug Percentage soluble matter extracted by Single maceration Double maceration Triple maceration 400 g 1200 ml 200 ml 83.3 91.8 92.2

Comparison of Maceration process for ‘Organised Drugs’ and Unorganised Drugs’ Drug along with the whole of the menstruum is used in maceration process Drug along with 4/5th of the menstruum is used in maceration process. The period of maceration is 7 days. The period of maceration is 2-7 days as specified. Strain off the liquid and press the marc. Decant the liquid. Marc is not pressed

Mix the pressed liquid with the macerate and clarify by subsidence or filtration. Filtrate is not adjusted to volume. Filter the liquid and pass the remaining 1/5th of menstruum through filter to make up the final volume. Examples of tinctures made by this process are: (a) Tincture of Orange (b) Tincture of Lemon (c) Tincture of Capsicum Examples of tinctures made by this process are: (a) Compound Tincture of Benzoin (b) Tincture of Tolu (c) Tincture of Myrrh

Comparison between ‘Maceration Process’ and ‘Infusion Process’ Menstruum used is usually alcohol, but it may be aqueous Cold or boiled water is used as menstruum. Drug is made in contact with menstruum for 2-7 days. Drug is made in contact with menstruum for 15minutes. The process is conducted at room temperature. The process may or may not be conducted at room temperature.

Marc is pressed after maceration except in modified maceration process. Marc is not pressed. Volume is not made up in simple maceration but adjustment to volume is done in modified maceration process. Volume is not made in infusion process.

Comparison Between ‘Double Maceration’ and ‘Triple Maceration’ 1. Menstruum is divided into two parts. 1. Menstruum is divided into three parts. 2.The drug is macerated for 48 hours in first maceration followed by second maceration. 2. The drug is macerated thrice having each maceration of one hour duration. 3. Strain the liquid after each maceration and press the marc. press the marc after the last maceration.

4.The pressed liquid is mixed with the strained liquids of both macerations and then the volume is adjusted after adding more of menstruum. 4. Combine the strained liquid obtained from the second and the third maceration evaporate it to a specified extent. Mix it with strained liquid obtained after first maceration. Add ‘alcohol 90%’ equal to 1/4th of the volume of the finished product 5. Alcohol 25% is used as menstruum. 5. Water is used as menstruum but ‘alcohol 90% is added at the end equal to 1/4th of the volume of the finished product.

Multiple Maceration Process Comparison Simple Maceration Multiple Maceration Process 1. The drug is macerated with the whole of the menstruum. 1. The menstruum is divided into two parts in double maceration and into three parts in triple maceration process. 2. The period of maceration is 7 days. 2. In Double Maceration The drug is macerated for 48 hours in the first maceration followed by a second maceration for 24 hours. In Triple Maceration The drug is macerated thrice of one hour duration in each case.

3. After maceration, strain the liquid and press the marc. 3. In Double Maceration After each maceration, strain the liquid and press the marc. In Triple Maceration Strain the liquid after each maceration and press the marc after the last maceration.

4. Mix the pressed liquid with the strained liquid and then filter. Volume is not made up. 4. In Double Maceration Mix the pressed liquid with the liquid obtained from the two macerations and then the volume is adjusted by adding more of menstruum. In Triple Maceration Combine the strained liquid of 2nd & 3rd maceration and evaporate to a specified extent. Mix it with the liquid obtained from the first maceration. Add alcohol 90% equal to 1/4th of the volume of the finished product.

5. The final volume is not made up. 5. The final volume is made up in multiple maceration process.

Percolation Derived from Greek word ‘Percolare’, meaning “I pass through”. Slow passage of menstruum under the influence of gravity through a column of the drug powder. Official method for tinctures and concentrated preparations.

Process of percolation is divided into eight steps Reduction in drug particle size, Moistening or imbibition, Packing, Maceration, Percolation, Pressing the marc, Adjustment of volume, Clarification.

1. Reduction in drug particle size: Finer the powder. Efficient is the extraction. 2. Moistening or imbibition: Drug powder is moistened with small quantity of menstruum. Allowed to stand for four hours.

Advantages of Moistening or imbibitions Drug swells Menstruum penetrates the cell walls. Packing will be more uniform. Intracellular air is removed, efficiency of percolation is increased.

3. Packing: A filter paper is placed for support, on perforated metallic plate. Imbibed drug lumps are broken, and packed uniformly layer by layer with moderate pressure. Drug should occupy almost two thirds of the column of the percolator. Surface is covered with filter paper or filter cloth. Layer of washed sand is spread over it.

Diagrams of: (a) Incorrect packing of drug showing incorrect flow of menstruum. (b) Correct packing of drug showing correct flow of menstruum. Fig: 46.1

The packing of imbibed drug in percolator, with very high or very low pressure, lead to inefficient extraction because Tightly packed column, will not allow, adequate flow of the menstruum, leaving the drug incompletely extracted. Light packing will give rapid down flow of menstruum.

Fig: 46.2 Diagram of a Packed Percolater assembly

4. Maceration: Sufficient quantity of menstruum is added. Stop cock is kept open, to displace air in the column. When the first few drops come out of the stop cock, it should be closed, enough quantity of menstruum has to be poured, so as to maintain 2cm layer on top. Percolator is closed, and allowed to stand for 24 hours.

5. Percolation: After maceration, opening the stop cock starts percolation, rate of percolation is adjusted to 30 drops/minute. When displacement of saturated solution formed during maceration period is started with optimum speed, fresh menstruum is added. Drug column should not be allowed to dry up. A bottleful of menstruum and carrying a delivery tube, is inverted over the percolator. So that delivery tube dips into the menstruum layer.

Fig: 46. 3 Diagram of percolator with an inverted bottleful of Fig: 46.3 Diagram of percolator with an inverted bottleful of menstruum to avoid drying up of drug column

Process is continued till 75% of finished product is collected. Last few milliliters of percolator are tested for complete exhaustion.

6. Pressing of marc: After completion of extraction, marc is taken out of the column and expressed in Tincture press or hydraulic press to obtain menstruum retained by it. Further the marc is subjected to distillation, in solvent recovery stills.

7. Adjustment of volume: Liquid obtained by pressing the marc, is mixed with the main percolate and final volume adjusted. For standardized preparations, volume is adjusted after the assay of the final product.

8. Clarification: Filtration or by decantation Percolation process is successful when the drug percolate or d / p ratio is not less than 1:4.

Modified Percolation a) Intermittent percolation, b) Re-percolation, c) Reserved percolation, d) Hot Continuous Extraction.

Intermittent Percolation Percolation and maceration alter with each other. 24 hours – maceration 12 hours – maceration 12 hours – percolation . menstruum remains in contact for longer time, with drug particles. Extraction is accomplished with 1:3 or higher d/p ratio.

Repercolation Drug powder is divided into 4 or 5 parts. First part extracted as simple percolation. Percolate used as menstruum for second part. Continued till the drug in first percolator is totally exhausted. Drug in final container is not totally extracted, this method is not accepted.

Reserved Percolation Preferred when drug : Percolate ratio is 1:1 or 2:1 Menstruum used is Hydro alcoholic solvents. Final product is liquid extract and concentrated infusion. First three fourth of the total product volume is reserved. Subsequent percolate is collected till complete extraction of drug is obtained. Marc is pressed and expressed liquid is mixed with subsequent percolate

Advantages Total percolate is concentrated to ¼ by distillation. Concentrate is mixed with reserved percolate. Final volume is adjusted. Advantages Reserved percolate is subjected to heat treatment. Economical

Hot Continuous Extraction PRINCIPLE: Small volume of menstruum is made to circulate through the extractor containing the drug, again and again by the method of evaporation and subsequent condensation of menstruum. DESIGN: It consists of main three parts. The flask holding the menstruum. Extractor. Reflux condensor.

The extractor, or cylindrical percolator possess a siphon assembly and a side tube for the passage of vapors of the menstruum, called the soxhlet extractor. Reflex condensor is fixed at the top of the soxhlet. Material to be extracted is packed in the extractor body. Menstruum is taken into the flask.

Method of working Heat applied allows the menstruum to boil. Vapors pass through the side tube of soxhlet and condense in the reflux condensor, return to the menstruum. Menstruum passes through the packed column dissolving the soluble matter present in the drug. Gradually, the extract in the flask becomes concentrated. To check for exhaustion, last few millilitres of percolate is tested.

Advantages Disadvantages Extraction process is rapid, Require small volume of menstruum. Disadvantages Not suitable for drugs containing thermo labile constituents. Pure solvent is required. Not suitable for extraction of unorganized drugs.

Soxhlet Extractor

Introduction to Ayurvedic Dosage Forms Ayurveda is a science of longevity. Genuine text is available in charakasamhita. It depends on tridosha theory, viz vatha pitha and kapha.

Introduction to Ayurvedic Dosage Forms Dhanvantari has classified ayurveda into eight well defined branches. KAYACHIKITSA BALACHIKITSA GRAHACHIKITSA URDVANGACHIKITSA SALYATANTRA AGADATANTRA RASAYANATANTRA VRISHYACHIKITSA

The crude drugs from Vegetable source Animal source Metals, Minerals Ghee, Oil, Stones are used to prepare dosage forms.

Ayurvedic Preparations ANJANS: Remedies intended to be used in eyes for their local effect. ARAKS or ARAKAS: Distilled essences or liquors made by soaking drugs in water for 24 to 48 hours and extracting their essence by distillation. Ex: Ajwan arkas, triphala arkas ,chirata arkas

ARISTA’S: Weak alcoholic preparations prepared by making a decotion of the drugs. Further fermented with raw sugar or honey –for 7-10 days in hot weather 15 – 30 days in cold weather. Eg: Abhyarista’s : as a laxative. Amristaristas : used in fevers.

ASAVARISHTAS: AVALEHAS: Medicated spirituous liquors. Prepared with honey and medicinal substances such as roots, leaves, barks etc. AVALEHAS: Lehas, linctuses or convections, decoctions, after straining, boiled to a thick soft consistency. Eg: Ashtangara lehas : Used in pneumonia and dry cough. Jirkadiava lehas : Used as tonic, for women.

BHASMAS: Bhasmas are alkaline ashes prepared from vegetable and mineral substances. Eg: AKIK BHASMAS : Used as heart tonic. ABHRAK BHASMAS : Used to improve sexual power. LOHA BHASMAS : Used to improve hemoglobin. PH 101.47

BHAVANA: CHOORNAS: Powders are soaked in various fluids ands dried. Choornas are powder mixtures prepared by powdering dry mineral, animal or vegetable substances in a mortar. Eg: AJMODADI CHOORNA: Used for rheumatism, sciatica. ASHWAGANDI CHOORNA: Used in alopecia and treatment of greying of hair. PH 101.47

GHRITAS: Preparations of medicated ghee or clarified butter. Purified butter is melted in an earthen pot, Copper or iron pan and then medicinal fluid or pastes are added till ghrita is free from froth. Eg: ARJUN GHRITAS : Used for indigestion. ASHOK GHRITAS : For rheumatic pain. PH 101.47

GUTIKAS: Gutikas are large pills or boluses less durable and kept well closed. Eg: ADITYA GUTIKA :For indigetion and colic pain RASAYANAS: Major medical preparations. Stored in glass bottles to keep them active and free from atmospheric contamination. Eg: AGNISANDIPAN RASA : Used as carminative. AMIR RASA : Used in purify blood. PH 101.47

TAILAMS: VATIKA: Medicated oils. Eg: BRAHMI AMLA TEL. Pills usually prepared by reducing a decoction of vegetable substances to a thick consistency, after then powders are added. Eg: GUDAD GUTIKA : Used in cough and cold. MERICHADI GUTIKA : Used as expectorant and antitussive. PH 101.47