PHARMACOGNOSY

Saturday, January 29, 2011



DEFINATION
      The term Pharmacognosy has been derived from the 2Greek words: I) pharmakon, which means a drug & ii) gnosis, which means knowledge of or gignosco, which means to acquire knowledge of. Thus the full meaning of the term Pharmacognosy is `knowledge of drugs’ or `to acquire knowledge of drugs’.
Pharmacognosy is the objective study of crud drugs & related substances.
Pharmacognosy is an applied science which is concerned with acquiring knowledge of crud drugs by the application of various scientific disciplines.
SCOPE
      Pharmacognosy is an important branch of Pharmacy, which is concerned with the study of crud drugs & natural products of pharmaceutical importence.
It deals with the scientific study of structural, physical, chemical & sensory characters of crud drugs obtained from plant, animal & mineral source.
It also includes the study of their history, distribution, cultivation, collection, preparation, identification, evaluation, preservation & commerce.
SUBJECT MATTERS OF PHARMACOGNOSY
 Pharmacognosy deals with the study of,
Naturally occurring substances having medical properties
Crud drugs & other natural substances of pharmaceutical importences
Chemical constituents of crude drugs & medicinal plants
Natural substances used as excipients or pharmaceutic necessities in the formulation & preparation of pharmaceutical &medicinal products. These include:
i) colouring & flavouring agents, ii) suspending agents, iii) diluents & disintegrating agents, iv) sweetening agents, v) binders, adhesives, solifyding agents, etc.
SUBJET MATTERS
      Substances, which are used as medical & pharmaceutical practices. Example of which include:
a) fibers & surgical dressings, b) anesthetic acids, c) filtering agents, such as diatomite & asbestos, d) basses & vehicles, such as agar, gelatin, wax, fixed oils & fats.
      Beverages with medicinal constituents, e.g. tea, coffee & cocoa which contain caffeine.
      Spices & condiments, which have medicinal properties, e.g. Cinnamon, Cardamon, Umbelliferous fruits (Coriander, Fennel, Cumin, etc.), Mustard seed, Clove, Ginger, Garlic, etc.
      Vitamins, enzymes, antibiotics, allergens, pesticides, etc.
Medicinal plants. &  Traditional medicine.
HISTORICAL DEVELOPMENT OF PHARMACOGNOSY
      Pharmacognosy is regarded as the mother of all science.
      History of pharmacognosy represents the history of pharmacy & medicine.
      Pharmacognosy had its origin in the health-related activities of the most primitive human race of the remote past.
      The early man sought to alleviate his sufferings of illness & injuries by using plants.
      They acquired knowledge of medicinal properties of plants in the following way:
a)  By guesswork or trial & error
b)  While searching for food
c)  By superficial resemblance between the plant parts & the affected organs, that is, by examining the “Signature of Nature”
d)  By observing other animals instinctive discrimination between toxic & palatable plants
e)  By accidental discovery
      By a combination of all these means the ancient people acquired a considerable volume of knowledge about drugs.
      In course of time a group of people emerged in each community who acquired expertise in collecting, testing & using medicinal plants for treating diseases. These people later became known as `Medicine Men'.
      The Medicine Men monopolized the knowledge of drugs and hide that knowledge in some mysterious incantations. They transferred this secret knowledge only to their trusted predecessors of the successive generations, who gradually increased the volume of knowledge about drugs and their uses.
      Initially the transfer of the acquired knowledge from generation to generation used to be done verbally by the use of signs & symbols. As civilization progressed, transfer and recording of the knowledge were done in writing.
According to recorded history:
      Babylonians (about 3000 BC) had knowledge of large number of medicinal plants and their properties.
      Some of the plants used are still used almost in the same way and for the same purposes.
      The Chinese pharmacopoeia, Pen Tsao, written between 3000 and 2730 BC, includes recipes and therapeutic uses of many Chinese traditional medicines.
      Ebers Papurus, written in 1550 BC, recorded that Egyptians possessed a good knowledge of human anatomy & medicinal uses of hundreds of plants which made them capable of embalming dead bodies for making mummies.
      Many of the present day drugs, such as Henbane, Mandrake, opium, Pomegranate, Caster oil, Aloe, Onion, many fixed oils & fats, were in common use in Egypt about 4500 years ago.
      The earliest plant medicines used in the Ayurvedic system were described around 1200 BC with a list of 127 plants.
      The Greek civilization witnessed a highly developed system of medicine which used medicinal plants and minerals. Arab Muslims further enriched this system and developed the Greco-Arabic or Unani system, which formed the basis of modern Allopathic system of medicine.     
The following people contributed significantly to the gradual development of Pharmacognosy:
      Hippocrates (460-370 BC). He is regarded as the `Father of medicine' for his contribution to human anatomy and physiology. He collected, identified and used a large number of medicinal plants.
      Aristotle (384-322 BC). A student of great philosopher Plato listed more than 500 plants of medicinal importance with their description & uses.                                        
Theophrastus (370-287 BC) collected, identified a large number of medicinal plants and recorded their medicinal properties.
      Dioscorides (1st Century AD), a Greek Physician, published five volumes of a book, entitled `De Materia Madica'  in 78 AD, which described more than 600 medicinal plants with their collection, storage & uses.
      Pliny de Elder (23-70 AD), a Greek botanist, collected and described a large number of medicinal plants with their uses.
      Galen (131-200 AD), a Greek pharmacist-physician, described methods of preparing pharmaceutical formulations containing plant and animal drugs. These methods & his other observations on medicinal plants have been recorded in as many as 20 volumes of books. The present day Galenical preparations or Galenicals are prepared according to those methods.
      So long the same person, the apothecary (pharmacist-physician), used to do all the works of collection, processing, preparation and dispensing of the medicaments (the works of the pharmacist) and also diagnosing the disease and prescribing the drug (the works of the physician).
      With the increase of knowledge of drugs, the volume of work also increased a lot and it become impossible for one person to manage them properly.
Thus at this point pharmacy & medicine started developing along two separate paths:
      a) One group specialized in diagnosing the disease and prescribing the drug and became known as the physicians or doctors;
      b) The other group specialized in collecting, processing, preparing & dispensing the drug and became known as the apothecaries or pharmacist.
In this way, Pharmacognosy progressed gradually and formed the basis and beginning of both pharmacy & medicine.
                                           

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Pharm.analysis: NON-AQUEOUS TITRATIONS

Thursday, January 27, 2011


                                              
It’s is used for the assay of certain materials which cannot be easily titrated in aqueous systems
Reasons for titration in NON-AQUEOUS solvents:-
-there are 3 common reasons
*      The reactants or products might be insoluble in water.
*      The reactants or products might react with water.
*      The analyte too weak an acid or base to be titrated in water.
Solvents in NON-AQUEOUS TITRATIONS:-
The solvents are classified into 4 types
1)    Protogenic solvents
2)    Protophillic solvents
3)    Amphiprotic solvents
4)    Aprotic solvents
1) Protogenic solvents:-
            They are acidic solvents they enhances the basicity of weak bases.
         E.g.:- sulfuric acid, formic acid
2) Protophilic solvents:-
            They are basic in nature .they enhances the acidity of weak acids.
         E.g.:-pyridine, n-butylamine, ethylene-di-amine,
3) Amphiprotic solvents:-
            They category of solvents behave as acid or base depending upon the substance dissolved in it.
            They accept or donate protons.
         E.g.:- Glacial acetic acid , Dioxon
4)Aprotic solvents:-
            Solvents in neutral in nature
            These solvents do not accept or donate protons.
            These are useful in dissolving the drugs & they act as solvents.
         E.g.:- Benzene, Carbon tetrachloride.
In non-aqueous solutions the Selection of solvents based on the following considerations:-
1)    Solubility & nature of sample
2)    There should not be any side reactions between the sample or titrant & the solvent
3)    The solvent should not effect on the sharpness of the End-point during titrations.
4)    The titrant & solubility should be readily miscible with the solvent.
5)    The solvent should have high dielectric constant.
6)    The solvent should be readily available of low toxicity, easily purified and in expensive.

SOLVENTS
Dielectric constant
Example of drugs
Formic acid
58.5
Levodop, methyl dopa
Ethylene diamine
12.9
Phenols
Acitic acid,glacial acetic acid
6.13
Adrenaline

Titrating in NON-AQUEOUS solvents:-
Acidic titrants
Basic titrants
Perchloric acid in Dioxon
Tetra alkyl ammonium hydroxide
Perchloric acid in glacial acetic acid
Tetra butyl ammonium hydroxide                                    
P-toluene sulphonic acid
Sodium methoxide
2,4-dinitrobenzene sulphonic acid
Potassium methoxide
2,4,6-trinitrobenzene sulphonic acid
Lithium methoxide

v  Among the acidic titrants perchloric acid in glacial acetic acid is mostly used.
v  In basic titrants methoxide of sodium or potassium or lithium & tetrabutylammonium hydroxide are widely used.
v  The titrants are standardized before the assay of any pharmaceutical substances.
v  The primary standards available for the standardization of acidic titrants are potassium hydrogen phthalate, diphenyl guanidine & anhydrous sodium carbonate.
v  Benzoic acid & phenyl cinchonic acid are suitable primary standards for the standardization of the basic titrations.
Detection of end point:-
            In non aqueous titrimetry, the end point can be detected by the color change of the indictors or by the potentiometric method.
            Ex:- crystal violet-violet-yellowish green
                    Orange blue –blue – pink
                    2-naphthol benzein – blue – dark green
Classification of  NON-AQUEOUS solvents:-
            They are mainly categorized mainly into two classes.
1)    Titration of basic substances
A.    Titration of primary, secondary & tertiary amines
B.    Titration of halogen acid slts of bases
2)    Titration of acidic substances

1) Titration of basic substances:-

                    Perchloric acid 0.1 N in glacial acetic acid:-
Preparation
Ø  Mix 8.5 ml Perchloric acid + 500ml  glacial acetic acid+ 30 ml of acetic anhydrade
Ø  Cool & add more glacial acetic acid to makeup 1000ml .Allow tht solution to stand for 24 hours before use.
Ø  Acetic anhydrade reacts with water in the perchloric acid & acetic anhydrade & readers the mixture virtually anhydrous.
Standardization
Ø  Weight accurately about 0.7g of potassium hydrogen phthalate dissolved in 50ml of glacial acetic acid.
Ø  Add 2 drops of crystal violet solution & titrate with perchloric acid solution until the violet changes to green.
Ø  Detect the volume of perchloric acid consumed by 50ml of  glacial acetic acid.
Each 0.0241g of potassium hydrogen phthalate is equivalent to 1ml of N\10 perchloric acid.
Titration of 10, 20 & 30 amines
Ø  Ex:-Adrenaline can be titrated with acetous perchloric acid.
Titration of halogen acid salts of bases
Ø  Chlorides, Bromides, iodide are very weakly basic & do not react quantitatively with acetous perchloric acid.
Ø  A solution of mercuric acetate is added during the titration.
Ø  This replaces the halides ion by an equivalent quantity of acetate ion. Which is strong base in acetic acid?
2R.NH2.Hcl                    2R+ NH2 + 2Cl-
(CH3 Coo)2 HG +2CL-                        HgCl2      +     2CH3Coo-
                                                                            (un dissolved)
                        2CH3 CooH2+ +2CH3Coo-               4CH3CooH
2) Titration of acedic substances:-
Ø  Basic titrants are used. Alkali methoxides or tetrabutyl ammonium hydroxide.
Ø  Lithium mithoxide is preferred because less quantity of lithium metal is required to prepare the solution & the solution is easy to prepare.
Ø  Solvents required to dissolves the substances include
·         dimethyl formamide
·         N-butylamine
·         Ethylene diamine
·         Pyridine

Lithium methoxide 0.1 N
Preparation
Ø  Dissolve 0.7 g of lithium +150ml of methyl alcohol cooling the flask during the addition of methyl
Ø  When the reaction is complete add 850ml of toluene
Ø  If cloudiness or precipitate occurs add sufficient methyl alcohol to clarity the solution
Ø  Store the solution in a container protected from co2 & moisture.
Standardization
Ø  Weigh accurately 0.25g of benzoic acid dissolved in 25ml of dimethylformamide & titrates with lithium methoxide solution.
Ø  Indicator is QUINOLINE RED.
Ø  Protect the solution from carbon dioxide during the titration.
Ø  Perform the blank titration using 25ml of dimethyl formamide.
Ø  Each 0.01221g of benzoic acid is equivalent to 1ml of 0.1 lithium methoxide.

Tetrabutyl ammonium hydroxide 0.1 N
Preparation
Ø  Dissolve 40g of tetrabutyl ammonium iodide in 90ml of dehydrated methanol in a glass stoppered flask.
Ø  Place the flask in ice bath add 20g of powdered silver oxide, insert the stopper in the flask and agitate vigorously for one hour.
Ø  Centrifuge a few minutes & test the super titrant liquid for iodide.
Ø  If the test is positive add another 2g of silver oxide, and continue to stir for 30 min when all iodide has reacted.
Ø  Filter through fine sintered glass filter.
Ø  Rinse  the flask & filter with three quantities
Ø  Each of 50ml anhydrous toluene
Ø  Add washing to the filtrate and dilute to 1000 ml with anhydrous toluene.
Ø  Flush the solution for 10min with dry carbon dioxide free nitrogen
Ø  Store the container protected from carbon dioxide and moisture
Standardization
Ø  Weigh accurately 0.25g of benzoic acid dissolved in 80ml of dimethylformamide.
Ø  Add 3 drops of 1% solution of thymol blue in dimethylformamide & titrate with tetra butyl ammonium hydroxide.
Ø  End point is blue.
Ø  Perform blank titration
Ø  Each 0.01221g of benzoic acid is equivalent to 1ml of 0.1 tetrabutyl ammonium hydroxide.