SOURCES OF IMPURITIES IN VARIOUS PHARMACEUTICAL SUBSTANCES 3 : -

 : - Atmospheric condition during manufacturing process - in the inustrial area the atmosphare is contaminited with dust particals and various gasses like sulpherdi oxide, hydrogen sulphide black smoke etc. 

- during the manufacturing purification of the pharmaceutical these impurities may be enter in our product.

- there are many pharmaceutical products which when manufactured are contaminited with atmospheric carbon di oxide and water vapours.

- due to this reaction NaoH should not be rept open for a long time during process therefore i.p. has prescribed death NaoH should not contains more thane 3% of Na carbonate.

:- deffect in manufacturing process - in many pharmaceutical process there are some diffects are present such as imperfect mixing.

eg; zinc oxide  may be prepared by heating metallic zinc to bright redness in a presence of air . the vapours of zinc burn to form zinc oxide which is collected as a fine white powder. but if there is less heat or air than zinc metal is not completly converted into zinc oxide.

- thus the final product may contain metallic zinc as an impurity in various process.

: - intremediate product in the manufacturing process - there are some intermediate product which are produce during the manufacturing process , sometime these intermediate may be carried through to the final product as an impurity .

eg; pottesium iodine may be prepared by reacting KOH and iodine . in this reaction pottesium iodide,pottesium ioded ( kio3) and water is form .

- the resulting solution is first evaporated and then with charcoal by this all kio3 is converted into KI .

-in this process if the intermediate product is not completly converted into KI than it may be present in our final product .

SOURCES OF IMPURITIES IN VARIOUS PHARMACEUTICAL SUBSTANCES 2 : -

 :-  demineralized water - it is obtained by passing water through packed columns with ions exchange reason  in this process we prepared pure water which is free from various divalent and monuvalent ions thus the final product is free from these impurities.

- the water obtained from  this source may still contains some organic impurities due to this reason if we use demineralise water in preparetion then our product may contains some organic impurities.

:-  ditilled water - it is free from old type of organic and inorganic impurities this water is most suitable for pharmaceutical preparation. but distilled water is very costely. 

:-  chemical process use in the manufacturing process - for the synthesis of various drugs or pharmaceutical many chemical reactions such as nitration , sulphonation , helogenation , oxidation , reduction , hydrolysis etc. are envolve .

- in these chemical reactions many chemicals are used.

- tap water generally used in  various process due to this various impurities are involve in our reaction mixture which are generally found in our final product .

:-  action of reaction vessel due to solvents - during manufacturing process some of the solvents add reagents under goes various reactins with the metal or material of the vessel . sometime these reactions dissolved some traces of metal into solvent due to this metal enters in our reaction mixture and contaminate our final product .

SOURCES OF IMPURITIES IN VARIOUS PHARMACEUTICAL SUBSTANCES : -

- there are many sources which affects the product or sometime process which is use in the manufacturing process .

some major sources are follows ;-

[1] RAW MATERIAL : - impuritites known to be associated with these chemicals may be carried out through the manufacturing process and contaminate the final product. 

- if impurities are present in raw material which are used in pharmaceutical preparation then those impurities may be present in the final product ,normally those manufacturing process to the final product and due to this reason our final product may be contaminated.

eg 1; preparation method of Nacl(rock salt) it can be prepared by the reaction of calsium sulphate and magnisium chloride  prepare rock salt contains some amount of Caso4 and Mgcl2 ,thus sodium chloride prepare from the source will contains traces of calsium and magnisium compound.

-impurities such as Arsenic, lead and other heavy metals are present in raw material and hence are found in substances , so it is necessary to use pure chemicals and substances as a raw material far the manufacturing process.

eg 2; copper sulphate may be prepared by the reaction  of  sulphuric acid on copper turnings are known to have iron and arsenic as an impurities large quantities of these impurities are present in the raw material (copper turnigs) then these may be present in the final product .

- dur to this reason i.p. precribes some limits of tolerance for arsenic as an impurity to be not more then 8 parts per million in copper sulphate some unites are prescribed for iron as an impurity in i.p.(indian pharmacopoeia) .

[2] REAGENTS USED IN PHARMACEUTICAL PROCESS : - if reagents used in the manufacturing process are not completly removed by washing then some impurities  may be present in the final product.

eg; ammonium mercury may be prepared by adding a solution of mercuric chloride to the dilute ammonia solution in this process mercuric chloride shows solution nature and  ammoniated mercury shows ppt.

- the precipitate of ammoniated mercury contains ammonium hydroxide as an impurity . thus this precipitate is required to wash with old water to remove impurities of ammonium hydroxide.

- if it is not remove completly by washing with water than these types of impurities may be present in the final product.

REAGENTS - a reagents is a substances or compound added to a reaction mixture or system to cause a chemical reaction or added to the mixture if a reaction occure.

the term reagent and reactant are often used.

[3] METHOD OR PROCESS  USED IN  MANUFACTURING : -  many drugs and chemicals are manufactured from different raw material by using different method.

- sometime impurities are incorporated into the main material during the manufacturing process and type of impurities present in the during various.

- in certain drug or chemical a multiple steps synthesis procedure are used which produces various intermediate steps or compounds in this condition purification or removel of  impurities is also importance other wise these impurities may be contaminited our final product.

- normaly there are various side reaction occurs in different - different process.

- impurities of the product side reaction also occurs in the substances this may introduce new impurities by any reagent or other chemical(contamination).

eg; some time reagent may produce impurity.

- calcium carbonite is obtain by the reaction of soluble calcium salt a soluble carbonate salt and due to this final product will contains some traces of alkali which can be remove by washing process.

- sometime some chemical agent can be use to remove impurities.

eg; potessium bromide contains traces of barium which is added in the manufacturing process to remove eccess of sulphate.

[4] SOLVENTS - water is the cheapest solvent and freely available normality distiled water is used in pharmaceutical method.

- Types of water -

:- tap water - tap water contains ions(ca,mg,na,cl,so4.etc,)

:- salt water - its obtained by allowing the tap water to pass through the sodium form at zealite which removes divalent ions or contains like ca ion and mg ion from tap water by exchange at sodium so salt water contains not and chlorine ion has an impurities.

SOURCES OF IMPURITIES IN PHARMACEUTICAL SUBSTANCES : -

 impure chemical compound :-

a compound is said to be impure if it is having foreigen matter in any pharmaceutical drug or any substances ,eg; impurities.

pure chemical compound :-

- a pure chemical compound reffers to that compound which is having no foreigen matter in any substances.

- chemical purity means freedom from various foreigen matter in substances. 

- practically or analytically 100% pure substances are not available for pharmaceutical method and traces of impurities must be present all substances.v

impurity means undesired material or practicals.

presense of impurity in the pharmaceutical substances may produces various toxic effect in human body and may also lower down the active strength of main drug or our pharmaceutical substances.

commonly present impurities in pharmaceutical substances include small quantities of chloride ,sulphite ,, lead,arsenic and various heavy metals etc. 

IMPURITIES COMMONLY FOUND IN PHARMACEUTICAL SUBSTANCES : -

[1] - impurities which have toxic effects on human body and bring about unpleasent reactions when present beyonds specific limits in various substances eg; arsenic and lead .

[2] - the impurities which are able to make substances incompatible with other substances .

[3] - the impurities which present beyonds limit sometime affects storage properties of drug substances.

[4] - sometimes impurities are present in substances but it is harmless .in this condition the amount of impurity lowers the active strength of the main drug substances or medicinal compound eg; sodium solution in pottesium salt.

[5] - sometime impurities may bring about technical proplans in the use of  substances.

[6] - impurities present in compoundn may also change some properties of compound such as test , order , colour which can be easilly ditected by sences and other identification procedures ex; sodium chloride becomes damp due to presense of magnissium salt.

ACID BASE INDICATOR THEORY'S

-  indicator is a substances which exhibits color change at a particular stage of chemical reaction.

-  these are the substances which have different colors at various value of PH .

-  acid-base indicator(weak organic acid and base) having different color depending upon the concentration of hydrogen ion in the solution.

- for acid-base titration we select an indicator which will show a distinct color change at PH close to equivalance point . 

- acid-base indicator also known as visual indicator.

types of acid-base indicator theory's :

                                                                [1] - litmus theory

                                                               [2] - ostwald theory

                                                              [3] - quinoiod theory

                    

                                            LITMUS THEORY :-

- according to litmus theory indicator are similar to litmus in their behaviour.

- litmus is a weak acid showing red color in unionised state and blue color is ionised state.

- in the presence of hydroxide ion ,litmus solution shows reaction between hydrooxide and hydrogen ion (litmus).

- this reaction released ionised litmus ion which gives blue color.

- the litmus solution in the presence of H+ ion excess amount results in the formation of unionised litmus which gives a red color.

                                          OSTWALD'S THEORY :-

 it state that;

 - color change of the acid base indicator is the result of  its ionisation because ionised and ionised form are differ in color.

 - acid base indicator is either weak acid or weak base ,it's ionisation  is highly affected in the presence of acid and base. 

 - if indicator is weak acid then it's ionisation in acid is very low (due to common H+ ion)and fairly well is alkali .in similar manner if the indicator is weak base it's ionisation in acid is high and low in alkali.

* ostwald's theory can be explain in following manner by taking phenophthalin.  

 

*CLASSIFICATION OF LIQ.  DOSAGE FORMS*

EXPIENTS USED IN FORMULATION OF LIQ. DOSAGE FORMS : -

LIQUID DOSAGE FORMS -:

meant for internal & external use.

-liquid dosage forms are essantial pharmaceutical preparations which involves a mixture of active drug ingredient (API) and excepients.

liquid dosage forms are prepared :

(a) - by dissolving the API in an aqueous or non-aqueous [eg.- glycerin,ether,alcohol] solvent.

(b) - by suspending the appropriat medium.

(c) - by incorporating the drug substances into an oil or water phase.[eg.- suspension,emulsion,syrups,elixirs.]

ADVANTAGES OF LIQ. DOSAGE FORMS - :

[1] - easy to swallow = very useful for those patients who have trouble in swallowing.

[2] - easy absorpation = solutions get absorbed easilly,thus produce the therapetic effect faster than solid dosage forms.

[3] - uniform distribution = the drug in solutions is uniformly distributes.

[4] - administered by number of routes = liq. dosage forms can be administered by various routes - oral,paranteral,enema for rectum use,otic(ear),naseland ophthalmic preparations.

[5] - easy to formulate = simple and fast to formulate and adujustment is possible.

[6] - economical = liq. dosage forms are more economical than solid dosage forms.

DISADVANTAGES OF LIQ. DOSAGE FORMS -:

[1]  transportation = the transportation of liq. is problematic,as there are bulky any container breakage occures during transportation the whole formulated to product is lose.

[2] -special storage conditions = it needs a lot of special storage conditions

[3] - shorter shelf life = the ingredients in liq. are liable to deteriorate and lose their potency. so they have limited stability and shorter shelf life.

[4] - growth of microorganisms = due to presence of sweeting and flavouring agents,liq dosage forms supports growth of microorganisms.

[5] - incompatible interations = the dissolved substances in the liquids may result inincompatible interactions.

[6] - dose inaccuracy = dose inaccuracy may occure if a patient takes a dose using household devices, like a teaspoon ,etc.

[7] - must be shaken = shaking is required for suspension and emulsions.

𝐈𝐍𝐃𝐈𝐀𝐍 𝐏𝐇𝐀𝐑𝐌𝐀𝐂𝐎𝐏𝐎𝐄𝐈𝐀 𝗔𝗗𝗗𝗜𝗧𝗜𝗢𝗡𝗦 -:

[1]  1955- 1ˢᵗ ᴀᴅᴅɪᴛɪᴏɴ»» 𝑓𝑖𝑟𝑠𝑡 𝑎𝑑𝑑𝑖𝑡𝑖𝑜𝑛 𝑓𝑜𝑙𝑙𝑜𝑤𝑒𝑑 𝑏𝑦 𝑖𝑡𝑠 𝑠𝑢𝑝𝑝𝑙𝑒𝑚𝑒𝑛𝑡 𝑖𝑛 1960.

[2] 1966- 2ⁿᵈ ᴀᴅᴅɪᴛɪᴏɴ»»  𝑠𝑒𝑐𝑜𝑛𝑑 𝑎𝑑𝑑𝑖𝑡𝑖𝑜𝑛 𝑓𝑜𝑙𝑙𝑜𝑤𝑒𝑑 𝑏𝑦 𝑖𝑡𝑠 𝑠𝑢𝑝𝑝𝑙𝑒𝑚𝑒𝑛𝑡 1975.

[3] 1985- 3ʳᵈ ᴀᴅᴅɪᴛɪᴏɴ»»  𝑓𝑜𝑙𝑙𝑜𝑤𝑒𝑑 𝑏𝑦 𝑖𝑡𝑠 𝑎𝑑𝑑𝑒𝑛𝑑𝑢𝑚 𝑖𝑛 1989 & 1991.

[4] 1996- 4ʳᵗ ᴀᴅᴅɪᴛɪᴏɴ»»  𝑖𝑡𝑠 𝑎𝑑𝑑𝑒𝑛𝑑𝑢𝑚 𝑖𝑛 2000 & 2002.

[5]  2007- 5ᵗʰ ᴀᴅᴅɪᴛɪᴏɴ»»  𝑖𝑡𝑠 𝑎𝑑𝑑𝑒𝑛𝑑𝑢𝑚 𝑖𝑛 2008.

☞︎︎︎ 𝑖𝑡 𝑖𝑠 𝑝𝑟𝑒𝑠𝑒𝑛𝑡𝑖𝑛𝑔 𝑖𝑛 𝑡ℎ𝑒 3-𝑣𝑜𝑙𝑢𝑚𝑒𝑠 •

*𝒗𝒐𝒍-1: 𝑔𝑒𝑛𝑒𝑟𝑎𝑙 𝑛𝑜𝑡𝑖𝑐𝑒𝑠,𝑠𝑡𝑟𝑢𝑐𝑡𝑢𝑟𝑒𝑠,𝑖𝑛𝑡𝑟𝑜𝑑𝑢𝑐𝑡𝑖𝑜𝑛,𝑔𝑒𝑛𝑒𝑟𝑎𝑙 𝑐ℎ𝑎𝑝𝑡𝑒𝑟.

*𝒗𝒐𝒍-2: 𝑑𝑒𝑎𝑙𝑠 𝑤𝑖𝑡ℎ 𝑔𝑒𝑛𝑒𝑟𝑎𝑙 𝑚𝑜𝑛𝑜𝑔𝑟𝑎𝑝ℎ 𝑜𝑛 𝑑𝑟𝑢𝑔 𝑠𝑢𝑏𝑠𝑡𝑎𝑛𝑐𝑒𝑠, 𝑑𝑜𝑔𝑒𝑠𝑒 𝑓𝑜𝑟𝑚 𝑎𝑛𝑑 𝑝ℎ𝑎𝑟𝑚𝑎𝑐𝑒𝑢𝑡𝑖𝑐𝑎𝑙 𝑎𝑖𝑑𝑠( 𝐴-𝑀).

*𝒗𝒐𝒍-3: 𝑐𝑜𝑛𝑡𝑎𝑖𝑛 𝑚𝑜𝑛𝑜𝑔𝑟𝑎𝑝ℎ 𝑜𝑛 𝑑𝑟𝑢𝑔 𝑠𝑢𝑏𝑠𝑡𝑎𝑛𝑐𝑒𝑠,𝑑𝑜𝑠𝑒𝑔𝑒 𝑓𝑜𝑟𝑚 𝑎𝑛𝑑 𝑝ℎ𝑎𝑟𝑚𝑎𝑐𝑒𝑢𝑡𝑖𝑐𝑎𝑙 𝑎𝑖𝑑𝑠(𝑀-𝑍).

☞︎︎︎ 𝑓𝑜𝑙𝑙𝑜𝑤𝑒𝑑 𝑏𝑦 𝑚𝑜𝑛𝑜𝑔𝑟𝑎𝑝ℎ 𝑜𝑛 𝑣𝑎𝑐𝑐𝑖𝑛𝑒𝑠 𝑓𝑜𝑟 ℎ𝑢𝑚𝑎𝑛𝑠 𝑢𝑠𝑒,ℎ𝑒𝑟𝑏𝑠 𝑎𝑛𝑑 ℎ𝑒𝑟𝑏𝑙𝑒 𝑝𝑟𝑜𝑑𝑢𝑐𝑡𝑠.

[6]  2010- 6ᵗʰ ᴀᴅᴅɪᴛɪᴏɴ »» 𝑖𝑡𝑠 𝑎𝑑𝑑𝑒𝑛𝑑𝑢𝑚 𝑖𝑛 2012.

[7]  2014-7ᵗʰ ᴀᴅᴅɪᴛɪᴏɴ »» 𝑖𝑡𝑠 𝑓𝑜𝑙𝑙𝑜𝑤𝑒𝑑 𝑖𝑛 2015.

[8] 2018-8ᵗʰ ᴀᴅᴅɪᴛɪᴏɴ »» 𝑖𝑡𝑠 𝑎𝑑𝑑𝑒𝑛𝑑𝑢𝑚 𝑖𝑛 2021

𝗣𝗥𝗘𝗦𝗖𝗥𝗜𝗣𝗧𝗜𝗢𝗡

 

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𝗣𝗛𝗔𝗥𝗠𝗔𝗖𝗢𝗣𝗢𝗘𝗜𝗔

•  ɪᴛ ɪs ᴀ ᴏғғᴏᴄɪᴀʟ ᴘᴜʙʟɪᴄᴀᴛɪᴏɴ ᴄᴏɴᴛᴀɪɴɪɴɢ  ᴍᴇᴛʜᴏᴅᴏʟᴏɢʏ ᴛᴏ ɪᴅᴇɴᴛɪғʏ ᴛʜᴇ ᴍᴇᴅɪᴄɪɴᴀʟ   ᴄᴏᴍᴘᴏᴜɴᴅs.

•  ɪᴛ ɪs ᴘᴜʙʟɪsᴇᴅ ʙʏ ɢᴏᴠ ᴀᴜᴛʜᴏʀɪᴛʏ,ᴍᴇᴅɪᴄᴀʟ ᴏʀ ᴘʜᴀʀᴍᴀsᴏᴄɪᴇᴛʏ ᴅᴇsᴄʀɪᴘᴛɪᴏɴ ᴏғ ᴛʜᴇ ᴄᴏᴍᴘᴏᴜɴᴅs ᴀʀᴇ ɢɪᴠᴇɴ ɪɴ ᴛʜᴇ ғᴏʀᴍ ᴏғ ᴍᴏɴᴏɢʀᴀᴘʜ ɪɴ ᴛʜᴇ ᴘʜᴀʀᴍᴀᴄᴏᴘᴏᴇɪᴀ.

•  ᴍᴀɴʏ ᴀᴅᴠᴀɴᴄᴇ ᴄᴏᴜɴᴛʀɪᴇs ᴘᴜʙʟɪsᴇᴅ ᴛʜᴇʀᴇ ᴏᴡɴ ᴘʜᴀʀᴍᴀᴄᴏᴘᴏᴇɪᴀ.

𝑒𝑔: ɪᴘ(ɪɴᴅɪᴀɴ ᴘʜᴀʀᴍᴀᴄᴏᴘᴏᴇɪᴀ),ʙᴘ(ʙʀɪᴛɪs ᴘ),ᴊᴘ(ᴊᴀᴘᴀɴɪᴇs ᴘ),ᴜsᴘ(ᴜɴɪᴛᴇᴅ sᴛᴀᴛᴇ ᴘ)     𝑒𝑡𝑐.