Qn No.in ExampaperExpected Answer1.1 Write a critical note on (i) the law governing filtration rate and factors affecting it(ii) any one continuous-vacuum filter with reference to its construction,operation, advantage, disadvantage and application.[P10:4,25,28,26,27,103,104,105]Filtration is a mechanical or physical operation which is used for theseparation of solids from fluids (liquids or gases) by interposing amedium through which only the fluid can pass. Oversize solids in thefluid are retained, but the separation is not complete; scontaminated with some fluid and filtrate will contain fine particles(depending on the pore size and filter thickness).The factors which affect the rate of filtration is expressed by Darcy’ s LawFACTORS AFFECTING RATE OF FILTRATIONA. Area of surface filterB. Particle size of the solids to be removedC. Pore size of the filter mediaD. Resistance of the filter cake and filter mediaE. Viscosity of the liquid to be filteredF. TemperatureG. Pressure difference across the filter1. Properties of the filter medium and filter cakeThe resistance of the filter medium and filter cake is denoted by R. The resistanceof filter medium is of less significance in industrial scale than the resistance offilter cake. The latter increases with time. The rate of fthickness of the cake increases. When the rate is uneconomically low thefiltration is stopped and the cake is removed mechanically; and the filtration isresumed.2on (i) the law governing filtration rate and factors affecting itvacuum filter with reference to its construction,operation, advantage, disadvantage and application.[P10:4,25,28,26,27,103,104,105] [P10:102, 64-98]is a mechanical or physical operation which is used for theseparation of solids from fluids (liquids or gases) by interposing amedium through which only the fluid can pass. Oversize solids in thefluid are retained, but the separation is not complete; solids will becontaminated with some fluid and filtrate will contain fine particles(depending on the pore size and filter thickness).The factors which affect the rate of filtration is expressed by Darcy’ s LawFACTORS AFFECTING RATE OF FILTRATIONArea of surface filterParticle size of the solids to be removedPore size of the filter mediaResistance of the filter cake and filter mediaViscosity of the liquid to be filteredPressure difference across the filterfilter medium and filter cakeThe resistance of the filter medium and filter cake is denoted by R. The resistanceof filter medium is of less significance in industrial scale than the resistance offilter cake. The latter increases with time. The rate of filtration decreases as thethickness of the cake increases. When the rate is uneconomically low thefiltration is stopped and the cake is removed mechanically; and the filtration isMarkson (i) the law governing filtration rate and factors affecting itvacuum filter with reference to its construction,is a mechanical or physical operation which is used for theseparation of solids from fluids (liquids or gases) by interposing amedium through which only the fluid can pass. Oversize solids in theolids will becontaminated with some fluid and filtrate will contain fine particlesThe factors which affect the rate of filtration is expressed by Darcy’ s LawThe resistance of the filter medium and filter cake is denoted by R. The resistanceof filter medium is of less significance in industrial scale than the resistance ofiltration decreases as thethickness of the cake increases. When the rate is uneconomically low thefiltration is stopped and the cake is removed mechanically; and the filtration is8
3The resistance also depends on the properties of the solids, e.g. particle size,particle size distribution, particle shape, and compressibility of the solid. In caseof compressible cake the porosity decreases with increasing pressure drop, sofilter aids are incorporated to increase the filtration rate.2. Area of filterThe rate of filtration can be increased by increasing the area of filtration. Thisarea can be increased by using larger filters or by using a number of small unitsin combination. In rotary filters the filter cake is continuously removedproviding an infinite area of filtration.3. Pressure dropRate of filtration can be increased by increasing the pressure drop across thefilter medium. Pressure drop can be achieved by (i) gravity, (ii) negativepressure (reduced pressure or under vacuum), (iii) positive pressure and (iv)centrifugal force.Gravity: The height of the slurry over the filter medium gives pressure undergravity. By increasing the height of the slurry the pressure drop can beincreased.Negative pressure: The pressure below the filter medium can be reduced belowatmospheric pressure by connecting the filtrate receiver to a vacuum pump.The disadvantage of this method is that the pressure drop can never be increasedabove one atmospheric pressure.The second disadvantage is that under reduced pressure the boiling point ofliquid is lowered and the liquid may boil in the filtrate receiver that may causeloss of liquid or may damage the vacuum pump.Positive pressure: The simplest method of raising the pressure difference acrossthe filter membrane is to increase the pressure to the surface of the slurry.The advantage is that greater pressure difference can be achieved.Centrifugal force: The gravitational force can be increased by centrifugal force.4. Viscosity of liquidAn increase in the viscosity of the liquid will decrease the flow rate. Theviscosity of the liquid can be decreased by raising the temperature of the slurryor by dilution with a miscible liquid.5. Thickness of the filter cakeThickness of the filter cake increases as the filtration progresses. Highlyconcentrated slurry is first decanted or strained to reduce the solid content andthen it is filtered (this reduces the cake thickness). In a rotary drum filter cake isremoved continuously so that the cake thickness is minimized.
4Rotary drum filters consist of a perforated metal drum wrapped with afilter cloth to act as filter mediumThe drum is partially immersed in the tank containing the slurry. Thedrum is rotated at a slow speed and vacuum is created. Thus the filtratewill enter the drum through the filter media and filter cake will bedeposited on the outer surface of the filter mediumThe cake can be removed by scrapping with a knife just before therotating drum repeats another cycle.Zone Position operationCake FormationZone(Pick-up)Slurrytrough withagitatorThe drum picks up the slurry as soon asit comes in contact with the slurrytrough. Cake builds up on the filter clothCake PredryingZoneDrainagefiltratereceiverUnder vacuum the filtrate is received infiltrate receiverCake WashingZoneWashingWash sprays Water is sprayed on the cake andsimultaneously drainage is taking place.
5Cake Final DryingZoneDryingDrying orHot AirblowerUnder vacuum the filter cake is dried.Cake DischargeZoneCake removalScrapperknifeVacuum is reversed i.e. Compressed air ispassed to this zone so that the cake maybe loosenDead Zone Cycle repeatsThe cake discharge may be carried out by:(i) Scrapper dischargeIn this method a knife is fitted to scrap a small thickness of the pre-coat alongwith the cake. But wear and tear on the filter cloth is considerable with scrapperknife so the cloth is frequently changed.(ii )String dischargeNumbers of endless strings are placed at about ½ inch pitch over the width ofthe drum. The run or this string is extended from an open conveyor systempassing over a discharge and return roller. As compared to scrapper, the wear offilter cloth is minimized.(iii)Belt dischargeIt makes the filter cloth to pass on the roller and material is discharged on thefirst roll and before its passage to the fed trough it is subjected to washing.Therefore, higher filtration rates may be achieved using belt discharge.Advantages(i) It is automatic and continuous; labor cost is low.(ii) Very high capacity. (iii) Thick slurries containing 15–30% of solids can befiltered. (iv) Variation of speed of rotation enables the cake thickness to becontrolled. E.g. For solids forming impenetrable cakes thickness is kept constantwithin 5 mm. For porous cakes thickness is kept within 100mm.Disadvantages(i) Complex design with many moving parts. (ii) Very expensive.(iii) The cake tends to crack under vacuum, so washing and drying are notefficient. (iv) As vacuum is applied, it is unsuitable for liquids near boiling point.(v) Gelatinous or slimy precipitates forming impenetrable cake will not separatecleanly from cloth.Application(i) Collection of calcium carbonate, magnesium carbonate, starch.(ii) Separation of the mycelium from the fermentation liquor in the manufactureof antibiotics.
7Qn No.in ExampaperExpected Answer Marks1.2 Explain the working principle of a planetary mixer. Discuss how vortexformation can be controlled in mixing tanks.[4MY2828.doc, Mixing and homogenization.pdf pg186] [4MY7070.doc](i) Planetary motion mixers:Construction: It consists of a circular base. Inside the container a blade rotates around its ownaxis. The axis of the blade again rotates along a shaft. Thus the motion of the blade is similar tothe motion of a planet around the sun. The planet is rotating along its own axis and at the sametime the planet is rotating around the sun. The design of the blade is as shown in the figure.There is very little clearance between the blade and the wall of the container.Working: This design allows the revolving blade to handle (mix) a small amount of mass at atime. Again the blade is moving, carrying the mass to other places. The blade is scraping thematerials those are sticking to the wall of the container.Application:1. This sturdy (strong) mixer is used to mix semisolid ointments.2. To prepare tablets the powder is mixed with binder solutions. During this wet massing stepplanetary mixer is used.Vortexing and its remedies:If the tangential component is dominant, a vortex forms and may deepen until it reaches theimpeller, and aeration occurs. Due to the high speed of the propellers vortexing and finallyaeration may occur; i.e. air may get entrapped which may be difficult to remove from theproduct and the air may encourage oxidation in some cases, causes blade to be less in contactwith liquid, therefore decrease efficiency of mixing.To avoid vortexing the following strategies can be worked out:(i) The propeller should be deep into the liquid and [fig (a)](ii) Symmetry should be avoided:(a) propeller shaft may be off-set from the center. [fig (b](b) propeller shaft may be mounted at an angle to the vertical wall of the container. [fig(c)](c) the shaft may enter side of the vessel [fig (d)](d) or, a vessel other than cylindrical may be used, (N.B. although this is liable to give4ContainerBladeShaftFig. Planetary mixer
8rise to ‘dead spots’ in corners)(iii) A push-pull type of propeller may be used in which two propellers of opposite pitch aremounted on the same shaft so that the rotating effects are in opposite directions and canceleach other. [fig (e)](iv) One or more baffles may be used which are usually vertical strips attached to the wall of thevessel. [fig (f)]fig (a) fig (b)fig (c) fig (d)fig (e)fig (f)
9Qn No.in ExampaperExpected Answer Marks2.1 Outline the classification of pharmaceutical dosage forms according to time-release of drug. Critically compare and contrast key features of routes ofadministration that bypass the first pass metabolism.Drugs are rarely administered in their original pure state. They are convertedinto suitable formulations which are called dosage forms. Every dosage form is acombination of the drug and other non-drug components. The non-dugcomponents are known as “additives”. The additives are used to give aparticular shape to the formulation, to increase its stability and also to increaseits palatability as well as to give more elegance to the preparation.According to drug release rate from the tablet :a- Immediate-release tablet:The tablet is intended to be released rapidly after administration, or the tablet isdissolved and administered as solution. It is the most common type andincludes:1- Disintegrating tablet (conventional or plain tablet)(with or w/o sugar, filmcoating)2- Chewable tablets3- Effervescent tablets4- Sublingual and Buccal tablets5- Lozenges, TrochesTablets for oral ingestion; Tablets for use in oral cavity; Tablets to preparesolutionsb- Modified-release tablet:They have release features based on; time, course or location. They must beswallowed intact.(1) Repeat -act ion tablets are layered or compression-coated tablets inwhich the outer layer or shel l rapidly disintegrates in the stomach (e.g. ,Repetabs, Scher ing; Extentabs, Wyeth) . The components of the inner layeror inner tablet are insoluble in gast ric media but soluble in intestinal media.(2) Delayed-act ion and enter ic-coated tablets delay the release of a drugf rom a dosage form. This delay is intended to prevent dest ruct ion of thedrug by gast ric juices, to prevent i rr i tat ion of the stomach l ining by thedrug, or to promote absorpt ion, which is better in the intestine than in thestomach.Enter ic-coated tablets are coated and remain intact in the stomach, but yieldthei r ingredients in the intestines (e.g. , Ecotr in, GSk). Enteric-coated tablets area form of delayed-act ion tablet . However , not all delayed-action tablets areenter ic or are intended to produce an enteric ef fect . Agents used to coat these6
10tablets include fats, fatty acids, waxes, shel lac, and cellulose acetate phthalate.(3) Other Sustained- release forms grouped according to their pharmaceuticalmechanism.a. Coated beads or granulesb. Microencapsulat ionc. Mat r ix tabletsd. Osmotic systemse. Ion-exchange resinsf . Complex formationWhen a drug is administered by oral route, it undergoes attack by gastric juicesand undergoes first pass metabolism when absorbed into the entero-hepaticcirculation, where a great fraction of it is rendered inactive. Some prodrugs areconverted to the active drug by the same mechanism.Routes that bypass the first pass metabolism are sublingual, rectal, parentral,transdermal and respiratory routes.Sublingual route:The drug diffuses into the blood, directly through tissues under the tongue incase of sublingual tablets and through oral mucosa in case of buccal tablets.Adv: Bypass first pass metabolism, Rapid action achievedEg: nitroglycerin sublingual tablet for relief of anginaRectal route:Suppositories administered rectally melt and dissolve to provide local action orachieve systemic absorption.Adv: Useful when oral administration is inappropriate, as with infants,debilitated or comatose patients, and patients who have nausea, vomiting, orgastrointestinal disturbances. Bypass first pass metabolism to some extentexcept where upper hemorrhoidal veins are involved.Dis: Uncertain/unpredictable absorption, local irritation and possible accidentalloss of the medication.Parentral route:Preparations injected directly into body tissue through the primary protectivesystems of the human body, the skin and mucous membranes must beexceptionally pure and free from contaminants.Adv: Immediate action; Dose can be adjusted accurately; useful for unconscious,uncoorporative patient, for drugs with poor oral absorption.Dis: require aseptic conditions, pain factor, risk of local irritation, difficulty incorrecting the error.
11Respiratory route: preparations are inhaled for local action or systemic action.Advantages: rapid onset of action; bypass the hepatic circulation; avoidance ofdegradation in the gastrointestinal tract; lower dosage that minimizes adversereactions; simple, convenient and acceptable therapy.Transdermal route: Preparations applied are absorbed through skin and providelocal and systemic action.Adv: transdermal delivery systems provide long term systemic delivery.Eg antianginals, analgesics(Durogesic), contraceptives
12Qn No.in ExampaperExpected Answer Marks2.2 (i) Which of the following amounts of copper sulphate is required to make400 mL of an aqueous stock solution, such that, when the stock solution isdiluted 50 times with water, a final solution of 0.1% w/v copper sulphate isproduced?A 0.2 g B 20.0 g C 0.4 g D 40.0 g E 50.0 gFinal conc.=0.1%w/vDilution factor=50Stock conc.=0.1 x 50 = 5%w/v100ml stock contains 5g CuSO4400ml stock contains 20gCuSO4Ans: B(ii) You have in your pharmacy a cream containing 0.05% w/w Clobetasone.You have been requested to use this cream as a base and to add in sufficientmiconazole such that the final concentration of miconazole in the new creamwill be 2.0% w/w. What is the concentration of Clobetasone in the newcream?A 0.025% w/w B 0.49% w/w C 0.5% w/w D 0.05% w/w E 0.049%w/w0 (100-2) 982100 -(0-2) 298part cream + 2part miconazole powder=100part mixture100g newcream contains 98gcream and 2gmiconazole0 (0.05-x) 2X0.05 (x) 9812part miconazole powder (containing 0%w/w colbetasone) when added to 988parts 0.05%w/w colbetasone cream dilutes colbetasone to a final concentrationof X%w/w.(0.05-x)/x=2/9898(0.05-x)=2x4.9-98x=2x8
134.9=100xX=0.049New cream contains 0.049%w/w colbetasone.Ans:E(iii) Toxic residues are sometimes found in drinking water in industrial areas.For compound Z, the safe limit for drinking water is 92 ppm. Analyticalresults for the amount of compound Z in the drinking water of variouslocations are given below. Which ONE of the following locations hasdrinking water that is NOT safe to drink?A Toome: 41.0 micrograms/mLB Blackhill: 0.3 mg/LC Drumhowan: 0.0045% w/vD Magheracloone: 0.00041 g/mlE Annagassan: 1 in 100 000Toome: 41 micrograms/mL = 41 mg/1000 mL = 41 g in1 000 000 mL or 41 ppm41 ppm < 92 ppm, so the water in Toome is drinkableBlackhill: 0.3 mg/L = 0.3 mg/1000 mL = 0.3 g/1000 000 mL or0.3 ppm0.3 ppm < 92 ppm, so the water in Blackhill is drinkableDrumhowan: 0.0045% w/v = 0.0045 g/100 mL = 0.045 g/1000 mL =45.0 g/1000 000 mL or 45 ppm45 ppm < 92 ppm, so the water in Drumhowan is drinkableMagheracloone: 0.00041 g/ mL = 0.41 g/1000 mL =410.0 g/1000 000 mL or 410 ppm410 ppm > 92 ppm, so the water in Magheracloone is not drinkableAnnagassan: 1 in 100 000 is the same as 10 in 1000 000 or 10 ppm10 ppm< 92 ppm, so the water in Annagassan is drinkable.Ans:D(iv) Match the comments in I) II) III) to the appropriate answer from A to E.I) The volume of an oral liquid medicine, available as 2 mg drug X/5 mL,which is required for a 14-day supply for a patient prescribed a dose of 4 mgdrug X three times daily.
14II) The volume of alcohol 95% v/v needed to produce 1.90 L of 50% v/v.III) The volume of concentrated peppermint water required to make 16.8 L ofsingle-strength peppermint water. (Single-strength peppermint water is 1part concentrate to 39 parts water.)A 100 mL B 1000 mL C 4200 mL D 420 mL E 4.2 mLI) DThe patient requires 4 mg drug X three times daily, so needs 12 mg/day. Ifthe drug is formulated at 2 mg/5 mL, then 6 × 5 mL doses are required perday. If the patient, therefore, needs 30 mL/day for 14 days, 420 mL arerequired. Accordingly, the correct answer is D.II) B1.90 L of 50% v/v contains 0.95 L alcohol95% v/v contains 95 mL alcohol in 100 mL. Therefore, the volume ofalcohol 95% v/v containing 0.95 L alcohol can be calculated as follows:(0.95/95) × 100 = 1.00 L or 1000 mL.Accordingly, the correct answer is B.III)DFor every 40 mL single-strength peppermint water you have 1 mLconcentrate. Therefore in 16.8 L, or 16 800 mL, you have 16 800/40 =420 mL.Accordingly, the correct answer is D.
15Qn No.in ExampaperExpected Answer Marks3.1 Classify extraction methods and compare them. Explain soxhelation with adiagram. Comment on the merits and demerits of continuous hot percolation.[P7:15, P7B:1], [P7B:14, P7:16] [P7:29-31, P7B:4-5]Extraction refers to processes for the isolation of the active ingredients from drugmaterial. This may be by physical means or by dissolving in a suitable solvent.-Expression is the physical act of applying pressure to squeeze out oils or juicesfrom plants. This was normally achieved with a tincture(hydraulic) press-Cold Methods: Maceration, Percolation and Infusion (used for thermolabilecomponents)-Hot Method: Decoction, Hot Continuous Extraction, DistillationExtractionmethodTime forextractionTemperature Characteristics of the activeconstituentsMacerationPercolationDigestionInfusionDecoction3-7 days24 hoursFew daysShort period15 minsRoom tempRoom tempModerately highCold or boilingwaterBoiling water• Soluble in the menstruum• Heat stable / unstable• Soluble in the menstruum• Heat stable / unstable• Heat stable• Readily soluble• Water soluble• Heat stableOr8EXTRACTION PROCESSESINFUSION DECOCTION MACERATION /DIGESTIONPERCOLATIONFreshInfusionConcentratedInfusionSimpleMacerationMaceration withadjustmentMultipleMacerationDoubleMacerationTripleMacerationSimplePercolationContinuousHot Percolation(Soxhlation)PercolationProcess forConc. PreparationReservedPercolationModifiedPercolation.
17soxhelationClassic techniques for the solvent extraction of activeconstituents from medicinal plant matrices are basedon the choice of solvent coupled with the use of heator agitation. Existing classic techniques used toobtain active constituents from plants include:Soxhlet, hydrodistillation and maceration with analcohol-water mixture or other organic solvents.Soxhlet extraction is a general and well-establishedtechnique, which surpasses in performance otherconventional extraction techniques except for, inlimited fields of application, the extraction ofthermolabile compounds.In a conventional Soxhlet system, as shown inFigure above, plant material is placed in a thimble-holder, which is filled with condensed fresh solventfrom a distillation flask. When the liquid reaches theoverflow level, a siphon aspirates the solution of thethimble-holder and unloads it back into thedistillation flask, carrying extracted solutes into thebulk liquid. Solute is left in the fl ask and freshsolvent passes back into the plant solid bed. Theoperation is repeated until complete extraction isachieved.This process is used for those drugs•where the penetration of the menstruum into thecellular tissues is very slow and•the solute is not readily soluble into the solvent and•the quantity of the menstruum is very less.In such cases Soxhlet extractor is used where small volume of hot menstruum ispassed over the drug time and again to dissolve out the active constituents untilthe drug is exhausted. The process is known as Soxhlation.Apparatus:i)A round bottom flask in which the menstruum is boiled.ii)An extraction chamber in which drug is filled, is fitted with side tube and asiphon.iii)A reflux condenser.The size of the drug is reduced.The drug is packed in a ‘thimble’ made of filter paper which is then placed intothe wider part of the extractor.[N.B. thimble is used to prevent choking of the lower part of the extractor.]
18Menstruum is placed in the flask and boiled. The vapor rises through the sidetube to the condenser, where the vapor is condensed and fall on the packeddrug, through which it percolates and extract out the active constituents.As the volume of menstruum in the extractor increases, the level of liquid in thesiphon also increases till it reaches the maximum point from where it is siphonedout into the flask.On further heating the menstruum vaporizes while the dissolved activeconstituents remain behind in the flask. The alternate filling and emptying of thebody of the extractor goes on continuously till the drug is exhausted. Thus thesame quantity of menstruum is made to percolate repeatedly, about 14 to 15times through the drug and the active constituents are collected in the flask.Merits/DemeritsDespite the economic advantages of solvent extraction, the use of volatileorganic solvents such as hexane, acetone and methanol for processing medicinalplants has been limited due to environmental considerations. Hot continuousextraction technology shall always remain the method of choice for highefficiency, economical extraction and with less capital investment.Advantages: Disadvantages:1. The displacement oftransfer equilibrium byrepeatedly bringing freshsolvent into contact with thesolid matrix.2. Maintaining a relativelyhigh extraction temperaturewith heat from the distillationfl ask.1. Agitation is not possible in the Soxhletdevice.2. The possibility of thermal decompositionof the target compounds cannot be ignoredas the extraction usually occurs at theboiling point of the solvent for a long time.Chemical constituents of the drug: Theprocess is unsuitable for thermolabile activeconstituents, e.g. enzymes, alkaloids,anthraquinone derivatives, esters etc3.Physical character of the drug: If thephysical character of the drug is such that itwould block the Soxhlet apparatus then thismethod is not suitable. e.g opium, gum,resin, orange peel etc.4.Solvent: Only pure solvents or constantboiling mixtures (like alcohol-water) can beused for this purpose.
19Qn No.in ExampaperExpected Answer Marks3.2 Explain the construction, operation, advantages, disadvantages and applicationsof hammer mills. List factors affecting choice of size reduction equipment.[P8A:28-29] [P8A: 37-38, 16-17].HAMMER MILLMethod of size reduction: ImpactConstruction and working :Hammer mill consists of a stoutmetal casing, enclosing a centralshaft to which four or morehammers are attached. These aremounted with swivel joints, sothat the hammers swing out to aradial position when the shaft isrotated. The lower part of thecasing consists of screen throughwhich materials can escape,when sufficiently size reduced.The material is collected in acontainer placed below thescreen.The screen can be changed according to the particle size required.According to the purpose of operation the hammers may be square-faced,tapered to a cutting form or have a stepped-form.The interior of the casing may be undulating in shape, instead of smoothcircular form for better impact.The rotor operates at a speed of 80cycles per second.Advantages:(a) It is rapid in action, and is capable of grinding many different types of materials.(b) The product can be controlled by variation of rotor speed, hammer type and size andshape of mesh. (c) Operation is continuous. (d) No surface moves against each other sovery little problem of contamination of mill materials.Disadvantages:(a) High speed of operation generates heat that may affect thermolabile materialsor drugs containing gum, fat or resin.(b) The rate of feed should be controlled otherwise the mill may be choked.(c) Because of high speed of operation, the hammer mill may be damaged ifsome foreign materials like stone, metal pieces etc. are present in the feed.Applications: Powdering of crystals and filter cakes.8
20Factors influencing choice of Size Reduction machinery1. Nature of the raw material: Drugs must be thoroughly dried before they aresubjected to size reduction. Drugs like belladonna, gentian, liquorice and squillare returned to the drying rooms to the drying rooms after they have beenpartially comminuted, as they rapidly absorb absorb moisture from theatmosphere and as the moisture may not be removed from all parts of the drugduring the initial drying stage. In the case of water insoluble substances, wetgrinding of the material can be done. For the preparation of aqueous dispersionsof drugs this method is very effective since deflocculating agents may beincluded to prevent agglomeration of the particles.Substances that are hygroscopic or volatile or very poisonous or that need-prolonged trituration are more easily prepared in closed porcelain ball mills.Fibrous material seed tearing apart of the fibres and this can be achieved in high-speed impact mills. Substances of a resinous or oily nature shall not be subjectedto heavy pressures or much heat as a pasty mass may result. Hence, a ball millwill not be suitable and they are better grounded in a micronizer or a hammermill. The replacement of air by an inert gas is necessary when grinding readilyoxidizable materials and ball mills and high-speed impact mills are generallyused in this way.2. Nature of the product: A powdered drug produced in a ball mill differs fromthe product in a micronizer or a disintegrator even though both powders may bescreened to the same fineness. Differences exist in the shape of the particles, theirtoughness and their internal pore structure. Powder obtained from grindingmills like ball mill is more compact and less porous than that obtained in highspeed impact mills like a disintegrator. For the grinding of a sterile materialunder aseptic conditions, a mill is required that can be easily sterilized andsealed to prevent contamination during the grinding operation. A batchoperation porcelain ball mill is most suitable for this purpose. When iron andcopper contamination of pharmaceutical products is to be avoided stainless steelor ceramic material may be used for the surfaces of a mill coming into contactwith the drug.3. Degree of comminution required: The degree of comminution of materialsvaries according to the purpose for which they are required. For the preparationof galenicals, the size of the vegetable drug powder employed for extractionvaries from coarse to fine powder. Tincture preparation requires bruised tomoderately coarse powders. For percolation, drug powders should not contain alarge proportions of fines to avoid uneven extraction. Coarse to moderatelycoarse powder, with a minimum of fine powder, are all most easily obtained byusing high speed mills of the impact type. Materials such as cascara, liquorice,belladonna leaf and root and ginger are all easily broken down in such mills. Thegrindability of different grades of a vegetable drug usually varies and duringcomminution the softer portions get size reduced first. Therefore it is sometimes
21useful to screen out the powdered drug and return the coarser material to themill for further size reduction. This prevents continued milling of the softerportions resulting in formation of too much fines. The same principle is alsoapplicable to crystalline drugs although they are of uniform composition. Therate of absorption of sparingly soluble drugs, either through the Gastro-intestinal tract or when administered parenterally, depends on particle size.Penicillin in a medium of aluminium monostearte and arachis oil appears to bemost effective when 90 % of the particles are smaller than 5 micrometers. Therelatively insoluble sulphonamides attain their maximum antibacterial activity atcrystal sizes of about 1 micrometer or below. For insufflations the drug shouldbe smaller than about 5 micrometers.
22Qn No.in ExampaperExpected Answer Marks3.3 Classify pharmaceutical additives. Comment on the relation between theirpurity and their quality with examples and on any safety concerns. List the idealproperties of pharmaceutical additives.[P6:6-7, 9-10,36 9,11-14,21] . [P6:1-4,23,36, 5]A pharmaceutical additive/excipient is defined as any substance (natural,semisynthetic or synthetic) other than the active drug or prodrug that isincluded in the manufacturing process or is contained in a finishedpharmaceutical dosage form.Classification of additives from regulatory point of view• First category (approved excipients) : compounds originating from thefood industry (generally recognised as safe or that have been present inuse for a very long time• Intermediate category (essentially new excipients): compounds obtainedby means of the structural modification of the excipients alreadyapproved or those already used in the food or cosmetic industries.• Third category : new compounds, never previously used in thepharmaceutical field and it is growing rapidly due to the present interestin modified-release formulations and the requirements of the modernhigh-productivity compressing/ tabletting machines.Classification of additives based on origin• animal (e.g. lactose, gelatin, stearic acid),• plant (e.g. starches, sugars, cellulose, arginates),• mineral (e.g. calcium phosphate, silica) and• synthesis (e.g. PEGs, polysorbates, povidone, etc.)Pharmaceutical additives must be submitted to more thorough-goinganalytical controls guarantee the quality required by the pharmaceuticalindustryImpurities to be kept at an acceptable minimum level esp if they are toxic.But at times their presence is functionally necessary eg (hemicellulose inmicro-crystalline cellulose.)“Pure” Excipients that don’t work includePure DiCalcium Phosphate doesn’t compact well due to absence of impurityrelated crystal defects.Pure Magnesium Stearate doesn’t lubricate due to absence of water (onlyhydrates lubricate)8
23Ideal properties of excipients. The ideal excipient should be1. Nontoxic, Chemically inert (nonreactive with the drug and otherexcipients) & Physiologically inert (inert in the human body).2. Physically & Chemically stable both by itself and in combination with thedrug.3. Free of unacceptable microbes & does not support mould growth.4. Colour compatible and maintains the uniformity of shades.(have pleasingorganoleptic properties)5. Have no deleterious effect on the bioavailability of active drug.6. able to fill numerous and important functions.7. Should perform, ie fulfill its inherent function8. have low equipment and process sensitivity,9. be well characterized and well accepted by the industry and regulatoryagencies.A limited choice of excipients with all of these attributes makes formulationdesign and excipient selection challenging.
24Qn No.in ExampaperExpected Answer Marks3.4 Describe the evolution of pharmaceutics in the twentieth century listing any 2technological breakthroughs. Enumerate the functions (duties) of the hospitaland community pharmacist.[P3:1-5] [P2A: 25-27, 30-34, 12-16, P2B:1-5]• The essence of pharmaceutics is the amalgamation of physical science(physical pharmacy) with aspects of biological science.• At its center is not only the dosage form with its active and inactiveingredients but also the behavior of the ensemble in the environment inwhich these medicines are used, generally in human subjects.• From the early days of the 20th century to the mid-1950s, it wasconcerned primarily with the science and practice of the manufacture ofmedicines (dosage forms) on small and large scales and the preparation ofgalenicals.• Pharmaceutics has progressed as drugs have developed first from naturalproduct extracts, through synthetic and generally small molecules topeptides, proteins, and oligonucleotides and DNA itself, into thebeginning era of cell-based therapies.• Initially not much regard was given to the fate of the dosage form in vivo.• However, technological break-through led to counter the liabilities of theinherent drug. E.g.• 1. Enteric coating of tablets to minimize drug’s irritant effect on theintestinal mucosa, to minimise degradation of drug by acidic pH.• 2. The first commercial sustained-release preparations emerged in the late1940s with the SpansuleTM, which contained wax-coated beads withdifferent release properties in a soluble capsule, thus controlling release ofthe drug in the GI tract.The day to day duties of a pharmacist varies from one setup to another.Community pharmacist– Provide drug information to other healthcare professionals– Provide patient care by identifying disease, educating patient on disease,precautions, life style changes, etc– Runs a business, supervise staff, maintain inventory– Gather patient information, screen, monitor and advice for self-treatmentwith over-the-counter (OTC) products sold without a prescription.– Prepare doses of Precompounded medication, Extemporaneouslycompounded nonsterile medications8
25– Dispensing, recordkeeping, and pricing– receiving a verbal, or oral, prescription in person or by telephone– preparing the written form of the verbal prescription– interpreting and evaluating prescriptions– reviewing patient profile & screen for (e.g., medication history,duplication of medications, drug interactions, Drug-diseasecontraindication, Incorrect dosage or duration of treatment, Drug-allergy interactions, Clinical abuse/misuse)– review and discuss with the patient the following• name and description of medication• dosage form• dose• route of administration• duration of drug therapy• action to take after a missed dose• common severe side effects or adverse effects• interactions and therapeutic contraindications, ways to preventthe same, and actions to be taken if they occur• methods for self-monitoring of the drug therapy• prescription refill information• proper storage of the drug• special directions and precautions for preparation,administration, and use by the patientHospital pharmacist– Dispenses oral medications– Prepares and dispenses parenteral medications and doses ofExtemporaneously Compounded Sterile Medications– Sometimes specializes, with advanced training in an area of patient care– Educates and counsels patients– Provides drug information– Supervise replenishing and transport of controlled drugs for floor stock– Administers a department by– developing policies and procedures– purchasing drugs and supplies– monitoring drug use in the hospital
26Qn No.in ExampaperExpected Answer Marks3.5 List the various methods of heating and comment on steam’s benefits andproblems. Using a phase diagram, explain lyophilisation and benefits of freezedrying.[P11:5-11] [P11:45-47 P11~lyoph.pdf:2-5]various methods of heating include• By burning fuels (coal, petroleum, natural gas)• By Electric heating elements(high resistance)- cheap, clean, rapidresponse, easy handling• Direct heating- material in direct contact with heat (high temperatureachieved, but material must be thermostable)• Indirect heating- material in contact with a medium or bath, inturn incontact with heat (controlled temperature achieved) water bath, steambath, paraffin-oil bath,In pharmaceutical processes at anything other than laboratory scale, the mostcommonly used heating medium is steam. Steam is also very important as asterilizing medium. The reasons for the widespread use of steam include:• The raw material (water) is cheap and plentiful.• It is easy to generate, distribute and control.• It is generally cheaper than viable alternative forms of heating, e.g. electricity.• It is clean, odourless and tasteless, and accidental contamination of the productis less likely to beserious.• It has a high heat content (in the form of latent heat) and can heat materialsvery quickly.• The heat is given up at a constant temperature, which is useful in controllingheating processes and in sterilization.One disadvantage of the use of steam is that it is used at pressures that aretypically two to three timeshigher than atmospheric, and thus steam presents potential safety problems andnecessitates the use ofhigh-strength piping. To appreciate why steam is used in pharmaceuticalprocessing and the principles of heat transfer using steam it is necessary toconsider how the steam is produced, its heat content, and how the heat contentvaries with pressure and temperature.• The temperature at which water boils depends on the pressure exerted on thewater surface. This is utilized in sterilization processes, where adjustment of thepressure allows selection of the temperature at which steam condenses andtherefore the temperature at which the articles to be sterilized are exposed.Similarly, in heat transfer processes, the desired temperature gradient can be8
achieved by adjusting the steam pressure.• Problems with Steam contaminated by airAir is a bad heat conductor and thus reduces heat transfer, increase heating timeand cost. From dalton’s law,Total Pressure= Partial Pressure(air)+Partial Pressure(steam).Thus lower pressure means lower steam temperature, lower heat gradient,higher heating time, possibly poor sterilization.Freeze drying or lyophilization• The solution is frozen prior to drying and the solvent is then sublimed(that is, converted to the gas phase directly from the solid phase), below themelting point of the solvent.• Freeze drying is often carriedout under reduced pressure (using avacuum pump) to allow drying toproceed at a reasonable rate.• This process avoids collapseof the solid structure, leading to alow-density, highly porous productthat can quickly reabsorb the solventwhen needed (lyophile means ‘‘likesthe solvent “)• This method was first usedindustrially to produce dehydratedvaccines, and to bring dehydratedblood to assist war casualties. It isregarded as the best method forpreserving the quality and biologicalactivity of proteins, vitamins, and other bioactive compounds.• In a typical phase diagram, the boundary between gas and liquid runsfrom the triple point to the critical point. Regular drying is shown by the greenarrow; freeze drying, by the blue arrow.27by adjusting the steam pressure.• Problems with Steam contaminated by airAir is a bad heat conductor and thus reduces heat transfer, increase heating timeFrom dalton’s law,Total Pressure= Partial Pressure(air)+Partial Pressure(steam).Thus lower pressure means lower steam temperature, lower heat gradient,possibly poor sterilization.Freeze drying or lyophilizationThe solution is frozen prior to drying and the solvent is then sublimede gas phase directly from the solid phase), below themelting point of the solvent.Freeze drying is often carriedout under reduced pressure (using avacuum pump) to allow drying toproceed at a reasonable rate.This process avoids collapsestructure, leading to adensity, highly porous productthat can quickly reabsorb the solventwhen needed (lyophile means ‘‘likesThis method was first usedindustrially to produce dehydratedvaccines, and to bring dehydratedssist war casualties. It isregarded as the best method forpreserving the quality and biologicalactivity of proteins, vitamins, and other bioactive compounds.In a typical phase diagram, the boundary between gas and liquid runsthe critical point. Regular drying is shown by the green, by the blue arrow.Air is a bad heat conductor and thus reduces heat transfer, increase heating timeThus lower pressure means lower steam temperature, lower heat gradient,The solution is frozen prior to drying and the solvent is then sublimede gas phase directly from the solid phase), below theIn a typical phase diagram, the boundary between gas and liquid runsthe critical point. Regular drying is shown by the green
28Lyophilization is a process which extracts the water from foods and otherproducts so that the foods or products remain stable and are easier to storeat room temperature (ambiant air temperature).Lyophilization is carried out using a simple principle of physics calledsublimation. Sublimation is the transition of a substance from the solid to thevapour state, without first passing through an intermediate liquid phase. Toextract water from foods, the process of lyophilization consists of:1. Freezing the food so that the water in the food become ice;2. Under a vacuum, sublimating the ice directly into water vapour;3. Drawing off the water vapour;4. Once the ice is sublimated, the foods are freeze-dried and can beremoved from the machine.Lyophilization has many advantages compared to other drying and preservingtechniques.1. Lyophilization maintains food/ biochemical and chemical reagentquality because they remains at a temperature that is belowthe freezing-point during the process of sublimation; The use oflyophilization is particularly important when processing lactic bacteria,because these products are easily affected by heat.2. Food/biochemicals and chemical reagents which are lyophilized canusually be stored without refrigeration, which results in a significantreduction of storage and transportation costs.3. Lyophilization greatly reduces weight, and this makes the productseasier to transport. For example, many foods contain as much as 90%water. These foods are 10 times lighter after lyophilization.4. Because they are porous, most freeze-dried products can be easilyrehydrated. Lyophilization does not significantly reduce volume,therefore water quickly regains its place in the molecular structure ofthe food/ biochemicals and chemical reagents.