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Brief trainning under pharmaceutical technology point of view
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TabletTabletssAssoc. Prof. Dr. Assoc. Prof. Dr.
Jomjai Jomjai PeerapattanaPeerapattana
Faculty of Faculty of Pharmaceutical Pharmaceutical
SciencesSciencesKhon Kaen Khon Kaen UniversityUniversity
ScopeScopeIntroductionIntroductionAdvantages and Advantages and disadvantages of disadvantages of compressed tabletscompressed tabletsTypes of tabletsTypes of tabletsTablet compression Tablet compression machinemachineTableting methodsTableting methods–Direct compressionDirect compression
IntroductionIntroduction18431843 a patent was granted to Thomas a patent was granted to Thomas Brockedon (Englishman) for Brockedon (Englishman) for manufacturing pills and lozengesmanufacturing pills and lozenges
18741874 both rotary and eccentric both rotary and eccentric pressespresses
18851885 glyceryl trinitrate tablets was in glyceryl trinitrate tablets was in the BPthe BP
No other tablet monograph appeared No other tablet monograph appeared until 1945until 1945
19801980 nearly 300 monographs for nearly 300 monographs for tablets tablets
AdvantagesAdvantagesProduction aspectProduction aspect– Large scale production at lowest costLarge scale production at lowest cost– Easiest and cheapest to package and Easiest and cheapest to package and shipship
– High stabilityHigh stabilityUser aspect (doctor, pharmacist, User aspect (doctor, pharmacist, patient)patient)– Easy to handlingEasy to handling– Lightest and most compactLightest and most compact– Greatest dose precision & least Greatest dose precision & least content variabilitycontent variability
– Coating can mark unpleasant tastes & Coating can mark unpleasant tastes & improve pt. acceptabilityimprove pt. acceptability
DisadvantagesDisadvantagesSome drugs resist compression into Some drugs resist compression into dense compactsdense compactsDrugs with Drugs with poor wetting, slow poor wetting, slow dissolution, intermediate to large dissolution, intermediate to large dosages dosages may be difficult or impossible to may be difficult or impossible to formulate and manufacture as a tablet formulate and manufacture as a tablet that provide adequate or full drug that provide adequate or full drug bioavailabilitybioavailabilityBitter taste drugs, drugs with an Bitter taste drugs, drugs with an objectionable odor, or sensitive to objectionable odor, or sensitive to oxygen or moistureoxygen or moisture may require may require encapsulation or entrapment prior to encapsulation or entrapment prior to compression or the tablets may require compression or the tablets may require coating coating
AbsorpAbsorption of tion of drug drug form form
tabletstablets
Ingredients used in Ingredients used in tablet formulationstablet formulationsDrugsDrugs
Fillers, diluent, bulking agentFillers, diluent, bulking agent– To make a reasonably sized tabletTo make a reasonably sized tabletBindersBinders– To bind powders together in the To bind powders together in the wet granulation processwet granulation process
– To bind granule together during To bind granule together during compressioncompression
DisintegrantsDisintegrants– To promote breakup of the tabletsTo promote breakup of the tablets– To promote rapid release of the To promote rapid release of the drugdrug
Lubricants Lubricants – To reduce the friction during tablet To reduce the friction during tablet ejection between the walls of the ejection between the walls of the tablet and the walls of the die cavitytablet and the walls of the die cavity
GlidantsGlidants– Reducing friction between the Reducing friction between the particlesparticles
– To improve the flow properties of To improve the flow properties of the granulations the granulations
AntiadherantsAntiadherants– To prevent adherence of the To prevent adherence of the granules to the punch faces and granules to the punch faces and diesdies
Dissolution (enhancers Dissolution (enhancers and retardants)and retardants)
Wetting agentsWetting agents
Antioxidants Antioxidants
PreservativesPreservatives
Coloring agentsColoring agents
Flavoring agentsFlavoring agents
Essential Essential properties of properties of
tabletstabletsAccurate dosageAccurate dosage of medicament, uniform of medicament, uniform in weight, appearance and diameterin weight, appearance and diameterHave the Have the strengthstrength to withstand the rigors to withstand the rigors of mechanical shocks encountered in its of mechanical shocks encountered in its production, packaging, shipping and production, packaging, shipping and dispensingdispensingReleaseRelease the medicinal agents in the body the medicinal agents in the body in a predictable and reproducible mannerin a predictable and reproducible mannerElegant product, acceptable size and Elegant product, acceptable size and shapeshapeChemical and physical Chemical and physical stabilitiesstabilities
Types of tabletsTypes of tabletsRoute of administrationRoute of administration– Oral tabletsOral tablets– Sublingual or buccal tabletsSublingual or buccal tablets– Vaginal tabletsVaginal tabletsProduction processProduction process– Compressed tabletsCompressed tablets– Multiple compressed tabletsMultiple compressed tablets
Tablet within a tablets: core Tablet within a tablets: core and shelland shell
Multilayer tabletMultilayer tablet
–Sugar coated tabletsSugar coated tabletsProtect tablets from Protect tablets from moisturemoisture
Mask odor and flavorMask odor and flavorEleganceElegance
–Film coated tabletsFilm coated tabletsThin film coatThin film coatSoluble or insoluble Soluble or insoluble polymer filmpolymer film
–Chewable tabletsChewable tabletsRapid disintegrateRapid disintegrateAntacid, flatulance: rapid Antacid, flatulance: rapid actionaction
Children drugChildren drug–Effervescent tabletsEffervescent tablets
Dissolve in the water Dissolve in the water before drinkbefore drink
Tablet Tablet productionproductionPowders intended for compression Powders intended for compression
into tablets must possess two into tablets must possess two essential propertiesessential properties–Powder fluidityPowder fluidity
The material can be transported The material can be transported through the hopper into the diethrough the hopper into the die
To produce tablets of a consistent To produce tablets of a consistent weightweight
Powder flow can be improved Powder flow can be improved mechanically by the use of vibrators, mechanically by the use of vibrators, incorporate the glidantincorporate the glidant
–Powder Powder compressibilitycompressibilityThe property of forming a The property of forming a stable, intact compact stable, intact compact mass when pressure is mass when pressure is appliedapplied
Tableting Tableting procedureprocedure
Filling Filling
Compression Compression
EjectionEjection
Tablet Tablet compression compression
machinesmachinesHopperHopper for holding and feeding for holding and feeding granulation to be compressedgranulation to be compressed
DiesDies that define the size and shape of that define the size and shape of the tabletthe tablet
PunchesPunches for compressing the granulation for compressing the granulation within the dieswithin the dies
Cam tracksCam tracks for guiding the movement of for guiding the movement of the punchesthe punches
Feeding mechanismsFeeding mechanisms for moving for moving granulation from the hopper into the diesgranulation from the hopper into the dies
Single punch Single punch machinemachine
The compression is The compression is applied by the upper applied by the upper punchpunch
Stamping pressStamping press
Upper andLower Collar
Collar locker
Single Punch Machine (Tablets)
Multi-station Multi-station rotary pressesrotary presses
The head of the tablet machine that The head of the tablet machine that holds the upper punches, dies and holds the upper punches, dies and lower punches in place rotateslower punches in place rotatesAs the head rotates, the punches are As the head rotates, the punches are guided up and down by fixed cam guided up and down by fixed cam tracks, which control the sequence tracks, which control the sequence of filling, compression and ejection. of filling, compression and ejection. The portions of the head that hold The portions of the head that hold the upper and lower punches are the upper and lower punches are called the called the upper an lower turretsupper an lower turrets
The portion holding the dies is The portion holding the dies is called the called the die tabledie table
The The pull down cam (C)pull down cam (C) guides guides the lower punches to the the lower punches to the bottom, allowing the dies to bottom, allowing the dies to overfilloverfill
The punches then pass over a The punches then pass over a weight-control cam (E),weight-control cam (E), which which reduces the fill in the dies to reduces the fill in the dies to the desired amountthe desired amount
A A swipe off blade (D)swipe off blade (D) at the end of at the end of the feed frame removes the excess the feed frame removes the excess granulation and directs it around granulation and directs it around the turret and back into the front of the turret and back into the front of the feed framethe feed frame
The lower punches travel over the The lower punches travel over the lower compression roll (F)lower compression roll (F) while while simultaneously the upper punches simultaneously the upper punches ride beneath the ride beneath the upper compression upper compression roll (G)roll (G)
The upper punches enter a fixed The upper punches enter a fixed distance into the dies, while the lower distance into the dies, while the lower punches are raised to squeeze and punches are raised to squeeze and compact the granulation within the diescompact the granulation within the dies
After the moment of compression, the After the moment of compression, the upper punches are withdrawn as they upper punches are withdrawn as they follow the follow the upper punch raising cam (H)upper punch raising cam (H)
The lower punches ride up the The lower punches ride up the cam (I)cam (I) which brings the tablets flush with or which brings the tablets flush with or slightly above the surface of the diesslightly above the surface of the dies
The tablets strike a sweep off The tablets strike a sweep off blade affixed to the front of blade affixed to the front of the the feed frame (A)feed frame (A) and slide and slide down a chute into a receptacledown a chute into a receptacle
At the same time, the lower At the same time, the lower punches re-enter the punches re-enter the pull pull down cam (C)down cam (C) and the cycle is and the cycle is repeatedrepeated
Although tablet compressing Although tablet compressing machinery has undergone numerous machinery has undergone numerous mechanical modifications over the mechanical modifications over the years, the compaction of materials years, the compaction of materials between a pair of moving punches between a pair of moving punches within a stationary die has within a stationary die has remained remained unchangedunchangedThe principle modification from The principle modification from earlier equipment has been an earlier equipment has been an increase in production rate which is increase in production rate which is regulated by regulated by – Number of tooling setsNumber of tooling sets– Number of compression stationsNumber of compression stations– Rotational speed of the press Rotational speed of the press
Special adaptations of tablet Special adaptations of tablet machines allow for the machines allow for the compression of layered tablets compression of layered tablets and coated tabletsand coated tablets
A device that chills the A device that chills the compression components to allow compression components to allow for the compression of low-for the compression of low-melting point substances such as melting point substances such as waxes i.e. suppositorieswaxes i.e. suppositories
Tableting Tableting methodsmethods
Dry methodsDry methods–Direct compressionDirect compression–Dry granulationDry granulation
Wet methodsWet methods–Wet granulationWet granulation
Direct Direct compressioncompression
Tablets are compressed Tablets are compressed directly from powder blends directly from powder blends of the active ingredient and of the active ingredient and suitable excipientssuitable excipients
No pretreatment of the No pretreatment of the powder blends by wet or dry powder blends by wet or dry granulation procedures is granulation procedures is necessarynecessary
AdvantagesAdvantages–EconomyEconomy
Machine: fewer Machine: fewer manufacturing steps and manufacturing steps and pieces of equipmentpieces of equipment
Labor: reduce labor costsLabor: reduce labor costsLess process vallidationLess process vallidationLower consumption of Lower consumption of powerpower
–Elimination of granulation Elimination of granulation processprocessHeat (wet granulation)Heat (wet granulation)Moisture (wet granulation)Moisture (wet granulation)High pressure (dry High pressure (dry granulation) granulation)
Processing without the need Processing without the need for moisture and heat which for moisture and heat which is inherent in most wet is inherent in most wet granulation proceduresgranulation procedures
Avoidance of high compaction Avoidance of high compaction pressures involves in pressures involves in producing tablets by slugging producing tablets by slugging or roll compactionor roll compaction
–Elimination of variabilities in Elimination of variabilities in wet granulation processingwet granulation processingBinders (temp, viscous, age)Binders (temp, viscous, age)
Viscosity of the granulating Viscosity of the granulating solution (depend on its temp), solution (depend on its temp),
How long it has been prepared,How long it has been prepared,
Rate of binder addition and Rate of binder addition and kneading can affect the kneading can affect the properties of the granules properties of the granules formedformed
The granulating solution, the The granulating solution, the type and length of mixing and type and length of mixing and the method and rate of wet the method and rate of wet and dry screening can change and dry screening can change the density and particle size of the density and particle size of the granules, which can have a the granules, which can have a major effect on fill weight and major effect on fill weight and compaction qualitiescompaction qualities
Type and rate of drying Type and rate of drying can lead not only to critical can lead not only to critical changes in equilibrium MC but changes in equilibrium MC but also to unblending as soluble also to unblending as soluble active ingredients migrate to active ingredients migrate to the surfaces of the drying the surfaces of the drying granulesgranules
More unit processes are More unit processes are incorporated in production, incorporated in production, the chances of batch-to-batch the chances of batch-to-batch variation are compounded variation are compounded
–Prime particle Prime particle dissociationdissociation Each primary drug Each primary drug particle is liberated from particle is liberated from the tablet mass and is the tablet mass and is available for dissolutionavailable for dissolution
Disintegrate rapidly to the Disintegrate rapidly to the primary particle stateprimary particle state
–Uniformity of particle sizeUniformity of particle size–Greater stability of tablet Greater stability of tablet on agingon agingColorColorDissolution rateDissolution rateFewer chemical stability Fewer chemical stability problems would be problems would be encountered as compared to encountered as compared to those made by the wet those made by the wet granulation processgranulation process
ConcernsConcerns–Excipient available from Excipient available from only one supplier and only one supplier and often cost more than filler often cost more than filler used in granulationused in granulation
–Procedure conservationProcedure conservation–Machine investmentsMachine investments–Lack of material Lack of material knowledgeknowledge
–Physical limitation of Physical limitation of drugdrugNo compressibilityNo compressibilityNo flowabilityNo flowability
–Physical characteristics Physical characteristics of materials (both drug of materials (both drug and excipient)and excipient)Size and size distributionSize and size distributionMoistureMoistureShape and surfaceShape and surface
FlowabilityFlowabilityDensityDensity
–Lot to lot variabilityLot to lot variability–Dusting problemDusting problem–ColoringColoring
Direct Direct compression fillerscompression fillers
Common materials that Common materials that have been modified in have been modified in the chemical the chemical manufacturing process manufacturing process to improve fluidity and to improve fluidity and compressibilitycompressibility
Soluble fillersSoluble fillersLactoseLactose–Spray dried lactoseSpray dried lactose
Lactose is placed in aqueous Lactose is placed in aqueous solution, removed impurities and solution, removed impurities and spray driedspray dried
Mixture of large alpha Mixture of large alpha monohydrate crystals and monohydrate crystals and spherical aggregates of smaller spherical aggregates of smaller crystalscrystals
Good flowability but less Good flowability but less compressibilitycompressibility
Poor dilution potential Poor dilution potential
Loss compressibility upon Loss compressibility upon initial compactioninitial compaction
Problem of browning due to Problem of browning due to contamination of 5-contamination of 5-hydroxyfurfural which was hydroxyfurfural which was accelerated in the presence accelerated in the presence of basic amine drugs and of basic amine drugs and catalyzed by tartrate, catalyzed by tartrate, citrate and acetate ionscitrate and acetate ions
–Fast-Flo lactose (early 1970s)Fast-Flo lactose (early 1970s)Spherical aggregates of Spherical aggregates of microcrystals lactose microcrystals lactose monohydratemonohydrate
Held together by a higher Held together by a higher concentration of glass concentration of glass (amorphous lactose)(amorphous lactose)
Much more compressibleMuch more compressibleHighly fluidHighly fluidNon hygroscopicNon hygroscopic
Tablets are three to four times Tablets are three to four times harder than regular spray harder than regular spray drieddried
–Tabletose: aggromerate form of Tabletose: aggromerate form of lactoselactoseMore compressible than spray More compressible than spray dried but less compressible dried but less compressible than Fast Flo lactosethan Fast Flo lactose
–Anhydrous lactose: free flowing Anhydrous lactose: free flowing crystalline lactosecrystalline lactoseProduced by crystallization Produced by crystallization above 93C which produces the above 93C which produces the beta formbeta form
Pass through steam heated Pass through steam heated rollersrollers
Good flow property, contained Good flow property, contained high amount of fines, its high amount of fines, its fluidity is less than optimalfluidity is less than optimal
Can be reworkedCan be reworked
At high RH anhydrous lactose At high RH anhydrous lactose will pick up moisture forming will pick up moisture forming the hydrated compound the hydrated compound increase in the size of tablets increase in the size of tablets if the excipient makes up a if the excipient makes up a large portion of the total large portion of the total tablet weighttablet weight
Excellent dissolution propertyExcellent dissolution property
SucroseSucrose–Di-Pac: cocrystallization of 97% Di-Pac: cocrystallization of 97% sucrose and 3% modified dextrinsucrose and 3% modified dextrinSmall sucrose crystals glued Small sucrose crystals glued together by dextrintogether by dextrin
Good flow properties and needs Good flow properties and needs a glidant only when a glidant only when atmospheric moisture levels are atmospheric moisture levels are high (>50%RH)high (>50%RH)
Excellent color stability on Excellent color stability on agingaging
Concentration of moisture is Concentration of moisture is extremely critical in terms of extremely critical in terms of product compressibilityproduct compressibility
compressibility increases compressibility increases rapidly in a moisture range rapidly in a moisture range of 0.3-0.4%, plateaus at a of 0.3-0.4%, plateaus at a level of 0.4-0.5% and rises level of 0.4-0.5% and rises again rapidly up to 0.8% again rapidly up to 0.8% when the product begins to when the product begins to cake and lose fluiditycake and lose fluidity
Dilution potential 20-35%Dilution potential 20-35%Tablets tend to harden Tablets tend to harden slightly during the first slightly during the first hours after compression or hours after compression or when aged at high when aged at high humidities and then dried humidities and then dried (this is typical of most (this is typical of most direct compression direct compression sucroses or dextroses)sucroses or dextroses)
–Nutab: 95.8% sucrose, 4% Nutab: 95.8% sucrose, 4% convert sugar (equimolecular convert sugar (equimolecular mixture of levulose and mixture of levulose and dextrose) and 0.1 to 0.2% dextrose) and 0.1 to 0.2% each of cornstarch and each of cornstarch and magnesium strarate magnesium strarate Large particle size Large particle size distribution and good distribution and good fluidityfluidity
Poor color stabilityPoor color stability
DextroseDextrose–Emdex: spray crystallizedEmdex: spray crystallized
90-92% dextrose, 3-5% 90-92% dextrose, 3-5% maltose and the remainder maltose and the remainder higher glucose higher glucose polysaccharidespolysaccharides
Available both anhydrous Available both anhydrous and a hydrate productand a hydrate product
Excellent compressibilityExcellent compressibilityLargest particle size, Largest particle size, blending problem may occurblending problem may occur
SorbitolSorbitol–Exists in a number of Exists in a number of polymorphic crystalline polymorphic crystalline forms and amorphous formforms and amorphous form
–Widely used in sugar-free Widely used in sugar-free mints and as a vehicle in mints and as a vehicle in chewable tabletschewable tablets
–Cool taste and good mouth Cool taste and good mouth feelfeel
–Forms a hard compactForms a hard compact
–Hygroscopic and will Hygroscopic and will clump in the feed frame clump in the feed frame and stick to the surfaces and stick to the surfaces of the die table when of the die table when tableted at humidities > tableted at humidities > 50% 50%
–Lubricant requirements Lubricant requirements increase when the MC of increase when the MC of the sorbitol drops below the sorbitol drops below 0.5% or exceeds 2%0.5% or exceeds 2%
MannitolMannitol–Exists in a number of Exists in a number of polymorphic formspolymorphic forms
–Not make as hard a tablet as Not make as hard a tablet as sorbitolsorbitol
–Less sensitive to humidityLess sensitive to humidity–Widely used where rapid and Widely used where rapid and complete solubility is requiredcomplete solubility is required
–Use as a filler in chewable tabletsUse as a filler in chewable tablets–Cool mouth feel but expensiveCool mouth feel but expensive
MaltodextrinMaltodextrin–Maltrin Maltrin
Highly compressibleHighly compressibleCompletely soluble Completely soluble Very low hygroscopicVery low hygroscopic
Insoluble fillersInsoluble fillersStarchStarch–Starch 1500: intact starch Starch 1500: intact starch grains and ruptured starch grains and ruptured starch grains that have been grains that have been partially hydrolyzed and partially hydrolyzed and subsequently aggromeratedsubsequently aggromeratedExtremely high MC (12-13%)Extremely high MC (12-13%)Does not form hard Does not form hard compacts compacts
Dilution potential is minimalDilution potential is minimal
Not generally used as filler-binder Not generally used as filler-binder but as filler disintegrantbut as filler disintegrant
–Retains the disintegrant properties Retains the disintegrant properties of starch without increasing the of starch without increasing the fluidity and compressibility of the fluidity and compressibility of the total formulationtotal formulation
–Deforms elastically when a Deforms elastically when a compression force is applied, it compression force is applied, it imparts little strength to compactsimparts little strength to compacts
–Lubricants tend to dramatically Lubricants tend to dramatically soften tablets containing high soften tablets containing high concentrations of Starch 1500concentrations of Starch 1500
–Spray dried starchSpray dried starchEra-Tab: spray-dried rice Era-Tab: spray-dried rice starchstarch
Good fluidity Good fluidity MC 10-13%MC 10-13%Compressibility depend Compressibility depend on moistureon moisture
ReworkabilityReworkabilityLow bulk densityLow bulk density
CeluloseCelulose–Microcrystalline cellulose Microcrystalline cellulose (Avicel)(Avicel)The most important tablet The most important tablet excipient developed in modern excipient developed in modern timestimes
Derived from a special grade of Derived from a special grade of purified alpha wood cellulose purified alpha wood cellulose by severe acid hydrolysis to by severe acid hydrolysis to remove the amorphous remove the amorphous cellulose portions, yielding cellulose portions, yielding particles consisting of bundles particles consisting of bundles of needlelike microcrystalsof needlelike microcrystals
PH101 powderPH101 powderPH102 more PH102 more agglomerated, larger agglomerated, larger particle size, slightly particle size, slightly better fluidity but not better fluidity but not significant decrease in significant decrease in compressibilitycompressibility
Most compressibleMost compressibleHighest dilution potentialHighest dilution potential
A strong compact is formed A strong compact is formed due to the extremely large due to the extremely large number of clean surfaces number of clean surfaces brought in contact during the brought in contact during the plastic deformation and the plastic deformation and the strength of the hydrogen strength of the hydrogen bonds formedbonds formed
Extremely low coefficient of Extremely low coefficient of friction, no lubricant friction, no lubricant requirement requirement
When >20% of drugs or other When >20% of drugs or other excipients are added, excipients are added, lubrication is necessarylubrication is necessary
Not used as the only filler Not used as the only filler because of its cost and because of its cost and densitydensity
Usually used in the conc Usually used in the conc of 10-25% as a filler-of 10-25% as a filler-binder-disintegrant, rapid binder-disintegrant, rapid passage of water into the passage of water into the compact and the compact and the instantaneous rupture of instantaneous rupture of hydrogen bondshydrogen bonds
Fluidity is poor because of its Fluidity is poor because of its relatively small particle size, relatively small particle size, small amount of glidant are small amount of glidant are recommended in the recommended in the formulations containing high formulations containing high conc of MCC conc of MCC
Tablets are soften on exposure Tablets are soften on exposure to high humiditiesto high humidities
This softening is reversible This softening is reversible when tablets are removed when tablets are removed from the humid environmentfrom the humid environment
>80% MCC may slow the >80% MCC may slow the dissolution rates of AI having dissolution rates of AI having low water solubilitylow water solubility
Small particles get Small particles get physically trapped between physically trapped between the deformed MCC particles, the deformed MCC particles, which delays wetting and which delays wetting and dissolutiondissolution
This phenomenon can be This phenomenon can be overcome by adding portions overcome by adding portions of water soluble excipientof water soluble excipient
Inorganic calcium saltsInorganic calcium salts–Dicalcium phosphate (Emcompress or Dicalcium phosphate (Emcompress or DiTab)DiTab)Free flowing aggregates of small Free flowing aggregates of small microcrystals that shatter upon microcrystals that shatter upon compactioncompaction
Inexpensive and possesses a high Inexpensive and possesses a high degree of physical and chemical degree of physical and chemical stabilitystability
Nonhygroscopic at a RH of up to Nonhygroscopic at a RH of up to 80%80%
Good fluidityGood fluidity
Slightly alkaline with a pH of Slightly alkaline with a pH of 7.0 to 7.37.0 to 7.3
Precludes its use with AI that Precludes its use with AI that are sensitive to even minimal are sensitive to even minimal amounts of alkalinityamounts of alkalinity
–Tricalcium phosphate (TriTab) is Tricalcium phosphate (TriTab) is less compressible and less less compressible and less soluble, higher ratio of calcium soluble, higher ratio of calcium ionsions
ReferencesReferences ยาเม็�ด ยาเม็�ด ((ม็ม็..ม็หิ�ดลม็หิ�ดล))
Pharmaceutics. The science of Pharmaceutics. The science of dosage forms design. (M.E. dosage forms design. (M.E. Aulton)Aulton)
The theory and practice of The theory and practice of industrial pharmacy.industrial pharmacy.
Pharmaceutical dosage forms : Pharmaceutical dosage forms : Tablets. Volume 2.Tablets. Volume 2.
Pharmaceutical dosage forms and Pharmaceutical dosage forms and drug delivery systems.drug delivery systems.
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