TEKNOLOGI SEDIAAN PADAT

PMSF 602445

SUTRIYO
 REFERENCE

Lieberman, Pharmaceutical Dosage Forms : Tablet Vol. 1

Lachman, L., Theory and Practice of Industrial Pharmacy.
Rowe, Handbook of Pharmaceutical Excipients
Pharmaceutical Granulation technology
Gibson, M, Pharmaceutical Preformulation.
Drug Formulation
 Ansel,H.C., Intoduction to Pharmaceutical Dosage Form
 KOMPETENSI MATA AJAR

1. Kompetensi (Sasaran Pemelajaran)

• Sasaran pemelajaran terminal
• Setelah selesai mengikuti perkuliahan mata ajar ini, mahasiswa
diharapkan mampu:
– Menjelaskan teori dasar bentuk-bentuk sediaan padat ( granul, tablet, kapsul
dan supositoria) serta prinsip-prinsip cara pembuatan obat yang baik. (C2
Komprehensif)
– Memilih dan menentukan metoda pembuatan sediaan padat yang paling
sesuai. (C4 Analisa)
– Mengidentifikasi dan menganalisa permasalahan-permasalahan yang timbul
pada proses pembuatan (C4 Analisa)
– Mendisain formula sediaan padat yang baik. (C5 Sintesis)
– Menyusun (menulis) prosedur pembuatan sediaan padat yang baik. (C5
Sintesis)
– Mendisain formula larutan penyalut lapis tipis dan penyalut gula. (C5 Sintesis)
– Menginterpretasi data evaluasi sediaan padat. (C6 Evaluasi)
– Menjelaskan dan menilai formula sediaan padat yang baik. (C6 Evaluasi)
– Menjelaskan jenis dan mekanisme pelepasan obat dari sediaan padat
– Menganalisa sistem pelepasan dan penghantaran obat dari sediaan padat
• Subkompetensi (Sasaran Pemelajaran Penunjang)
– Mahasiswa mampu menjelaskan karakteristik sediaan padat yang baik.
– Mahasiswa mampu menjelaskan sifat-sifat fisikokimia obat.
– Mahasiswa mampu menjelaskan komponen formulasi sediaan padat
– Mahasiswa mampu menjelaskan karakteristik bahan eksipien dalam sediaan
padat.
– Mahasiswa mampu menjelaskan metoda-metoda pembuatan tablet
– Mahasiswa mampu menganalisis permasalahan yang terjadi dalam
pencetakan
– Mahasiswa mampu menjelaskan jenis, prosedur, alat dan persyaratan evaluasi
sediaan padat
– Mahasiswa mampu menganalisis hasil evaluasi sediaan padat.
– Mahasiswa mampu menjelaskan pengaruh faktor fisikokimia obat, formulasi
dan metoda pembuatan terhadap mutu sediaan tablet yang baik.
– Mahasiswa mampu menjelaskan formula larutan penyalut, proses dan
permasalahan yang timbul dalam proses penyalutan tablet dengan salut gula,
– Mahasiswa mampu menjelaskan formula larutan penyalut, proses dan
permasalahan yang timbul dalam proses penyalutan tablet dengan salut lapis
tipis
– Mahasiswa mampu menganalisis permasalahan yang terjadi dalam
penyalutan tablet
– Mahasiswa mampu menjelaskan formulasi sediaan granul effervescent.
– Mahasiswa mampu menjelaskan formulasi sediaan kapsul keras dan kapsul
lunak
– Mahasiswa mampu menjelaskan, formulasi dan evaluasi sediaan supositoria
– Mahasiswa mampu menjelaskan jenis pelepasan obat berdasarkan bentuk
fisik, rute pemberian dan mekanisme pelapasan dari sediaan padat.
– Mahasiswa mampu menjelaskan mekanisme pelepasan obat dari tablet
konvensional dan tablet lepas cepat
– Mahasiswa mampu menjelaskan mekanisme pelepasan obat dari tablet lepas
lambat
– Mahasiswa mampu menjelaskan mekanisme pelepasan obat dari tablet dan
transdermal lepas terkendali
– Mahasiswa mampu menjelaskan mekanisme pelepasan obat dari tablet lepas
tunda
– Mahasiswa mampu menjelaskan konsep penghantaran targeting
 DESKRIPSI
Mata ajaran ini bertujuan agar mahasiswa :
a. mengetahui, memahami dan mampu menjelaskan teori
dasar sediaan solid (padat) meliputi sediaan granul,
kapsul dan supositoria,
b. memahami karakteristik sediaan padat yang baik,
c. mampu merancang formula,
d. mengidentifikasi permasalahan-permasalahan yang
timbul dalam proses pembuatan,
e. menganalisis faktor-faktor penyebabnya, (baik faktor
formulasi, fisikokimia maupun proses pembuatannya).
f. dapat melakukan proses pembuatan dan evaluasi
terhadap berbagai bentuk sediaan padat.
POKOK BAHASAN
DEFINISI DAN JENIS SEDIAAN TABLET

STUDI PRA FORMULASI

FORMULASI SEDIAAN TABLET
METODE PEMBUATAN SEDIAAN TABLET

PERMASALAHAN SEDIAAN TABLET

EVALUASI SEDIAAN TABLET

PHARMACEUTICAL DOSAGE FORM

is a drug delivery system which is formed

by technological processing (drug
formulation)

WHY ???
Why
????
SEDIAAN PADAT
 DEFINITION

• Various shapes: round, triangular, square, rectangular, etc...

• Thick or thin, flat or convex,
• Carry a symbol used for indentification, may be colored
 DEFINISI
• Farmakope Indonesia III : sediaan padat kompak,
dibuat secara kempa/cetak, dalam
bentuk tabung pipih atau sirkuler, kedua
permukaannya rata atau cembung, mengandung
satu jenis obat atau lebih dengan atau tanpa zat
tambahan.
• Tablet (Menurut FI IV) adalah sediaan padat
mengandung bahan obat dengan atau tanpa
bahan pengisi, dibuat terutama dengan cara
kompresi. Sejumlah tertentu dari tablet dibuat
dengan mencetak
 TYPES OF TABLETS

COMPRESSED TABLET MOLDED TABLET

Conventional tablets
• Multiple compressed tablets
• Sugar-coated tablets
• Film-coated tablets • Triturates Tablets
• Enteric coated tablets • Hypodermic tablets
• Buccal & Sublingual tablets
• Chewable tablets
• Effervescent tablets
 Advantages and Disadvantages of
tablets
Most stable of all oral preparations
Unit dose
Simple to identify

•Problems with bioavailability

•Some drugs resist compression into tablet.
•Difficulty in swallowing in some patients; pediatrics
and geriatrics.
 Properties of Tablet
must be sufficiently Strong and resistant to abrasion
(Hardness and Friability Test)

must be Uniform in weight and drug content (uniformity test)

the drug content of the tablet must be bioavailable (disintegration,

Dissolution, BA-BE Test)

must be elegant in appearance (Organoleptik)

Must be retain stability and efficacy (stability)

 GRANULES OR FINES
AGGREGATES PARTICLE

DRUG IN
SOLUTION

DRUG IN BLOOD AND OTHER

BIOLOGICAL FLUIDS AND
TISSUES
DRUG PROFILE
 Multiple compressed tablets
– more than one compression step is involved.
– results in a multiple-layered tablet within a tablet (shell and core).
– each layer is usually colored with a different color.
Advantage:
medicinal agents are separated to prevent incompatibility, or
each layer provides drug release at a different stage or for
coating purposes.

Disadvantage:
expensive process requires
accurate and precise machinery
 Sugar-coated tablets
coating is sugar-based, water soluble
and quickly dissolves after
swallowing.
coating may be colorless or colored.
Advantages:
1. protects drugs from the effects of
air and humidity.
2. masks unpleasant odor and taste.
3. enhances the appearance of
compressed tablets.
Disadvantage:
1. time and expertise required for
the process.
2. increase in the size and weight of
the tablet (50% increase).
 FILM AND ENTERIC COATED TABLETS
Film-coated tablets:
covered by a film of water-insoluble polymer that
ruptures in the GI tract.
Enteric coated tablets:
1. coating resist dissolution or disruption in the
stomach but not the intestines
2. protects drugs that are destroyed in acid
medium
3. protects the stomach from drugs that cause
irritation to the gastric mucosa.
4. used when by-pass of the stomach greatly
enhances drug absorption
FILM & ENTERIC
COATED TABLET
 Buccal or sublingual tablets
a. sublingual tablets are the one that dissolves when held
beneath the tongue, permitting direct absorption of the
active ingredient by the oral mucosa
b. Generally flat, oval tablets intended to disslove in the
buccal pouch or beneath the tongue for absorption
through the oral mucosa.
c. Tablets intended for buccal administration are formulated
to dissolve slowly (progesterone tablets) whereas those
for sublingual adminstration dissolve to give rapid drug
effects.
d. used for drugs that are destroyed by gastric juice and/or
are poorly absorbed from the GI tract
Sub Lingual & Buccal
Tablet
 Advantages
• Rapid absorption
• Rapid onset of action
• Increased bioavailability
• Effective dose is less
• No first pass metabolism
 Disadvantages :
• High dose can not be administered
• Surface area for absorption is limited
• Highly ionic drugs can not be formulated
• Drugs which are irritating and undesirable taste
cannot be used
• Noncompliance to patient
• Patient should avoid eating, drinking, chewing,
smoking and possible talking in order to keep the
tablet in place
 Choice Of Drug
• The drug should have following characteristics:
• Undergo passive diffusion
• Optimum partition coefficient
• Aqueous solubility
• Optimum pKa value
• Dose of the drug should be low (10mg – 15mg)
• The drug should not be highly ionic or at least
capable of being buffered in tablet form
Structure of Oral mucosa
Sublingual tablets
 Chewable tablets
• Have a smooth rapid disintegration when
chewed to dissolve in the mouth.
• Formulated in mannitol.
• Used mainly for children’s multivitamin
tablets and for the administration of antacids
and anti-flatulents.
 Effervescent tablets
• Prepared by compression
of granular effervescent
salts that release gas
when in contact with
water.
• Fast disintegration and
dissolution of drug for
rapid action
 Reaction
Citric Acid
3 NaHCO3 + C6H8O7H2O ---> 4H2O + 3CO2 + Na3 C6H5O7
3 mol  1 mol
1 gram of citric acid reacts with 1.2 g sodium bicarbonate.

Tartaric Acid
2 NaHCO3 + C4H6O6 ---> 2 H2O + 2 CO2 + Na2 C4H4O6
2 mol  1 mol : (2 x 84  1 mol

1 grams of tartaric acid reacts with 1.12 g of sodium bicarbonate

 EFFERVESCENT MIX
Acid Sources
1. Food Acids 3. Acid Salts
» Citric Acid • Sodium Dihydrogen
» Tartaric Acid Phospate (Monosodium
» Ascorbic Acid Phospate)
» Fumaric Acid • Disodium Dihydrogen
» Malic Acid Pyrophospate (Sodium Acid
» Adipic And Succinic Acids Pyrophospate)
» Acetyl SalicYLIC ACID
• Acid Citrate Salts
2. Acid Anhydrides
• Amino Acid Hydrochlorides
• Citric anhydride
• Sodium Acid Sulphite
• succinic anhydride
 Carbonate Sources
• Sodium Bicarbonate
• Sodium Carbonate
• Potassium Bicarbonate And Potassium Carbonate
• Sodium Sesquicarbonate
• Sodium Glycine Carbonate
• L-lysine Carbonate
• Arginine Carbonate
• Amorphous Calcium Carbonate
• Calcium Carbonate
 Hypodermic tablets
• Tablet triturates originally intended to be
dissolved by a physician
• in a suitable vehicle and parenteral
administration
 Tablet triturates
• Small, usually cylindrical molded or compressed
tablets containing small amounts of usually potent
drugs.
• Diluent is usually sucrose and lactose, water-insoluble
materials are avoided in the formulation
• tablet triturates must be readily soluble in water.
Uses:
• oral or sublingual adminstration of drugs (e,g
Nitroglycerin).
• insert directly one or more of these in a capsule for
accurate dosing.
• to fortify liquid preparations.
STUDI PRA FORMULASI

Definition

Goal

Physicochemical characteristics
 Preformulation
• Development stage where physical and
chemical properties of a drug material are
characterized for the purpose of making a
stable, effective and safe dosage form.
• focuses mainly on investigation to obtain basic
and general information on how to make an
effective and stable preparation
 Goals of Preformulation
(1). To establish necessary physicochemical
parameters of drug substance;
(2). To determine its kinetic rate profiles;
(3). To establish its physicochemcal characteristics;
(4). To establish its mechanical characteristics
(4). To establish its compatibility with common
excipients.
PHYSICOCHEMICAL PROPERTIES
Ionization
constant

compatibility Partition coefficient

PHYSICOCHEMICAL solubility
hygroscopicity PROPERTIES

polymorphism
stability
 pKa Determinations
• Many potential candidate drugs are weak
acids or bases.
• the ionization of weak acids or bases is
dependent on pH
pH-pKa Relationship with proportion
unionized.
For weak acidic drugs:

pH  pK a  log
I
 log
 A
U  HA
For weak basic drugs:

pH  pK a  log
U
 log
B
I  HB 

Gastrointestinal (GI) Physiology
 Organs pH Fluid pH
Buccal approx 6 Aqueous humour 7.2
Oesophagus 5-6 Blood 7.4
Stomach 1.7-3.5
Colon 5-8
Duodenum 5-7 Duodenum (fasting) 4.4-6.6
6 – 7.5 Duodenum (fed) 5.2-6.2
Small Intestine
Saliva 6.4
Large intestine 6.8 - 7
Small intestine 6.5
Stomach (fasting) 1.4-2.1
Stomach (fed) 3-7
Sweat 5.4
Urine 5.5-7.0
PARTITION COEFFICIENT
• The lipophilicity of an organic
compound is usually
described in terms of a
partition coefficient, log P,
• The partition coefficient can
be defined as the ratio of the
concentration of the
unionized compound, at
equilibrium, between organic
and aqueous phases
• log P = 0 means that the compound is equally
soluble in water and in the partitioning
solvent.
• log P = 5, then the compound is 100,000 times
more soluble in the partitioning solvent.
• log P = –2 means that the compound is 100
times more soluble in water, it is quite
hydrophilic.
 SOLUBILITY
• The solubility of a candidate drug may be the critical
factor determining its usefulness, since aqueous
solubility dictates the amount of compound that will
dissolve and, therefore, the amount available for
absorption.
 Particle size
(milling)

Cristallinity
Solvate/
hydrate (solid
dispersion)
solubility

Polymorphism Prodrugs
(stable, meta (salt,complex,
stable, unstable
form) ester, etc)
 TERM OF SOLUBILITY

Parts of solvent required

Description
for one part of solute
Very soluble <1
Freely soluble 1 - 10
Soluble 10 - 30
Sparingly soluble 30 - 100
Slightly soluble 100 - 1000
Very slightly soluble 1000 - 10,000
Insoluble > 10,000
 Noyes-Whitney equation

• where dC/dt is the rate of

dissolution
• D is the diffusion coefficient of
the drug in solution in g.i. fluid
dC DS
  C s  Ct  • S is the effective surface area
of drug particle in contact with
dt h the g.i. fluid,
• Cs is the saturation solubility
of the drug in the diffusion
layer and
• Ct is the concentration of drug
in solution in the bulk medium
(g.i. fluid).
STABILITY
hydrolysis

stability

Epimerization
racemerization
 Hydrolysis
• Degradation by hydrolysis is affected by a
number of factors, of which
– solution pH,
– Buffer salts and
– ionic strength
 Hydrolysis
CLASS EXAMPLE
ESTER ASPIRIN
THIOL ESTER SPIROLACTONE
AMIDE CHLORAMPHENICOL
SULPHONAMIDE SULPHAPYRAZINE
IMIDE PHENOBARBITONE
LACTAM METHICILLIN
LACTONE SPIRONOLACTONE
HALOGENATED ALIPHATIC CHLORAMBUCIL
Hydrolysis of cefotaxime sodium
Oxidation of Vitamine C
Isomerization (racemization) of
epinephrine
Epimerization of tetracycline
 Polymorphism
• Capacity of a compound existing in more than one
crystalline form.
• Different packing of molecules in crystal
• Polymorphism occurs only to drug materials with crystalline
properties.
• Polymorphism is just a physical phenomenon, the
chemistry remains identical
• May have different melting points, IR, Xray density,
solubility
• Enantiotropic : forms can change reversibly from one form
to another with the change in temperatures or pressure
• Monotropic : the change between the two forms is
irreversible
 Effect of Crystalline/polymorphic form on
dissolution rate of Chloramphenicol palmitate
 PARTICLE SIZE
• The particle size of pharmaceuticals is important since it can
affect the formulation characteristics and bioavailability of a
compound (Chaumeil 1998).
• Size also plays a role in the homogeneity of the final tablet
• When large differences in size exist between the active
components and excipients,mutual sieving (demixing) effects
can occur making thorough mixing difficult
• Size can also be a factor in stability; fine materials are
relatively more open to attack from atmospheric oxygen,
heat, light, humidity, and interacting exipients than coar-se
materials
PARTICLE SIZE
 CRYSTALLINITY
• Habit : The external shape of a crystal
• Crystal morphology or habit is important, since it can
influence many properties of the compound.
– powder flow properties,
– compaction and
– stability
• Ex. tolbutamide B (plate like) caused powder bridging in the
hopper and a capping problem when tableted.
 Crystal Habits
Habit Description Habit Description
Acicular Elongated prism, Irregular Lacking any symmetry
needlelike
Angular Sharp edged, roughly Nodular Rounded irregular shape
polyhedral
Bladed Flattened acicular Flaky/Platy Plate or saltlike
Crystalline Geometric shape fully Prismatic Columnar prism
developed in fluid
Dendritic Branched crystalline Spherical Global shape
Fibrous Regular or irregular Tabular Rectangular with a pair of
threadlike parallel faces
Granular Equidimensional irregular
shape
CRYSTALLINITY
 Hygroscopicity
• Hygroscopicity is the rate and extent of
moisture adsorbed/absorbed by a solid
substance
• important to study the moisture absorption
behavior of drugs to choose the processing
and storage conditions for the drug
HYGROSCOPICITY
 Degree Of Hygroscopicity
No Class
1 Non-hygroscopic
2 Slightly hygroscopic
3 Moderately hygroscopic
4 Very hygroscopic
Increase in mass
Essentially no moisture increases occur at
relative humidities below 90%.
Essentially no moisture increases occur at
relative humidities below 80%.
Moisture content does not increase more
than 5% after storage for 1 week at relative
humidities below 60%.
Moisture content increase may occur at
relative humidities as low as 40 to 50%.

*) Callaghan et al. (1982) Equilibrium moisture content of pharmaceutical

excipients., in Drug Dev. Ind. Pharm., Vol. 8, pp. 355–369. Marcel Dekker,
Inc.
DRUG-EXCIPIENT COMPATIBILITY STUDY

DRUG No Interaction

50 % Mixture DSC Recomended

Excipient
EXCIPIENT
Interaction

Alternative Significant
Excipient Breakdown
Difractogram DSC
Particle, Powder, and Compact
Characterization

• Particle size and distributions

• Crystalinity
• shape

• Density (true, bulk, tapped)

• Flowability

• Deformation (elastic, plastic , brittle fracture/ductile)

• Compressibility
• Compactibility
 DENSITY
• The true density of a substance is the average mass of the particles
divided by the solid volume, exclusive of all the voids
• Bulk density is the mass per unit volume of a loose powder bed.
Bulk Density (g/mL) = (M/Vo)
where M mass in grams and Vo untapped apparent volume in
milliliters.
• Tapped density of a powder is the ratio of the mass of the powder
to the volume occupied by the powder after it has been tapped for
a defined period of time
Tapped Density(g/mL) = (M/Vf)
where M mass in grams, and Vf the tapped volume in milliliters.
• Tapped density values are generally higher for more regularly
shaped particles (i.e., spheres), as compared to irregularly shaped
particles such as needles
• The formulation should have sufficient
flowability to ensure that the appropriate
quantity of powder flows into the dies of the
tablet machine on a consistent basis
 ANGEL OF REPOSE
−𝟏
𝒉
𝜶 = 𝐭𝐚𝐧
𝒓

h

r
Fixed Funnel Method

Angle of Repose () is the maximum angle between the

surface of a pile of powder and horizontal plane
 BULK-TAPPED DENSITY

𝒎 𝒎
𝑻𝒂𝒑𝒑𝒆𝒅 𝑫𝒆𝒏𝒔𝒊𝒕𝒚 𝝆𝒕 = 𝑩𝒖𝒍𝒌 𝑫𝒆𝒏𝒔𝒊𝒕𝒚 𝝆𝒐 =
𝑽𝒇 𝑽𝟎
 Carr’s Index dan Hausner Ratio
𝝆𝒕𝒂𝒑𝒑𝒆𝒅 −𝝆𝒃𝒖𝒍𝒌
𝑪𝒐𝒎𝒑𝒓𝒆𝒔𝒔𝒊𝒃𝒊𝒍𝒊𝒕𝒚 𝑪𝒂𝒓𝒓′ 𝒔 𝑰𝒏𝒅𝒆𝒙 % = x 100
𝝆𝒕𝒂𝒑𝒑𝒆𝒅

𝑻𝒂𝒑𝒑𝒆𝒅 𝒅𝒆𝒏𝒔𝒊𝒕𝒚
𝑯𝒂𝒖𝒔𝒏𝒆𝒓 𝑹𝒂𝒕𝒊𝒐𝒏 =
𝑩𝒖𝒍𝒌 𝒅𝒆𝒏𝒔𝒊𝒕𝒚
 Scale of Flowability
Angle of Compressibility Hausner
Flow Character
Repose () Index (%) Ratio

Excellent 25-30  10 1.00-1.11

Good 31-35 11-15 1.12-1.18
Fair 36-40 16-20 1.19-1.25
Passable 41-45 21-25 1.26-1.34
Poor 46-55 26-31 1.35-1.45
Very Poor 56-65 32-37 1.46-1.59
Very Very Poor >66 > 38 >1.60
Ref. Powder Flow" in USP 29–NF 24 (US Pharmacopeial
Convention, Rockville, MD), p. 3017
Classification of Powder by Fineness
Classification of Powder d50 sieve opening (µm)
Very Coarse  1000
Coarse 355 - 1000
Moderately Fine 180 - 355
Fine 125 - 180
Very Fine 90 - 125
 Deformation
(elastic, plastic , brittle fracture/ductile)
• Elactic deformation : A change in shape caused by the
applied stress is completely reversible, and the
specimen will return to its original shape on release of
the applied stress
• Plastic deformation is the permanent change in shape
of a specimen due to applied stress
• brittle fracture or ductile fracture; fracture being the
separation of a body into two or more parts.
• Ductile fracture is characterized by extensive plastic
deformation followed by fracture. Ductile failure is not
typically seen with compacts of pharmaceutical
materials.
 COMPACTION
• There are two principal types of compaction studies
used to characterise material:
– pressure/volume relationships and
– pressure/strength relationships.
• the pressure/volume relationships provide the
information about the compaction properties of a
material that allows an appropriate formulation to be
developed
• Compressibility and compactibility
 Compressibility
• compressibility of a powder as the ability to decrease in
volume under pressure. and
• Compressibility of powders is characterized
from the density-compression pressure
relationship according to the Heckel plot
1
• 𝑙𝑛 = 𝑘𝑃 + 𝐴
1−𝐷𝑟
– 𝐷𝑟: relative density; P is the compressional
pressure; k and A are constants
 compactibility
• Compactibility : as the ability of the powdered material to be
compressed into a tablet of specified tensile strength
(Lueuenberger and Rohera)
• The compactibillty of pharmaceutical powders can be
characterized by studying tensile strength and indentation
hardness
• Hiestand and Smith used tensile strength and indentation
hardness to determine three dimensionless parameters Strain
index, bonding index, and brittle fracture index-to characterize
tableting performance of individual components and mixtures
 Compression
• Compression is the process of applying pressure to a material.
• In pharmaceutical tableting an appropriate volume of
granules in a die cavity is compressed between an upper and
a lower punch to consolidate the material into a single solid
matrix, which is subsequently ejected from the die cavity as
an intact tablet.
 Compression
• The subsequent events that occur in the
process of compression are
a. transitional repacking,
b. deformation at points of contact,
c. fragmentation and/or deformation,
d. bonding,
e. deformation of the solid body,
f. decompression, and
g. ejection.
 Preformulation Study
1. Background
2. Organoleptic properties
3. Microscopic examination
4. Physical characteristics
5. Solution properties
6. Stability (solid)
7. Drug-excipient compatibility studies
8. Solution stability
9. Recommendations
 Background
1. Compound:
2. Chemical name:
3. Chemical structure
4. Lot numbers
5. Solvents of recrystallization
6. Purity
7. Therapeutic category
8. Anticipated dose
 Physical characteristics
1. Density
2. Particle size
3. Surface area
4. Static charge
5. Flow properties
6. Compressibility
7. Hygroscopicity
8. Polymorphism
 Solution properties
1. pH of 1% Suspension
2. pKa
3. Solubility
4. Effect of solUbilizing agents
5. Partition coefficient
6. Dissolution rates
TABLET COMPOSITION

Lain-lain
 Excipients
Filler/diluent/bulking agent
• To increase bulk in order to produce a tablet of practical weight for
compression

Disintegrant
• To facilitate rapid breakup and disintegration after administration.

Binder
• To impart cohesive properties to the powders by the formulation of granules

Lubricant
• To reduce interparticulate friction and to facilitate tablet ejection
from the die (lubricants),
• To prevent sticking/adhesion of powder to the surfaces of punches
and dies (anti adherent),
• to improve flow characteristics of the granulation (glidant)
 EXCIPIENTS
1. MUST BE PHYSIOLOGICALLY INERT
2. MUST BE ACCEPTABLE TO REGULATORY AGENCIES
3. MUST BE PHYSICALLY AND CHEMICALLY STABLE
4. MUST BE FREE OF ANY BACTERIA PATHOGENIC
5. MUST BE INTERFERE WITH THE BIOAVAILABILITY OF THE
DRUG
6. MUST BE COMMERCIALLY AVAILABLE AND PURITY
7. COST MUST BE RELATIVELY INEXPENSIVE
8. MUST BE CONFORM TO ALL CURRENT REGULATORY
REQUIREMENTS
 BAHAN PENGISI
(DILUENT/FILLER/BULKING AGENT)
Water insoluble Water soluble
• Starch
• Powdered cellulose
• Lactose
• Microcrystalline cellulose • Sucrose
• Calcium carbonate
• Dicalcium phosphate • Mannitol
• Calcium triphosphate • Modified starch
• Magnesium carbonate
• Sorbitol, etc.
Selection of diluent
compressibility,
solubility, flowability,
disintegration qualities,
hygroscopicity, lubricity ,
stability, etc
 Filler Characteristics
Characteristics
Filler A B C D E F G
Dextrose 3 2 4 2 1 2 3
Spray-dried Lactose 3 5 4 3 1 2 4
Fast-Flo Lactose 4 4 4 4 1 2 4
Anhydrous Lactose 2 3 4 4 5 2 4
Emdex 5 4 5 3 1 2 3
Sucrose 4 3 5 4 4 1 4
Starch 2 1 0 4 3 3 3
Sta-Rx 1500 3 2 2 4 3 2 4
Dicalcium phosphate 3 4 1 2 1 2 5
Emcompress 3 4 0 4 1 1 3
Avicel 5 1 0 2 2 4 3

A = compressibility B = flowability C = solubility D = disintegration

E = Higroscopisity F = Lubricity G = Stability
0 = tidak ada 1 = jelek/ rendah 5 = baik/ tinggi
 Filler Characteristics
Characteristics
Filler A B C D E F G
Calcium carbonate 2 4 0 3 b 2 1
Dicalcium phosphate 2 2 0 4 b 2 0
Calcium triphosphate 3 2 0 5 b 2 0
Magnesium carbonate 2 2 0 4 b 1 1
Sodium chloride 5 5 5 2 a 3 2

A = availability B = flowability C = solubility

D = absorbansi E = asam (a)/ basa (b) F = friability G = lubricity
0 = tidak ada 1 = jelek/ rendah 5 = baik/ tinggi
 TRADE NAME DESCRIPTION
Fast Flo lactose® It is spray processed lactose which is a mixture of crystalline α-lactose monohydrate
and amorphous lactose.
Microcellac® 75% lactose and 25% MCC (MicroCrystalline Cellulose)

Ludipress® 93% α-lactose monohydrate, 3.5% polyvinylpyrrolidone, and 3.5% crospovidone.

Nu-Tab® Sucrose 95-97%, invert sugar 3-4% and magnesium stearate 0.5%

Di-Pac® Sucrose 97% and modified dextrins 3%

Sugartab® Sucrose 90-93% and invert sugar 7-10%.

Emdex® Dextrose 93-99% and maltose 1-7%

Cal-Tab® Calcium sulfate 93% and vegetable gum 7%

Cal-Carb® Calcium carbonate 95% and maltodextrins 5%

Calcium 90® Calcium carbonate (minimum) 90% and Starch, NF (maximum) 9%

EMCOMPRESS Dibasic Calcium Phosphate USP (Special Size Praction)

STA-RX 1500 Pregelatinized (Compressible)
EMCOCEL Microcrystallin Cellulose NF
AVICEL 101, 102 Microcrystallin Cellulose NF
TRITAB Tricalcium Phosphat Anhydrous (DC)
Coprocessed Product Containing 30 % Calcium Carbonate And 70 % Microcrystalline
VITACEL Cellulose)
BINDERS To impart cohesive properties to the powders by
the formulation of granules

SUGAR NATURAL BINDERS SYNTHETIC/SEMISYNTHETIC

POLYMER
Sucrose : Acacia : 10-25 % Cellulose derivate (HPMC, HPC,
50-75 % NaCMC, EC,MC) : 5-10 %
Liquid glucose: Tragacanth : 3-10% Polyvinyl Pyrrolidone (PVP) : 3-15 %
25-50 %
Sorbitol : Gelatine : 10-20 % Polyvinyl Alcohol (PVA)
10-25 %
Starch Paste : 5-10% Polyethylene Glycol (PEG)
Pregelatinezed Starch : 1-5 % Polymethacrylates : 5-15 %
Alginic acid : 5-10 %
Cellulose
Sodium Alginate 3-5 %
 DIRECT COMPRESSION BINDER
DC BINDER CLASS
Avicel (PH 101) MCC
SMCC (50) SMCC (Silicified MCC)
UNI-PURE(DW) Partially PGS (Pregelatinized Starch)
UNI-PURE (LD) Low density starch
DC Lactose DC lactose anhydrous
DI TAB DC-DCPD (Dibasic Calcium Phosphate Dihydrate)

Flow Behavior DI TAB > SMCC(50) > DC Lactose , UNI PURE(DW) > Avicel (PH 101) > UNI PURE(LD)

Compressibility UNI PURE(LD) > SMCC(50) , Avicel (PH 101) > UNI PURE(DW) , DC Lactose > DI TAB

Crushing Strength UNI PURE(LD) > SMCC(50) > UNI PURE(DW) > Avicel(PH 101) > DC Lactose &gt DITAB
 LUBRICANT
Oil to the system
 To reduce interparticulate friction and to facilitate tablet ejection
from the die (lubricants),
 To prevent sticking/adhesion of powder to the surfaces of punches
and dies (anti adherent),
 to improve flow characteristics of the granulation (glidant),
 Too much can cause waterproofing
CONCENTRATION GLYDANT ANTI-ADHERENT LUBRICANT
LUBRICANT (%) PROPERTIES PROPERTIES PROPERTIES

METALLIC 1 OR LESS NONE GOOD EXCELLENT

(Ca/Mg)
STEARATES
TALC 1–5 GOOD EXCELLENT POOR
STEARIC ACID 1-5 NONE POOR GOOD
CAB-O-SIL 1 OR LESS EXCELLENT GOOD NONE
CORN STARCH 5 - 10 EXCELLENT EXCELLENT POOR
 WATER SOLUBLE LUBRICANT
WATER SOLUBLE LUBRICANT CONCENTRATION (%)

BORIC ACID 1
SODIUM CHLORIDE 5
SODIUM BENZOIC 5
SODIUM ACETATE 5
PEG 4000 1-4
PEG 6000 1-4
DL-LEUCIN 1-5
Na LAURYL SULPHATE 1-5
Mg LAURYL SULPHATE 1-2
 DISINTEGRANTS
 To facilitate rapid breakup and disintegration
after administration.
 Will be added during (internal/intragranular) and
after granulation (external/extragranular)
Mechanism of tablet disintegrants
1. By capillary action
2. By swelling
3. Because of heat of wetting (AIR EXPANSION)
4. Due to disintegrating particle/particle
repulsive forces
5. Due to deformation
6. Due to release of gases
7. By enzymatic action
 CONCENTRATION IN
DISINTEGRANTS SPECIAL COMMENTS
GRANULES (%W/W)

Starch USP 5-20 Higher amount is required, poorly

compressible
Starch 1500 5-15 -
Avicel®(PH 101, PH 10-20 Lubricant properties and directly
102) compressible
Solka floc® 5-15 Purified wood cellulose
Alginic acid 1-5 Acts by swelling
Na alginate 2.5-10 Acts by swelling
Explotab® 2-8 Sodium starch glycolate, superdisintegrant.
Polyplasdone®(XL) 0.5-5 Crosslinked PVP
Amberlite® (IPR 88) 0.5-5 Ion exchange resin

Methyl cellulose, Na 5-10 -

CMC, HPMC
AC-Di-Sol® 1-3 Direct compression