Powerpoint TemplatesPage 1
PREFORMULATION, FORMULATION, PACKAGING, & ANALITYCAL METHOD OF DRUG
M. AKBAR EMBERIK (260112110062)TONI FATONI (260112110064)MITA OLIVINA (260112110066)FEBRINA AMELIA SAPUTRI (260112110068)MARINA SUSANTI (260112110070)
Powerpoint TemplatesPage 2
“A phase of a research and development process where the pre formulation scientist characterizes the physical, chemical and mechanical properties of a new drug substance in order to develop stable, safe and effective dosage forms”
PREFORMULATION
Powerpoint TemplatesPage 3
WHY PREFORMULATION IMPORTANT ?
Preformulation is the foundation of developing robust formulations
Good preformulation will inevitably lead to simple and elegant formulations and successful commercial products.
Powerpoint TemplatesPage 4
GOALS OF PREFORMULATION
To establish the physico -chemical
properties of a new drug (API)
To establish the data on Drug-
Excipient compatibility
To establish its (API) kinetic rate
profile
Powerpoint TemplatesPage 5
PREFORMULATION
• Chemical characterization • Physical characterization
API / Excipient Characterization
involves:• Monograph or regulatory requirements • Identification tests (UV/HPLC/IR) • Limit tests (Heavy metals, sulphated ash, etc) • Assay • Impurities
Chemical characterization
basically involves:
• Monograph as well as • Formulation dependent
Physical characterization
basically involves:
Powerpoint TemplatesPage 6
Organoleptic properties
Purity
Particle size, shape and surface area
Solubility
EVALUATED PARAMETER
Powerpoint TemplatesPage 7
CONT
Dissolution
Partition coefficient, ionization constant and Kp
Crystal properties and polymorphism
Density, hygroscopicity, flowability, wettability etc.
Stability studies
Powerpoint TemplatesPage 8
Excipient
TABLET FORMULATION
Diluent
Binder
Disintegrant
Lubricants
Anti adhesive
Glidants
Weting/ surface active agents
Colours/ pigments
Powerpoint TemplatesPage 9
• used to enlarge the volume of tablets. The diluent that can be used to direct compression called filler-binder, which has the ability to enhance the flow and mass tablet compatibility.
DILUENT
Powerpoint TemplatesPage 10
DISINTEGRANT (1)
Disintegrant are added to facilitate the breaking of tablet when in contact with the fluids of the gastrointestinal tract, may have a function to bind a water, so the tablet will expand and broke to constituent part so as to release the drug and cause the effect.
Powerpoint TemplatesPage 11
DISINTEGRANT (2)
MEC
HAN
ISM Swelling
Deformation
Wicking
Repultion
Powerpoint TemplatesPage 12
BINDER
Binder give a function to form a granules and to increase the cohesiveness for tablets that make with direct compresion
Class of binder
Nature polymer
Synthetic polymer
Powerpoint TemplatesPage 13
LUBRICANT
Talc Mg Stearic (0,2-0,3%)
PEG 4000-7000 etc
Powerpoint TemplatesPage 15
INTRODUCTION
The packaging of a pharmaceutical product fulfills a variety of roles such as
product presentation, identification, convenience,
protection until administration
or use.
Powerpoint TemplatesPage 16
used as a barrier to protect the pharmaceutical preparations against external factors that can degrade them and consequently decrease their effectiveness and increase toxic effects
PACKAGING MATERIAL
Powerpoint TemplatesPage 17
TYPE OF PACKAGING MATERIAL
to assure the therapeutic effectiveness during its shelf life.
physicochemical properties,
including quality control
tests,
size, shape, capacit
y,
specification of the products
Powerpoint TemplatesPage 18
Solid oral dosage forms generally need to be protected from the potential adverse effects of the following:
1. Water vapor 2. Incident light
3. Reactive gases
Powerpoint TemplatesPage 19
QUALITY CONTROL OF PACKAGING MATERIAL
[Food and Drug Administration (FDA), British Pharmacopoeia, WHO, USP] have issued guidelines on the safety evaluation of materials and container closure systems.
An important step in such evaluations is characterization of the packaging materials and the chemicals that can migrate or extract from container closure system components to the drug product.
Powerpoint TemplatesPage 20
Powerpoint TemplatesPage 21
• .
FDA ’ s guidance document requires the evaluation of four attributes to establish suitability:
protection, compatibility,
safety, and performance/drug delivery
Powerpoint TemplatesPage 22
• exposure to light, loss of solvent, exposure to reactive gases (e.g., oxygen), absorption of water vapor, and microbial contamination
• Analytical method :spectrophotometer, with the required sensitivity and accuracy
• Most common test : dye penetration and microbial ingress
PROTECTION
• will not interact sufficiently to cause unacceptable changes in the quality of either the dosage form or the packaging component.
• Analytical method : Chromatography/mass spectrometry (LC/ MS), gas chromatography/mass spectrometry (GC/ MS),inductively coupled plasma (ICP) spectroscopy
COMPATIBILITY
Powerpoint TemplatesPage 23
• not leach harmful or undesirable amounts of substances to which a patient will be exposed when being treated with the drug product.
• Analytical Method : physicochemical tests, Liquid and gas chromatography and MS
SAFETY
• functionality that may improve patient compliance
• drug delivery, which is the ability of the packaging system to deliver the right amount or rate
PERFORMANCE
Powerpoint TemplatesPage 25
OFFICIAL STANDARD TABLET PREPARATION TESTING
Testing in the BP-USP• Drug content, indirectly controlling
weight / weight of the tablet /
Physical quality
Powerpoint TemplatesPage 26
BP USPUniformity of weight Variations in weight
Active ingredients Determination (assay)
Uniformity of content (BBPP) uniformity of content
Disintegran Disintegran
Dissolution (some) Dissolution (some)
Powerpoint TemplatesPage 27
TOLERANCE OF TABLET’S VARIAN WEIGHT
Pharmacopeia Weight of tablet (mg) 10% of difference (n-2) No defference (n-0)
BP < 80 10 15
80-250 7,5 12,5
> 250 5 10
USP < 130 10 20
130-234 7,5 15
> 324 5 10
PH Eropa < 13 15 -
13-130 10 -
> 130 7,5 15
Powerpoint TemplatesPage 28
CONTENT UNIFORMITYPharmacope
a
Dose Limit ( % ) N
BP. F Eropa < 2 mg or < 2 %
b/b
85-115 10
If < 85>115 1
Then 75-125 0
Because of that 85-
115
30
< 85>115 2
75-125 1
USP commonly use As above 10
RSD < 6,0 10
RSD <7,8 30
Powerpoint TemplatesPage 29
DISINTEGRATION
interpretation:
Disintegration occurs when there is no tablet particles remain on the sieve.
Disintegration equipment:Used glass tube with a diameter of 2.8 cm. At the bottom of that was used sieve mesh No. 10, speeds up and down
the tool 30 times per minute, 7.5 cm through 37o C.
Powerpoint TemplatesPage 30
DISINTEGRATION TESTTime and condition
BPNot coated tablet <15 minutescoated : thin layer <30 minutes sugar <60 minutes in 0,1 N HCl enteric >120 minutes in 0,2 N HCl
<60 minutes PH 6,8 ( phosphat )Eferfesen <5 minutes in 200 ml of water, 20o CSoluble <3 minutesDispersible <3 minutes 2 tablets in 100 ml of water,
dispersed, through the 710 μmUSPNot coated tablet <time of monographCoated tablet <time of monographEnterik undamage for 60 minutes in simulated
gastric fluid, and disintegrated in the simulated intestinal fluid <time of monograph
buccal <4 hoursSublingual <time of monograph
Type of tablet
Powerpoint TemplatesPage 31
DISSOLUTION TEST
to predict bioavailability and
bioequivalence formulated in IVIVC
(invitroinvivo-correlation).
Tablet dosage may be or may not
disintegrate when interacting with
gastrointestinal fluid when given orally.
Powerpoint TemplatesPage 32
THE NONCOMPENDIAL PROPERTIES
break the tablet with your fingers
drop the tablet from a certain height onto the floor
the tablet is given pressure by apparatus, then read on the scale tool
1. HARDNESS TESTS
Powerpoint TemplatesPage 33
Tensile strength testNormally carried horizontally and transversely to the axis of the longest 90o (Brazilian Test) using an average basis
2. TENSILE STRENGTH
Powerpoint TemplatesPage 34
Resistance to abrasion or friability is a very important test
disintegration, dissolution and ruggedness can be quickly measured,they also interdependence
3. FRIABILITY
Powerpoint TemplatesPage 35
Tablets (known weight)
Wheeling in friabilitor (d = 12 inchis, rotate
4 minutes)
Recheck tablets weight
Count F% = (Wo-W)/Wo x 100
F = < 1% or F = 0,5% for better result
For product development: F =
<0,1% for 20 minutes
Powerpoint TemplatesPage 36
Work of failure is an aplication from viscoelastic principle to investigate tablet cracking using eqution:
This concept aplicated for tightly stretched energy characteristic of polymer thin layer.
Tablet with high hardess and low rigidness is useless than tablet with low hardess and high rigidness.
W f = 2 > p . d x / π D T
4. Work of Failure
Powerpoint TemplatesPage 37
• Equation for three point bend test:
F = 3f / 4dT2 . (Mpa)
where:P = load at failure (kP)f = distance between the two tablets (the fulcrum)d = diameter of the smallest and the form of tabletsT = thickness of the tablet
5. Three Point Bend
Powerpoint TemplatesPage 38
With the application of three-point test can be performed indentation testing tablets are used for half (score tablet) or one quarter.
Properties Descriptionsizeformprofilelineformulationstyle tensestiffnessCoated thin-layer
Diameter> 7.5 <12 mmPillows> capsule> oval>>> circularThin (3:1), averageIn (1 mm), the form VBrittle (plastic, too stiff)<1 MPa at 8 mm<4 JPromote brittle cracks
Tables for the requirements of halved tablets (diameter).
6. Tablet Diameter (score)
Powerpoint TemplatesPage 39
Tablet structure is anisotropic. Strength, porosity, and disintegration friability influenced by the porosity. Varies along the surface and the thickness of the tablet. Friction on the surface layer produces a more tightly. To prevent this, added magnesium stearate.Identity is a measure of resistance against plastic deformation, dikuantitasi through Brinell hardness.
BH = P / πDh
Where:P = Load appliedh = depth of penetration of an indenter with a diameter D.
7. The Nature of The Surface (Indentation)
Powerpoint TemplatesPage 40
CONTENT UNIFORMITY TESTING
DRUG ANALYSIS METHOD• Analysis of drug compounds for identifying the drugs solubility
in the biological fluids used chromatographic methods can be seen in early 1920s
• In the 1995's, the method of ascending paper chromatography (ascending) and down (descending) has appeared on various Pharmacopoeia for the analysis of medicinal products.
• Pharmacopoeia edition started using advanced methods of high performance liquid chromatography (HPLC) and gas chromatography (GC) for analysis of drugs and also the spectrophotometric method (Rohman, 2007)
Powerpoint TemplatesPage 41
UV-VISIBLE SPECTROPHOTOMETRY
Spectrophotometry is a combination of UV
and Visible spectrophotometry
SPectrophotometry system, UV-Vis most widely available and most popularly used
Ease of this method is that it can be used
both for color sample to colorless one
Powerpoint TemplatesPage 42
EQUIPMENTS OF UV-VISIBLE SPECTROPHOTOMETRY
• tungsten lamp for Visible light (visible light = 38 - 780nm) and deuterium lamp for Ultra Violet light (180-380nm) in video light large
light source,
• to gives light a rainbow in the video, because of there is then we can choose the right wavelengthMonochromator
• that's where we store the samples and the other for the blankCuvette
• here occurs the conversion of light into a number of data to be displayed on the readerLight detector
Powerpoint TemplatesPage 43
CIRCUIT EQUIPMENT OF UV-VISIBLE SPECTROPHOTOMETRY
Powerpoint TemplatesPage 44
High Performance Liquid Chromatography (HPLC)
Be able to separate molecules from a mixture Easy to implement Speed of analysis and high
sensitivity
Be able to avoid the occurrence of
decomposition / destruction of
materials being analyzed
Good resolution Can use a variety of detector
Columns can be reused Easy to do a "sample recovery"
Powerpoint TemplatesPage 46
GAS CHROMATOGRAPHY1 All forms of
chromatography consists of stationary phase and mobile phase.
2 In gas-liquid chromatography, mobile phase is a gas such as helium and the stationary phase is a liquid that has a high boiling point absorbed on solids.
3 The speed of a particular compound moves through the machine, will depend on how much time is spent on moving the gas and attached to the liquid with the same path.
Powerpoint TemplatesPage 47
CIRCUIT EQUIPMENT OF GAS CHROMATOGRAPHY
Powerpoint TemplatesPage 48
SOURCES OF ERROR IN THE MEASUREMENT
Factors that affected precision can be caused by errors that occur due to various causes. According to Miller & Miller (2001) type of errors in analytical measurement can be
divided into three, namely:
1. Serious errors (gross errors)
2. Random error
(random error)
3. Systematic
error (Systematic
error)
Powerpoint TemplatesPage 49
SYSTEMATIC ERROR (SYSTEMATIC ERROR)
Systematic error is a type of error that caused all the result of incorrect data with a resemblance. This can be
overcome by:
a. standardization of procedures
b. standardization
of materialsc. instrument
calibration
Powerpoint TemplatesPage 50
In general, factors that become sources of error in the measurements, giving rise to variations in the results, include:
1. Differences found on the object being measured.This can be overcome by:a. Object to be analyzed is treated in such a way as to
obtain a homogeneous quality measuresb. Use traditional sampling techniques properly and
correctly
Powerpoint TemplatesPage 51
Cont’d
2. Situation at the time of measurement differences
3. Differences tools and instrumentation used4. Differences implementation / administration