Ppt Formula n Analisis

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PREFORMULATION, FORMULATION, PACKAGING, & ANALITYCAL METHOD OF DRUG

M. AKBAR EMBERIK (260112110062)TONI FATONI (260112110064)MITA OLIVINA (260112110066)FEBRINA AMELIA SAPUTRI (260112110068)MARINA SUSANTI (260112110070)

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“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

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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.

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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

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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:

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Organoleptic properties

Purity

Particle size, shape and surface area

Solubility

EVALUATED PARAMETER

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CONT

Dissolution

Partition coefficient, ionization constant and Kp

Crystal properties and polymorphism

Density, hygroscopicity, flowability, wettability etc.

Stability studies

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Excipient

TABLET FORMULATION

Diluent

Binder

Disintegrant

Lubricants

Anti adhesive

Glidants

Weting/ surface active agents

Colours/ pigments

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• 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

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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.

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DISINTEGRANT (2)

MEC

HAN

ISM Swelling

Deformation

Wicking

Repultion

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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

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LUBRICANT

Talc Mg Stearic (0,2-0,3%)

PEG 4000-7000 etc

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PACKAGING

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INTRODUCTION

The packaging of a pharmaceutical product fulfills a variety of roles such as

product presentation, identification, convenience,

protection until administration

or use.

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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

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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

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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

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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.

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• .

FDA ’ s guidance document requires the evaluation of four attributes to establish suitability:

protection, compatibility,

safety, and performance/drug delivery

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• 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

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• 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

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TABLETS PREPARATION TEST

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OFFICIAL STANDARD TABLET PREPARATION TESTING

Testing in the BP-USP• Drug content, indirectly controlling

weight / weight of the tablet /

Physical quality

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BP USPUniformity of weight Variations in weight

Active ingredients Determination (assay)

Uniformity of content (BBPP) uniformity of content

Disintegran Disintegran

Dissolution (some) Dissolution (some)

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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

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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

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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.

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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

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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.

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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

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Tensile strength testNormally carried horizontally and transversely to the axis of the longest 90o (Brazilian Test) using an average basis

2. TENSILE STRENGTH

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Resistance to abrasion or friability is a very important test

disintegration, dissolution and ruggedness can be quickly measured,they also interdependence

3. FRIABILITY

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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

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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

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• 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

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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)

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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)

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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)

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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

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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

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CIRCUIT EQUIPMENT OF UV-VISIBLE SPECTROPHOTOMETRY

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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"

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CIRCUIT EQUIPMENT OF HPLC

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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.

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CIRCUIT EQUIPMENT OF GAS CHROMATOGRAPHY

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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)

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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

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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

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Cont’d

2. Situation at the time of measurement differences

3. Differences tools and instrumentation used4. Differences implementation / administration