Quality.pptx

A SEMINAR ONANALYSIS OF SOLID ORAL DOSAGE FORM

QUALITY:

The regulatory authorities all over the world have accepted that a pharmaceutical product which meets the following five characteristic can be accepted an a quality product. These five characteristic are

Identity

Strength

Safety

Purity and

Efficacy

QUALITY ASSURANCE(WHO) :

Quality assurance is a wide ranging concept covering all matters that individually or collectively influence the quality of a product. With regard to pharmaceuticals, quality assurance can be divided into four major areas: quality control, production, distribution, and inspections.

QUALITY CONTROL (WHO) :

Q.C.is the part of GMP concerned with sampling specification, testing with organization, documentation and release procedure which ensure that necessary and relevant test are actually carried out and that material are neither released for use nor product release for sale or supply until their quality has been satisfactory.

PHYSICOCHEMICAL CHARACTERIZATION TECHNIQUES

Help us to understand the mechanism of drug delivery.

A) Microscopy

Techniques that can provide the composition and homogeneity of the API throughout the dosage form.

Sometimes a prediction of the dosage forms performance characteristics.

e.g. dissolution profile, ruggedness of the product and potential flaws in the coating that imparts the controlled-release characteristics to the product.

B) X-Ray Powder Diffraction

When a beam of X-rays is incident upon lattice, X-rays are diffracted.

Every crystal form of a compound produces its own characteristic X-ray diffraction pattern.

This technique is useful for distinguishing between solid-state forms of a bulk drug substance and for characterizing changes in the solid state

e.g.

1) Scanning electron micrograph of a pellet after one hour of dissolution.

2) X-ray powder diffraction patterns of crushed tablets, crushed placebo tablets

C) Thermal Analyses

TG/DTA is a useful technique for the solid-state characterization of pharmaceutical materials.

Loss on drying, phase transition temperatures, thermal stability, and whether or not water is bound or unbound.

e.g. Thermogravimetric and differential thermal analysis results from a granulation blend of a hydrated API.

D) FT-IR Microspectroscopy

Technique that can be utilized to analyze small samples and to chemically map locations by identifying components within the sample.

e.g. Micrograph of excised crystals found on tablets during a stability study.

E) NMR Spectroscopy

1) NMR Imaging

Understanding structural changes that occur in controlled-release dosage forms as they interact with physiological fluids is critical to understand.

e.g. The spectra obtained from the final dosage pellets, the hydrochloride salt of the drug substance, and the free base of the drug substance

2) Solid-State NMR

Used to study the characteristics of an API in melt-extruded pellets.

The purpose of the study was to determine whether the high temperatures at which the melt extrusion process was conducted caused physical changes in the drug substance.

F) Mass Spectrometry

Generation of molecular weight data.

Allows complete specificity, even in the presence of related substances, impurities.

G) Raman Spectroscopy

Does not require any sample preparation.

Resolution of approximately 2 m is possible.

To analyze solid dispersions to evaluate the physical properties and determine the distribution

e.g. Raman spectroscopy was used to analyze solid dispersions to evaluate the physical properties and determine the distribution of ibuprofen in extrudates of polyvinylpyrrolidone.

Q.C. TEST OF SOLID DOSAGE FORM :

TABLET:-EVOLUTION TEST OF TABLET:

OFFICAL EVOLUTION TEST OF TABLET:-

WEIGT VARIATION TEST

DISINTIGRATION TEST

DISSOLUTION TEST

UNIFORMITY OF CONTENT

CONTENT OF ACTIVE INGREDIENT IN TABLET

UNIFORMITY OF CONTAINER CONTENT

NONOFFICIAL TEST OF TABLET :

General appearance

Size and shape

Identification marking

Hardness and friability test

Organoleptic properties

Evaluation of Tablet

1)General Appearance: The general appearance of a tablet, its identity and general elegance is essential for consumer acceptance, for control of lot-to-lot uniformity and tablet-to-tablet uniformity. The control of general appearance involves the measurement of size, shape, color, presence or absence of odor, taste etc.

2) Size & Shape: It can be dimensionally described & controlled. The thickness of a tablet is only variables. Tablet thickness can be measured by micrometer or by other device. Tablet thickness should be controlled within a 5% variation of standard value.

3) Unique identification marking: These marking utilize some form of embossing, engraving or printing. These markings include company name or symbol, product code, product name etc.

4) Organoleptic properties: Color distribution must be uniform with no mottling. For visual color comparison compare the color of sample against standard color.

5) Hardness and Friability: Tablet requires a certain amount of strength or hardness and resistance to friability to withstand mechanical shakes of handling in manufacture, packaging and shipping. Hardness generally measures the tablet crushing strength

6.Friability: Friability of a tablet can determine in laboratory by Roche friabilator. This consist of a plastic chamber that revolves at 25 rpm, dropping the tablets through a Distance of six inches in the friabilator, which is then operate for 100 revolutions. The tablets are reweighed. Compress tablet that lose less than 0.5 to 1.0 % of the Tablet weigh are consider acceptable

(I) Weight Variation test (U.S.P.): Take 20 tablet and weighed individually. Calculate average weight and compare the individual tablet weight to the average. The tablet pass the U.S.P. test if no more that 2 tablets are outside the percentage limit and if no tablet differs by more than 2 times the percentage limit.

(II) Content Uniformity Test: Randomly select 30 tablets. 10 of these assayed individually. The Tablet pass the test if 9 of the 10 tablets must contain not less than 85% and not more than 115% of the labeled drug content and the 10th tablet may not contain less than 75% and more than 125% of the labeled content. If these conditions are not met, remaining 20 tablet assayed individually and none may fall out side of the 85 to 115% range.

( III) Disintegration Test (U.S.P.):

The U.S.P. device to test disintegration uses 6 glass tubes that are 3 long; open at the top and 10 mesh screen at the bottom end.

To test for disintegration time, one tablet is placed in each tube and the basket rack is positioned in a 1-L beaker of water, simulated gastric fluid or simulated intestinal fluid at 37 20 C such that the tablet remain 2.5 cm below the surface of liquid on their upward movement and not closer than 2.5 cm from the bottom of the beaker in their downward movement.

Move the basket containing the tablets up and down through a distance of 5-6 cm at a frequency of 28 to 32 cycles per minute.

Floating of the tablets can be prevented by placing perforated plastic discs on each tablet.

According to the test the tablet must disintegrate and all particles must pass through the 10 mesh screen in the time specified. If any residue remains, it must have a soft mass.

Disintegration time:

Uncoated tablet : 5-30 minutes

Coated tablet : 1-2 hours

Disintegration test apparatus

Dissolution Test (U.S.P.):

Apparatus-1: A single tablet is placed in a small wire mesh basket attached to the bottom of the shaft connected to a variable speed motor.

The basket is immersed in a dissolution medium contained in a 100 ml flask.

The flask is cylindrical with a hemispherical bottom. The flask is maintained at 370.50C by a constant temperature bath.

The motor is adjusted to turn at the specified speed and sample of the fluid are withdrawn at intervals to determine the amount of drug in solutions.

Apparatus-2:

It is same as apparatus-1, except the basket is replaced by a paddle.

The dosage form is allowed to sink to the bottom of the flask before stirring.

For dissolution test U.S.P. specifies the dissolution test medium and volume, type of apparatus to be used, rpm of the shaft, time limit of the test and assay procedure for.

The test tolerance is expressed as a % of the labeled amount of drug dissolved in the time limit

DISSOLUTION TEST APPARATUS

Apparatus 3 (Reciprocating Cylinder)

The assembly consists of a set of cylindrical, flat-bottomed glass vessels; a set of glass reciprocating cylinders; inert fittings and a motor and drive assembly to reciprocate the cylinders vertically inside the vessels and, if desired, index the reciprocating cylinders horizontally to a different row of vessels.

The vessels are partially immersed in a suitable water bath of any convenient size that permits holding the temperature at 37 0.5 during the test.

A device is used that allows the reciprocation rate to be selected and maintained at the specified dip rate given in the individual monograph within 5%.

The vessels are provided with an evaporation cap that remains in place for the duration of the test.

Apparatus 4 (Flow-Through Cell)

The assembly consists of a reservoir and a pump for the Dissolution Medium; a flow-through cell; and a water bath that maintains the Dissolution Medium at 37 0.5.

Use the specified cell size as given in the individual monograph.

The pump forces the Dissolution Medium upwards through the flow-through cell.

The pump has a delivery range between 240 and 960 mL per hour, with standard flow rates of 4, 8, and 16 mL per minute.

It must deliver a constant flow (5% of the nominal flow rate); the flow profile is sinusoidal with a pulsation of 120 10 pulses per minute.

The flow-through cell of transparent and inert material, is mounted vertically with a filter system that prevents escape of undissolved particles from the top of the cell; standard cell diameters are 12 and 22.6 mm; the bottom cone is usually filled with small glass beads of about 1-mm diameter with one bead of about 5 mm positioned at the apex to protect the fluid entry tube; and a tablet holder is available for positioning of special dosage forms.

The cell is immersed in a water bath, and the temperature is maintained at 37 0.5.

Evolution test of capsule:

Uniformity of wt

Content of active ingredient in the capsule

Dissolution test

Disintegration test.

Dissolution test

USP Apparatus 1: Basket

Paddle Apparatus

Q.C. TEST FOR DISPERSED SYSTEM:

SUSPENSION :

SEDIMENTATION METHOD

RHEOLOGICAL METHOD

ELECTROKINETIC METHOD

MICROMERITIC METHOD

F=0.5

F=1.0

F=1.5

Sediment Volume

F={volume of sediment Vu}/{original volume Vo}

Vo

Vu

Vo

Vu

SUSPENSION

SEDIMENTATION METHOD

Sedimentation volume-

F = Vsed/Vtot

The value of F normally lies between 0 to 1 for any pharmaceutical suspension.

The value of F provides a qualitive

knowledge about the physical stability of the suspension.

Zeta potential

Potential difference between the ions in the tightly bound layer and the electroneutral region, referred to as zeta potential.

THIXOTROPIC SUSPENSION

A thixotropic suspension is the one which is viscous during storage but loses consistency and become fluid upon shaking.

A well-formulated thixotropic suspension would remain fluid long enough for the easy dispense of a dose but would slowly regain its original viscosity within a short time.

EMULSION:

MACROISCOPIC EXAMINATION

GLOBULE SIZE ANALYSIS

VISCOSITY CHANGES

RHEOLOGICAL ASSESMENT

Quality control for pharmaceutical aerosols

Propellants

Valves, actuator and dip tubes

Testing procedure

Valve acceptance

Containers

Weight checking

Leak testing

Spray testing

Evaluation parameters of pharmaceutical aerosols

A. Flammability and combustibility

Flash point

Flame extension, including flashback

B. Physiochemical characteristics

Vapor pressure

Density

Moisture content

Identification of propellant(s)

Concentrate-propellant ratio

C. Performance

Aerosol valve discharge rate

Spray pattern

Dosage with metered valves

Net contents

Foam stability

Particle size determination

Leakage

D. Biologic characteristics

E. Therapeutic activity

Flame Projection

This test indicates the effect of an aerosol formulation on the extension of an open flame.

Product is sprayed for 4 sec. into flame.

Depending on the nature of formulation, the fame is extended, and exact length was measured with ruler.

Flash point

Determined by using standard Tag Open Cap Apparatus.

Step involves are :

Aerosol product is chilled to temperature of - 25 0 F and transferred to the test apparatus.

Temperature of test liquid increased slowly, and the temperature at which the vapors ignite is taken a flash point.

Calculated for flammable component, which in case of topical hydrocarbons.

Vapor pressure

Determined by pressure gauge.

Variation in pressure indicates the presence of air in headspace.

A can punctuating device is available for accurately measuring vapor pressure.

Density

Determined by hydrometer or a pycnometer.

This method is use for non aerosol, modification to accommodate liquefied gas preparation.

Step involves are :

A pressure tube is fitted with metal fingers and hoke valve, which allow for the introduction of liquids under pressure.

The hydrometer is placed in to the glass pressure tube.

Sufficient sample is introduced through the valve to cause the hydrometer to rise half way up the length of the tube.

The density can be read directly.

Moisture content

Method used : Karl Fischer method

G. C

Identification of propellants

G.C,

I.R spectrophotometry

Aerosol valve discharge rate

Determined by taking an aerosol known weight and discharging the contents for given time using standard apparatus.

By reweighing the container after time limit has expired, the change in weight per time dispensed is discharge rate,

Expressed as gram per seconds.

Dosage with metered valves

Reproducibility of dosage each time the valve is dispersed

Amt. of medication actually received by the patient.

Reproducibility has been determined by assay technique,

Another method is that, involves accurate weighing of filled container fallowed by dispersing of several doses, container can reweighed, and difference in weight divided by No. of dose, gives the average dosage.

Net contents

Weight method

Filled full container, and dispensing the contents

Foam stability

Visual evaluation

Time for a given mass to penetrate the foam

Times for given rod that is inserted into the foam to fall

The use of rotational viscometers

Particle size determination

Cascade impactor

Light scatter decay method

Cascade impactor

Operates on the projected through a series of nozzle and glass slides at high viscosity, the large particles become impacted first on the lower velocity stages, and the smaller particals pass on and are collected at high velocity stages.

These practical ranging from 0.1 to 30 micron and retaining on RTI.

Modification made to improve efficacy

Porush, Thiel and Young used light scattering method to determine particle size.

As aerosols settle in turbulent condition , the change in light intensity of Tyndall beam is measured

Sciarra and Cutie developed method based on practical size distribution.

Q.C TEST OF SEMISOLID

Suppositories :

Physical analysis

Visual examination Color and the surface characteristics of the suppository are relatively easy to assess. It is important to check for the absence of fissuring, pitting, fat blooming, exudation, sedimentation, and the migration of the active ingredients. Suppositories can be observed as an intact unit and also by splitting them longitudinally.

Shape

It is advisable to check the shape of the suppository to see if it is consistent, irrespective of whether the suppository is give or torpedo shaped. Surface condition The following can be checked: brilliance, dullness, mottling, cracks, dark regions, axial cavities, bursts, air bubbles, holes, etc.

Color

The intensity, nature and homogeneity of the color should be verified.

Odor Verification of odor can prevent confusion when similar suppositories are being processed. A change in the odor may also be indicative of degradation process.

Weight Suppositories can be weighed on an automatic balance, obtaining the weight of 10 suppositories

Melting range (melting point, melting zone)

MICROMELTING RANGE:-

The time taken for the entire suppositories melt when immersed in a constant temp.370c water bath.

Apparatus :-USP tablet disintegrating app.

Liquefaction time

BREAKING TEST:-

DISSOLUTION TESTING

Reference :

Handbook of Modern Pharmaceutical Analysis; edited by Satinder Ahuja and Stephen Scypinski; volume 3; series edited by Satinder Ahuja; Separation Science and Technology; pg : 235-263

The theory and practical of industry pharmacy; Leon Lachman, Herbert A. Lieberman, Joseph L. Kanig; 3rd edition; Varghese Publishing House; pg no : 296-303, 585-587, 613-618

United States Pharmacopoeia 32NF27; Second Supplement June 1, 2009; pg : 711