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GOVT COLLEGE OF PHARMACY AMRAVATI

TOPIC:- “VALIDATION OF SOLID DOSAGE FORMS”

Prepared By:- A.R KHAN

M.PHARM 1ST YEAR(Q.A)

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Introduction:-• Validation is a systematic approach to identifying,

measuring, evaluating, documenting, and re-evaluating a series of steps in the manufacturing process to ensure a reproducible final product.

• According to US-FDA, 1987“Process Validation” is establishing documented

evidence which provides a high degree of assurance that a specified process will consistently produce a product meeting its pre-determined specifications and quality characteristics.”

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Types of process validation

PROCESS VALIDATION

RETROSPECTIVE PROCESS VALIDATION

PROSPECTIVE PROCESS

VALIDATION

CONCRURRENT PROCESS VALIDATION

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PRODUCT VALIDATION

product validation involves following steps:• validation of raw materials and excipients.• analytical methods of validation.• equipment and facility validation .• process variables and limits.

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VALIDATION OF RAW MATERIALS AND EXCIPIENTS

The validation process of solid dosage form begins with the validation of raw materials ,both API and excipients.• validation of raw materials is one of the major causes

of product variation or deviation from specification.• preformulation is one of the critical step to be

validated in product validation -Physical characters such as drug and particle size

can affect material flow and blend uniformity. -Chemical characters like impurities can effect

stability of drug.

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Excipients can represent less then 1% of a tablet formula

Factors to be aware of are • The grade and source of the excipients• Particle size and shape characteristics and• Lot-to-lot variability

VALIDATION OF EXCIPIENTS-

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VALIDATION OF ANALYTICAL METHODS

• Accuracy of method:• Precision of method:• Specificity:• Repeatability• Reproducibility:• precision:• Ruggedness:

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EQUIPMENT VALIDATION -

This protocol can be divided into • Design qualification• Installation qualification• Operation qualification• Performance qualification• Maintaince (calibration, cleaning, repair) qualification

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Validation of tablets

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Validation protocol for tablets

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INDUSTRIAL PROCESS FOR SOLID DOSAGE FORMS

Steps &Process parameter are following-

1.MIXING OR BLENDINGTechniques- 1.Diffussion(tumble) 2.convection(planetary or fluid bed).

Mixing and blending depends upon various factors-

1.Mixing speed2.Mixing Time3.drug and excipient uniformity4.equipment capacity

EQUIPMENTS-

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2.WET GRANULATIONwhat type of wet granulation to be used LOW SHEAR HIGH SHEAR

wet granulation parameters are• Binder addition-• Binder conc-• Amount of binder solution- • Granulation end point-

EQUIPMENTS-

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3.WET MILLING

Does the wet granulation needs to break up the lumps and enhance the drying of granulation

factors –• screen size • mill speed• feed rate

EQUIPMENTS-

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4.DRYING

Drying is a most important and It is important to keep the residual moisture low to prevent product deterioration and ensure free flowing properties.

factors-• Inlet/outlet temp-• Airflow-• Moisture uniformity-• Equipment capacity-

EQUIPMENTS-

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5.LUBRICATIONFactors:-1.selection of lubricant-2.amount of lubricant-3.mixing time-

The compression is done either by single punch machine (stamping press) or by multi station machine (rotary press).

factors-• compression speed-• compression or ejection force-

6.TABLET COMPRESSION

EQUIPMENTS-

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In process test in compression The following in-process tests should be examined during the

compression stage-• Appearance• Hardness• Tablet weight• Friability-0.5-1%• Disintegration• Weight uniformity

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7.THE TABLET COATING PROCESS

Many solid pharmaceutical dosage mediums are produced with coatings, .

key areas –• equipment type- (convectional or perforated

pan and fluid bed coaters are potential.)• pan speed-.• spray rate-

EQUIPMENTS-

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APPEARANCE TEST FOR TABLET COATING

• cracking or peeling of the tablet• intagliation fill-in• color uniformity• coating efficiency should be determined for

the coating operation

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• Moisture content of dried granulation- usually less then 2%

• Granulation particle size distribution

• Individual tablet weight• Tablet hardness• Tablet thickness• Disintegration • Impurity profile

8.TESTSIN PROCESS TESTS

FINISHED PRODUCT TESTS

• Appearance• Assay• content uniformity• Tablet hardness• Tablet thickness• Impurity profile• dissolution

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Validation of capsules

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CAPSULE COMPOSITION

• 1.capsule shell provide – the presence of each ingredient in the capsule formulae. Justify the level and grade of each ingredient .

• Explain the selection of the capsule size and shape • Discuss the need for capsule identification(color).

• 2. capsule shell contents- establish the compatibility of the capsule shell and the capsule contents.

• Determine the hygroscopic nature of the capsule formulation .• For example, a hygroscopic formulation(API /excipients)can pull

water from the capsule shell, which could effect the API stability.

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EQUIPMENTS

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PROCESS EVALUATION AND SELECTION

• The process to manufacture the contents of a hard gelatin capsule is the same as the tablet. It may required only a blending step, such as a direct compression tablet, or such as a wet granulation tablet (eg mixing, wet milling, drying, dry milling and blending).In either case, the materials are then encapsulated in a capsule shell.

• ENCAPSULATION-• Encapsulation is a critical step in the production of

capsules, similar to the compression for tablet dosage forms. The materials to be encapsulated will need to have good flow properties and a consistent density.

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Quality control testsPHYSICAL TEST

• Disintegration test• Weight variation

CHEMICAL TEST• Dissolution test• Assay• Content uniformity• Stability testing• Moisture permeation

test

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• Solid dosage form validation should be part of comprehensive validation program within an industry.

• The validation team must identify the product and process characteristics to ensure that product will meet all quality, manufacturing and regulatory requirements.

• Continuous awareness of validation will produce reproducibility.

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CONCLUSION

REFERENCE

• http//www.pharmainfo.net/reviews/guidelines-general-principles-validation-solid-dosage.

• Berry I.R., and Nash R.A., ”Pharmaceutical

Process validation” second edition, revised and expanded; Marcel Dekker series; 83-110

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