Quality Assurance Handbook.pdf

QA HAND BOOK A Compendium of Guidelines and Related Materials EDITION I PHARMACEUTICAL FORMULATIONS 2022 Ajay Thakur QA HAND BOOK Page 2 of 534 INDEX S No QUALITY ASSURANCE BASIC PAGE NO 1 QUALITY ASS[.]

QA HAND

2022

Ajay Thakur

QA HAND BOOK

INDEX

Data from these studies, in addition to long term stability studies, can be used to assess longer term chemical effects at non-accelerated conditions and to evaluate the effect of short term excursions outside the label storage conditions such as might occur during shipping Results from accelerated testing studies are not always predictive of physical changes

Active Ingredient

An active pharmaceutical ingredient (API) is the chemical substance contained in a pharmaceutical dosage form, which is responsible for its therapeutic effect

Adverse Reaction (Adverse Drug Reaction), ADR

An adverse drug reaction is a response to a medicinal product which is noxious and unintended and which occurs at doses normally used in man for the prophylaxis, diagnosis or therapy of disease or for the restoration, correction or modification of physiological function

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QUALITY ASSURANCE

BASIC

QA HAND BOOK Why Companies Have Difficulties

Why? Incorrect Root Cause Identified

Analyze: Not done

Verify: Problem recurrence

Review: Preventive Action does not work

Implement: Corrective Action wrong

Identify : Problem but not root cause

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CLEANING VALIDATION

It is a document act of demonstrating that cleaning procedure for the equipment used in the fabrication/packaging will reduce to an acceptable level of all residues the (product & cleaning agent) and to demonstrating that routine cleaning & storage of equipment does not allow microbial proliferation

Importance of Cleaning Validation

• “Particular attention should be accorded to the validation of … cleaning procedures” (WHO)

• “Cleaning validation should be performed in order to confirm the effectiveness of a cleaning procedure” (PIC/s)

• “The data should support a conclusion that residues to an acceptable level” (FDA)

Cleaning validation Studies

Following cleaning validation related studies shall be carried out:

Cleaned Equipment Hold Time Study (CEHT)

Hold time study shall be carried out to ensure the suitability of cleaned equipment, stored in its prescribed storage conditions, and does not increase the microbial contamination level more than the limit for freshly cleaned equipment

Dirty Equipment Hold Time Study (DEHT)

The dirty equipment hold time studies shall be carried out to ensure the microbial proliferation over a period of time and the same shall be possible to clean

Sampling Techniques

Direct Surface sampling (Swab method)

Rinse Samples (Indirect method)

Document Approval and Distribution

Each manufacturer shall designate and individuals(s) to review for adequacy and approve prior

to issuance all documents established to meet the requirements of this part

The approval, including the date and signature of the individuals approving the document, shall be documented

Documents established to meet the requirement of regulatory agency shall be available at all locations for which they designated, used, or otherwise necessary, and all obsolete documents shall be promptly removed from all points of use or otherwise prevented from unintended use

Repository

of audit

NA

Table B: Documents/ Activities require for qualification of New Vendor

Documents/Activities required for Qualification of New vendor

RM other than KRM

5 Stability Data / Shelf

Life Declaration / Retest

other than

KE

RM other than KRM

7 TSE / BSE Declaration /

TSE / BSE risk

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Quality / Facility Audits

Audits are conducted to ascertain the validity and reliability of the information; also to provide

an assessment of the internal control of a system

It provides management with information on the efficiency with which the company controls the quality of its processes and products

In FDA & ISO environments, auditing of both compliance and performance is essential

Pharmaceutical audit experience includes the drafting and revision of validation policies, guidelines and SOP from project qualification to performance evaluation phases

If implemented correctly; it can be one of the most effective means of improvement

With proper preparation and planning, the audit itself must easily achieve the intended purpose

Effective auditing and proper compliance with standards will help build brand reputation and avoid the negative effects of non-compliance, such as fines, bad public relations and court proceedings

Objectives

Audit objectives may include:

• Evaluating conformity of requirements to ISO 9001

• Evaluating conformity of documents to ISO 9001

• Judging conformity of implementation to documentation

The aim to achieve a wide global harmonization of quality specifications for selected pharmaceutical products, excipients and dosage forms came with increased globalization and reciprocal collaboration

History of these approaches goes back to 1902-1925 when agreements established a “Unified” Pharmacopoeia In 1929 the “Brussels Agreement” stipulated the League of Nations to carry out related administrative functions

Eight year later in 1937, the first meeting of the “Technical commission of Pharmaceutical Experts” was held An important date in the history of quality assurance of medicines is 1948, when the First World Health Assembly (WHA) approved the Expert Committee on Unification

of Pharmacopoeias to continue this work One year later, the WHA renamed it the Expert Committee on International Pharmacopoeia

Each country has legislation on pharmaceutical preparations which sets a standards and required quality indices for medicament, raw materials and preparations employed in the manufacturer of drugs

These regulations are presented in separate articles General and specific matters relating to

individual drugs are published in the form of a book called a Pharmacopoeia

On 15th December 1820, the first United States Pharmacopoeia (U.S.P) was released

In 1864, the first British Pharmacopoeia (B.P) was published

In 1955, the first Indian Pharmacopoeia (IP) was published

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two supplements between the editions after JP12 and partial revision at any time if immediate necessity United State of America (Ph

biannually Korea* The Korean Pharmacopoeia Currently revised in every 5

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Answer

What is IPQA department?

The main goal of IPQA department is to help create a quality product Their Job is not only bug searching and regular product testing, but to also prevent defects accordingly They ensure the high quality of the development process and its results

What is IPQA Chemist?

IPQA is determined by quality proceedings in standards and specifications of manufactured products to prevent mistakes, problems to customer services

What are the IPQA activities?

• Verify the area label with the process going on in the area

• Verify the cleanliness of area and operation

• The status label verification of the equipment with process stage

• Verify whether the activities are carried out in accordance with relevant SOPs and

instructions in BMR & BPR

• Verify timely completion of batch documents

• Personal practices verification including gowning

• Verify pressure differential of areas and shall be within limits defined on the respective

Magnehelic gauge

• The temperature and relative humidity of areas shall be in compliance as per SOP

• Verify status label where relevant

• Verify the calibration status and records of the balances

• Verify the Equipment Re-Qualification status

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• To verify the Inward and Outward entries of material

• To perform the calibration of the Instruments i.e DT, Friability, Hardness tester,

Moisture Analyzer

• To perform the In-Process at various stages as per frequency

• To maintain the GMP on the shop floor

• To perform the sampling at various stages

Ware House

The Warehouse plays a pivotal role in manufacturing quality products, as it is responsible for all incoming goods (including labeling and packaging) and for releasing finished products Therefore there are GMP rules in place to ensure that materials are handled and stored properly, while appropriate documentation is maintained

Once a finished product is received into the warehouse, it does not undergo any further inspections or quality control tests If the product is degraded or damaged at this point, there

is nothing that stops it from being given to the patient The Warehouse must rely upon procedures and well trained staff to ensure that product arrives safely and with the same quality as when they left manufacturing

There have been many cases of product being affected by poor warehouse storage conditions

or rough handling on transport Biopharmaceutical products have temperature sensitive active ingredients that breakdown or degrade if exposed to heat or lights, thus becoming ineffective

A pharmaceutical warehouse must be expertly managed and run in compliance in order for the company to protect and distribute a quality product

These compliant practices include control over receiving goods, quality control, storing materials, components and products, fulfilling picking requests and shipping the product to the market place These practices must be completely traceable in order to protect the integrity and stability of the product and its packaging

What is the role of IPQA in Warehouse?

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In process Quality Assurance (IPQA) plays a prominent role in every activity in warehouse and ensures that the results produced meets the GMP specifications

• IPQA is responsible for affixing hold labels to the damaged packs

• Ensuring the recording of temperature and RH in storage areas

• To identify the documentation errors wherever found out

• Identification of approved vendors and new vendors

• Ensuring the status of the materials i.e Quarantine, Approved and rejected

• Ensuring that the materials stored in appropriate storage areas

IPQA giving Line clearance for the dispensing of batches and verification of weighing balances, Calibration and cross contamination of the materials can be prevented by the role of IPQA

What is GWP vs GDP?

GWP refers to the practices specifically within the company warehouse GDP refers specifically

to the transport and distribution of the product

• Good Distribution Practice (GDP) and Good Warehousing Practices (GWP) are each special parts of GMP GDP refers specifically to the transport and distribution of the product GWP refers to the practices specifically within the company warehouse

• GDP and GWP each have their own legal definition and regulations These regulations recognize that product quality can be significantly impacted offer manufacturing and packaging has taken place

• GMP for the warehouse incorporates practices, rules, and regulations spanning GMP, GDP, and GWP

What are the GMP rules for the Warehouse?

• Protect medicines from damage during storage and transport

• Prevent degradation of the product by exposure to adverse temperature conditions

• Avoid mix-ups and contamination by other materials

• Maintain product identity and traceability

• Prevent time-expired or damaged material or product from being used

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What comes into the Warehouse?

The following goods generally do not appear on any production bill of materials, and have a simplified check and release Often, they do not have an in-house lot number applied, but this varies from company to company

• Non-production consumables (non-GMP material), e.g toilet paper, Stationery

• Production materials consumed in processing e.g filters

• Laboratory reagents e.g Buffers, Chemicals

The last two items above will usually have their own QC approval processes

The following goods will always appear on any production or packaging bill of materials They are each governed by GMP quality control and release procedure All these goods will be issued with unique lot numbers

• Manufacturing starting materials and chemical

• Packaging components, e.g blister pack film, bottles, caps, vials, seals

• Printed matter, e.g labels, cartons, inserts/leaflets, pre-printed tubes

How the Warehouses are classified?

Warehouses are typically classified by the types of material they contain, For example, Raw materials, Packaging materials, Intermediate or Bulk product and Finished product

A typical warehouse will contain some or all of the areas described below

• Quarantine area for storing goods that have not yet been inspected or tested Materials stored in Quarantine cannot be used or released until approved by QC

• Some warehouses have a Dangerous Goods storage area to ensure the safety of staff and the facility For example, Flammable goods such as ethanol would be stored in this area Special storage conditions, such as Flame Proof Cabinets, are used here

• Some warehouses have a locked area for restricted goods, such as poisons and drug of addiction This area is restricted to specifically authorized staff

• A separate area for isolating faulty or recalled goods, ensuring that they are not issued

or sold by mistake

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Granulation

Granulation is a process of producing granules generally In pharmaceutical manufacturing, granulation process implies the techniques that are used to combine powdered particles to from relatively bigger ones called granules This process is used for commercial production of tablets

The granulation process of size enlargement used within the pharmaceutical industry has its roots in ancient times The practice of delivering medicinal powder by hand rolling into pill by using honey or sugar has been used for centuries It is still the practice to deliver the botanical and herbal extract in homeopathic and ayurvedic branches of medicines, which are still practiced in India along with allopathic medicine

The term “granulated” material is derived from the Latin word “granulatum” meaning grained The granulated material can be obtained by direct size enlargement of primary particles, or size reduction from dry compacted material In modern times, granulation technology has been widely used by a wide range of industries, such as coal, mining, and agrochemical These industries employ agglomeration techniques to reduce dust, provide ease of handling, and enhance the material’s ultimate utility

The development of pharmaceutical granulation was driven by the invention of the tablet press by W Brockedon in 1843 Subsequent improvements in the tablet machinery were

API Color & Flavor

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patented in the United States by J A McFerran 1874, T.J young 1874, and J Dunton 1876 The demands on the granulation properties were further enhanced in the 1970s as high speed tablet and capsule filling machine with automated controls were introduced

The continuous refinements in the regulatory requirements such as low-dose products requiring blend uniformity/ content uniformity necessitated knowledge and technology to produce the required granule characteristics The high speed compression and capsule filling machines require a uniform flow of material to the dies or filling stations that produce pharmaceutical dosage form

Granulation methods can be divided into two major types: Wet methods which utilize some form of liquid to bind the primary particles, and dry methods which do not utilize any liquid

What are the types of Granulation?

There are two types of granulation

(1) Dry Granulation

(2) Wet Granulation

Dry Granulation

• Dry Granulation is the process of forming granules without using any liquid solution

• Involves the direct compression of a finely ground powder

• Requires finely powdered compound and tablet pressers or roll compactors

• Required when producing tablets from highly moisture and heat sensitive compounds

Wet Granulation

• Wet granulation is the process of forming granules by adding a granulating liquid

• Involves mixing the powder with a granulating fluid, followed by forcing through a sieve

to make tablets

• Requires powder particles, a granulating fluid and a sieve

• Required to avoid the destruction of active components in the powder

What are the reasons for Granulation?

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• Good flow properties

• Binding capacity to from tablets of low friability

• Adequate hardness

What is the difference between wet granulation and dry granulation?

There are three types of granulations as dry granulation, wet granulation, and direct blending The main difference between dry and wet granulation is that dry granulation is the formation

of granules without using any liquid solution whereas wet granulation is the formation of

granules by adding a granulating liquid

What is dry granulation?

Dry granulation is a powder agglomeration process used in the pharmaceutical industry to improve the flow ability of powders by increasing the particle size (granules)

What is roll compactor?

Roller compaction is a dry granulation process used to make coarse granules prior to final compression Typical excipients used in roller compaction are Lactose, Microcrystalline Cellulose, and Magnesium Stearate as the lubricant

What is dry granulation process?

Basic principles of Dry Granulation and Roller Compaction Technology Granulation is a process

in which powder particles are made to adhere to each other, resulting in larger, multi-particle entities, so called granules If such a process is performed without adding liquids, this is called dry granulation

What is dry granulation method?

Dry granulation is a simple and low cost method, once extremely common and again becoming more popular because of its simplicity and cost efficiency Dry granulation helps to increase the size of granules within powders, making it easier to form them into tablets or capsules

(2) Dry Granulation

Dry granulation does not involve the use of a liquid lubricating agent This is because constituents utilized might chemically react with the agent used, thus dry granulation equipment technique is used

Dispensing: The first step in dry granulation is dispensing of the API and excipients used, in specified amount

Dry mixing or Blending:Once both constitutes are dispensed, API and intragranular excipients are mixed together through dry mixing

Compaction:After dry mixing of the materials, they are passed through roller powder compactors for compaction This results in the formation of slugs Slugs are the rough form of tablets, usually quite large in size

Milling or crushing:The slugs are then milled or crushed until the required granule size is obtained Depending upon the product requirement, sieves are used to attain granules of the right size At this stage, further mixing is done with the addition of extra granular excipients Extra granular excipients do not form the part of the main mixture; instead they are added after the granulation has taken place Extra granular excipients include diluents, disintegrating

in the wet powder bed

How to measure tip speed of RMG?

Blade speed (tip speed), measures how far a point on the outer most edge of the disperse blade travels in a given amount of time You may remember from early math classes that the circumference of a circle is equal to:

So if we take a 1 foot diameter (D) blade and turn it one complete revolution, a point on its edge would have travelled pi(π)3.14 feet By multiplying by rpm (n) we get the Tip speed

• n – Impeller rotation speed (fpm)

Why we measure RMG in liters?

Because every powder product has different bulk density so we can’t mention it in kg We always mention in liters and products can be calculated in kg by factor

What is Kneading?

Kneading time is a wet mixing process after addition of binder solution in any of the mixer either RMG or low shear mixer granulator

• Improve Hot air circulation in tray dryer for uniform drying for this check blower speed

• Load the product trolley according to its capacity

• In FBD increase fan motor speed for proper fluidization

• Use stirrer to properly mix granules in product trolley for uniform drying

• Use shakers or blowback systems to prevent filter clogging during drying

Mottling/Color Migration

Mottling or color migration is a defect that occurs during the drying of granules in which we use color

Reason

• Dye colors are water soluble and migrate along with the evaporation of water

• Excessive drying without stirring the granules in the product trolley

• Most products dried in a tray dryer show a mottling effect

Solution

• The use of lake colors prevents color migration because lakes are not soluble in water

• Do not over-dry the granules

• Use a stirring mechanism during drying which brings new surfaces in contact with heat

• The use of microcrystalline cellulose in product formulation prevents color migration

Problems during Sieving of Dried Mass

Dry sieving is the process in which we convert dried granules into uniformly sized granules using a specified mesh or sieve in an oscillating granulator or dry mill

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CPP & CQA of Granulation stage

Sr No Unit Operation Critical Process Parameters Critical Quality Attributes

1 Mixing

• Order of addition

• Mixer load level

• Impeller speed and time

• Chopper speed and time

• Chopper On/OFF pattern

• Mixing time

• Particle size distribution

• Binder addition rate and time

• Post granulation mix time

• Blend Uniformity Flow

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stroke machines and Manesty tooling was not changeable with Stroke machines Manesty named its small machines B3B and large machines D3a

In the start of 1900 unique model of Kilian was developed in Italy by Kilian Gmbh The Kilian

machine was different from B and D standards In Kilian compression machine the traditional punch head system which guides the upper punch was not used instead it has its own punch shape in which punch is guided by cam angle on side of upper punch barrel

In 1997 unique model was developed by “Ima called ima comprise” using a unique feeding

system based on centrifugal forces created by the rotation of the turret In Ima machine tablet ejection system was also unique; the tablet is ejected from the bottom of the die cavity using the force of gravity

In 2005 Fette developed most advance high-speed machines with the concept of segmented dies Segmented dies reduce set up hours

What is aTablet?

Tablets are solid dose pharmaceutical preparation containing drug substances usually prepared with the aid of suitable pharmaceutical excipients That may vary in size, shape, weight, hardness, thickness, disintegration, and dissolution characteristics and in other aspects, depending on their intended use and method of manufacture

It has been estimated that solid dosage forms constitute approximately 90% of all dosage forms clinically used to provide systematic administration of therapeutic agents The widespread use of tablets has been achieved as a result of their convenience and also the diversity of tablets types

Tablets are prepared primarily by compression of granules or powder blends, with a limited number prepared by molding Most tablets are used in the oral administration of drugs Many

of these are prepared with colorants and coatings of various types Other tablets, such as sublingual, buccal, or vaginal tablets, are prepared to have features most applicable to their particular route of administration

Define general properties of Tablets?

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• Various mathematical equations have been used to describe the compaction process

• Kawatika equation is modified form of heckel’s equation

What is Powder Porosity?

Ratio of the volume of voids between particles, plus the volume of pores, to the volume

occupied by the powder, including voids and pores

Which factor influence the Flow properties of powders?

Flow properties of powders are basically mechanical properties The behaviors of bulk powders are very much similar to the non-Newtonian fluids due to its plastic flow and dilatancy The iteration of particles is influenced by the attractive forces, such as van der Waals, particle size, shape, porosity, moisture content and bulk density

Define Flow Property?

Good flow property of a pharmaceutical powder is essential to ensure proper die fill during compression, especially in direct compaction process

Angle of repose is commonly used to measure flow of powders, and is the maximum angle between the plane of powder and horizontal surface

Flow Property Carr’s Index (%) Hausner’s ratio

Very, very poor >38 >1.60

Fair-aid not needed 36-40

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Very, very poor >66

What is angle of repose?

The angle of repose is an engineering property of granular materials It is the maximum angle

of a stable slope of pile formed on horizontal surface

When bulk granular materials are poured onto a horizontal surface, a conical pile will form The internal angle between the surface of the pile and the horizontal surface is known as the angle of repose and is related to the density, surface area, and coefficient of friction of the material

Material with a low angle of repose forms flatter piles than material with a high angle of repose The exact angle depends upon conditions such as a size, shape, and density of the powder, sorting or mixture of sizes and the height of fall of the powders

What is compression machine?

Tablets are being formed by compressing the granules using the compression machines Different innovations to tablet compression machines are being done to improve the production rates and now it is possible to produce more than 5000,000 tablets per hour A tablet formation takes place by the combined pressing action of two punches and a die

What is the principle of Compression machine?

The basic principle behind the tablet compression machine is hydraulic pressure The pressure

is transmitted unreduced through the static fluid Any externally applied pressure is transmitted via static fluid to all the directions in the same proportion It also makes it possible

to multiply the force as needed

What are the different stages of compression machine process?

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Tablet press hoppers come in a wide range of shapes and designs Whatever the shapes and designs Whatever the shape, it should be such that material can flow seamlessly into the tablet compression chamber

Again, since it is one station that is in direct contact with the material, it is made of stainless steel Depending on the design of a tablet press machine, you can fill the powder manually or using other automated systems

As tablet press machine manufacturer, we put every measure in place to ensure there is a consistent flow of powder from the hopper to compression systems

Here are major concerns that are addressed so far:

• Hoppers may feature optimal flow angles to facilitate flow, especially where it is nearly impossible to adjust formulation

• Some hoppers may feature vibratory rods This is done carefully to enhance product flow and to prevent possible product separation

At any given point, the design of these tablet compression machine parts aim to eliminate possible feeder starvation

Feeder System

This yet another critical part of the tablet compression process Remember, at any given time, the design of the system should be such that it allows an accurate and consistent amount of powder to flow to the punch and die system

Compression machine feeder system is made up two critical components:

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• Use good quality tooling

• Properly adjust the lower punch position

Chipping

Tablet chipping is a problem or defect in which the edges of the tablet chip during tablet

compression

Reasons for Tablet Chipping

• Worn out, punches and dies

• The lower punches position is not adjusted properly

• The highlight of the scrapper blade is high over the turret

Solution

• Regularly inspect punches and dies

• Adjust lower punches and scrapper blade

Tablet Sticking and Picking

There is a difference between sticking and picking but the reasons for both problems are almost the same

Formulation Related Reasons for Tablet Sticking & Picking

• Higher moisture content in the blend

What is Content Uniformity?

Content uniformity is a test used to evaluate the equality of the dosage of a pharmaceutical drug The method is applicable for tablets which contain the active ingredient in less than 10mg or 10% w/w

Also, this test is not applicable to multivitamin drugs or trace elements During this test, 10 tablets can be taken randomly from a sample in order to determine the amount of active pharmaceutical ingredient in them

Then the mean value can be calculated The mean value of an active pharmaceutical ingredient has to be within 85-115% or 75-125% of the average value

After that same test is performed for another 20 tablets if 2-3 tablets are out of range

The sample is not considered as fulfilling the required does if the total sample of 30 tablets has more than three tablets that are out of the range of 85 to 115% or more than three tablets that are out of range of 75 to 125%

What is an Assay?

An assay is another analytical procedure used to characterize the main functional component

of a sample Also, an assay can be an either quantitative and/ or qualitative test

Moreover, the original application of assays is widely used in pharmaceutical industry to characterize the active pharmaceutical ingredient

In addition, assays are widely used in other areas including laboratory medicine, pharmacology, environmental biology, immunology, molecular biology and biochemistry

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Sampling with AQL addressed these concerns By pulling a sample of bullets randomly from a lot, the military was able to test part of the lot and use those results to estimate the quality of the total lot

What is Critical defect in AQL?

It is one that will affect the quality of the finished product (unsafe) and cause a potential risk

to the patient The AQL for critical defects is very low i.e 0.0%

What is a Major defect in AQL?

It is one that will likely to cause non-conformance of product during manufacturing/packaging, testing, shipment, storage or use Such failures do not constitute a potential risk to the patient The AQL for major defects normally ranges from 0.0 to 2.5%

What are Minor defects in AQL?

It is one that will not affect the quality of the finished product (unsafe) and cause no potential risk to the patient The AQL for minor defects normally ranges from 0.0 to 6.5%

What are the classifications of compression critical, major & minordefects for AQL?

In critical defects

Embedded Specks / Hair

embedded / Fiber

Particles, which are foreign, extraneous, or contaminant particles

to the tablet The particles are embedded in or in the surface of the tablets, which cannot be wiped or blown off

Capped/ Layer separation

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Dissolution Dwell Time Thickness, Hardness,

Dissolution Feeder Speed Weight variation, Hardness,

Thickness Upper Punch entry Hardness, Thickness Tooling type used Hardness, Thickness Verification of tooling before use Product Mix-up

COATING

The use of coating material for solid dosage form is very old and its first reference is found in Islamic literature where Rhazes describe the coating of pills

Tablet coating is a common pharmaceutical technique of applying a thin polymer-based film to

a tablet or a granule containing API Solid dosage forms are coated for a number of reasons, the most important the most of which is controlling the release profiles

Tablets are usually coated in horizontal rotating pans with the coating solution sprayed onto the free surface of the tablet bed The advantages of the tablet coating are taste masking, physical and chemical protection, protect the drug from gastric environment etc

There are various techniques for tablet coating such as sugar coating, film coating and enteric coating Recent trends in pharmaceutical technologies are the development of coating methods which overcomes the various disadvantages associated with solvent based coatings

In these latest technologies coating materials are directly coated on the surface of the solid dosage for without using any solvent Various solvent less coatings are available such as electrostatic dry coating, magnetically assisted impaction coating, compression coating, hot melt coating, powder coating and supercritical coating

“Panning” was the original word for the process of adding a coating to a tablet The word panning is still a common term which is used in the confectionary business In past years coating perform basically using a rotating drum (pan) on a stand

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A coating solution was added, while the rotation of the pan distributed the solution throughout the bed of tablets The main disadvantage of this technology was slow waiting for coating solution to dry; and the trick was to get it to dry evenly

With the advent of film coating a film or thin membrane, usually representing 1-3% of the total tablet weight, was sprayed on using a perforated pan To decrease the overall process time, holes were made through the pan so that treated air (hot or cold) could be pulled through the pan so that treated air (hot or cold) could be pulled through the pan, much like a clothes dryer, allowing the tablets to dry more quickly

With this advent of improved drying came the ability to switch the film coating solution from a solvent based solution to a water based solution

Coating of pharmaceutical dosage forms has been practiced for many centuries The historical development of coating technique is mentioned below

LAST 40 YEARS

Features

• Introduction of the side-vented tablet coating pans (with perforations)

• Evolution was required for the introduction of aqueous based film coating polymers to the pharmaceutical industry

• Carbon steel construction except for pan

• Many screws, not welded in places

• Does not complywith GMP

LAST 30 YEARS

Introduction of reliable microprocessor based process control systems required to insure process control and repeatability

Features

• Improved design spray nozzles for tablet coating

• Specific applications (all stainless steel)

• Improved air preparation systems required for consistent aqueous process drying

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Evaporation of organic solvent requires less heat Organic solvent are costly so the cost of this process us increased

Aqueous + Organic Solvent Coating

In the aqueous + organic solvent coating, the solvent used is a mixture of water and organic solvent Usually, 90% organic solvent and 10% water is used

(3) Plasticizers

• Plasticizers are one of the important components of coating suspension

• Plasticizers are low molecular weight materials and are used to increase the film forming capacity of polymers

• Polymers are long chain molecules and plasticizers break the long-chain polymer interaction and rearrange them to enhance their film forming capacity

polymer-• Plasticizers decrease the glass transition temperature of polymers

When the coating film is peeled from the surface of the tablet it is due to the fact that coating suspension does not have a plasticizer or the amount of plasticizer is low

(4) Colorants

• Color may be added to the formulation depending upon the requirements

• Color gives an attractive and appealing look to the tablets

• Different colors are used for different strengths of the same product to prevent mix up

• FD&C or D&C type colors are used

• For coating lakes and dyes are used

• Dyes are water soluble so when the heat is applied dye migration occurs and these results in color variation

• Lakes are water insoluble so during drying they are resistant to migration and prevent the problem of color variation

Classifications of Colors

Colors are classified into following classes,

• Organic dyes and their lakes